Pengfei Zhang, Lei Zhou, Rui Wang, Xinyu Zhou, Jiapei Jiang, Zijian Wan, Shaopeng Wang. Evanescent scattering imaging of single protein binding kinetics and DNA conformation changes. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-30046-8
To fully understand proteins and their myriad functions, researchers have developed sophisticated means to see and study them through advanced microscopy, improving light detection, imaging software, and the integration of advanced hardware systems.
In a new study, corresponding author Shaopeng Wang and his colleagues at Arizona State University describe a new technique that promises to revolutionize the imaging of proteins and other vital biomolecules, allowing these tiny entities to be visualized with unprecedented clarity and by simpler means than existing methods.
“The method we report in this study uses normal cover glass instead of gold coated cover glass, which has two advantages over our previously reported label-free single-protein imaging method, Wang says. It is compatible with fluorescence imaging for in-situ cross validation, and it reduces the light-induced heating effect that could harm the biological samples. Pengfei Zhang, an outstanding postdoctoral researcher in my group, is the technical lead of this project.”
Wang has a joint faculty position in the Biodesign Center for Bioelectronics and Biosensors and School of Biological and Health Systems Engineering. The group’s research findings appear in the current issue of the journal Nature Communications.
The new method, known as evanescent scattering microscopy (ESM), is based on an optical property first recognized in antiquity, known as total internal reflection. This occurs when light passes from a high-refractive medium, (like glass) into a low-refractive medium (like water).
When the angle of incident light is moved away from the perpendicular (relative to the surface), it eventually reaches the “critical angle,” resulting in all the incident light being reflected, rather than passing through the second medium. (To properly illuminate biological samples, laser light is used.)
Total internal reflection produces an evanescent field, which can excite cells or molecules like proteins at the glass-water interface, when such molecules are affixed to a cover glass, allowing researchers to visualize them in startling detail.
Previous methods commonly label the biomolecules of interest with fluorescent tags known as fluorophores, to better image them. This process can interfere with the subtle interactions being observed and requires cumbersome sample preparation. The ESM technique is a label-free imaging method requiring no fluorescent dye or gold coating for sample slides.
Instead, the method exploits subtle irregularities in the surface of the cover glass to produce images of razor-sharp contrast. This is achieved by imaging the interference of evanescent light scattered by the single-molecule samples and the rough texture of the cover glass.
The use of evanescent wave scattering allows samples, including proteins, to be probed at extremely shallow depth, typically
The new study describes the use of ESM to detect four model proteins: bovine serum albumin (BSA), mouse immunoglobulin G (IgG), human immunoglobulin A (IgA), human immunoglobulin M (IgM).
Protein-protein interactions, including the rapid binding and dissociation of individual proteins were observed in a series of experiments. Understanding such binding kinetics is essential for the design of safer and more effective drugs. The researchers also used ESM to keenly observe conformational changes in DNA, further demonstrating the power and versatility of the new method.
Pengfei Zhang, Lei Zhou, Rui Wang, Xinyu Zhou, Jiapei Jiang, Zijian Wan, Shaopeng Wang. Evanescent scattering imaging of single protein binding kinetics and DNA conformation changes. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-30046-8
To fully understand proteins and their myriad functions, researchers have developed sophisticated means to see and study them through advanced microscopy, improving light detection, imaging software, and the integration of advanced hardware systems.
In a new study, corresponding author Shaopeng Wang and his colleagues at Arizona State University describe a new technique that promises to revolutionize the imaging of proteins and other vital biomolecules, allowing these tiny entities to be visualized with unprecedented clarity and by simpler means than existing methods.
“The method we report in this study uses normal cover glass instead of gold coated cover glass, which has two advantages over our previously reported label-free single-protein imaging method, Wang says. It is compatible with fluorescence imaging for in-situ cross validation, and it reduces the light-induced heating effect that could harm the biological samples. Pengfei Zhang, an outstanding postdoctoral researcher in my group, is the technical lead of this project.”
Wang has a joint faculty position in the Biodesign Center for Bioelectronics and Biosensors and School of Biological and Health Systems Engineering. The group’s research findings appear in the current issue of the journal Nature Communications.
The new method, known as evanescent scattering microscopy (ESM), is based on an optical property first recognized in antiquity, known as total internal reflection. This occurs when light passes from a high-refractive medium, (like glass) into a low-refractive medium (like water).
When the angle of incident light is moved away from the perpendicular (relative to the surface), it eventually reaches the “critical angle,” resulting in all the incident light being reflected, rather than passing through the second medium. (To properly illuminate biological samples, laser light is used.)
Total internal reflection produces an evanescent field, which can excite cells or molecules like proteins at the glass-water interface, when such molecules are affixed to a cover glass, allowing researchers to visualize them in startling detail.
Previous methods commonly label the biomolecules of interest with fluorescent tags known as fluorophores, to better image them. This process can interfere with the subtle interactions being observed and requires cumbersome sample preparation. The ESM technique is a label-free imaging method requiring no fluorescent dye or gold coating for sample slides.
Instead, the method exploits subtle irregularities in the surface of the cover glass to produce images of razor-sharp contrast. This is achieved by imaging the interference of evanescent light scattered by the single-molecule samples and the rough texture of the cover glass.
The use of evanescent wave scattering allows samples, including proteins, to be probed at extremely shallow depth, typically
The new study describes the use of ESM to detect four model proteins: bovine serum albumin (BSA), mouse immunoglobulin G (IgG), human immunoglobulin A (IgA), human immunoglobulin M (IgM).
Protein-protein interactions, including the rapid binding and dissociation of individual proteins were observed in a series of experiments. Understanding such binding kinetics is essential for the design of safer and more effective drugs. The researchers also used ESM to keenly observe conformational changes in DNA, further demonstrating the power and versatility of the new method.
[date_timestamp] => 1651207402
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[1] => Array
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[title] => Chi è Mino Raiola, il re del calciomercato: la sua storia
[link] => https://packagingnewsonline.com/crypto-news/chi-e-mino-raiola-il-re-del-calciomercato-la-sua-storia/
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[pubdate] => Fri, 29 Apr 2022 04:32:25 +0000
[category] => Crypto NewsCalciomercatoCHIDelMinoRaiolastoriasua
[guid] => https://packagingnewsonline.com/crypto-news/chi-e-mino-raiola-il-re-del-calciomercato-la-sua-storia/
[description] => A 15 anni era contabile in una pizzeria, a 19 ha fatto i primi soldi...
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A 15 anni era contabile in una pizzeria, a 19 ha fatto i primi soldi vendendo un McDonald. Poi è diventato l’agente più spregiudicato del calcio mondiale: ogni anno porta a casa l’equivalente di una manovra finanziaria
Furio Zara
Il più potente, il più bravo, il più discusso, il più temuto – dai club – il più amato – dai suoi assistiti. Uno dei più ricchi, sicuro, il Paperon dei Paperoni del calcio 2.0 che ogni anno porta a casa l’equivalente di una manovra finanziaria.
Patrimonio stimato da Forbes nel 2020: fatturato da 84,7 milioni di dollari, giro d’affari di 847,7 milioni. Ricordando il primo incontro con Ibra, Mino Raiola ha raccontato: “Dal primo istante capìi che era uno str*** arrogante. Esattamente come lo ero io”. Bisogna necessariamente partire da qua – da questa ironica ammissione – per raccontare il “Consigliori”, l’agente spregiudicato e dal fiuto finissimo, il padre putativo di molti suoi assistiti, il Belzebù del pallone, il Jerry Maguire con la valigia di cartone, il Faraone delle commissioni, il “Ciccione che ha modi da mafioso” per Alex Ferguson, addirittura l’uomo – secondo un sondaggio di un paio d’anni fa di “Voetbal International” – più influente del calcio olandese, più di Cruijff per dire.
SOLO PUROSANGUE NELLA SUA SCUDERIA
Provare a definire i contorni della sua figura non è semplice. La Storia non gli addice, gli si addice la Cronaca. Per cominciare basti dire che: ha stravolto un mondo. Ha alzato sempre il tiro, muovendo a proprio piacimento i top-player sulla scacchiera del calcio europeo. Sono sue le pedine, il sospetto è che sia sua anche la scacchiera. Ora il mal di pancia, ora l’ambizione, ora la divergenza di obiettivi. Arrivano in una squadra, dopo sei mesi ne vogliono un’altra. Soldi, questione di. Soldi. Soldi. Soldi. Ne ha mossi tantissimi, Raiola. Sua la commissione record di tutti i tempi. 26,154 milioni intascati nel 2016 per portare Paul Pogba dalla Juventus al Manchester United. Negli ultimi anni si attesta su una media di 65-70 milioni l’anno di commissioni, sul podio degli agenti più ricchi, dopo Jorge Mendes e Jonathan Barnett. Solo cavalli pregiati nella sua scuderia, solo purosangue. Ibra, ovviamente. Pogba. Lukaku. Donnarumma. De Ligt.
HA CAMBIATO RUOLO E MISSIONE DELL’AGENTE
Va detto con chiarezza: Raiola ha ribaltato la figura dell’agente, la cui evoluzione – in questi ultimi vent’anni – è andata di pari passo con quella del calciatore che da dipendente – il cartellino era della società – si è trasformato in azienda, con modalità di azione riconducibili al celebre slogan femminista: il corpo è mio e lo gestisco io. È andata esattamente così. A Raiola va il merito – la colpa? – di aver ribaltato anche la dinamica dei rapporti con i calciatori. È Raiola a scegliere i suoi assistiti, come un sovrano indica i vassalli; mai il contrario. È Raiola a trattare – dall’alto in basso – con le società. Se entri nel giro di Raiola sei sicuro che il tuo valore balzi alle stelle. La deregulation varata dalla Fifa di Joseph Blatter nel 2015 ha reso il calciomercato una giungla. Di questa giungla, Raiola è il padrone incontrastato. Di più: l’intermediario abilissimo nel trattare per conto di chi vende, di chi compra, dello stesso oggetto della compravendita. Raiola, uno e trino.
VIA LE CRAVATTE, MEGLIO BERMUDA E POLO
Sempre a Ibra ha detto: “Vuoi diventare il miglior calciatore al mondo o quello che guadagna di più?”. Con Raiola buona la seconda. Con lui i calciatori sono legati da un rapporto fortissimo, un patto di sangue prima ancora che professionale. Sali sulla giostra, non scendi più. Esemplare il caso Balotelli. Ad un certo punto SuperMario valeva perché era Raiola a decretarne il valore, non certo le prestazioni in campo. Raiola ha avuto anche un ruolo cruciale nel costume del nostro calcio. Prima di lui, per decenni, l’agente si manifestava signorile nei modi, azzimato nel porgersi. Doveva fare bella figura, essere credibile. Giacca, cravatta, polsini alla camicia, Rolex da sfoggiare, diploma anche no, a che serve in fondo? Con Raiola tutto questo è diventato fuffa. Abolite le cravatte, inutile il doppiopetto. Polo extralarge, da bagnino svogliato. Bermuda che – negli incontri nei grandi hotel – sembravano persino offensivi. È in realtà un modo per marcare il territorio, per ribadire: sono io quello che comanda. Forse è un retaggio dell’infanzia da immigrato, forse lo sberleffo dell’uomo partito dal nulla, il self made man che si è fatto da sé e che – dopo aver covato tanto rancore – si prende la sua rivincita.
DAL PROFONDO SUD ALL’OLANDA
La sua biografia andrebbe studiata nelle scuole. Nato di otto mesi a Nocera Inferiore, 4 novembre 1967, ma solo perché ad Angri, nel Salernitano, dove vivevano i suoi, l’ospedale non c’era. Profondo Sud, quando ha un anno affronta seduto sul seggiolino della macchina il viaggio che gli cambierà la vita. Il padre ha un’officina dell’Alfa Romeo e una pompa di benzina sulla Napoli-Salerno statale 18, ma intuisce che i soldi veri li può fare in Olanda. Cresciuto ad Haarlem, pizzaiolo per la leggenda, certo, di pizze ne avrà infornate un paio per gioco, in realtà tuttofare nella pizzeria del padre, denominata inevitabilmente “Napoli”. Il ragazzo è sveglio, si dà da fare. A 15 anni fa il contabile in pizzeria. A 17 anni si fidanza con un’Olandesona di dodici anni più grande di lui, tanto che verrebbe da dire: ne prende la procura. A 19 anni acquista un McDonald, lo rivende quasi subito e fa i primi soldi veri.
ROY E BERGKAMP I PRIMI COLPI
Intanto gioca a calcio, nell’Haarlem. Non ha futuro da calciatore, così, a forza di tormentare il presidente, che è cliente della pizzeria del padre, si fa assumere come direttore sportivo. Retroscena: ad un cerio punto contatta il presidente del Napoli Corrado Ferlaino e sta per convincerlo a comprare l’Haarlem per farne un club satellite del Napoli. Ha fiuto, occhio lungo, ma lo frega il carattere, naturalmente inclinato al litigio. Se ne va dal club, fonda la “Intermezzo”, agenzia che cura i trasferimenti dei giocatori olandesi in Italia. Il primo è l’ala sinistra Brian Roy, dall’Ajax al Foggia, anno di grazia 1992. A Foggia conosce anche la ragazza che diventerà sua moglie. Intanto Rob Jansen, il boss dei procuratori olandesi dell’epoca, gli chiede di fare da interprete nel trasferimento di Dennis Bergkamp dall’Ajax all’Inter, siamo nel 1993.
IL METODO RAIOLA E L’OPERAZIONE NEDVED
Di Mino Raiola si comincia a parlare in giro. Ma il primo vero colpo è Pavel Nedved alla Lazio. Il trasferimento è facilitato anche dall’amicizia che Raiola ha con Zdenek Zeman, conosciuto ai tempi di Foggia. E’ sempre grazie a Nedved che prede per la prima volta forma il “Metodo Raiola”. L’ha raccontato lui stesso: nel 2001 Nedved lascia la Lazio, c’è la Juve ad attenderlo. Chi decide che è ora di partire? Nedved o Raiola? Indovinate. Jet privato, fuga da Roma, incontro segreto a Torino. Segreto mica tanto. Luciano Moggi, d.s. della Juve, ha convocato i giornalisti in aeroporto all’insaputa di Raiola. Che se la lega al dito e nella trattativa sarà ferocissimo. Con Moggi c’era un precedente: una decina d’anni prima, in un ristorante di Torino, i due si erano casualmente incrociati e Mino aveva mancato di rispetto a Big Luciano.
MI SOTTOVALUTANO? MEGLIO, COSì GUADAGNO DI PIù
Il phisique du role è un’arma in più. Tracagnotto, i capelli arruffati, lo sguardo impigrito, l’aria volutamente inoffensiva, da pizzicotto sulla guancia o birra al locale di sotto, non certo da firma con penna d’oro a piè di un contratto milionario. Come no. E infatti, ha detto: “Vesto così male che quando parliamo di affari tutti mi sottovalutano e io guadagno di più”. In realtà Raiola – moglie, due figli, residenza a Montecarlo, case ad Amstedam e a Miami, vacanze di famiglia a Villa Maria a Francavilla – sette lingue parlate, tutte imparate da autodidatta, anche l’italiano. Non è una battuta, a casa Raiola si parla solo il dialetto. L’inglese l’ha imparato guardando Mickey Mouse sul canale olandese. E aveva comunque studiato per due anni giurisprudenza, aveva lavorato come mediatore per banche: il suo compito – ah, il destino – era quello di dirimere le lamentele dei clienti e dei fornitori. Clienti di qua, fornitori di là. In mezzo lui. Ma anche: sia di qua che di là. Per tutta la vita si è sentito risuonare nelle orecchie l’amorevole consiglio di mamma Nunzia: “Mino, conciati meglio”. Per tutta la vita se n’è fregato. Contava la sostanza, aveva ragione. Partire dal nulla, arrivare ad avere il mondo ai tuoi piedi. Lo stile è un lusso, a mandare avanti il mondo è il fatturato.
Vesto così male che quando parliamo di affari tutti mi sottovalutano e io guadagno di più
)
[summary] => A 15 anni era contabile in una pizzeria, a 19 ha fatto i primi soldi...
[atom_content] =>
A 15 anni era contabile in una pizzeria, a 19 ha fatto i primi soldi vendendo un McDonald. Poi è diventato l’agente più spregiudicato del calcio mondiale: ogni anno porta a casa l’equivalente di una manovra finanziaria
Furio Zara
Il più potente, il più bravo, il più discusso, il più temuto – dai club – il più amato – dai suoi assistiti. Uno dei più ricchi, sicuro, il Paperon dei Paperoni del calcio 2.0 che ogni anno porta a casa l’equivalente di una manovra finanziaria.
Patrimonio stimato da Forbes nel 2020: fatturato da 84,7 milioni di dollari, giro d’affari di 847,7 milioni. Ricordando il primo incontro con Ibra, Mino Raiola ha raccontato: “Dal primo istante capìi che era uno str*** arrogante. Esattamente come lo ero io”. Bisogna necessariamente partire da qua – da questa ironica ammissione – per raccontare il “Consigliori”, l’agente spregiudicato e dal fiuto finissimo, il padre putativo di molti suoi assistiti, il Belzebù del pallone, il Jerry Maguire con la valigia di cartone, il Faraone delle commissioni, il “Ciccione che ha modi da mafioso” per Alex Ferguson, addirittura l’uomo – secondo un sondaggio di un paio d’anni fa di “Voetbal International” – più influente del calcio olandese, più di Cruijff per dire.
SOLO PUROSANGUE NELLA SUA SCUDERIA
Provare a definire i contorni della sua figura non è semplice. La Storia non gli addice, gli si addice la Cronaca. Per cominciare basti dire che: ha stravolto un mondo. Ha alzato sempre il tiro, muovendo a proprio piacimento i top-player sulla scacchiera del calcio europeo. Sono sue le pedine, il sospetto è che sia sua anche la scacchiera. Ora il mal di pancia, ora l’ambizione, ora la divergenza di obiettivi. Arrivano in una squadra, dopo sei mesi ne vogliono un’altra. Soldi, questione di. Soldi. Soldi. Soldi. Ne ha mossi tantissimi, Raiola. Sua la commissione record di tutti i tempi. 26,154 milioni intascati nel 2016 per portare Paul Pogba dalla Juventus al Manchester United. Negli ultimi anni si attesta su una media di 65-70 milioni l’anno di commissioni, sul podio degli agenti più ricchi, dopo Jorge Mendes e Jonathan Barnett. Solo cavalli pregiati nella sua scuderia, solo purosangue. Ibra, ovviamente. Pogba. Lukaku. Donnarumma. De Ligt.
HA CAMBIATO RUOLO E MISSIONE DELL’AGENTE
Va detto con chiarezza: Raiola ha ribaltato la figura dell’agente, la cui evoluzione – in questi ultimi vent’anni – è andata di pari passo con quella del calciatore che da dipendente – il cartellino era della società – si è trasformato in azienda, con modalità di azione riconducibili al celebre slogan femminista: il corpo è mio e lo gestisco io. È andata esattamente così. A Raiola va il merito – la colpa? – di aver ribaltato anche la dinamica dei rapporti con i calciatori. È Raiola a scegliere i suoi assistiti, come un sovrano indica i vassalli; mai il contrario. È Raiola a trattare – dall’alto in basso – con le società. Se entri nel giro di Raiola sei sicuro che il tuo valore balzi alle stelle. La deregulation varata dalla Fifa di Joseph Blatter nel 2015 ha reso il calciomercato una giungla. Di questa giungla, Raiola è il padrone incontrastato. Di più: l’intermediario abilissimo nel trattare per conto di chi vende, di chi compra, dello stesso oggetto della compravendita. Raiola, uno e trino.
VIA LE CRAVATTE, MEGLIO BERMUDA E POLO
Sempre a Ibra ha detto: “Vuoi diventare il miglior calciatore al mondo o quello che guadagna di più?”. Con Raiola buona la seconda. Con lui i calciatori sono legati da un rapporto fortissimo, un patto di sangue prima ancora che professionale. Sali sulla giostra, non scendi più. Esemplare il caso Balotelli. Ad un certo punto SuperMario valeva perché era Raiola a decretarne il valore, non certo le prestazioni in campo. Raiola ha avuto anche un ruolo cruciale nel costume del nostro calcio. Prima di lui, per decenni, l’agente si manifestava signorile nei modi, azzimato nel porgersi. Doveva fare bella figura, essere credibile. Giacca, cravatta, polsini alla camicia, Rolex da sfoggiare, diploma anche no, a che serve in fondo? Con Raiola tutto questo è diventato fuffa. Abolite le cravatte, inutile il doppiopetto. Polo extralarge, da bagnino svogliato. Bermuda che – negli incontri nei grandi hotel – sembravano persino offensivi. È in realtà un modo per marcare il territorio, per ribadire: sono io quello che comanda. Forse è un retaggio dell’infanzia da immigrato, forse lo sberleffo dell’uomo partito dal nulla, il self made man che si è fatto da sé e che – dopo aver covato tanto rancore – si prende la sua rivincita.
DAL PROFONDO SUD ALL’OLANDA
La sua biografia andrebbe studiata nelle scuole. Nato di otto mesi a Nocera Inferiore, 4 novembre 1967, ma solo perché ad Angri, nel Salernitano, dove vivevano i suoi, l’ospedale non c’era. Profondo Sud, quando ha un anno affronta seduto sul seggiolino della macchina il viaggio che gli cambierà la vita. Il padre ha un’officina dell’Alfa Romeo e una pompa di benzina sulla Napoli-Salerno statale 18, ma intuisce che i soldi veri li può fare in Olanda. Cresciuto ad Haarlem, pizzaiolo per la leggenda, certo, di pizze ne avrà infornate un paio per gioco, in realtà tuttofare nella pizzeria del padre, denominata inevitabilmente “Napoli”. Il ragazzo è sveglio, si dà da fare. A 15 anni fa il contabile in pizzeria. A 17 anni si fidanza con un’Olandesona di dodici anni più grande di lui, tanto che verrebbe da dire: ne prende la procura. A 19 anni acquista un McDonald, lo rivende quasi subito e fa i primi soldi veri.
ROY E BERGKAMP I PRIMI COLPI
Intanto gioca a calcio, nell’Haarlem. Non ha futuro da calciatore, così, a forza di tormentare il presidente, che è cliente della pizzeria del padre, si fa assumere come direttore sportivo. Retroscena: ad un cerio punto contatta il presidente del Napoli Corrado Ferlaino e sta per convincerlo a comprare l’Haarlem per farne un club satellite del Napoli. Ha fiuto, occhio lungo, ma lo frega il carattere, naturalmente inclinato al litigio. Se ne va dal club, fonda la “Intermezzo”, agenzia che cura i trasferimenti dei giocatori olandesi in Italia. Il primo è l’ala sinistra Brian Roy, dall’Ajax al Foggia, anno di grazia 1992. A Foggia conosce anche la ragazza che diventerà sua moglie. Intanto Rob Jansen, il boss dei procuratori olandesi dell’epoca, gli chiede di fare da interprete nel trasferimento di Dennis Bergkamp dall’Ajax all’Inter, siamo nel 1993.
IL METODO RAIOLA E L’OPERAZIONE NEDVED
Di Mino Raiola si comincia a parlare in giro. Ma il primo vero colpo è Pavel Nedved alla Lazio. Il trasferimento è facilitato anche dall’amicizia che Raiola ha con Zdenek Zeman, conosciuto ai tempi di Foggia. E’ sempre grazie a Nedved che prede per la prima volta forma il “Metodo Raiola”. L’ha raccontato lui stesso: nel 2001 Nedved lascia la Lazio, c’è la Juve ad attenderlo. Chi decide che è ora di partire? Nedved o Raiola? Indovinate. Jet privato, fuga da Roma, incontro segreto a Torino. Segreto mica tanto. Luciano Moggi, d.s. della Juve, ha convocato i giornalisti in aeroporto all’insaputa di Raiola. Che se la lega al dito e nella trattativa sarà ferocissimo. Con Moggi c’era un precedente: una decina d’anni prima, in un ristorante di Torino, i due si erano casualmente incrociati e Mino aveva mancato di rispetto a Big Luciano.
MI SOTTOVALUTANO? MEGLIO, COSì GUADAGNO DI PIù
Il phisique du role è un’arma in più. Tracagnotto, i capelli arruffati, lo sguardo impigrito, l’aria volutamente inoffensiva, da pizzicotto sulla guancia o birra al locale di sotto, non certo da firma con penna d’oro a piè di un contratto milionario. Come no. E infatti, ha detto: “Vesto così male che quando parliamo di affari tutti mi sottovalutano e io guadagno di più”. In realtà Raiola – moglie, due figli, residenza a Montecarlo, case ad Amstedam e a Miami, vacanze di famiglia a Villa Maria a Francavilla – sette lingue parlate, tutte imparate da autodidatta, anche l’italiano. Non è una battuta, a casa Raiola si parla solo il dialetto. L’inglese l’ha imparato guardando Mickey Mouse sul canale olandese. E aveva comunque studiato per due anni giurisprudenza, aveva lavorato come mediatore per banche: il suo compito – ah, il destino – era quello di dirimere le lamentele dei clienti e dei fornitori. Clienti di qua, fornitori di là. In mezzo lui. Ma anche: sia di qua che di là. Per tutta la vita si è sentito risuonare nelle orecchie l’amorevole consiglio di mamma Nunzia: “Mino, conciati meglio”. Per tutta la vita se n’è fregato. Contava la sostanza, aveva ragione. Partire dal nulla, arrivare ad avere il mondo ai tuoi piedi. Lo stile è un lusso, a mandare avanti il mondo è il fatturato.
Vesto così male che quando parliamo di affari tutti mi sottovalutano e io guadagno di più
[date_timestamp] => 1651206745
)
[2] => Array
(
[title] => Higher COVID-19 death rates in the southern U.S. due to behavior variations, study finds – NovLink
[link] => https://packagingnewsonline.com/health-science-news/higher-covid-19-death-rates-in-the-southern-u-s-due-to-behavior-variations-study-finds-novlink/
[dc] => Array
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[creator] => Betty Foster
)
[pubdate] => Fri, 29 Apr 2022 03:42:16 +0000
[category] => Health & Science News
[guid] => https://packagingnewsonline.com/health-science-news/higher-covid-19-death-rates-in-the-southern-u-s-due-to-behavior-variations-study-finds-novlink/
[description] => Journal Reference: Michael A. Stoto, Samantha Schlageter, John D. Kraemer. COVID-19 mortality in the United...
[content] => Array
(
[encoded] =>
Journal Reference:
Michael A. Stoto, Samantha Schlageter, John D. Kraemer. COVID-19 mortality in the United States: It’s been two Americas from the start. PLOS ONE, 2022; 17 (4): e0265053 DOI: 10.1371/journal.pone.0265053
The study, by Georgetown University’s School of Nursing & Health Studies researchers, appeared April 28, 2022, in PLOS ONE.
Excess mortality, which helps account for avoidable deaths from a new disease or situation, is defined by the difference between total current deaths and deaths expected based on earlier time period, usually the previous decade or so. The U.S. Centers for Disease Control and Prevention (CDC) calculates these numbers weekly. For this study, the CDC excess mortality data were analyzed for the period between January 3, 2020, to September 26, 2021. For regional comparison purposes, areas of the country were broken down into the Northeast, Midwest, South and West.
“Our goal was to carefully examine regional differences in COVID-19 death rates based on reliable statistical data,” says Michael Stoto, Ph.D., professor of Health Systems Administration and Population Health at the School of Nursing & Health Studies and corresponding author of the study. “Our study is the first to quantify avoidable deaths and confirm that both COVID-19 deaths and avoidable deaths disproportionately occurred in the South.”
The investigators found that regional differences in COVID-19 mortality rates have persisted throughout the pandemic. The southern part of the United States has had higher mortality rates than the rest of the U.S. since the start of summer in 2020. Since October 2020, 48% of COVID-19 deaths were in the South, which makes up 38% of the population, pointing to disproportionate outcomes regionally.
The researchers also determined that between January 2020 and September 2021 there were 895,693 excess deaths associated with COVID-19, which is 26% more than reported by other experts who track disease. Although the official total neared on one million deaths in the U.S due to COVID-19 by late April 2022, based on this undercount the scientists believe that threshold was actually passed at the beginning of 2022.
These estimates of undercounts are important because most studies have looked at excess mortality at the state and county level in the U.S., but because of small population sizes, the studies have not examined patterns over time. Some earlier studies explored the relationship between COVID-19 mortality and age, education, and other factors as well as vaccine uptake, party affiliation, and other factors. But most studies have used reported COVID-19 deaths rather than excess deaths, as compared to what Dr. Stoto and collaborators have done, and may not be as statistically reliable.
“This is one of a series of planned studies to look carefully at the response to COVID-19 in the U.S. and other countries and to learn from the experience in order to strengthen preparedness for future potential outbreaks,” says Stoto. “Our team has also looked at testing and surveillance, and other COVID-19 metrics to understand how communities have come together to effectively deal with the pandemic.”
In addition to Stoto, the other authors from Georgetown include Samantha Schlageter, who conducted this work as an undergraduate in the Health Care Management & Policy program at the School of Nursing & Health Studies (NHS), and John D. Kraemer, an associate professor in Department of Health Systems Administration at NHS.
)
[summary] => Journal Reference: Michael A. Stoto, Samantha Schlageter, John D. Kraemer. COVID-19 mortality in the United...
[atom_content] =>
Journal Reference:
Michael A. Stoto, Samantha Schlageter, John D. Kraemer. COVID-19 mortality in the United States: It’s been two Americas from the start. PLOS ONE, 2022; 17 (4): e0265053 DOI: 10.1371/journal.pone.0265053
The study, by Georgetown University’s School of Nursing & Health Studies researchers, appeared April 28, 2022, in PLOS ONE.
Excess mortality, which helps account for avoidable deaths from a new disease or situation, is defined by the difference between total current deaths and deaths expected based on earlier time period, usually the previous decade or so. The U.S. Centers for Disease Control and Prevention (CDC) calculates these numbers weekly. For this study, the CDC excess mortality data were analyzed for the period between January 3, 2020, to September 26, 2021. For regional comparison purposes, areas of the country were broken down into the Northeast, Midwest, South and West.
“Our goal was to carefully examine regional differences in COVID-19 death rates based on reliable statistical data,” says Michael Stoto, Ph.D., professor of Health Systems Administration and Population Health at the School of Nursing & Health Studies and corresponding author of the study. “Our study is the first to quantify avoidable deaths and confirm that both COVID-19 deaths and avoidable deaths disproportionately occurred in the South.”
The investigators found that regional differences in COVID-19 mortality rates have persisted throughout the pandemic. The southern part of the United States has had higher mortality rates than the rest of the U.S. since the start of summer in 2020. Since October 2020, 48% of COVID-19 deaths were in the South, which makes up 38% of the population, pointing to disproportionate outcomes regionally.
The researchers also determined that between January 2020 and September 2021 there were 895,693 excess deaths associated with COVID-19, which is 26% more than reported by other experts who track disease. Although the official total neared on one million deaths in the U.S due to COVID-19 by late April 2022, based on this undercount the scientists believe that threshold was actually passed at the beginning of 2022.
These estimates of undercounts are important because most studies have looked at excess mortality at the state and county level in the U.S., but because of small population sizes, the studies have not examined patterns over time. Some earlier studies explored the relationship between COVID-19 mortality and age, education, and other factors as well as vaccine uptake, party affiliation, and other factors. But most studies have used reported COVID-19 deaths rather than excess deaths, as compared to what Dr. Stoto and collaborators have done, and may not be as statistically reliable.
“This is one of a series of planned studies to look carefully at the response to COVID-19 in the U.S. and other countries and to learn from the experience in order to strengthen preparedness for future potential outbreaks,” says Stoto. “Our team has also looked at testing and surveillance, and other COVID-19 metrics to understand how communities have come together to effectively deal with the pandemic.”
In addition to Stoto, the other authors from Georgetown include Samantha Schlageter, who conducted this work as an undergraduate in the Health Care Management & Policy program at the School of Nursing & Health Studies (NHS), and John D. Kraemer, an associate professor in Department of Health Systems Administration at NHS.
[date_timestamp] => 1651203736
)
[3] => Array
(
[title] => Seven hours of sleep is optimal in middle and old age, say researchers – NovLink
[link] => https://packagingnewsonline.com/health-science-news/seven-hours-of-sleep-is-optimal-in-middle-and-old-age-say-researchers-novlink/
[dc] => Array
(
[creator] => Betty Foster
)
[pubdate] => Fri, 29 Apr 2022 02:41:17 +0000
[category] => Health & Science News
[guid] => https://packagingnewsonline.com/health-science-news/seven-hours-of-sleep-is-optimal-in-middle-and-old-age-say-researchers-novlink/
[description] => Journal Reference: Yuzhu Li, Barbara J. Sahakian, Jujiao Kang, Christelle Langley, Wei Zhang, Chao Xie,...
[content] => Array
(
[encoded] =>
Journal Reference:
Yuzhu Li, Barbara J. Sahakian, Jujiao Kang, Christelle Langley, Wei Zhang, Chao Xie, Shitong Xiang, Jintai Yu, Wei Cheng, Jianfeng Feng. The brain structure and genetic mechanisms underlying the nonlinear association between sleep duration, cognition and mental health. Nature Aging, 2022; DOI: 10.1038/s43587-022-00210-2
Sleep plays an important role in enabling cognitive function and maintaining good psychological health. It also helps keep the brain healthy by removing waste products. As we get older, we often see alterations in our sleep patterns, including difficulty falling asleep and staying asleep, and decreased quantity and quality of sleep. It is thought that these sleep disturbances may contribute to cognitive decline and psychiatric disorders in the aging population.
In research published today in Nature Aging, scientists from the UK and China examined data from nearly 500,000 adults aged 38-73 years from the UK Biobank. Participants were asked about their sleeping patterns, mental health and wellbeing, and took part in a series of cognitive tests. Brain imaging and genetic data were available for almost 40,000 of the study participants.
By analysing these data, the team found that both insufficient and excessive sleep duration were associated with impaired cognitive performance, such as processing speed, visual attention, memory and problem-solving skills. Seven hours of sleep per night was the optimal amount of sleep for cognitive performance, but also for good mental health, with people experiencing more symptoms of anxiety and depression and worse overall wellbeing if they reported sleeping for longer or shorter durations.
The researchers say one possible reason for the association between insufficient sleep and cognitive decline may be due to the disruption of slow-wave — ‘deep’ — sleep. Disruption to this type of sleep has been shown to have a close link with memory consolidation as well as the build-up of amyloid — a key protein which, when it misfolds, can cause ‘tangles’ in the brain characteristic of some forms of dementia. Additionally, lack of sleep may hamper the brain’s ability to rid itself of toxins.
The team also found a link between the amount of sleep and differences in the structure of brain regions involved in cognitive processing and memory, again with greater changes associated with greater than or less than seven hours of sleep.
Having a consistent seven hours’ sleep each night, without too much fluctuation in duration, was also important to cognitive performance and good mental health and wellbeing. Previous studies have also shown that interrupted sleep patterns are associated with increased inflammation, indicating a susceptibility to age-related diseases in older people.
Professor Jianfeng Feng from Fudan University in China said: “While we can’t say conclusively that too little or too much sleep causes cognitive problems, our analysis looking at individuals over a longer period of time appears to support this idea. But the reasons why older people have poorer sleep appear to be complex, influenced by a combination of our genetic makeup and the structure of our brains.”
The researchers say the findings suggest that insufficient or excessive sleep duration may be a risk factor for cognitive decline in ageing. This is supported by previous studies that have reported a link between sleep duration and the risk of developing Alzheimer’s disease and dementia, in which cognitive decline is a hallmark symptom.
Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge, one of the study’s authors, said: “Getting a good night’s sleep is important at all stages of life, but particularly as we age. Finding ways to improve sleep for older people could be crucial to helping them maintain good mental health and wellbeing and avoiding cognitive decline, particularly for patients with psychiatric disorders and dementias.”
The research was supported by the National Key R&D Program of China, the Shanghai Municipal Science and Technology Major Project, the Shanghai Center for Brain Science and Brain-Inspired Technology, the 111 Project, the National Natural Sciences Foundation of China and the Shanghai Rising Star Program.
)
[summary] => Journal Reference: Yuzhu Li, Barbara J. Sahakian, Jujiao Kang, Christelle Langley, Wei Zhang, Chao Xie,...
[atom_content] =>
Journal Reference:
Yuzhu Li, Barbara J. Sahakian, Jujiao Kang, Christelle Langley, Wei Zhang, Chao Xie, Shitong Xiang, Jintai Yu, Wei Cheng, Jianfeng Feng. The brain structure and genetic mechanisms underlying the nonlinear association between sleep duration, cognition and mental health. Nature Aging, 2022; DOI: 10.1038/s43587-022-00210-2
Sleep plays an important role in enabling cognitive function and maintaining good psychological health. It also helps keep the brain healthy by removing waste products. As we get older, we often see alterations in our sleep patterns, including difficulty falling asleep and staying asleep, and decreased quantity and quality of sleep. It is thought that these sleep disturbances may contribute to cognitive decline and psychiatric disorders in the aging population.
In research published today in Nature Aging, scientists from the UK and China examined data from nearly 500,000 adults aged 38-73 years from the UK Biobank. Participants were asked about their sleeping patterns, mental health and wellbeing, and took part in a series of cognitive tests. Brain imaging and genetic data were available for almost 40,000 of the study participants.
By analysing these data, the team found that both insufficient and excessive sleep duration were associated with impaired cognitive performance, such as processing speed, visual attention, memory and problem-solving skills. Seven hours of sleep per night was the optimal amount of sleep for cognitive performance, but also for good mental health, with people experiencing more symptoms of anxiety and depression and worse overall wellbeing if they reported sleeping for longer or shorter durations.
The researchers say one possible reason for the association between insufficient sleep and cognitive decline may be due to the disruption of slow-wave — ‘deep’ — sleep. Disruption to this type of sleep has been shown to have a close link with memory consolidation as well as the build-up of amyloid — a key protein which, when it misfolds, can cause ‘tangles’ in the brain characteristic of some forms of dementia. Additionally, lack of sleep may hamper the brain’s ability to rid itself of toxins.
The team also found a link between the amount of sleep and differences in the structure of brain regions involved in cognitive processing and memory, again with greater changes associated with greater than or less than seven hours of sleep.
Having a consistent seven hours’ sleep each night, without too much fluctuation in duration, was also important to cognitive performance and good mental health and wellbeing. Previous studies have also shown that interrupted sleep patterns are associated with increased inflammation, indicating a susceptibility to age-related diseases in older people.
Professor Jianfeng Feng from Fudan University in China said: “While we can’t say conclusively that too little or too much sleep causes cognitive problems, our analysis looking at individuals over a longer period of time appears to support this idea. But the reasons why older people have poorer sleep appear to be complex, influenced by a combination of our genetic makeup and the structure of our brains.”
The researchers say the findings suggest that insufficient or excessive sleep duration may be a risk factor for cognitive decline in ageing. This is supported by previous studies that have reported a link between sleep duration and the risk of developing Alzheimer’s disease and dementia, in which cognitive decline is a hallmark symptom.
Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge, one of the study’s authors, said: “Getting a good night’s sleep is important at all stages of life, but particularly as we age. Finding ways to improve sleep for older people could be crucial to helping them maintain good mental health and wellbeing and avoiding cognitive decline, particularly for patients with psychiatric disorders and dementias.”
The research was supported by the National Key R&D Program of China, the Shanghai Municipal Science and Technology Major Project, the Shanghai Center for Brain Science and Brain-Inspired Technology, the 111 Project, the National Natural Sciences Foundation of China and the Shanghai Rising Star Program.
Maine Christos, Subir Sachdev, Mathias S. Scheurer. Correlated Insulators, Semimetals, and Superconductivity in Twisted Trilayer Graphene. Physical Review X, 2022; 12 (2) DOI: 10.1103/PhysRevx.12.021018
Since the first successful fabrication of a two-dimensional structure of carbon atoms about 20 years ago, graphene has fascinated scientists. A few years ago, researchers discovered that two layers of graphene, slightly twisted against each other, can conduct electric current without loss. In recent years, this discovery has prompted scientists to explore such layered materials in greater detail. A recent notable example is mirror-symmetric twisted trilayer graphene, where three layers of graphene are stacked with alternating twist angles. It is the first moiré system that can both be efficiently tuned with a perpendicular electric field and was demonstrated experimentally to exhibit robust superconductivity, alongside various other phases. “This establishes trilayer graphene as an exciting platform for complex many-body physics, but the nature of the observed interaction-induced insulators, semi-metals, and superconductivity remains unknown,” says Mathias Scheurer from the Department of Theoretical Physics of the University of Innsbruck.
In a paper published in Physical Review X, a team led by Scheurer numerically and analytically studied the phase diagram of this system for different numbers of electrons per moiré unit cell and as a function of electric field. “This is a very challenging problem as the system has both flat and highly dispersive bands,” says the theoretical physicist. “Nonetheless, we managed to show that the ground state of the system in the absence of a field decouples into a product of the ground state of graphene and the ground state of twisted bilayer graphene,” a property that has subsequently been confirmed by experiments. Their results further establish the dominance of insulating and semi-metallic phases in the presence of an electric field which are unique to the trilayer system, i.e., are not realized in twisted bilayer graphene. “We are able to use our resulting phase diagram for the correlated normal states to constrain the form of the superconductor,” says Scheurer. “Among other aspects, the resulting two superconducting candidate states we get are consistent with the unexpected stability of the superconductor in magnetic field seen in experiment.”
The relevance of the findings for the physics of twisted trilayer graphene is further attested by a subsequent collaboration with the group of Abhay Pasupathy from Columbia university. In a recent paper in Science, they report scanning tunneling microscopy (STM) data on this system. “We show that the measured tunneling spectra exhibit significant interaction effects that can be qualitatively captured by the numerics of our work,” says Mathias Scheurer.
)
[summary] => Journal Reference: Maine Christos, Subir Sachdev, Mathias S. Scheurer. Correlated Insulators, Semimetals, and Superconductivity in...
[atom_content] =>
Journal Reference:
Maine Christos, Subir Sachdev, Mathias S. Scheurer. Correlated Insulators, Semimetals, and Superconductivity in Twisted Trilayer Graphene. Physical Review X, 2022; 12 (2) DOI: 10.1103/PhysRevx.12.021018
Since the first successful fabrication of a two-dimensional structure of carbon atoms about 20 years ago, graphene has fascinated scientists. A few years ago, researchers discovered that two layers of graphene, slightly twisted against each other, can conduct electric current without loss. In recent years, this discovery has prompted scientists to explore such layered materials in greater detail. A recent notable example is mirror-symmetric twisted trilayer graphene, where three layers of graphene are stacked with alternating twist angles. It is the first moiré system that can both be efficiently tuned with a perpendicular electric field and was demonstrated experimentally to exhibit robust superconductivity, alongside various other phases. “This establishes trilayer graphene as an exciting platform for complex many-body physics, but the nature of the observed interaction-induced insulators, semi-metals, and superconductivity remains unknown,” says Mathias Scheurer from the Department of Theoretical Physics of the University of Innsbruck.
In a paper published in Physical Review X, a team led by Scheurer numerically and analytically studied the phase diagram of this system for different numbers of electrons per moiré unit cell and as a function of electric field. “This is a very challenging problem as the system has both flat and highly dispersive bands,” says the theoretical physicist. “Nonetheless, we managed to show that the ground state of the system in the absence of a field decouples into a product of the ground state of graphene and the ground state of twisted bilayer graphene,” a property that has subsequently been confirmed by experiments. Their results further establish the dominance of insulating and semi-metallic phases in the presence of an electric field which are unique to the trilayer system, i.e., are not realized in twisted bilayer graphene. “We are able to use our resulting phase diagram for the correlated normal states to constrain the form of the superconductor,” says Scheurer. “Among other aspects, the resulting two superconducting candidate states we get are consistent with the unexpected stability of the superconductor in magnetic field seen in experiment.”
The relevance of the findings for the physics of twisted trilayer graphene is further attested by a subsequent collaboration with the group of Abhay Pasupathy from Columbia university. In a recent paper in Science, they report scanning tunneling microscopy (STM) data on this system. “We show that the measured tunneling spectra exhibit significant interaction effects that can be qualitatively captured by the numerics of our work,” says Mathias Scheurer.
[date_timestamp] => 1651196362
)
[5] => Array
(
[title] => Gene mutations that contribute to head and neck cancer also provide ‘precision’ treatment targets – NovLink
[link] => https://packagingnewsonline.com/health-science-news/gene-mutations-that-contribute-to-head-and-neck-cancer-also-provide-precision-treatment-targets-novlink/
[dc] => Array
(
[creator] => Betty Foster
)
[pubdate] => Fri, 29 Apr 2022 00:38:21 +0000
[category] => Health & Science News
[guid] => https://packagingnewsonline.com/health-science-news/gene-mutations-that-contribute-to-head-and-neck-cancer-also-provide-precision-treatment-targets-novlink/
[description] => Journal Reference: Hoi-Lam Ngan, Chun-Ho Law, Yannie Chung Yan Choi, Jenny Yu-Sum Chan, Vivian Wai...
[content] => Array
(
[encoded] =>
Journal Reference:
Hoi-Lam Ngan, Chun-Ho Law, Yannie Chung Yan Choi, Jenny Yu-Sum Chan, Vivian Wai Yan Lui. Precision drugging of the MAPK pathway in head and neck cancer. npj Genomic Medicine, 2022; 7 (1) DOI: 10.1038/s41525-022-00293-1
Keys to targeting that vulnerability include individualized genomic analysis to identify a patient’s specific mutation, and finding the drugs that directly target it, investigations that should be given more attention in cancer therapy development, they report in a review article in the journal NPJ Genomic Medicine.
The MAPK pathway is a “signaling hub” for cells important to the usual development of the head and neck region, and activating key pathway constituents, like the genes MAPK1 and HRAS, is known to drive the growth of a variety of cancers, says Dr. Vivian Wai Yan Lui, molecular pharmacologist and translational scientist at the Georgia Cancer Center and Medical College of Georgia and the paper’s corresponding author.
But the mutations in the genes in the MAPK pathway that enable tumor growth can also make it sensitive to drug therapy, says Lui. While a lot of discovery is still needed to find more mutations in the MAPK pathway and the drugs that target them, Lui says they are among the most logical treatment targets for this tough-to-treat cancer.
As she speaks, she is looking in her lab for drugs that kill head and neck primary tumors from patients, and at the genetics behind how they kill.
“It’s critical to the survival of the cancer,” says Lui, and every cancer type likely has one or more drug-sensitizing mutations that may vary in individuals depending on how they got cancer.
If these types of studies continue to find the methodology works, gene panels might need to be developed to expedite target discovery in this very heterogenous cancer, the scientists write.
More clinical trials around the globe at institutions like MCG and the Georgia Cancer Center are essential to identifying these specific mutations and drugs that target them in a precision manner, Lui notes.
Also, next on the horizon is combining this “precision medicine” approach with immunotherapy that better enables a patient’s immune system to also target the cancer, she says.
Lui’s interest in the MAPK pathway solidified almost a decade ago at the University of Pittsburgh where she did her postdoctoral studies and eventually joined the faculty. Her mentor was Dr. Jennifer R. Grandis (now at the University of California, San Francisco), who led the head and neck cancer program there. The patient in his 30s, a heavy smoker and drinker, had stage four head and neck squamous cell carcinoma that had metastasized to his lymph nodes. The patient went to Pittsburgh for removal of the lymph nodes and the primary tumor but was fortunate enough to be eligible for a “window of opportunity” trial there. Before starting any standard treatment, he received a trial drug for 13 days, in his case an epidermal growth factor receptor, or EGFR, blocker. The receptor is involved in cell growth, and is found on some normal cells, including in the head and neck area where there is a lot of natural cell turnover because of exposure to things like food and drink. However, in cancer cells, including head and neck cancer cells, EGFR is abundantly expressed for the rapid growth critical to a tumor’s spread and survival.
The patient was given the drug, erlotinib, which was not known to be particularly effective in these cancers but was being looked at to see if it would quieten signaling of this factor that was important to the cancer’s growth. When he went for surgery following the trial, the surgeon called to report there was no cancer on his tongue and studies of his 36 lymph nodes indicated they also now showed no evidence of cancer. The patient was still doing well by the time the Pittsburgh colleagues published the paper two years later in 2015 in JAMA Oncology.
His was rightly called an “exceptional response,” the first Lui and her colleagues had found in head and neck cancer, and she had to figure out the mutation the drug targeted to enable such a response. Exceptional responders are how the National Cancer Institute describes people who have more than a six-month response to a therapy when they are running out of treatment options.
An EGFR gene mutation was a logical choice for his mutation. Harvard investigators had previously found that in non-small cell lung cancer, EGFR activating mutations could activate tumor cell growth, which also made tumor cells “addicted” to the signal from the mutated EGFR. The drug erlotinib could break the addiction and inhibit cancer cell growth.
Lui didn’t find an EGFR mutation in this young man’s pretreatment biopsy but reasoned the mutation had to have something to do with the receptor’s signaling network. She was surprised — and the first — to find it was a MAPK1 gene mutation, MAPK1 p.E322K specifically, that could also be found in liver, breast and other cancers.
When they later engineered the mutation in head and neck cancer cells, the already aggressive cells grew even faster, Lui says of a mutation that can result from habits like heavy smoking and drinking. They would also find that the particular mutation was very common in the United States in patients with head and neck cancer, while there was a wider spectrum of mutations present in Asians with the cancer.
Erlotinib had actually failed in clinical trials because it wasn’t given to the right patients, which is what precision medicine is, Lui notes. In fact, laboratory studies had indicated that activation of MAPK1 confers resistance to erlotinib, she says, while this patient’s response clearly counters that. Follow up work by Grandis indicated that in patients actually, the higher the MAPK1 activation, the better the cancer responded to erlotinib.
To help move cancer treatment forward, Lui encourages physicians who come across these types of “exceptional responses” to report them, work with scientists to study them, then pursue clinical trials when appropriate.
For patients, her message is not to give up because with more high-level analysis of tumors, there might be a certain mutation that makes their cancer vulnerable to a specific medication, she says of these “gene-drug responses” that are the focal point of her translational work.
“There are secrets that make the cancer vulnerable,” Lui says. “When cancer cells have an important gene mutation that they are activating or that cancer cells are addicted to for survival, then when you hit that signaling pathway, the cancer cells will die or be really well controlled.”
Prior to the era of genomic medicine, when scientists began to identify and target a specific gene mutation, “non-precision” drug treatment of the MAPK pathway in head and neck cancers as well as other cancers were “futile,” and typically “failed miserably” in clinical trials, Lui and her colleagues write.
While the reasons may be uncertain, they likely include the wrong drug for that specific, problematic mutation, Lui says, as well as the fact that some MAPK pathway mutations are known to convey drug resistance.
Either way, there is a lot of work to do. Today there are just a handful of drugs that target specific, cancer-causing mutations in head and neck cancer but there aren’t effective precision drugs for about 80% of patients, Lui and her coauthors write.
But there is mounting evidence that targeting specific MAPK pathway mutations in the pathway like MAPK1, HRAS, KRAS and BRAF can be very effective for these patients.
As an example, the RAS inhibitor tipifarnib received Breakthrough Therapy Designation by the Food and Drug Administration in February 2021 for patients with a specific recurrent or metastatic HRAS-mutant head and neck squamous cell cancer. HRAS is involved in cell growth signaling.
Also, studies indicate that EGFR targeted therapy in metastatic non-small cell lung cancer, increases progression-free survival to a median of 18.9 months and median overall survival beyond three years and reduces death rates about 52%. In 2016 the Food and Drug Administration modified its approval of erlotinib to treat non-small cell lung cancer patients with the specific EGFR mutations. In 2020, the FDA approved erlotinib in combination with ramucirumab, a monoclonal antibody that binds to a receptor for vascular endothelial growth factor, or VEGF, which tumors use to grow the blood vessels they need to thrive, as a frontline treatment for these cancers. The FDA granted Breakthrough Therapy Designation to tipifarnib, an inhibitor of a protein which has the downstream effect of interfering in this case with mutations of the gene HRAS, which is also involved in cell division and in the MAPK pathway. There are now more than 1.5 million people with non-small cell lung cancer on precision medicine because of investigators who continued to examine the initial few responders, Lui says.
Lui is a native of Hong Kong, who was on the faculty of The Chinese University of Hong Kong before joining the MCG faculty in October 2021. In 2020 Lui and her colleagues reported that MAPK pathway mutations are a factor in about one-fifth of head and neck cancer patients and that “unexpectedly” these mutations are associated with longer patient survival than other causes like human papillomavirus.
Head and neck cancer is typically aggressive and often both the disease and its treatment are painful and disfiguring. It carries a higher risk of suicide than many other cancer types. The incidence of head and neck cancer is going up across the world, with causes including tobacco and/or alcohol use, air pollutants, cancer causing viruses like the sexually transmitted HPV, and Epstein-Barr virus, one of the most common viruses that is primarily spread by saliva and can cause problems like infectious mononucleosis. Other causes include poor dental hygiene and chewing betel nut, a stimulant which comes from the Areca palm plant, and is used as a recreational drug and as a still-unproven treatment for problems like schizophrenia and glaucoma. Chewing betel nut is a common cultural practice in South and Southeast Asia and the Asian Pacific. It’s often chewed with products like tobacco and has been associated with cancer and a host of other medical problems like a slow heart rate and stomach ulcers.
The carcinogens largely damage the lining of the head and neck region resulting in one or more mutations that can lead to cancer.
Hoi-Lam Ngan, Chun-Ho Law, Yannie Chung Yan Choi, Jenny Yu-Sum Chan, Vivian Wai Yan Lui. Precision drugging of the MAPK pathway in head and neck cancer. npj Genomic Medicine, 2022; 7 (1) DOI: 10.1038/s41525-022-00293-1
Keys to targeting that vulnerability include individualized genomic analysis to identify a patient’s specific mutation, and finding the drugs that directly target it, investigations that should be given more attention in cancer therapy development, they report in a review article in the journal NPJ Genomic Medicine.
The MAPK pathway is a “signaling hub” for cells important to the usual development of the head and neck region, and activating key pathway constituents, like the genes MAPK1 and HRAS, is known to drive the growth of a variety of cancers, says Dr. Vivian Wai Yan Lui, molecular pharmacologist and translational scientist at the Georgia Cancer Center and Medical College of Georgia and the paper’s corresponding author.
But the mutations in the genes in the MAPK pathway that enable tumor growth can also make it sensitive to drug therapy, says Lui. While a lot of discovery is still needed to find more mutations in the MAPK pathway and the drugs that target them, Lui says they are among the most logical treatment targets for this tough-to-treat cancer.
As she speaks, she is looking in her lab for drugs that kill head and neck primary tumors from patients, and at the genetics behind how they kill.
“It’s critical to the survival of the cancer,” says Lui, and every cancer type likely has one or more drug-sensitizing mutations that may vary in individuals depending on how they got cancer.
If these types of studies continue to find the methodology works, gene panels might need to be developed to expedite target discovery in this very heterogenous cancer, the scientists write.
More clinical trials around the globe at institutions like MCG and the Georgia Cancer Center are essential to identifying these specific mutations and drugs that target them in a precision manner, Lui notes.
Also, next on the horizon is combining this “precision medicine” approach with immunotherapy that better enables a patient’s immune system to also target the cancer, she says.
Lui’s interest in the MAPK pathway solidified almost a decade ago at the University of Pittsburgh where she did her postdoctoral studies and eventually joined the faculty. Her mentor was Dr. Jennifer R. Grandis (now at the University of California, San Francisco), who led the head and neck cancer program there. The patient in his 30s, a heavy smoker and drinker, had stage four head and neck squamous cell carcinoma that had metastasized to his lymph nodes. The patient went to Pittsburgh for removal of the lymph nodes and the primary tumor but was fortunate enough to be eligible for a “window of opportunity” trial there. Before starting any standard treatment, he received a trial drug for 13 days, in his case an epidermal growth factor receptor, or EGFR, blocker. The receptor is involved in cell growth, and is found on some normal cells, including in the head and neck area where there is a lot of natural cell turnover because of exposure to things like food and drink. However, in cancer cells, including head and neck cancer cells, EGFR is abundantly expressed for the rapid growth critical to a tumor’s spread and survival.
The patient was given the drug, erlotinib, which was not known to be particularly effective in these cancers but was being looked at to see if it would quieten signaling of this factor that was important to the cancer’s growth. When he went for surgery following the trial, the surgeon called to report there was no cancer on his tongue and studies of his 36 lymph nodes indicated they also now showed no evidence of cancer. The patient was still doing well by the time the Pittsburgh colleagues published the paper two years later in 2015 in JAMA Oncology.
His was rightly called an “exceptional response,” the first Lui and her colleagues had found in head and neck cancer, and she had to figure out the mutation the drug targeted to enable such a response. Exceptional responders are how the National Cancer Institute describes people who have more than a six-month response to a therapy when they are running out of treatment options.
An EGFR gene mutation was a logical choice for his mutation. Harvard investigators had previously found that in non-small cell lung cancer, EGFR activating mutations could activate tumor cell growth, which also made tumor cells “addicted” to the signal from the mutated EGFR. The drug erlotinib could break the addiction and inhibit cancer cell growth.
Lui didn’t find an EGFR mutation in this young man’s pretreatment biopsy but reasoned the mutation had to have something to do with the receptor’s signaling network. She was surprised — and the first — to find it was a MAPK1 gene mutation, MAPK1 p.E322K specifically, that could also be found in liver, breast and other cancers.
When they later engineered the mutation in head and neck cancer cells, the already aggressive cells grew even faster, Lui says of a mutation that can result from habits like heavy smoking and drinking. They would also find that the particular mutation was very common in the United States in patients with head and neck cancer, while there was a wider spectrum of mutations present in Asians with the cancer.
Erlotinib had actually failed in clinical trials because it wasn’t given to the right patients, which is what precision medicine is, Lui notes. In fact, laboratory studies had indicated that activation of MAPK1 confers resistance to erlotinib, she says, while this patient’s response clearly counters that. Follow up work by Grandis indicated that in patients actually, the higher the MAPK1 activation, the better the cancer responded to erlotinib.
To help move cancer treatment forward, Lui encourages physicians who come across these types of “exceptional responses” to report them, work with scientists to study them, then pursue clinical trials when appropriate.
For patients, her message is not to give up because with more high-level analysis of tumors, there might be a certain mutation that makes their cancer vulnerable to a specific medication, she says of these “gene-drug responses” that are the focal point of her translational work.
“There are secrets that make the cancer vulnerable,” Lui says. “When cancer cells have an important gene mutation that they are activating or that cancer cells are addicted to for survival, then when you hit that signaling pathway, the cancer cells will die or be really well controlled.”
Prior to the era of genomic medicine, when scientists began to identify and target a specific gene mutation, “non-precision” drug treatment of the MAPK pathway in head and neck cancers as well as other cancers were “futile,” and typically “failed miserably” in clinical trials, Lui and her colleagues write.
While the reasons may be uncertain, they likely include the wrong drug for that specific, problematic mutation, Lui says, as well as the fact that some MAPK pathway mutations are known to convey drug resistance.
Either way, there is a lot of work to do. Today there are just a handful of drugs that target specific, cancer-causing mutations in head and neck cancer but there aren’t effective precision drugs for about 80% of patients, Lui and her coauthors write.
But there is mounting evidence that targeting specific MAPK pathway mutations in the pathway like MAPK1, HRAS, KRAS and BRAF can be very effective for these patients.
As an example, the RAS inhibitor tipifarnib received Breakthrough Therapy Designation by the Food and Drug Administration in February 2021 for patients with a specific recurrent or metastatic HRAS-mutant head and neck squamous cell cancer. HRAS is involved in cell growth signaling.
Also, studies indicate that EGFR targeted therapy in metastatic non-small cell lung cancer, increases progression-free survival to a median of 18.9 months and median overall survival beyond three years and reduces death rates about 52%. In 2016 the Food and Drug Administration modified its approval of erlotinib to treat non-small cell lung cancer patients with the specific EGFR mutations. In 2020, the FDA approved erlotinib in combination with ramucirumab, a monoclonal antibody that binds to a receptor for vascular endothelial growth factor, or VEGF, which tumors use to grow the blood vessels they need to thrive, as a frontline treatment for these cancers. The FDA granted Breakthrough Therapy Designation to tipifarnib, an inhibitor of a protein which has the downstream effect of interfering in this case with mutations of the gene HRAS, which is also involved in cell division and in the MAPK pathway. There are now more than 1.5 million people with non-small cell lung cancer on precision medicine because of investigators who continued to examine the initial few responders, Lui says.
Lui is a native of Hong Kong, who was on the faculty of The Chinese University of Hong Kong before joining the MCG faculty in October 2021. In 2020 Lui and her colleagues reported that MAPK pathway mutations are a factor in about one-fifth of head and neck cancer patients and that “unexpectedly” these mutations are associated with longer patient survival than other causes like human papillomavirus.
Head and neck cancer is typically aggressive and often both the disease and its treatment are painful and disfiguring. It carries a higher risk of suicide than many other cancer types. The incidence of head and neck cancer is going up across the world, with causes including tobacco and/or alcohol use, air pollutants, cancer causing viruses like the sexually transmitted HPV, and Epstein-Barr virus, one of the most common viruses that is primarily spread by saliva and can cause problems like infectious mononucleosis. Other causes include poor dental hygiene and chewing betel nut, a stimulant which comes from the Areca palm plant, and is used as a recreational drug and as a still-unproven treatment for problems like schizophrenia and glaucoma. Chewing betel nut is a common cultural practice in South and Southeast Asia and the Asian Pacific. It’s often chewed with products like tobacco and has been associated with cancer and a host of other medical problems like a slow heart rate and stomach ulcers.
The carcinogens largely damage the lining of the head and neck region resulting in one or more mutations that can lead to cancer.
Yuta Dobashi, Dickson Yao, Yael Petel, Tan Ngoc Nguyen, Mirza Saquib Sarwar, Yacine Thabet, Cliff L. W. Ng, Ettore Scabeni Glitz, Giao Tran Minh Nguyen, Cédric Plesse, Frédéric Vidal, Carl A. Michal, John D. W. Madden. Piezoionic mechanoreceptors: Force-induced current generation in hydrogels. Science, 2022; 376 (6592): 502 DOI: 10.1126/science.aaw1974
These hydrogels can generate voltages when touched, but scientists did not clearly understand how — until a team of researchers at UBC devised a unique experiment, published today in Science.
“How hydrogel sensors work is they produce voltages and currents in reaction to stimuli, such as pressure or touch — what we are calling a piezoionic effect. But we didn’t know exactly how these voltages are produced,” said the study’s lead author Yuta Dobashi, who started the work as part of his master’s in biomedical engineering at UBC.
Working under the supervision of UBC researcher Dr. John Madden, Dobashi devised hydrogel sensors containing salts with positive and negative ions of different sizes. He and collaborators in UBC’s physics and chemistry departments applied magnetic fields to track precisely how the ions moved when pressure was applied to the sensor.
“When pressure is applied to the gel, that pressure spreads out the ions in the liquid at different speeds, creating an electrical signal. Positive ions, which tend to be smaller, move faster than larger, negative ions. This results in an uneven ion distribution which creates an electric field, which is what makes a piezoionic sensor work.”
The researchers say this new knowledge confirms that hydrogels work in a similar way to how humans detect pressure, which is also through moving ions in response to pressure, inspiring potential new applications for ionic skins.
“The obvious application is creating sensors that interact directly with cells and the nervous system, since the voltages, currents and response times are like those across cell membranes,” says Dr. Madden, an electrical and computer engineering professor in UBC’s faculty of applied science. “When we connect our sensor to a nerve, it produces a signal in the nerve. The nerve, in turn, activates muscle contraction.”
“You can imagine a prosthetic arm covered in an ionic skin. The skin senses an object through touch or pressure, conveys that information through the nerves to the brain, and the brain then activates the motors required to lift or hold the object. With further development of the sensor skin and interfaces with nerves, this bionic interface is conceivable.”
Another application is a soft hydrogel sensor worn on the skin that can monitor a patient’s vital signs while being totally unobtrusive and generating its own power.
Dobashi, who’s currently completing his PhD work at the University of Toronto, is keen to continue working on ionic technologies after he graduates.
“We can imagine a future where jelly-like ‘iontronics’ are used for body implants. Artificial joints can be implanted, without fear of rejection inside the human body. Ionic devices can be used as part of artificial knee cartilage, adding a smart sensing element. A piezoionic gel implant might release drugs based on how much pressure it senses, for example.”
Dr. Madden added that the market for smart skins is estimated at $4.5 billion in 2019 and it continues to grow. “Smart skins can be integrated into clothing or placed directly on the skin, and ionic skins are one of the technologies that can further that growth.”
The research includes contributions from UBC chemistry PhD graduate Yael Petel and Carl Michal, UBC professor of physics, who used the interaction between strong magnetic fields and the nuclear spins of ions to track ion movements within the hydrogels. Cédric Plesse, Giao Nguyen and Frédéric Vidal at CY Cergy Paris University in France helped develop a new theory on how the charge and voltage are generated in the hydrogels.
)
[summary] => Journal Reference: Yuta Dobashi, Dickson Yao, Yael Petel, Tan Ngoc Nguyen, Mirza Saquib Sarwar, Yacine...
[atom_content] =>
Journal Reference:
Yuta Dobashi, Dickson Yao, Yael Petel, Tan Ngoc Nguyen, Mirza Saquib Sarwar, Yacine Thabet, Cliff L. W. Ng, Ettore Scabeni Glitz, Giao Tran Minh Nguyen, Cédric Plesse, Frédéric Vidal, Carl A. Michal, John D. W. Madden. Piezoionic mechanoreceptors: Force-induced current generation in hydrogels. Science, 2022; 376 (6592): 502 DOI: 10.1126/science.aaw1974
These hydrogels can generate voltages when touched, but scientists did not clearly understand how — until a team of researchers at UBC devised a unique experiment, published today in Science.
“How hydrogel sensors work is they produce voltages and currents in reaction to stimuli, such as pressure or touch — what we are calling a piezoionic effect. But we didn’t know exactly how these voltages are produced,” said the study’s lead author Yuta Dobashi, who started the work as part of his master’s in biomedical engineering at UBC.
Working under the supervision of UBC researcher Dr. John Madden, Dobashi devised hydrogel sensors containing salts with positive and negative ions of different sizes. He and collaborators in UBC’s physics and chemistry departments applied magnetic fields to track precisely how the ions moved when pressure was applied to the sensor.
“When pressure is applied to the gel, that pressure spreads out the ions in the liquid at different speeds, creating an electrical signal. Positive ions, which tend to be smaller, move faster than larger, negative ions. This results in an uneven ion distribution which creates an electric field, which is what makes a piezoionic sensor work.”
The researchers say this new knowledge confirms that hydrogels work in a similar way to how humans detect pressure, which is also through moving ions in response to pressure, inspiring potential new applications for ionic skins.
“The obvious application is creating sensors that interact directly with cells and the nervous system, since the voltages, currents and response times are like those across cell membranes,” says Dr. Madden, an electrical and computer engineering professor in UBC’s faculty of applied science. “When we connect our sensor to a nerve, it produces a signal in the nerve. The nerve, in turn, activates muscle contraction.”
“You can imagine a prosthetic arm covered in an ionic skin. The skin senses an object through touch or pressure, conveys that information through the nerves to the brain, and the brain then activates the motors required to lift or hold the object. With further development of the sensor skin and interfaces with nerves, this bionic interface is conceivable.”
Another application is a soft hydrogel sensor worn on the skin that can monitor a patient’s vital signs while being totally unobtrusive and generating its own power.
Dobashi, who’s currently completing his PhD work at the University of Toronto, is keen to continue working on ionic technologies after he graduates.
“We can imagine a future where jelly-like ‘iontronics’ are used for body implants. Artificial joints can be implanted, without fear of rejection inside the human body. Ionic devices can be used as part of artificial knee cartilage, adding a smart sensing element. A piezoionic gel implant might release drugs based on how much pressure it senses, for example.”
Dr. Madden added that the market for smart skins is estimated at $4.5 billion in 2019 and it continues to grow. “Smart skins can be integrated into clothing or placed directly on the skin, and ionic skins are one of the technologies that can further that growth.”
The research includes contributions from UBC chemistry PhD graduate Yael Petel and Carl Michal, UBC professor of physics, who used the interaction between strong magnetic fields and the nuclear spins of ions to track ion movements within the hydrogels. Cédric Plesse, Giao Nguyen and Frédéric Vidal at CY Cergy Paris University in France helped develop a new theory on how the charge and voltage are generated in the hydrogels.
[date_timestamp] => 1651189034
)
[7] => Array
(
[title] => Sampling the deep graveyard of Earth’s earliest crust – NovLink
[link] => https://packagingnewsonline.com/health-science-news/sampling-the-deep-graveyard-of-earths-earliest-crust-novlink/
[dc] => Array
(
[creator] => Betty Foster
)
[pubdate] => Thu, 28 Apr 2022 22:36:19 +0000
[category] => Health & Science News
[guid] => https://packagingnewsonline.com/health-science-news/sampling-the-deep-graveyard-of-earths-earliest-crust-novlink/
[description] => Journal Reference: Jonas Tusch, J. Elis Hoffmann, Eric Hasenstab, Mario Fischer-Gödde, Chris S. Marien, Allan...
[content] => Array
(
[encoded] =>
Journal Reference:
Jonas Tusch, J. Elis Hoffmann, Eric Hasenstab, Mario Fischer-Gödde, Chris S. Marien, Allan H. Wilson, Carsten Münker. Long-term preservation of Hadean protocrust in Earth’s mantle. Proceedings of the National Academy of Sciences, 2022; 119 (18) DOI: 10.1073/pnas.2120241119
This finding is unexpected because the plate tectonic regime of our planet progressively recycles crustal material via large-scale mantle convection at much smaller time scales. Therefore, it has been assumed that vestiges of early geological processes on Earth can only be found as analogues, on other terrestrial planets (Mercury, Venus, and Mars), asteroids, or the Moon. However, according to their study ‘Long-term preservation of Hadean protocrust in Earth’s mantle’, which has recently appeared in the Proceedings of the National Academy of Sciences (PNAS), magmatic rocks that erupted throughout Earth’s history can still carry signatures that provide detailed information about the nature of the first crust, its long-term preservation in a graveyard in the lower-most mantle, and its resurrection via younger volcanism.
For their study, the geologists investigated up to 3.55 billion years old rocks from southern Africa. The analysis of these rocks revealed small anomalies in the isotope composition of the element tungsten (W). The origin of these isotope anomalies, namely the relative abundance of 182W, relates to geological processes that must have occurred immediately after the formation of the Earth more than 4.5 billion years ago.
Model calculations by the authors show that the observed 182W isotope patterns are best explained by the recycling of Earth’s earliest crust into mantle material that ascends via plumes from the lower mantle to generate lavas erupting at Earth’s surface. Intriguingly, the study shows that similar isotope patterns can be observed in distinct types of modern volcanic rocks (ocean island basalts), which demonstrates that Earth’s earliest crust is still buried in the lowermost mantle.
‘We assume that the lower layers of the crust — or the roots of the primordial continents — became heavier than their surroundings due to a geological maturation process and therefore sank into the Earth’s underlying mantle. Similar to a lava lamp,’ geochemist Dr Jonas Tusch from the University of Cologne’s Institute of Geology and Mineralogy remarked. ‘This fascinating insight provides a geochemical fingerprint of the young Earth, allowing us to better understand how large continents formed over the history of our planet. It also explains how our current, oxygen-rich atmosphere evolved — setting the stage for the origin of complex life,’ Dr Elis Hoffmann of Freie Universität Berlin added.
The geochemical fingerprint of the early Earth can also be compared with findings about other planets obtained during space missions. For example, data from Mars missions and studies of Martian meteorites show that Mars still has a very old surface due to the lack of plate tectonics, and that its composition may correspond to that of the young Earth.
)
[summary] => Journal Reference: Jonas Tusch, J. Elis Hoffmann, Eric Hasenstab, Mario Fischer-Gödde, Chris S. Marien, Allan...
[atom_content] =>
Journal Reference:
Jonas Tusch, J. Elis Hoffmann, Eric Hasenstab, Mario Fischer-Gödde, Chris S. Marien, Allan H. Wilson, Carsten Münker. Long-term preservation of Hadean protocrust in Earth’s mantle. Proceedings of the National Academy of Sciences, 2022; 119 (18) DOI: 10.1073/pnas.2120241119
This finding is unexpected because the plate tectonic regime of our planet progressively recycles crustal material via large-scale mantle convection at much smaller time scales. Therefore, it has been assumed that vestiges of early geological processes on Earth can only be found as analogues, on other terrestrial planets (Mercury, Venus, and Mars), asteroids, or the Moon. However, according to their study ‘Long-term preservation of Hadean protocrust in Earth’s mantle’, which has recently appeared in the Proceedings of the National Academy of Sciences (PNAS), magmatic rocks that erupted throughout Earth’s history can still carry signatures that provide detailed information about the nature of the first crust, its long-term preservation in a graveyard in the lower-most mantle, and its resurrection via younger volcanism.
For their study, the geologists investigated up to 3.55 billion years old rocks from southern Africa. The analysis of these rocks revealed small anomalies in the isotope composition of the element tungsten (W). The origin of these isotope anomalies, namely the relative abundance of 182W, relates to geological processes that must have occurred immediately after the formation of the Earth more than 4.5 billion years ago.
Model calculations by the authors show that the observed 182W isotope patterns are best explained by the recycling of Earth’s earliest crust into mantle material that ascends via plumes from the lower mantle to generate lavas erupting at Earth’s surface. Intriguingly, the study shows that similar isotope patterns can be observed in distinct types of modern volcanic rocks (ocean island basalts), which demonstrates that Earth’s earliest crust is still buried in the lowermost mantle.
‘We assume that the lower layers of the crust — or the roots of the primordial continents — became heavier than their surroundings due to a geological maturation process and therefore sank into the Earth’s underlying mantle. Similar to a lava lamp,’ geochemist Dr Jonas Tusch from the University of Cologne’s Institute of Geology and Mineralogy remarked. ‘This fascinating insight provides a geochemical fingerprint of the young Earth, allowing us to better understand how large continents formed over the history of our planet. It also explains how our current, oxygen-rich atmosphere evolved — setting the stage for the origin of complex life,’ Dr Elis Hoffmann of Freie Universität Berlin added.
The geochemical fingerprint of the early Earth can also be compared with findings about other planets obtained during space missions. For example, data from Mars missions and studies of Martian meteorites show that Mars still has a very old surface due to the lack of plate tectonics, and that its composition may correspond to that of the young Earth.
Marina Sanaki-Matsumiya, Mitsuhiro Matsuda, Nicola Gritti, Fumio Nakaki, James Sharpe, Vikas Trivedi, Miki Ebisuya. Periodic formation of epithelial somites from human pluripotent stem cells. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-29967-1
The spinal column consists of 33 vertebrae, which form pairs of precursor structures called somites. Somites give rise to not only our vertebrae, but also our ribs and skeletal muscles. To ensure that these structures are formed correctly, somite development is tightly regulated, and each pair of somites arises at a particular sequential time point in development. This process is controlled by the segmentation clock, which is a group of genes that creates oscillatory waves, every wave giving rise to a new pair of somites.
“For the first time, we have been able to create periodic pairs of human mature somites linked to the segmentation clock in the lab,” said Marina Sanaki-Matsumiya, first author of the study published in Nature Communications. Using this approach, the researchers developed a 3D in vitro model of human somite formation, also known as ‘somitogenesis’.
Creating a robust somitogenesis process
The team cultured human induced pluripotent stem cells (hiPSC) in the presence of a cocktail of signalling molecules that induce cell differentiation. Three days later, the cells started to elongate and create anterior (top) and posterior (bottom) axes. At that point, the scientists added Matrigel to the culture mix. Matrigel is what some scientists call the magic powder: a protein mixture that is critical to many developmental processes. This process eventually led to the formation of somitoids — in vitro equivalents of human somite precursor structures.
To test whether the segmentation clock regulates somitogenesis in these somitoids, the researchers monitored the expression patterns of HES7, the core gene involved in the process. They found clear evidence of oscillations, especially when somitogenesis was about to start. The somites that formed also had clear markers of epithelization — an important step in their maturation.
Somite size matters
The Ebisuya group studies how and why we humans are different from other species when it comes to embryonic development. One of the model systems they use to understand interspecies differences is the segmentation clock. In 2020, the group uncovered that the oscillation period of the human segmentation clock is longer than the mouse segmentation clock.
The current study also shows a link between the size of somites and the segmentation clock. “The somites that were generated had a constant size, independently of the number of cells used for the initial somitoid. The somite size did not increase even if the initial cell number did.” explained Sanaki-Matsumiya. “This suggests that the somites have a preferred species-specific size, which might be determined by local cell-cell interactions, the segmentation clock, or other mechanisms.”
To study this further, Miki Ebisuya and her group are now planning to grow somitoids of different species and compare them. The researchers are already working on several mammalian species, including rabbits, cattle, and rhinoceroses, setting up a ‘stem cell zoo’ in the lab.
“Our next project will focus on creating somitoids from different species, measure their cell proliferation and cell migration speed to establish what and how somitogenesis is different among species,” said Ebisuya.
Marina Sanaki-Matsumiya, Mitsuhiro Matsuda, Nicola Gritti, Fumio Nakaki, James Sharpe, Vikas Trivedi, Miki Ebisuya. Periodic formation of epithelial somites from human pluripotent stem cells. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-29967-1
The spinal column consists of 33 vertebrae, which form pairs of precursor structures called somites. Somites give rise to not only our vertebrae, but also our ribs and skeletal muscles. To ensure that these structures are formed correctly, somite development is tightly regulated, and each pair of somites arises at a particular sequential time point in development. This process is controlled by the segmentation clock, which is a group of genes that creates oscillatory waves, every wave giving rise to a new pair of somites.
“For the first time, we have been able to create periodic pairs of human mature somites linked to the segmentation clock in the lab,” said Marina Sanaki-Matsumiya, first author of the study published in Nature Communications. Using this approach, the researchers developed a 3D in vitro model of human somite formation, also known as ‘somitogenesis’.
Creating a robust somitogenesis process
The team cultured human induced pluripotent stem cells (hiPSC) in the presence of a cocktail of signalling molecules that induce cell differentiation. Three days later, the cells started to elongate and create anterior (top) and posterior (bottom) axes. At that point, the scientists added Matrigel to the culture mix. Matrigel is what some scientists call the magic powder: a protein mixture that is critical to many developmental processes. This process eventually led to the formation of somitoids — in vitro equivalents of human somite precursor structures.
To test whether the segmentation clock regulates somitogenesis in these somitoids, the researchers monitored the expression patterns of HES7, the core gene involved in the process. They found clear evidence of oscillations, especially when somitogenesis was about to start. The somites that formed also had clear markers of epithelization — an important step in their maturation.
Somite size matters
The Ebisuya group studies how and why we humans are different from other species when it comes to embryonic development. One of the model systems they use to understand interspecies differences is the segmentation clock. In 2020, the group uncovered that the oscillation period of the human segmentation clock is longer than the mouse segmentation clock.
The current study also shows a link between the size of somites and the segmentation clock. “The somites that were generated had a constant size, independently of the number of cells used for the initial somitoid. The somite size did not increase even if the initial cell number did.” explained Sanaki-Matsumiya. “This suggests that the somites have a preferred species-specific size, which might be determined by local cell-cell interactions, the segmentation clock, or other mechanisms.”
To study this further, Miki Ebisuya and her group are now planning to grow somitoids of different species and compare them. The researchers are already working on several mammalian species, including rabbits, cattle, and rhinoceroses, setting up a ‘stem cell zoo’ in the lab.
“Our next project will focus on creating somitoids from different species, measure their cell proliferation and cell migration speed to establish what and how somitogenesis is different among species,” said Ebisuya.
[date_timestamp] => 1651181743
)
[9] => Array
(
[title] => Resilient system using only non-volatile memory – NovLink
[link] => https://packagingnewsonline.com/health-science-news/resilient-system-using-only-non-volatile-memory-novlink/
[dc] => Array
(
[creator] => Betty Foster
)
[pubdate] => Thu, 28 Apr 2022 20:33:18 +0000
[category] => Health & Science News
[guid] => https://packagingnewsonline.com/health-science-news/resilient-system-using-only-non-volatile-memory-novlink/
[description] => “We mounted non-volatile memory on a system board prototype and created an operating system to...
[content] => Array
(
[encoded] =>
“We mounted non-volatile memory on a system board prototype and created an operating system to verify the effectiveness of LightPC,” said Professor Myoungsoo Jung. The team confirmed that LightPC validated its execution while powering up and down in the middle of execution, showing up to eight times more memory, 4.3 times faster application execution, and 73% lower power consumption compared to traditional systems.
Professor Jung said that LightPC can be utilized in a variety of fields such as data centers and high-performance computing to provide large-capacity memory, high performance, low power consumption, and service reliability.
In general, power failures on legacy systems can lead to the loss of data stored in the DRAM-based main memory. Unlike volatile memory such as DRAM, non-volatile memory can retain its data without power. Although non-volatile memory has the characteristics of lower power consumption and larger capacity than DRAM, non-volatile memory is typically used for the task of secondary storage due to its lower write performance. For this reason, nonvolatile memory is often used with DRAM. However, modern systems employing non-volatile memory-based main memory experience unexpected performance degradation due to the complicated memory microarchitecture.
To enable both data and execution persistent in legacy systems, it is necessary to transfer the data from the volatile memory to the non-volatile memory. Checkpointing is one possible solution. It periodically transfers the data in preparation for a sudden power failure. While this technology is essential for ensuring high mobility and reliability for users, checkpointing also has fatal drawbacks. It takes additional time and power to move data and requires a data recovery process as well as restarting the system.
In order to address these issues, the research team developed a processor and memory controller to raise the performance of non-volatile memory-only memory. LightPC matches the performance of DRAM by minimizing the internal volatile memory components from non-volatile memory, exposing the non-volatile memory (PRAM) media to the host, and increasing parallelism to service on-the-fly requests as soon as possible.
The team also presented operating system technology that quickly makes execution states of running processes persistent without the need for a checkpointing process. The operating system prevents all modifications to execution states and data by keeping all program executions idle before transferring data in order to support consistency within a period much shorter than the standard power hold-up time of about 16 minutes. For consistency, when the power is recovered, the computer almost immediately revives itself and re-executes all the offline processes immediately without the need for a boot process.
The researchers will present their work (LightPC: Hardware and Software Co-Design for Energy-Efficient Full System Persistence) at the International Symposium on Computer Architecture (ISCA) 2022 in New York in June.
)
[summary] => “We mounted non-volatile memory on a system board prototype and created an operating system to...
[atom_content] =>
“We mounted non-volatile memory on a system board prototype and created an operating system to verify the effectiveness of LightPC,” said Professor Myoungsoo Jung. The team confirmed that LightPC validated its execution while powering up and down in the middle of execution, showing up to eight times more memory, 4.3 times faster application execution, and 73% lower power consumption compared to traditional systems.
Professor Jung said that LightPC can be utilized in a variety of fields such as data centers and high-performance computing to provide large-capacity memory, high performance, low power consumption, and service reliability.
In general, power failures on legacy systems can lead to the loss of data stored in the DRAM-based main memory. Unlike volatile memory such as DRAM, non-volatile memory can retain its data without power. Although non-volatile memory has the characteristics of lower power consumption and larger capacity than DRAM, non-volatile memory is typically used for the task of secondary storage due to its lower write performance. For this reason, nonvolatile memory is often used with DRAM. However, modern systems employing non-volatile memory-based main memory experience unexpected performance degradation due to the complicated memory microarchitecture.
To enable both data and execution persistent in legacy systems, it is necessary to transfer the data from the volatile memory to the non-volatile memory. Checkpointing is one possible solution. It periodically transfers the data in preparation for a sudden power failure. While this technology is essential for ensuring high mobility and reliability for users, checkpointing also has fatal drawbacks. It takes additional time and power to move data and requires a data recovery process as well as restarting the system.
In order to address these issues, the research team developed a processor and memory controller to raise the performance of non-volatile memory-only memory. LightPC matches the performance of DRAM by minimizing the internal volatile memory components from non-volatile memory, exposing the non-volatile memory (PRAM) media to the host, and increasing parallelism to service on-the-fly requests as soon as possible.
The team also presented operating system technology that quickly makes execution states of running processes persistent without the need for a checkpointing process. The operating system prevents all modifications to execution states and data by keeping all program executions idle before transferring data in order to support consistency within a period much shorter than the standard power hold-up time of about 16 minutes. For consistency, when the power is recovered, the computer almost immediately revives itself and re-executes all the offline processes immediately without the need for a boot process.
The researchers will present their work (LightPC: Hardware and Software Co-Design for Energy-Efficient Full System Persistence) at the International Symposium on Computer Architecture (ISCA) 2022 in New York in June.
