Fabrication and properties of L-arginine-doped PCL electrospun composite scaffolds

The article describes fabrication and properties of composite fibrous scaffolds obtained by electrospinning of the solution of poly({\epsilon}-caprolactone) and arginine in common solvent. The influence of arginine content on structure, mechanical, surface and biological properties of the scaffolds was investigated. It was found that with an increase of arginine concentration diameter of the scaffold fibers was reduced, which was accompanied by an increase of scaffold strength and Young modulus. It was demonstrated that porosity and water contact angle of the scaffold are independent from arginine content. The best cell adhesion and viability was shown on scaffolds with arginine concentration from 0.5 to 1 % wt

Research of vein-protective effect of the preparation "Agsular”® on the models of 106 vascular pathology

Varicose disease is the most common vascular pathology of lower extremities that causes development of chronic venous insufficiency (CVI). Modern Russian pharmaceutical market of medicines external application used in phlebology is mainly presented by expensive imported medicines. That's why development of original Russian high-effective and. available medicines for prevention, and. treatment of chronic venous insufficiency is an actual problem of medical and. pharmaceutical sciences. Pharmacologically active substance 'Asgular®" that has hypolipidemic and anticoagulant activity was developed in A.E. Favorsky Irkutsk Institute of Chemistry SB RAS as the result of chemical modification of polysaccharide of Siberian larch. Original pharmaceutical compositions (preparation. "Asgular®") in solid and. liquid medicinal forms for external application in forms of hydrophilic gel and rectal capsules with hydrophilic gel were developed on the basis of that active substance. Veinprotective effect of "Agsular®" preparation was studied on the models of vascular pathology. It was determined. that antiinflammatory activity and. anti-transudative effect — decrease of vessels' permeability and increase of their walls' tone — were of most importance in the mechanism of veinprotective effect of the preparation "Agsular"®. Anti-inflammatory activity is developed in decrease of intensity of neutrophil infiltration in wound, area and. in anti-exudative effect that is presented by the decrease of stroma and cell hypostases. Thus our researches indicates prospectivity of use of "Agsular'® preparation for prevention and. treatment of chronic venous insufficiency and varicosis in particular

Continuous symmetry of C60 fullerene and its derivatives

Conventionally, the Ih symmetry of fullerene C60 is accepted which is supported by numerous calculations. However, this conclusion results from the consideration of the molecule electron system, of its odd electrons in particular, in a close-shell approximation without taking the electron spin into account. Passing to the open-shell approximation has lead to both the energy and the symmetry lowering up to Ci. Seemingly contradicting to a high-symmetry pattern of experimental recording, particularly concerning the molecule electronic spectra, the finding is considered in the current paper from the continuous symmetry viewpoint. Exploiting both continuous symmetry measure and continuous symmetry content, was shown that formal Ci symmetry of the molecule is by 99.99% Ih. A similar continuous symmetry analysis of the fullerene monoderivatives gives a reasonable explanation of a large variety of their optical spectra patterns within the framework of the same C1 formal symmetry exhibiting a strong stability of the C60 skeleton.Comment: 11 pages. 5 figures. 6 table

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer

Objectives: To characterize the safety, tolerability, and anti-tumor activity of cemiplimab as monotherapy or in combination with hypofractionated radiation therapy (hfRT) in patients with recurrent or metastatic cervical cancer. To determine the association between histology and programmed death-ligand 1 (PD-L1) expression. Methods: In non-randomized phase I expansion cohorts, patients (squamous or non-squamous histology) received cemiplimab 3 mg/kg intravenously every 2 weeks for 48 weeks, either alone (monotherapy cohort) or with hfRT during week 2 (combination cohort). Due to insufficient tissue material, PD-L1 protein expression was evaluated in commercially purchased samples and mRNA expression levels were analyzed from The Cancer Genome Atlas (TCGA). Results: Twenty patients enrolled in both cohorts in total; 10 had squamous histology. The most common adverse events of any grade were diarrhea, fatigue, and hypokalemia, occurring in 35%, 25%, and 25%, respectively. Objective response rate was 10% in each cohort; responders had squamous histology. Duration of response was 11.2 months and 6.4 months for the responder in the monotherapy and combination cohort, respectively. Irradiated lesions were not included in the response assessments. In separate archived specimens (N = 155), PD-L1 protein expression in tumor and immune cells was negative (<1%) more commonly in adenocarcinoma than in squamous tumors. PD-L1 mRNA levels were lower in adenocarcinoma than squamous cell tumors (1.2 vs 5.0 mean transcripts per million, respectively) in TCGA. Conclusions: Cemiplimab has activity in cervical squamous cell carcinoma. The phase I results, combined with results from other anti-PD-1 trials in cervical cancer and our biomarker analyses have informed the design of the ongoing phase III trial, with the primary overall survival hierarchical analyses being done first in patients with squamous histology

CMB Telescopes and Optical Systems

The cosmic microwave background radiation (CMB) is now firmly established as a fundamental and essential probe of the geometry, constituents, and birth of the Universe. The CMB is a potent observable because it can be measured with precision and accuracy. Just as importantly, theoretical models of the Universe can predict the characteristics of the CMB to high accuracy, and those predictions can be directly compared to observations. There are multiple aspects associated with making a precise measurement. In this review, we focus on optical components for the instrumentation used to measure the CMB polarization and temperature anisotropy. We begin with an overview of general considerations for CMB observations and discuss common concepts used in the community. We next consider a variety of alternatives available for a designer of a CMB telescope. Our discussion is guided by the ground and balloon-based instruments that have been implemented over the years. In the same vein, we compare the arc-minute resolution Atacama Cosmology Telescope (ACT) and the South Pole Telescope (SPT). CMB interferometers are presented briefly. We conclude with a comparison of the four CMB satellites, Relikt, COBE, WMAP, and Planck, to demonstrate a remarkable evolution in design, sensitivity, resolution, and complexity over the past thirty years.Comment: To appear in: Planets, Stars and Stellar Systems (PSSS), Volume 1: Telescopes and Instrumentatio

ДИНАМИКА IN VITRO ДЕГРАДАЦИИ НЕТКАНЫХ МАТРИКСОВ ИЗ ПОЛИМОЛОЧНОЙ КИСЛОТЫ В МОДЕЛЬНОЙ БИОЛОГИЧЕСКОЙ ЖИДКОСТИ

The weekly in vitro degradation of fibrous-porous non-woven polylactide scaffolds made by aerodynamic formation in a turbulent gas flow has been studied with 37 °С in model RPMI-1640 medium imitated body fluid of organism. Lactate monomers released into solution exponentially and reached slowly a maximum value the end of the observation (5th week of dissolution). At the same time, reducing the concentrations of calcium and inorganic phosphorus ions in solutions contacted with tested samples (10×10×1 mm2) testified about chemical elements adsorption on artificial material. Ions exchange with biological fluids may be a basis of regulated bioactivity of fibrous-porous non-woven biodegradable material in application to intercellular matrix bioengineering for regenerative medicineИзучена понедельная деградация in vitro при температуре 37 °С волокнисто-пористых нетканых скеффолдов из полимолочной кислоты, полученных аэродинамическим формированием в турбулентном газовом потоке, в модельной среде RPMI-1640, имитирующей телесную жидкость организма. Мономеры молочной кислоты выделялись в раствор по экспоненциальному закону и медленно достигали максимальных концентраций к концу наблюдений (5-я нед растворения). В то же время снижение концентраций ионов кальция и неорганического фосфора в растворах, контактирующих с тестируемыми образцами (10 ´ 10 ´ 1 мм2 ), свидетельствовало об адсорбции химических элементов на искусственном материале. Обмен ионами с биологическими жидкостями могут быть основой регулируемой биоактивности волокнисто-пористого биодеградируемого материала в приложении к биоинженерии межклеточного матрикса для регенеративной медицины

Radioactivity control strategy for the JUNO detector

602siopenJUNO is a massive liquid scintillator detector with a primary scientific goal of determining the neutrino mass ordering by studying the oscillated anti-neutrino flux coming from two nuclear power plants at 53 km distance. The expected signal anti-neutrino interaction rate is only 60 counts per day (cpd), therefore a careful control of the background sources due to radioactivity is critical. In particular, natural radioactivity present in all materials and in the environment represents a serious issue that could impair the sensitivity of the experiment if appropriate countermeasures were not foreseen. In this paper we discuss the background reduction strategies undertaken by the JUNO collaboration to reduce at minimum the impact of natural radioactivity. We describe our efforts for an optimized experimental design, a careful material screening and accurate detector production handling, and a constant control of the expected results through a meticulous Monte Carlo simulation program. We show that all these actions should allow us to keep the background count rate safely below the target value of 10 Hz (i.e. ∼1 cpd accidental background) in the default fiducial volume, above an energy threshold of 0.7 MeV. [Figure not available: see fulltext.]openAbusleme A.; Adam T.; Ahmad S.; Ahmed R.; Aiello S.; Akram M.; An F.; An Q.; Andronico G.; Anfimov N.; Antonelli V.; Antoshkina T.; Asavapibhop B.; de Andre J.P.A.M.; Auguste D.; Babic A.; Baldini W.; Barresi A.; Basilico D.; Baussan E.; Bellato M.; Bergnoli A.; Birkenfeld T.; Blin S.; Blum D.; Blyth S.; Bolshakova A.; Bongrand M.; Bordereau C.; Breton D.; Brigatti A.; Brugnera R.; Bruno R.; Budano A.; Buscemi M.; Busto J.; Butorov I.; Cabrera A.; Cai H.; Cai X.; Cai Y.; Cai Z.; Cammi A.; Campeny A.; Cao C.; Cao G.; Cao J.; Caruso R.; Cerna C.; Chang J.; Chang Y.; Chen P.; Chen P.-A.; Chen S.; Chen X.; Chen Y.-W.; Chen Y.; Chen Y.; Chen Z.; Cheng J.; Cheng Y.; Chetverikov A.; Chiesa D.; Chimenti P.; Chukanov A.; Claverie G.; Clementi C.; Clerbaux B.; Conforti Di Lorenzo S.; Corti D.; Cremonesi O.; Dal Corso F.; Dalager O.; De La Taille C.; Deng J.; Deng Z.; Deng Z.; Depnering W.; Diaz M.; Ding X.; Ding Y.; Dirgantara B.; Dmitrievsky S.; Dohnal T.; Dolzhikov D.; Donchenko G.; Dong J.; Doroshkevich E.; Dracos M.; Druillole F.; Du S.; Dusini S.; Dvorak M.; Enqvist T.; Enzmann H.; Fabbri A.; Fajt L.; Fan D.; Fan L.; Fang J.; Fang W.; Fargetta M.; Fedoseev D.; Fekete V.; Feng L.-C.; Feng Q.; Ford R.; Formozov A.; Fournier A.; Gan H.; Gao F.; Garfagnini A.; Giammarchi M.; Giaz A.; Giudice N.; Gonchar M.; Gong G.; Gong H.; Gornushkin Y.; Gottel A.; Grassi M.; Grewing C.; Gromov V.; Gu M.; Gu X.; Gu Y.; Guan M.; Guardone N.; Gul M.; Guo C.; Guo J.; Guo W.; Guo X.; Guo Y.; Hackspacher P.; Hagner C.; Han R.; Han Y.; Hassan M.S.; He M.; He W.; Heinz T.; Hellmuth P.; Heng Y.; Herrera R.; Hor Y.K.; Hou S.; Hsiung Y.; Hu B.-Z.; Hu H.; Hu J.; Hu J.; Hu S.; Hu T.; Hu Z.; Huang C.; Huang G.; Huang H.; Huang W.; Huang X.; Huang X.; Huang Y.; Hui J.; Huo L.; Huo W.; Huss C.; Hussain S.; Ioannisian A.; Isocrate R.; Jelmini B.; Jen K.-L.; Jeria I.; Ji X.; Ji X.; Jia H.; Jia J.; Jian S.; Jiang D.; Jiang X.; Jin R.; Jing X.; Jollet C.; Joutsenvaara J.; Jungthawan S.; Kalousis L.; Kampmann P.; Kang L.; Karaparambil R.; Kazarian N.; Khan W.; Khosonthongkee K.; Korablev D.; Kouzakov K.; Krasnoperov A.; Kruth A.; Kutovskiy N.; Kuusiniemi P.; Lachenmaier T.; Landini C.; Leblanc S.; Lebrin V.; Lefevre F.; Lei R.; Leitner R.; Leung J.; Li D.; Li F.; Li F.; Li H.; Li H.; Li J.; Li M.; Li M.; Li N.; Li N.; Li Q.; Li R.; Li S.; Li T.; Li W.; Li W.; Li X.; Li X.; Li X.; Li Y.; Li Y.; Li Z.; Li Z.; Li Z.; Liang H.; Liang H.; Liao J.; Liebau D.; Limphirat A.; Limpijumnong S.; Lin G.-L.; Lin S.; Lin T.; Ling J.; Lippi I.; Liu F.; Liu H.; Liu H.; Liu H.; Liu H.; Liu H.; Liu J.; Liu J.; Liu M.; Liu Q.; Liu Q.; Liu R.; Liu S.; Liu S.; Liu S.; Liu X.; Liu X.; Liu Y.; Liu Y.; Lokhov A.; Lombardi P.; Lombardo C.; Loo K.; Lu C.; Lu H.; Lu J.; Lu J.; Lu S.; Lu X.; Lubsandorzhiev B.; Lubsandorzhiev S.; Ludhova L.; Luo F.; Luo G.; Luo P.; Luo S.; Luo W.; Lyashuk V.; Ma B.; Ma Q.; Ma S.; Ma X.; Ma X.; Maalmi J.; Malyshkin Y.; Mantovani F.; Manzali F.; Mao X.; Mao Y.; Mari S.M.; Marini F.; Marium S.; Martellini C.; Martin-Chassard G.; Martini A.; Mayer M.; Mayilyan D.; Mednieks I.; Meng Y.; Meregaglia A.; Meroni E.; Meyhofer D.; Mezzetto M.; Miller J.; Miramonti L.; Montini P.; Montuschi M.; Muller A.; Nastasi M.; Naumov D.V.; Naumova E.; Navas-Nicolas D.; Nemchenok I.; Nguyen Thi M.T.; Ning F.; Ning Z.; Nunokawa H.; Oberauer L.; Ochoa-Ricoux J.P.; Olshevskiy A.; Orestano D.; Ortica F.; Othegraven R.; Pan H.-R.; Paoloni A.; Parmeggiano S.; Pei Y.; Pelliccia N.; Peng A.; Peng H.; Perrot F.; Petitjean P.-A.; Petrucci F.; Pilarczyk O.; Pineres Rico L.F.; Popov A.; Poussot P.; Pratumwan W.; Previtali E.; Qi F.; Qi M.; Qian S.; Qian X.; Qian Z.; Qiao H.; Qin Z.; Qiu S.; Rajput M.U.; Ranucci G.; Raper N.; Re A.; Rebber H.; Rebii A.; Ren B.; Ren J.; Ricci B.; Robens M.; Roche M.; Rodphai N.; Romani A.; Roskovec B.; Roth C.; Ruan X.; Ruan X.; Rujirawat S.; Rybnikov A.; Sadovsky A.; Saggese P.; Sanfilippo S.; Sangka A.; Sanguansak N.; Sawangwit U.; Sawatzki J.; Sawy F.; Schever M.; Schwab C.; Schweizer K.; Selyunin A.; Serafini A.; Settanta G.; Settimo M.; Shao Z.; Sharov V.; Shaydurova A.; Shi J.; Shi Y.; Shutov V.; Sidorenkov A.; Simkovic F.; Sirignano C.; Siripak J.; Sisti M.; Slupecki M.; Smirnov M.; Smirnov O.; Sogo-Bezerra T.; Sokolov S.; Songwadhana J.; Soonthornthum B.; Sotnikov A.; Sramek O.; Sreethawong W.; Stahl A.; Stanco L.; Stankevich K.; Stefanik D.; Steiger H.; Steinmann J.; Sterr T.; Stock M.R.; Strati V.; Studenikin A.; Sun S.; Sun X.; Sun Y.; Sun Y.; Suwonjandee N.; Szelezniak M.; Tang J.; Tang Q.; Tang Q.; Tang X.; Tietzsch A.; Tkachev I.; Tmej T.; Treskov K.; Triossi A.; Troni G.; Trzaska W.; Tuve C.; Ushakov N.; van den Boom J.; van Waasen S.; Vanroyen G.; Vassilopoulos N.; Vedin V.; Verde G.; Vialkov M.; Viaud B.; Vollbrecht M.C.; Volpe C.; Vorobel V.; Voronin D.; Votano L.; Walker P.; Wang C.; Wang C.-H.; Wang E.; Wang G.; Wang J.; Wang J.; Wang K.; Wang L.; Wang M.; Wang M.; Wang M.; Wang R.; Wang S.; Wang W.; Wang W.; Wang W.; Wang X.; Wang X.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Z.; Wang Z.; Wang Z.; Wang Z.; Waqas M.; Watcharangkool A.; Wei L.; Wei W.; Wei W.; Wei Y.; Wen L.; Wiebusch C.; Wong S.C.-F.; Wonsak B.; Wu D.; Wu F.; Wu Q.; Wu Z.; Wurm M.; Wurtz J.; Wysotzki C.; Xi Y.; Xia D.; Xie X.; Xie Y.; Xie Z.; Xing Z.; Xu B.; Xu C.; Xu D.; Xu F.; Xu H.; Xu J.; Xu J.; Xu M.; Xu Y.; Xu Y.; Yan B.; Yan T.; Yan W.; Yan X.; Yan Y.; Yang A.; Yang C.; Yang C.; Yang H.; Yang J.; Yang L.; Yang X.; Yang Y.; Yang Y.; Yao H.; Yasin Z.; Ye J.; Ye M.; Ye Z.; Yegin U.; Yermia F.; Yi P.; Yin N.; Yin X.; You Z.; Yu B.; Yu C.; Yu C.; Yu H.; Yu M.; Yu X.; Yu Z.; Yu Z.; Yuan C.; Yuan Y.; Yuan Z.; Yuan Z.; Yue B.; Zafar N.; Zambanini A.; Zavadskyi V.; Zeng S.; Zeng T.; Zeng Y.; Zhan L.; Zhang A.; Zhang F.; Zhang G.; Zhang H.; Zhang H.; Zhang J.; Zhang J.; Zhang J.; Zhang J.; Zhang J.; Zhang P.; Zhang Q.; Zhang S.; Zhang S.; Zhang T.; Zhang X.; Zhang X.; Zhang X.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Z.; Zhang Z.; Zhao F.; Zhao J.; Zhao R.; Zhao S.; Zhao T.; Zheng D.; Zheng H.; Zheng M.; Zheng Y.; Zhong W.; Zhou J.; Zhou L.; Zhou N.; Zhou S.; Zhou T.; Zhou X.; Zhu J.; Zhu K.; Zhu K.; Zhu Z.; Zhuang B.; Zhuang H.; Zong L.; Zou J.Abusleme, A.; Adam, T.; Ahmad, S.; Ahmed, R.; Aiello, S.; Akram, M.; An, F.; An, Q.; Andronico, G.; Anfimov, N.; Antonelli, V.; Antoshkina, T.; Asavapibhop, B.; de Andre, J. P. A. M.; Auguste, D.; Babic, A.; Baldini, W.; Barresi, A.; Basilico, D.; Baussan, E.; Bellato, M.; Bergnoli, A.; Birkenfeld, T.; Blin, S.; Blum, D.; Blyth, S.; Bolshakova, A.; Bongrand, M.; Bordereau, C.; Breton, D.; Brigatti, A.; Brugnera, R.; Bruno, R.; Budano, A.; Buscemi, M.; Busto, J.; Butorov, I.; Cabrera, A.; Cai, H.; Cai, X.; Cai, Y.; Cai, Z.; Cammi, A.; Campeny, A.; Cao, C.; Cao, G.; Cao, J.; Caruso, R.; Cerna, C.; Chang, J.; Chang, Y.; Chen, P.; Chen, P. -A.; Chen, S.; Chen, X.; Chen, Y. -W.; Chen, Y.; Chen, Y.; Chen, Z.; Cheng, J.; Cheng, Y.; Chetverikov, A.; Chiesa, D.; Chimenti, P.; Chukanov, A.; Claverie, G.; Clementi, C.; Clerbaux, B.; Conforti Di Lorenzo, S.; Corti, D.; Cremonesi, O.; Dal Corso, F.; Dalager, O.; De La Taille, C.; Deng, J.; Deng, Z.; Deng, Z.; Depnering, W.; Diaz, M.; Ding, X.; Ding, Y.; Dirgantara, B.; Dmitrievsky, S.; Dohnal, T.; Dolzhikov, D.; Donchenko, G.; Dong, J.; Doroshkevich, E.; Dracos, M.; Druillole, F.; Du, S.; Dusini, S.; Dvorak, M.; Enqvist, T.; Enzmann, H.; Fabbri, A.; Fajt, L.; Fan, D.; Fan, L.; Fang, J.; Fang, W.; Fargetta, M.; Fedoseev, D.; Fekete, V.; Feng, L. -C.; Feng, Q.; Ford, R.; Formozov, A.; Fournier, A.; Gan, H.; Gao, F.; Garfagnini, A.; Giammarchi, M.; Giaz, A.; Giudice, N.; Gonchar, M.; Gong, G.; Gong, H.; Gornushkin, Y.; Gottel, A.; Grassi, M.; Grewing, C.; Gromov, V.; Gu, M.; Gu, X.; Gu, Y.; Guan, M.; Guardone, N.; Gul, M.; Guo, C.; Guo, J.; Guo, W.; Guo, X.; Guo, Y.; Hackspacher, P.; Hagner, C.; Han, R.; Han, Y.; Hassan, M. S.; He, M.; He, W.; Heinz, T.; Hellmuth, P.; Heng, Y.; Herrera, R.; Hor, Y. K.; Hou, S.; Hsiung, Y.; Hu, B. -Z.; Hu, H.; Hu, J.; Hu, J.; Hu, S.; Hu, T.; Hu, Z.; Huang, C.; Huang, G.; Huang, H.; Huang, W.; Huang, X.; Huang, X.; Huang, Y.; Hui, J.; Huo, L.; Huo, W.; Huss, C.; Hussain, S.; Ioannisian, A.; Isocrate, R.; Jelmini, B.; Jen, K. -L.; Jeria, I.; Ji, X.; Ji, X.; Jia, H.; Jia, J.; Jian, S.; Jiang, D.; Jiang, X.; Jin, R.; Jing, X.; Jollet, C.; Joutsenvaara, J.; Jungthawan, S.; Kalousis, L.; Kampmann, P.; Kang, L.; Karaparambil, R.; Kazarian, N.; Khan, W.; Khosonthongkee, K.; Korablev, D.; Kouzakov, K.; Krasnoperov, A.; Kruth, A.; Kutovskiy, N.; Kuusiniemi, P.; Lachenmaier, T.; Landini, C.; Leblanc, S.; Lebrin, V.; Lefevre, F.; Lei, R.; Leitner, R.; Leung, J.; Li, D.; Li, F.; Li, F.; Li, H.; Li, H.; Li, J.; Li, M.; Li, M.; Li, N.; Li, N.; Li, Q.; Li, R.; Li, S.; Li, T.; Li, W.; Li, W.; Li, X.; Li, X.; Li, X.; Li, Y.; Li, Y.; Li, Z.; Li, Z.; Li, Z.; Liang, H.; Liang, H.; Liao, J.; Liebau, D.; Limphirat, A.; Limpijumnong, S.; Lin, G. -L.; Lin, S.; Lin, T.; Ling, J.; Lippi, I.; Liu, F.; Liu, H.; Liu, H.; Liu, H.; Liu, H.; Liu, H.; Liu, J.; Liu, J.; Liu, M.; Liu, Q.; Liu, Q.; Liu, R.; Liu, S.; Liu, S.; Liu, S.; Liu, X.; Liu, X.; Liu, Y.; Liu, Y.; Lokhov, A.; Lombardi, P.; Lombardo, C.; Loo, K.; Lu, C.; Lu, H.; Lu, J.; Lu, J.; Lu, S.; Lu, X.; Lubsandorzhiev, B.; Lubsandorzhiev, S.; Ludhova, L.; Luo, F.; Luo, G.; Luo, P.; Luo, S.; Luo, W.; Lyashuk, V.; Ma, B.; Ma, Q.; Ma, S.; Ma, X.; Ma, X.; Maalmi, J.; Malyshkin, Y.; Mantovani, F.; Manzali, F.; Mao, X.; Mao, Y.; Mari, S. M.; Marini, F.; Marium, S.; Martellini, C.; Martin-Chassard, G.; Martini, A.; Mayer, M.; Mayilyan, D.; Mednieks, I.; Meng, Y.; Meregaglia, A.; Meroni, E.; Meyhofer, D.; Mezzetto, M.; Miller, J.; Miramonti, L.; Montini, P.; Montuschi, M.; Muller, A.; Nastasi, M.; Naumov, D. V.; Naumova, E.; Navas-Nicolas, D.; Nemchenok, I.; Nguyen Thi, M. T.; Ning, F.; Ning, Z.; Nunokawa, H.; Oberauer, L.; Ochoa-Ricoux, J. P.; Olshevskiy, A.; Orestano, D.; Ortica, F.; Othegraven, R.; Pan, H. -R.; Paoloni, A.; Parmeggiano, S.; Pei, Y.; Pelliccia, N.; Peng, A.; Peng, H.; Perrot, F.; Petitjean, P. -A.; Petrucci, F.; Pilarczyk, O.; Pineres Rico, L. F.; Popov, A.; Poussot, P.; Pratumwan, W.; Previtali, E.; Qi, F.; Qi, M.; Qian, S.; Qian, X.; Qian, Z.; Qiao, H.; Qin, Z.; Qiu, S.; Rajput, M. U.; Ranucci, G.; Raper, N.; Re, A.; Rebber, H.; Rebii, A.; Ren, B.; Ren, J.; Ricci, B.; Robens, M.; Roche, M.; Rodphai, N.; Romani, A.; Roskovec, B.; Roth, C.; Ruan, X.; Ruan, X.; Rujirawat, S.; Rybnikov, A.; Sadovsky, A.; Saggese, P.; Sanfilippo, S.; Sangka, A.; Sanguansak, N.; Sawangwit, U.; Sawatzki, J.; Sawy, F.; Schever, M.; Schwab, C.; Schweizer, K.; Selyunin, A.; Serafini, A.; Settanta, G.; Settimo, M.; Shao, Z.; Sharov, V.; Shaydurova, A.; Shi, J.; Shi, Y.; Shutov, V.; Sidorenkov, A.; Simkovic, F.; Sirignano, C.; Siripak, J.; Sisti, M.; Slupecki, M.; Smirnov, M.; Smirnov, O.; Sogo-Bezerra, T.; Sokolov, S.; Songwadhana, J.; Soonthornthum, B.; Sotnikov, A.; Sramek, O.; Sreethawong, W.; Stahl, A.; Stanco, L.; Stankevich, K.; Stefanik, D.; Steiger, H.; Steinmann, J.; Sterr, T.; Stock, M. R.; Strati, V.; Studenikin, A.; Sun, S.; Sun, X.; Sun, Y.; Sun, Y.; Suwonjandee, N.; Szelezniak, M.; Tang, J.; Tang, Q.; Tang, Q.; Tang, X.; Tietzsch, A.; Tkachev, I.; Tmej, T.; Treskov, K.; Triossi, A.; Troni, G.; Trzaska, W.; Tuve, C.; Ushakov, N.; van den Boom, J.; van Waasen, S.; Vanroyen, G.; Vassilopoulos, N.; Vedin, V.; Verde, G.; Vialkov, M.; Viaud, B.; Vollbrecht, M. C.; Volpe, C.; Vorobel, V.; Voronin, D.; Votano, L.; Walker, P.; Wang, C.; Wang, C. -H.; Wang, E.; Wang, G.; Wang, J.; Wang, J.; Wang, K.; Wang, L.; Wang, M.; Wang, M.; Wang, M.; Wang, R.; Wang, S.; Wang, W.; Wang, W.; Wang, W.; Wang, X.; Wang, X.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Z.; Wang, Z.; Wang, Z.; Wang, Z.; Waqas, M.; Watcharangkool, A.; Wei, L.; Wei, W.; Wei, W.; Wei, Y.; Wen, L.; Wiebusch, C.; Wong, S. C. -F.; Wonsak, B.; Wu, D.; Wu, F.; Wu, Q.; Wu, Z.; Wurm, M.; Wurtz, J.; Wysotzki, C.; Xi, Y.; Xia, D.; Xie, X.; Xie, Y.; Xie, Z.; Xing, Z.; Xu, B.; Xu, C.; Xu, D.; Xu, F.; Xu, H.; Xu, J.; Xu, J.; Xu, M.; Xu, Y.; Xu, Y.; Yan, B.; Yan, T.; Yan, W.; Yan, X.; Yan, Y.; Yang, A.; Yang, C.; Yang, C.; Yang, H.; Yang, J.; Yang, L.; Yang, X.; Yang, Y.; Yang, Y.; Yao, H.; Yasin, Z.; Ye, J.; Ye, M.; Ye, Z.; Yegin, U.; Yermia, F.; Yi, P.; Yin, N.; Yin, X.; You, Z.; Yu, B.; Yu, C.; Yu, C.; Yu, H.; Yu, M.; Yu, X.; Yu, Z.; Yu, Z.; Yuan, C.; Yuan, Y.; Yuan, Z.; Yuan, Z.; Yue, B.; Zafar, N.; Zambanini, A.; Zavadskyi, V.; Zeng, S.; Zeng, T.; Zeng, Y.; Zhan, L.; Zhang, A.; Zhang, F.; Zhang, G.; Zhang, H.; Zhang, H.; Zhang, J.; Zhang, J.; Zhang, J.; Zhang, J.; Zhang, J.; Zhang, P.; Zhang, Q.; Zhang, S.; Zhang, S.; Zhang, T.; Zhang, X.; Zhang, X.; Zhang, X.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Z.; Zhang, Z.; Zhao, F.; Zhao, J.; Zhao, R.; Zhao, S.; Zhao, T.; Zheng, D.; Zheng, H.; Zheng, M.; Zheng, Y.; Zhong, W.; Zhou, J.; Zhou, L.; Zhou, N.; Zhou, S.; Zhou, T.; Zhou, X.; Zhu, J.; Zhu, K.; Zhu, K.; Zhu, Z.; Zhuang, B.; Zhuang, H.; Zong, L.; Zou, J

PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma

BACKGROUNDNo systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.METHODSWe report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review.RESULTSIn the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event.CONCLUSIONSAmong patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors

Construction status and prospects of the Hyper-Kamiokande project

The Hyper-Kamiokande project is a 258-kton Water Cherenkov together with a 1.3-MW high-intensity neutrino beam from the Japan Proton Accelerator Research Complex (J-PARC). The inner detector with 186-kton fiducial volume is viewed by 20-inch photomultiplier tubes (PMTs) and multi-PMT modules, and thereby provides state-of-the-art of Cherenkov ring reconstruction with thresholds in the range of few MeVs. The project is expected to lead to precision neutrino oscillation studies, especially neutrino CP violation, nucleon decay searches, and low energy neutrino astronomy. In 2020, the project was officially approved and construction of the far detector was started at Kamioka. In 2021, the excavation of the access tunnel and initial mass production of the newly developed 20-inch PMTs was also started. In this paper, we present a basic overview of the project and the latest updates on the construction status of the project, which is expected to commence operation in 2027

Prospects for neutrino astrophysics with Hyper-Kamiokande

Hyper-Kamiokande is a multi-purpose next generation neutrino experiment. The detector is a two-layered cylindrical shape ultra-pure water tank, with its height of 64 m and diameter of 71 m. The inner detector will be surrounded by tens of thousands of twenty-inch photosensors and multi-PMT modules to detect water Cherenkov radiation due to the charged particles and provide our fiducial volume of 188 kt. This detection technique is established by Kamiokande and Super-Kamiokande. As the successor of these experiments, Hyper-K will be located deep underground, 600 m below Mt. Tochibora at Kamioka in Japan to reduce cosmic-ray backgrounds. Besides our physics program with accelerator neutrino, atmospheric neutrino and proton decay, neutrino astrophysics is an important research topic for Hyper-K. With its fruitful physics research programs, Hyper-K will play a critical role in the next neutrino physics frontier. It will also provide important information via astrophysical neutrino measurements, i.e., solar neutrino, supernova burst neutrinos and supernova relic neutrino. Here, we will discuss the physics potential of Hyper-K neutrino astrophysics