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BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with chronic liver disease (CLD) and liver transplant (LT) recipients remains a concern. The aim of this study was to report the impact of coronavirus disease 2019 (COVID-19) infection among patients at the tertiary health care centre Centre hospitalier de l’Université de Montréal (CHUM) during the first wave of the SARS-CoV-2 pandemic. METHODS: This real-world, retrospective cohort included all patients admitted to our liver unit and/or seen as an outpatient with CLD with or without cirrhosis and/or LT recipients who tested positive to SARS-CoV-2 infection. Cases were considered positive as defined by the detection of SARS-CoV-2 by reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. RESULTS: Between April 1 and July 31, 2020, 5,637 were admitted to our liver unit and/or seen as outpatient. Among them, 42 were positive for SARS-CoV-2. Twenty-two patients had CLD without cirrhosis while 16 patients had cirrhosis at the time of the infection (13, 2, and 1 with Child–Pugh A, B, and C scores, respectively). Four were LT recipients. Overall, 15 of 42 patients (35.7%) were hospitalized; among them, 7 of 42 (16.7%) required respiratory support and 4 of 42 (9.5%) were transferred to the intensive care unit. Only 4 of 42 (9.5%) patients died: 2 with CLD without cirrhosis and 2 with CLD with cirrhosis. Overall survival was 90.5%. CONCLUSION: This real-world study demonstrates an unexpectedly low prevalence and low mortality in the context of SARS-CoV-2 infection among patients with CLD with or without cirrhosis and LT recipients.

Diagnosis of chronic hepatitis B virus (HBV) infection, initial staging of infection and monitoring of treated and untreated patients are mainly based on clinical, biological and imaging criteria allowing a complete non-invasive management for the majority of patients. Along to the conventional virological tools, rapid diagnostic tests and blotting paper tests for HBV DNA are validated alternatives. After diagnosis, the initial work-up should include HIV, HCV and HDV serologies, HBeAg status, and HBsAg and HBV DNA quantification. Assessment of severity (inflammation and fibrosis) is based on ALT serum levels and non-invasive evaluation of liver fibrosis by elastography or blood tests, which must be interpreted cautiously using specific cut-offs and taking into account ALT levels. Taken together, these parameters allow disease classification and treatment decision. Decision of hepatocellular carcinoma screening by ultra-sound every six months may be difficult in non-cirrhotic patients and the use of risk-scores such as PAGE-B is encouraged. Chronic HBV infection often has a dynamic and often unpredictable profile and regular monitoring is mandatory. In untreated patients, regular (3-12 months) follow-up should include ALT and HBV DNA serum levels. Periodical HBsAg quantification and non-invasive evaluation of liver fibrosis may refine disease outcome and prognosis. In treated patients, checking efficacy is mainly based on HBV DNA negativity. In patients with advanced fibrosis, evolution of liver stiffness can be useful for portal hypertension evaluation, but its improvement should not be considered to stop hepatocellular carcinoma screening. Finally, new parameters (HBV RNA, HBcrAg) are promising but their use is still restricted for research.

Graphene's linear bandstructure and two-dimensional density of states provide an implicit advantage for sensing charge. Here, these advantages are leveraged in a deeply depleted graphene-oxide-semiconductor (D2GOS) junction detector architecture to sense carriers created by ionizing radiation. Specifically, the room temperature response of the silicon-based D2GOS junction is analyzed during irradiation with 20 MeV Si4+ ions. Detection was demonstrated for doses ranging from 12-1200 ions with device functionality maintained with no substantive degradation. To understand the device response, D2GOS pixels were characterized post-irradiation via a combination of electrical characterization, Raman spectroscopy, and photocurrent mapping. This combined characterization methodology underscores the lack of discernible damage caused by irradiation to the graphene while highlighting the nature of interactions between the incident ions and the silicon absorber., Comment: 15 pages, 4 figures

Background & aims Spontaneous bacterial empyema (SBE) is defined as the spontaneous infection of hepatic hydrothorax. It is a rare infectious complication of portal hypertension in cirrhotic patients. The aim of this study was to evaluate the outcomes in patients diagnosed with SBE compared to cirrhotic patients without this complication. Methods We performed a retrospective cohort study of cirrhotic patients from a tertiary care center. The primary outcome was time to death or liver transplantation within one year after diagnosis of infection. We integrated three groups: patients with SBE (Group A), patients with spontaneous bacterial peritonitis (SBP, Group B), and cirrhotic patients without SBP/SBE (Group C), matched by age, MELD-Na score, and year of infection. Outcome was analyzed using a Cox regression model adjusting for cardiovascular risk factors and MELD-Na. Results Between January 1999 and February 2019, 4829 patients with cirrhosis were identified. Among them, 73 (1.5%) had a HH of whom 22 (30.1%) were diagnosed with SBE. Median age of the patients with SBE was 58 years (IQR 52-64), 11 patients (50%) were men, median Child Pugh score was 10 (IQR 8-11) and median MELD-Na was 21 (IQR 15-27). TFS was 9.1% (2/22), vs 41% (18/44) vs 52.2% (23/44) in Group A, B and C, respectively (log rank test p Conclusion Our results suggest that patients with SBE had a lower one-year survival rate. Patients who develop SBE should have prompt referral for transplant evaluation. SBE might emerge as new indication that could benefit from MELD exception points. This article is protected by copyright. All rights reserved.

International audience; Background & Aims: Hepatic ischemia-reperfusion injury is a complication of liver surgery that involves mitochondrial dysfunction resulting from mitochondrial permeability transition pore (mPTP) opening. Cyclophilin D (PPIF or CypD) is a peptidyl-prolyl cis-trans isomerase that regulates mPTP opening in the inner mitochondrial membrane. We investigated whether and how recently created small-molecule inhibitors of CypD prevent opening of the mPTP in hepatocytes and the resulting effects in cell models and livers of mice undergoing ischemia/reperfusion injuryMethods: We measured the activity of 9 small-molecule inhibitors of cyclophilins in an assay of CypD activity. The effects of the small-molecule CypD inhibitors or vehicle on mPTP opening were assessed by measuring mitochondrial swelling and calcium retention in isolated liver mitochondria from C57BL/6J (wild-type) and Ppif–/– (CypD knockout) mice and in primary mouse and human hepatocytes by fluorescence microscopy. We induced ischemia/reperfusion injury in livers of mice given a small-molecule CypD inhibitor or vehicle before and during reperfusion and collected samples of blood and liver for histologic analysis.Results: The compounds inhibited peptidyl-prolyl isomerase activity (half maximal inhibitory concentration values, 0.2–16.2 μmol/L) and, as a result, calcium-induced mitochondrial swelling, by preventing mPTP opening (half maximal inhibitory concentration values, 1.4–132 μmol/L) in a concentration-dependent manner. The most potent inhibitor (C31) bound CypD with high affinity and inhibited swelling in mitochondria from livers of wild-type and Ppif–/– mice (indicating an additional, CypD-independent effect on mPTP opening) and in primary human and mouse hepatocytes. Administration of C31 in mice with ischemia/reperfusion injury before and during reperfusion restored hepatic calcium retention capacity and oxidative phosphorylation parameters and reduced liver damage compared with vehicle.Conclusions:Recently created small-molecule inhibitors of CypD reduced calcium-induced swelling in mitochondria from mouse and human liver tissues. Administration of these compounds to mice during ischemia/reperfusion restored hepatic calcium retention capacity and oxidative phosphorylation parameters and reduced liver damage. These compounds might be developed to protect patients from ischemia/reperfusion injury after liver surgery or for other hepatic or nonhepatic disorders related to abnormal mPTP opening.

The deeply depleted graphene-oxide-semiconductor (D2GOS) junction detector provides an effective architecture for photodetection, enabling direct readout of photogenerated charge. Because of an inh...

Hepatitis C virus (HCV) genotype 4 is highly heterogeneous. HCV subtype 4r has been suggested to be less responsive to direct-acting antiviral (DAA) drug treatment than other genotype 4 subtypes. Among 537 DAA-treated patients who experienced a virological failure (VF) in France between 2015 and 2018, 121 (22.5%) were infected with genotype 4 and 27 of them (22.3%) with subtype 4r; subtype 4r was thus over-represented as compared to its prevalence in the French general population. Population sequencing of the nonstructural protein (NS) 3, NS5A, and NS5B genes was performed in all subtype 4r patients at treatment failure and in 6 at baseline, whereas full-length HCV genome sequencing was performed in two baseline and three treatment failure samples by means of an original shotgun metagenomics method based on deep sequencing. At treatment failure, all subtype 4r patients harbored two to three dominant NS5A resistance-associated substitutions (RASs), including at least L28A/C/I/M/V and L30R. Among 13 patients exposed to sofosbuvir and an NS5A inhibitor (daclatasvir, ledipasvir, or velpatasvir), 5 (38.5%) also harbored NS5B S282C/T RASs at treatment failure. An additional patient harbored S282C/T RASs at treatment failure by deep sequencing. Prevalence of S282C/T RASs at treatment failure was significantly higher in patients infected with genotype 4r than with other genotypes, including other subtypes of genotype 4. Conclusion: The lower rates of sustained virological response in patients infected with subtype 4r are related to the frequent preexistence at treatment baseline and subsequent selection by DAA treatment of both NS5A and NS5B S282 RASs. Our study suggests that these patients should be identified and receive a triple DAA combination regimen as first-line treatment.

Mitochondrial permeability transition pore (mPTP) opening is a key event in cell death during myocardial ischemia reperfusion. Inhibition of its modulator cyclophilin D (CypD) by cyclosporine A (CsA) reduces ischemia-reperfusion injury. The use of cyclosporine A in this indication is debated; however, targeting mPTP remains a major goal to achieve. We investigated the protective effects of a new original small-molecule cyclophilin inhibitor C31, which was specifically designed to target CypD. CypD peptidylprolyl cis-trans isomerase (PPIase) activity was assessed by the standard chemotrypsin-coupled assay. The effects of C31 on mPTP opening were investigated in isolated mouse cardiac mitochondria by measuring mitochondrial swelling and calcium retention capacity (CRC) in rat H9C2 cardiomyoblasts and in adult mouse cardiomyocytes by fluorescence microscopy in isolated perfused mouse hearts and ex vivo after drug infusion in mice. C31 potently inhibited CypD PPIase activity and mitochondrial swelling. C31 was more effective at increasing mitochondrial CRC than CsA and was still able to increase CRC in Ppif−/− (CypD-inactivated) cardiac mitochondria. C31 delayed both mPTP opening and cell death in cardiomyocytes subjected to hypoxia reoxygenation. However, high concentrations of both drugs were necessary to reduce mPTP opening in isolated perfused hearts, and neither CsA nor C31 inhibited mPTP opening in heart after in vivo infusion, underlying the importance of myocardial drug distribution for cardioprotection. C31 is an original inhibitor of mPTP opening involving both CypD-dependent and -independent mechanisms. It constitutes a promising new cytoprotective agent. Optimization of its pharmacokinetic properties is now required prior to its use against cardiac ischemia-reperfusion injury. SIGNIFICANCE STATEMENT This study demonstrates that the new cyclophilin inhibitor C31 potently inhibits cardiac mitochondrial permeability transition pore (mPTP) opening in vitro and ex vivo. The dual mechanism of action of C31 allows the prevention of mPTP opening beyond cyclophilin D inhibition. Further development of the compound might bring promising drug candidates for cardioprotection. However, the lack of effect of both C31 and cyclosporine A after systemic administration demonstrates the difficulties of targeting myocardial mitochondria in vivo and should be taken into account in cardioprotective strategies.

Background Despite concerns that patients with liver transplants might be at increased risk of adverse outcomes from COVID-19 because of coexisting comorbidities and use of immunosuppressants, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on this patient group remains unclear. We aimed to assess the clinical outcomes in these patients. Methods In this multicentre cohort study, we collected data on patients with laboratory-confirmed SARS-CoV-2 infection, who were older than 18 years, who had previously received a liver transplant, and for whom data had been submitted by clinicians to one of two international registries (COVID-Hep and SECURE-Cirrhosis) at the end of the patient's disease course. Patients without a known hospitalisation status or mortality outcome were excluded. For comparison, data from a contemporaneous cohort of consecutive patients with SARS-CoV-2 infection who had not received a liver transplant were collected from the electronic patient records of the Oxford University Hospitals National Health Service Foundation Trust. We compared the cohorts with regard to several outcomes (including death, hospitalisation, intensive care unit [ICU] admission, requirement for intensive care, and need for invasive ventilation). A propensity score-matched analysis was done to test for an association between liver transplant and death. Findings Between March 25 and June 26, 2020, data were collected for 151 adult liver transplant recipients from 18 countries (median age 60 years [IQR 47–66], 102 [68%] men, 49 [32%] women) and 627 patients who had not undergone liver transplantation (median age 73 years [44–84], 329 [52%] men, 298 [48%] women). The groups did not differ with regard to the proportion of patients hospitalised (124 [82%] patients in the liver transplant cohort vs 474 [76%] in the comparison cohort, p=0·106), or who required intensive care (47 [31%] vs 185 [30%], p=0·837). However, ICU admission (43 [28%] vs 52 [8%], p Interpretation Liver transplantation was not independently associated with death, whereas increased age and presence of comorbidities were. Factors other than transplantation should be preferentially considered in relation to physical distancing and provision of medical care for patients with liver transplants during the COVID-19 pandemic. Funding European Association for the Study of the Liver, US National Institutes of Health, UK National Institute for Health Research.

Graphene plasmons provide a compelling avenue toward chip-scale dynamic tuning of infrared light. Dynamic tunability emerges through controlled alterations in the optical properties of the system defining graphene's plasmonic dispersion. Typically, electrostatic induced alterations of the carrier concentration in graphene working in conjunction with mobility have been considered the primary factors dictating plasmonic tunability. We find here that the surrounding dielectric environment also plays a primary role, dictating not just the energy of the graphene plasmon but so too the magnitude of its tuning and spectral width. To arrive at this conclusion, poles in the imaginary component of the reflection coefficient are used to efficiently survey the effect of the surrounding dielectric on the tuning of the graphene plasmon. By investigating several common polar materials, optical phonons (i.e., the Reststrahlen band) of the dielectric substrate are shown to appreciably affect not only the plasmon's spectral location but its tunability, and its resonance shape as well. In particular, tunability is maximized when the resonances are spectrally distant from the Reststrahlen band, whereas sharp resonances (i.e., high-$Q$) are achievable at the band's edge. These observations both underscore the necessity of viewing the dielectric environment in aggregate when considering the plasmonic response derived from two-dimensional materials and provide heuristics to design dynamically tunable graphene-based infrared devices.

Knowing the most likely clinical prognosis for a patient infected with SARS-Cov-2 could offer guidelines for tracking their medical evolution, improving attention, and assigning resources. Aiming to assess a patient’s status quantitatively, we explore the analysis of existing clinical information using data-driven methods. Our goal is to extract the characteristics distinguishing between those COVID-19 patients that improve and those who die. In our approach, we select the relevant features using the algorithm of Boruta, a wrapper framework that takes input from classifiers generating relevance assessment of the predictors. Using the extracted features, we train machine learning classifiers, including Random Forests, Support Vector Machine, Extreme Gradient Boosting, and Neural Networks. We assess the performance of the classifiers using Precision-Recall and ROC analysis, establishing the ranges at which risk assessment permits effective decision-making. Our research highlights that local regions present unique sets of essential features, that it is possible to construct effective classifiers based on clinical data, and that an ensemble of classifiers results in the best performing discriminant.

Liver progenitor cells (LPCs)/ductular reactions (DRs) are associated with inflammation and implicated in the pathogenesis of chronic liver diseases. However, how inflammation regulates LPCs/DRs remains largely unknown. Identification of inflammatory processes that involve LPC activation and expansion represent a key step in understanding the pathogenesis of liver diseases. In the current study, we found that diverse types of chronic liver diseases are associated with elevation of infiltrated interleukin (IL)-17-positive (+) cells and cytokeratin 19 (CK19)+ LPCs, and both cell types colocalized and their numbers positively correlated with each other. The role of IL-17 in the induction of LPCs was examined in a mouse model fed a choline-deficient and ethionine-supplemented (CDE) diet. Feeding of wild-type mice with the CDE diet markedly elevated CK19+Ki67+ proliferating LPCs and hepatic inflammation. Disruption of the IL-17 gene or IL-27 receptor, alpha subunit (WSX-1) gene abolished CDE diet-induced LPC expansion and inflammation. In vitro treatment with IL-17 promoted proliferation of bipotential murine oval liver cells (a liver progenitor cell line) and markedly up-regulated IL-27 expression in macrophages. Treatment with IL-27 favored the differentiation of bipotential murine oval liver cells and freshly isolated LPCs into hepatocytes. Conclusion: The current data provide evidence for a collaborative role between IL-17 and IL-27 in promoting LPC expansion and differentiation, respectively, thereby contributing to liver regeneration. (Hepatology Communications 2018;2:329-343).

Nonalcoholic fatty liver disease (NAFLD) is a well-recognized health problem, with an estimated worldwide prevalence of 25%.1 It is associated with metabolic syndrome (MetSx) and complications such as cirrhosis and hepatocellular carcinoma. However, the main cause of death in patients with NAFLD is derived from cardiovascular disease, and outcome seems to be determined by the degree of hepatic fibrosis.2 The prevalence of NAFLD and associated cardiovascular risk factors in asymptomatic patients in Mexico are poorly documented, despite having one of the highest rates of obesity and metabolic syndrome worldwide.3.

We assessed the broadly used, off-label combination of sofosbuvir, daclatasvir, simeprevir, and ribavirin in direct-acting antiviral-experienced patients, as recommended in current guidelines despite scarce data. After 24 weeks' treatment, sustained virological response 12 weeks after the end of treatment was achieved in 6 patients (60%). Two cirrhotic patients relapsed and 2 discontinued treatment due to serious adverse events.

Herein, we report on chemical vapor deposition (CVD) of partially oxidized graphene (POG) films on electropolished polycrystalline copper foils at relatively low temperature under near-atmospheric pressure. The structural, chemical, and electronic properties of the films are studied in detail using several spectroscopic and microscopic techniques. The content of carbon and oxygen in the films is identified by chemical mapping at near-atomic scale. Electron diffraction patterns of the films possess clear diffraction spots with a six-fold pattern that is consistent with the hexagonal lattice. The fine structure of the carbon K-edge signal in STEM-EELS spectra of the films is distinguishable from that of graphene and graphite. The presence of oxygen in the films is further supported by a clear oxygen K-edge. Raman spectroscopy and XPS results provide direct evidence for a lower degree of oxidation. The work function of the films is found to be much higher than that of graphene, using UPS measurements.

The deeply depleted graphene-oxide-semiconductor junction $(\mathrm{D}^{2}\mathrm{GOS})$ architecture has been shown to be a highly sensitive light detector [1]. In this architecture, photogenerated charge in the depletion region of the semiconductor is separated and then directly readout by an adjacent graphene layer similarly to a photoFET. Although detection of (electrons and light) radiation using graphene has been previously demonstrated, only limited work has been conducted on other types of ionizing radiation detection with graphene [2]–[3]. In this work we demonstrate advances made in high energy (2 & 20 MeV), heavy ion (Si+) detection using the $\mathrm{D}^{2}\mathrm{GOS}$ junction, leveraging our previous experience and fabrication improvements for visible light detection using a silicon absorber substrate.

Introduction This document is a summary of the French Intergroup guidelines regarding the management of hepatocellular carcinoma (HCC) published in March 2019. Method It is a collaborative work under the auspices of most of the French medical societies involved in the management of HCC. It is based on the previous guidelines published in 2017. Recommendations are graded in 3 categories according to the level of evidence of data found in the literature. Results The diagnosis and staging of HCC is essentially based on clinical, biological and imaging features. A pathological analysis obtained by a biopsy of tumoral and non-tumoral liver is recommended. HCCs can be divided into 2 groups, taking into account not only the tumor stage, but also liver function. HCCs accessible to curative treatments are tumors that are in Milan criteria or with an AFP score ≤ 2, mainly treated by surgical resection, local ablation or liver transplantation. Intermediate and advanced HCCs with no liver insufficiency, accessible only to palliative treatments, benefit from TACE, SIRT or systemic therapy according to the presence or absence of macrovascular invasion or extrahepatic spread. Conclusion Such recommendations are in permanent optimization and each individual case must be discussed in a multidisciplinary expert board.

UNLABELLED Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral-based regimens is commonly associated with emergence of resistance-associated variants (RAVs). To avoid cross-resistance, recent guidelines recommend that patients who have failed on nonstructural protein 5A (NS5A) inhibitors should be retreated with sofosbuvir (SOF; NS5B inhibitor) combined with simeprevir (SIM; protease inhibitor [PI]); however, supporting evidence is lacking. This "real-world" study comprised patients who had failed to achieve SVR on previous NS5A-based therapy with daclatasvir (DCV) plus pegylated interferon (Peg-IFN) and ribavirin (RBV), with (n = 3) or without (n = 13) asunaprevir (ASV; PI). All 16 patients were retreated for 12 weeks with SOF plus SIM, without RBV. Antiviral efficacy was evaluated using the primary endpoint of SVR12 (SVR 12 weeks post-treatment); on-treatment response was also assessed. Patients (N = 16; 13 male; mean age: 54 years [range, 43-73]) were chronically infected with HCV genotype (GT) 1 (1a, n = 11; 1b, n = 3) or 4 (n = 2); they had advanced fibrosis or compensated cirrhosis (FibroScan, 9.6-70 kPa; cirrhosis, n = 9); median baseline HCV-RNA level was 1.38 × 10(6) IU/mL. No patient discontinued treatment because of adverse events or virological failure. All patients achieved HCV RNA below lower limit of quantification (

Here, the design, fabrication, and characterization of an actively tunable long-wave infrared detector, made possible through direct integration of a graphene-enabled metasurface with a conventional type-II superlattice infrared detector, are reported. This structure allows for post-fabrication tuning of the detector spectral response through voltage-induced modification of the carrier density within graphene and, therefore, its plasmonic response. These changes modify the transmittance through the metasurface, which is fabricated monolithically atop the detector, allowing for spectral control of light reaching the detector. Importantly, this structure provides a fabrication-controlled alignment of the metasurface filter to the detector pixel and is entirely solid-state. Using single pixel devices, relative changes in the spectral response exceeding 8% have been realized. These proof-of-concept devices present a path toward solid-state hyperspectral imaging with independent pixel-to-pixel spectral control through a voltage-actuated dynamic response.

Esta investigación surge a través de mis vivencias y experiencias como estudiante y profesor de inglés como lengua extranjera. Esto debido a que, durante mi aprendizaje de la lengua inglesa, las clases se enfocaban en desarrollar, en la mayoría de ellas, la competencia lingüística; sin tomar en cuenta la competencia pragmática.

Coupling of metasurfaces to intersubband transitions (ISTs) in semiconductor quantum wells (QWs) has been extensively studied for various applications ranging from generating giant nonlinear optical response to designing tunable metasurfaces for applications such as ultrafast spatial optical modulators and voltage tunable filters. In this work, we experimentally demonstrate a fundamentally new approach of actively controlling the coupling of ISTs in QWs to a metasurface for voltage tuning its optical response. Unlike previous approaches, we use voltage-controlled quantum tunneling to control the carrier concentration in the QWs for turning on/off the ISTs. We design a multi-quantum well structure consisting of four undoped InGaAs wells with AlInAs barriers grown on top of a highly doped InGaAs layer that acts as an electron reservoir. The heterostructure is optimized such that the first IST in all the wells is at 11µm. A complementary gold metasurface with dipole resonances at 11µm is fabricated on top of the QW structure. We designed the heterostructure such that by applying a bias of 1V, the energy bands of all the QWs get aligned simultaneously, leading to the occupation of the ground state of all the QWs via quantum tunneling of the electrons from the electron reservoir. The ISTs which were turned off due to negligible electron density gets turned on at 1V, and this leads to coupling between the ISTs and the dipoles resonances of the metasurface. The voltage induced coupling leads to reflectance modulation which we confirmed experimentally by rapid scan double modulation FTIR measurements.

Metasurfaces have been investigated for various applications ranging from beam steering, focusing, to polarization conversion. Along with passive metasurfaces, significant efforts are also being made to design metasurfaces with tunable optical response. Among various approaches, voltage tuning is of particular interest because it creates the possibility of integration with electronics. In this work, we demonstrate voltage tuning of reflectance from a complementary metasurface strongly coupled to an epsilon-near-zero (ENZ) mode in an ultrathin semiconductor layer. Our approach involves electrically controlling the carrier concentration of the ENZ layer to modulate the polaritonic coupling between the dipole resonances of the metasurface and the ENZ mode for modulating the reflectance of the metasurface. The hybrid structure we fabricate is similar to MOSCAP configuration where the complementary metasurface offers a continuous gold top layer for biasing and positive/negative bias to the metasurface leads to accumulation/depletion of carriers in the ENZ layer beneath it. We optimized our structure by using InGaAs as the ENZ material because of its high mobility and low effective mass. This allowed us to reduce the doping requirement and thereby reduce the ionized impurity scattering as well as the reverse bias required to deplete the ENZ layer. For low leakage and efficient modulation of carrier density, we used Hafnia as the gate dielectric. We further added a reflecting backplane below the ENZ layer to enhance the interaction and by applying bias, we achieved spectral shifts of 500 nm and amplitude modulation of 11% of one of the polariton branches at 14 µm.

Although members of the Flaviviridae display high incidence, morbidity, and mortality rates, the development of specific antiviral drugs for each virus is unlikely. Cyclophilins, a family of host peptidyl-prolyl cis-trans isomerases (PPIases), play a pivotal role in the life cycles of many viruses and therefore represent an attractive target for broad-spectrum antiviral development. We report here the pangenotypic anti-hepatitis C virus (HCV) activity of a small-molecule cyclophilin inhibitor (SMCypI). Mechanistic and modeling studies revealed that the SMCypI bound to cyclophilin A in competition with cyclosporine (CsA), inhibited its PPIase activity, and disrupted the CypA-nonstructural protein 5A (NS5A) interaction. Resistance selection showed that the lead SMCypI hardly selected amino acid substitutions conferring low-level or no resistance in vitro . Interestingly, the SMCypI selected D320E and Y321H substitutions, located in domain II of the NS5A protein. These substitutions were previously associated with low-level resistance to cyclophilin inhibitors such as alisporivir. Finally, the SMCypI inhibited the replication of other members of the Flaviviridae family with higher 50% effective concentrations (EC 50 s) than for HCV. Thus, because of its chemical plasticity and simplicity of synthesis, our new family of SMCypIs represents a promising new class of drugs with the potential for broad-spectrum anti- Flaviviridae activity as well as an invaluable tool to explore the role of cyclophilins in viral life cycles.

Optimization of the electrode/electrolyte double-layer interface is a key factor for improving electrode performance of aqueous electrolyte based supercapacitors (SCs). Here, we report the improved functionality of carbon materials via a non-invasive, high-throughput, and inexpensive UV generated ozone (UV-ozone) treatment. This process allows precise tuning of the graphene and carbon nanotube hybrid foam (GM) transitionally from ultrahydrophobic to hydrophilic within 60 s. The continuous tuning of surface energy can be controlled by simply varying the UV-ozone exposure time, while the ozone-oxidized carbon nanostructure maintains its integrity. Symmetric SCs based on the UV-ozone treated GM foam demonstrated enhanced rate performance. This technique can be readily applied to other CVD-grown carbonaceous materials by taking advantage of its ease of processing, low cost, scalability, and controllability.

A sensitive optical detector is presented based on a deeply depleted graphene-insulator-semiconducting (D2GIS) junction, which offers the possibility of simultaneously leveraging the advantages of both charge integration and localized amplification. Direct read-out and built-in amplification are accomplished via photogating of a graphene field-effect transistor (GFET) by carriers generated within a deeply depleted low-doped silicon substrate. Analogous to a depleted metal-oxide-semiconducting junction, photo-generated charge collects in the potential well that forms at the semiconductor/insulator interface and induces charges of opposite polarity within the graphene film modifying its conductivity. This device enables simultaneous photo-induced charge integration with continuous “on detector” readout through use of graphene. The resulting devices exhibit responsivities as high as 2,500 A/W (25,000 S/W) for visible wavelengths and a dynamic range of 30 dB. As both the graphene and device principles are transferrable to arbitrary semiconductor absorbers, D2GIS devices offer a high-performance paradigm for imaging across the electromagnetic spectrum.

BACKGROUND The combination of sofosbuvir (SOF) plus an NS5A inhibitor for 12 weeks is highly efficacious in patients with chronic hepatitis C. As the costs of generic production of sofosbuvir and NS5A inhibitor are rapidly decreasing, the combination of these DAAs will be the standard treatment in most low- to middle-income countries in the future. AIM To identify key predictors of response that can be used to tailor treatment decisions. METHODS A cohort of 216 consecutive patients infected with HCV genotype 1 (1a: n = 57; 1b: n = 77), 2 (n = 4), 3 (n = 33) or 4 (n = 44) were treated with sofosbuvir (SOF) + daclatasvir (n = 176) or SOF + ledipasvir (n = 40) for 12 weeks. The viral kinetics was analysed using the biphasic model and the cure boundary was used to predict time to clear HCV. RESULTS The overall SVR rate was high (94.4%; n = 204), regardless of the time to viral suppression or low-level viraemia at the end of treatment. The model-based predicted HCV RNA levels at the end of treatment could not differentiate patients who did from those who did not achieve SVR. The presence of NS5A resistance-associated substitutions [position 28 (OR = 70.3, P