Long-range correlations in elastic moduli and local stresses at the unjamming transition.

We explore the behaviour of spatially heterogeneous elastic moduli as well as the correlations between local moduli in model solids with short-range repulsive potentials. We show through numerical simulations that local elastic moduli exhibit long-range correlations, similar to correlations in the local stresses. Specifically, the correlations in local shear moduli exhibit anisotropic behavior at large lengthscales characterized by pinch-point singularities in Fourier space, displaying a structural pattern akin to shear stress correlations. Focussing on two-dimensional jammed solids approaching the unjamming transition, we show that stress correlations exhibit universal properties, characterized by a quadratic p2 dependence of the correlations as the pressure p approaches zero, independent of the details of the model. In contrast, the modulus correlations exhibit a power-law dependence with different exponents depending on the specific interaction potential. Furthermore, we illustrate that while affine responses lack long-range correlations, the total modulus, which encompasses non-affine behavior, exhibits long-range correlations.

Atypical activation of the RNA sensor MDA5 by hepatitis C virus.

Hepatitis C virus (HCV) is a significant human pathogen that can cause a number of serious diseases including chronic inflammation of the liver, cirrhosis, and hepatocellular carcinoma. A key enzyme in the HCV life cycle is the nonstructural protein 5B (NS5B), which functions as an RNA-dependent RNA polymerase (RdRp) responsible for replicating the viral RNA genome. In their recent study, Dansako and colleagues showed that HCV NS5B induces type I interferon via activation of the RNA receptor MDA5, an activity that was dependent on the RdRp enzymatic activity but independent of viral RNA replication. Their data further indicated that the NS5B enzymes of HCV and the related GB virus-B produce cellular double-stranded RNA (dsRNA) species with potential immunostimulatory activity. These findings unveil an unconventional mechanism of activation of MDA5-mediated host immunity by viral RdRp enzymes, which is expected to spur new research directions in viral immunology.

Reliability Assessment of On-Wafer AlGaN/GaN HEMTs: The Impact of Electric Field Stress on the Mean Time to Failure.

We present the mean time to failure (MTTF) of on-wafer AlGaN/GaN HEMTs under two distinct electric field stress conditions. The channel temperature (Tch) of the devices exhibits variability contingent upon the stress voltage and power dissipation, thereby influencing the long-term reliability of the devices. The accuracy of the channel temperature assumes a pivotal role in MTTF determination, a parameter measured and simulated through TCAD Silvaco device simulation. Under low electric field stress, a gradual degradation of IDSS is noted, accompanied by a negative shift in threshold voltage (ΔVT) and a substantial increase in gate leakage current (IG). Conversely, the high electric field stress condition induces a sudden decrease in IDSS without any observed shift in threshold voltage. For the low and high electric field conditions, MTTF values of 360 h and 160 h, respectively, were determined for on-wafer AlGaN/GaN HEMTs.

Effect of Trap Behavior on the Reliability Instability of Metamorphic Buffer in InAlAs/InGaAs MHEMT on GaAs.

Our investigation focused on assessing the influence of the metamorphic buffer in metamorphic high-electron-mobility transistors (MHEMT) that were grown on GaAs substrates. While an MHEMT exhibited elevated off-state current levels, its direct current (DC) and radio frequency (RF) traits were found to be comparable to those of InP-based lattice-matched high-electron-mobility transistors (LM-HEMTs). However, the Pulsed I-V measurement results confirmed the presence of the fast transient charging effect, leading to a more substantial degradation in drain current observed in MHEMT. In addition, through the low-frequency noise characteristics, it was confirmed that the dominant trapping location was located in the bulk site. The slope of the 1/f noise measurement indicated that the primary trapping site was in proximity to the bulk traps. The carrier-number-fluctuation (CNF) model was employed to extract the bulk trap density (Nt). For the LM-HEMTs, the value was at 3.27 × 1016 eV-1·cm-3, while for the MHEMT, it was 3.56 × 1017 eV-1·cm-3.

Enhanced vibrational stability in glass droplets.

We show through simulations of amorphous solids prepared in open-boundary conditions that they possess significantly fewer low-frequency vibrational modes compared to their periodic boundary counterparts. Specifically, using measurements of the vibrational density of states, we find that the D(ω)∼ω4 law changes to D(ω)∼ωδ with δ≈5 in two dimensions and δ≈4.5 in three dimensions. Crucially, this enhanced stability is achieved when utilizing slow annealing protocols to generate solid configurations. We perform an anharmonic analysis of the minima corresponding to the lowest frequency modes in such open-boundary systems and discuss their correlation with the density of states. A study of various system sizes further reveals that small systems display a higher degree of localization in vibrations. Lastly, we confine open-boundary solids in order to introduce macroscopic stresses in the system, which are absent in the unconfined system and find that the D(ω)∼ω4 behavior is recovered.

Impact of Charge-Trapping Effects on Reliability Instability in AlxGa1-xN/GaN High-Electron-Mobility Transistors with Various Al Compositions.

In this study, we present a detailed analysis of trapping characteristics at the AlxGa1-xN/GaN interface of AlxGa1-xN/GaN high-electron-mobility transistors (HEMTs) with reliability assessments, demonstrating how the composition of the Al in the AlxGa1-xN barrier impacts the performance of the device. Reliability instability assessment in two different AlxGa1-xN/GaN HEMTs [x = 0.25, 0.45] using a single-pulse ID-VD characterization technique revealed higher drain-current degradation (∆ID) with pulse time for Al0.45Ga0.55N/GaN devices which correlates to the fast-transient charge-trapping in the defect sites near the interface of AlxGa1-xN/GaN. Constant voltage stress (CVS) measurement was used to analyze the charge-trapping phenomena of the channel carriers for long-term reliability testing. Al0.45Ga0.55N/GaN devices exhibited higher-threshold voltage shifting (∆VT) caused by stress electric fields, verifying the interfacial deterioration phenomenon. Defect sites near the interface of the AlGaN barrier responded to the stress electric fields and captured channel electrons-resulting in these charging effects that could be partially reversed using recovery voltages. The quantitative extraction of volume trap density (Nt) using 1/f low-frequency noise characterizations unveiled a 40% reduced Nt for the Al0.25Ga0.75N/GaN device, further verifying the higher trapping phenomena in the Al0.45Ga0.55N barrier caused by the rougher Al0.45Ga0.55N/GaN interface.

Explicit Thermal Resistance Model of Self-Heating Effects of AlGaN/GaN HEMTs with Linear and Non-Linear Thermal Conductivity.

We presented an explicit empirical model of the thermal resistance of AlGaN/GaN high-electron-mobility transistors on three distinct substrates, including sapphire, SiC, and Si. This model considered both a linear and non-linear thermal resistance model of AlGaN/GaN HEMT, the thickness of the host substrate layers, and the gate length and width. The non-linear nature of channel temperature-visible at the high-power dissipation stage-along with linear dependency, was constructed within a single equation. Comparisons with the channel temperature measurement procedure (DC) and charge-control-based device modeling were performed to verify the model's validity, and the results were in favorable agreement with the observed model data, with only a 1.5% error rate compared to the measurement data. An agile expression for the channel temperature is also important for designing power devices and monolithic microwave integrated circuits. The suggested approach provides several techniques for investigation that could otherwise be impractical or unattainable when utilizing time-consuming numerical simulations.

miR-451a Regulates Neuronal Apoptosis by Modulating 14-3-3ζ-JNK Axis upon Flaviviral Infection.

Japanese Encephalitis Virus (JEV)/West Nile Virus (WNV)-induced encephalitis, although observed in selective cases, is associated with fatal consequences ranging from decline in cognitive abilities among recovered patients to coma/death. Loss of neuronal cells following viral infection-induced neuronal death imposes significant challenge to the central nervous system (CNS) homeostasis eventually resulting in loss of CNS tissue integrity and poor disease outcome in patients. In our present study, we aim to evaluate the role played by miRNA in modulating neuronal death upon neurotropic flaviviral infections. Infection of neuronal cell line resulted in upregulation of miR-451a abundance. Upon its upregulation, miR-451a has been demonstrated to target 3'-UTR of 14-3-3ζ transcript culminating into downregulation of 14-3-3ζ at the protein level. In response to 14-3-3ζ protein depletion in the cytosol upon flavivirus infection, increased phosphorylation of JNK protein has been shown to take place thus paving way for the cell to undergo apoptosis. Reversal of virus-induced miR-451a-upregulation helped abrogate neuronal apoptosis which is accompanied by a restoration of 14-3-3ζ protein and phosphorylated-JNK abundance to its normal level. Our findings hence provide a possible therapeutic target for preventing JEV/WNV-induced neuronal apoptosis thus improving disease outcome in flaviviral infection-associated encephalitis. IMPORTANCE Neuronal infection by JEV/WNV culminates into neuronal cell death thus contributing to signs and symptoms exhibited by patients that suffer from and that have recovered from JEV/WNV-induced encephalitis. In the present study we have evaluated the role of miRNA in promoting flavivirus-induced neuronal apoptosis. miR-451a has been demonstrated to promote neuronal cell death by targeting 14-3-3ζ protein function. The function of miR-451a in modulating neuronal physiology toward self-destruction has been shown to be independent of its effect upon the virus infection life cycle. The 14-3-3ζ transcript upon being targeted by miR-451a promotes JNK phosphorylation hence culminating into neuronal death by activation of apoptotic machinery. Inhibition of miR-451a upon neuronal infection by JEV/WNV helped reduce apoptotic machinery activation hence providing us with possible future therapeutic strategy in ameliorating flavivirus-induced neurological manifestations and overall disease burden in terms of morbidity.

Comprehensive Schottky Barrier Height Behavior and Reliability Instability with Ni/Au and Pt/Ti/Pt/Au on AlGaN/GaN High-Electron-Mobility Transistors.

The reliability instability of inhomogeneous Schottky contact behaviors of Ni/Au and Pt/Ti/Pt/Au gate contacts on AlGaN/GaN high-electron-mobility transistors (HEMTs) was investigated via off-state stress and temperature. Under the off-state stress condition, Pt/Ti/Pt/Au HEMT showed abruptly reduced reverse leakage current, which improved the Schottky barrier height (SBH) from 0.46 to 0.69 eV by suppression of the interfacial donor state. As the temperature increased, the reverse leakage current of the Pt/Ti/Pt/Au AlGaN/GaN HEMT at 308 K showed more reduction under the same off-state stress condition while that of the Ni/Au AlGaN/GaN HEMT increased. However, with temperatures exceeding 308 K under the same off-state stress conditions, the reverse leakage current of the Pt/Ti/Pt/Au AlGaN/GaN HEMT increases, which can be intensified using the inverse piezoelectric effect. Based on this phenomenon, the present work reveals the necessity for analyzing the concurrent SBH and reliability instability due to the interfacial trap states of the MS contacts.

Catching hold of COVID-19-related encephalitis by tracking ANGPTL4 signature in blood: An Editorial Highlight for "Endothelial cell biomarkers in critically ill COVID-19-patients with encephalitis": An Editorial Highlight for "Endothelial cell biomarkers in critically ill COVID-19-patients with encephalitis" on page 492.

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in humans is characterized by a plethora of symptoms varying in intensity, such as non-specific febrile illness, dry cough, dyspnea, hypoxemia to severe lung damage, and even death. In addition to pulmonary complications associated with coronavirus disease-19 (COVID-19), perturbations in the physiology of multiple other organ systems have been reported, resulting in multiorgan failure (MoF) that is frequently observed in severe COVID-19 cases. Central nervous system (CNS) infection by SARS-CoV-2 is characterized by neurological impairments in patients with COVID-19, with the development of encephalopathy at the severe end of the spectrum. While mechanistic investigations of SARS-CoV-2-related encephalitis may reveal promising therapeutic candidates for reducing COVID-19-associated disease morbidity, the discovery of biomarkers capable of diagnosing and predicting prognosis in patients with encephalitis upon SARS-CoV-2 infection will afford significant value for the rapid detection of encephalitis and predicting disease outcomes. This will ultimately enable appropriate modifications of therapeutic regimens aimed at reducing disease morbidity and mortality. In this editorial, we highlight a study by Le Guennec and colleagues, entitled "Endothelial cell biomarkers in critically ill COVID-19-patients with encephalitis", reporting the association of increased serum angiopoietin-like 4 (ANGPTL4) abundance with COVID-19-related encephalitis. The study highlights ANGPTL4 as a potential molecular marker for this disease. These novel findings may catalyze developments in the field of COVID-19-associated encephalitis by facilitating accurate and rapid diagnosis of encephalitis and timely treatment initiation, thus improving patient outcomes by ameliorating disease burden.

Pyruvate dehydrogenase kinase 1 promotes neuronal apoptosis upon Japanese encephalitis virus infection.

Infection by Japanese Encephalitis Virus (JEV) in humans is primarily characterized by signs and symptoms including non-specific febrile illness, arthralgia, myalgia etc. followed by its resolution due to joint action of host innate and adaptive immunity. However, in selective cases, complications arise owing to invasion of central nervous system (CNS) by JEV. Patients being unable to control peripheral viral replication owing to differences in host genetics and immunity experience JEV-associated neurological complications manifested in the form of headache, nausea, meningoencephalitis, coma and eventual death. Entry of JEV into CNS activates complex cascade of events resulting in loss of neuronal physiology and thus CNS tissue integrity. In present study, we have demonstrated role played by JEV in modulation of neuronal pyruvate dehydrogenase kinase 1 (PDK1) abundance and its effect upon neuronal health. Infection of neuron by JEV culminates into upregulation of PDK1 abundance. Albeit inhibition of JEV-induced PDK1-upregulation was accompanied by enhanced JEV propagation in neurons, abrogation of PDK1-upregulation was demonstrated to ameliorate neuronal apoptosis. PDK1 inhibition-associated reduction in neuronal death was observed to be associated with reduced generation of reactive oxygen species (ROS) in neurons. Our study hence provides a possible therapeutic target which upon modulation might help combat JEV infection-associated neuronal apoptosis via restoration of JEV-associated ROS generation.

The COVID-19 pandemic: catching up with the cataclysm.

Infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the Coronaviridae family and is a positive-sense single-stranded RNA virus originating from Wuhan, China, was declared a global public health emergency on 11 March 2020. SARS-CoV-2 infection in humans is characterized by symptoms such as fever and dyspnea accompanied by infrequent incidence of lymphopenia, gastrointestinal complications such as elevated hepatic aminotransferases, and diarrhea. Originating in bats, the SARS-CoV-2 virus has been transmitted to humans likely via an intermediate host that is yet to be discovered. Owing to the absence of any vaccines or definite anti-viral drugs alongside the greater mobility of people across the globe, international and national efforts in containing and treating SARS-CoV-2 infection are experiencing severe difficulties. In this review, we have provided a picture of SARS-CoV-2 epidemiological characteristics, the clinical symptoms experienced by patients of varying age groups, the molecular virology of SARS-CoV-2, and the treatment regimens currently employed for fighting SARS-CoV-2 infection as well as their outcomes.

miR-301a Regulates Inflammatory Response to Japanese Encephalitis Virus Infection via Suppression of NKRF Activity.

Microglia being the resident macrophage of brain provides neuroprotection following diverse microbial infections. Japanese encephalitis virus (JEV) invades the CNS, resulting in neuroinflammation, which turns the neuroprotective role of microglia detrimental as characterized by increased microglial activation and neuronal death. Several host factors, including microRNAs, play vital roles in regulating virus-induced inflammation. In the current study, we demonstrate that the expression of miR-301a is increased in JEV-infected microglial cells and human brain. Overexpression of miR-301a augments the JEV-induced inflammatory response, whereas inhibition of miR-301a completely reverses the effects. Mechanistically, NF-κB-repressing factor (NKRF) functioning as inhibitor of NF-κB activation is identified as a potential target of miR-301a in JEV infection. Consequently, miR-301a-mediated inhibition of NKRF enhances nuclear translocation of NF-κB, which, in turn, resulted in amplified inflammatory response. Conversely, NKRF overexpression in miR-301a-inhibited condition restores nuclear accumulation of NF-κB to a basal level. We also observed that JEV infection induces classical activation (M1) of microglia that drives the production of proinflammatory cytokines while suppressing alternative activation (M2) that could serve to dampen the inflammatory response. Furthermore, in vivo neutralization of miR-301a in mouse brain restores NKRF expression, thereby reducing inflammatory response, microglial activation, and neuronal apoptosis. Thus, our study suggests that the JEV-induced expression of miR-301a positively regulates inflammatory response by suppressing NKRF production, which might be targeted to manage viral-induced neuroinflammation.

Infections: A Possible Risk Factor for Type 2 Diabetes.

Diabetes mellitus is one of the biggest challenges to human health globally, with an estimated 95% of the global diabetic population having type 2 diabetes. Classical causes for type 2 diabetes, such as genetics and obesity, do not account for the high incidence of the disease. Recent data suggest that infections may precipitate insulin resistance via multiple mechanisms, such as the proinflammatory cytokine response, the acute-phase response, and the alteration of the nutrient status. Even pathogen products, such as lipopolysaccharide and peptidoglycans, can be diabetogenic. Therefore, we argue that infections that are known to contribute to insulin resistance should be considered as risk factors for type 2 diabetes.

Protein arginylation regulates cellular stress response by stabilizing HSP70 and HSP40 transcripts.

ATE1-mediated post-translational addition of arginine to a protein has been shown to regulate activity, interaction, and stability of the protein substrates. Arginylation has been linked to many different stress conditions, namely ER stress, cytosolic misfolded protein stress, and nitrosative stress. However, clear understanding about the effect of arginylation in cellular stress responses is yet to emerge. In this study, we investigated the role of arginylation in heat-stress response. Our findings suggest that Ate1 knock out (KO) cells are more susceptible to heat stress compared with its wild-type counterparts due to the induction of apoptosis in KO cells. Gene expression analysis of inducible heat-shock proteins (HSP70.1, HSP70.3, and HSP40) showed induction of these genes in KO cells early in the heat shock, but were drastically diminished at the later period of heat shock. Further analysis revealed that loss of ATE1 drastically reduced the stability of all three HSP mRNAs. These phenotypes were greatly restored by overexpression of Ate1 in KO cells. Our findings show that arginylation plays a protective role during heat stress by regulating HSP gene expression and mRNA stability.

Network analysis reveals common host protein/s modulating pathogenesis of neurotropic viruses.

Network analysis through graph theory provides a quantitative approach to characterize specific proteins and their constituent assemblies that underlie host-pathogen interactions. In the present study, graph theory was used to analyze the interactome designed out of 50 differentially expressing proteins from proteomic analysis of Chandipura Virus (CHPV, Family: Rhabdoviridae) infected mouse brain tissue to identify the primary candidates for intervention. Using the measure of degree centrality, that quantifies the connectedness of a single protein within a milieu of several other interacting proteins, DJ-1 was selected for further molecular validation. To elucidate the generality of DJ-1's role in propagating infection its role was also monitored in another RNA virus, Japanese Encephalitis Virus (JEV, Family: Flaviviridae) infection. Concurrently, DJ-1 got over-expressed in response to reactive oxygen species (ROS) generation following viral infection which in the early phase of infection migrated to mitochondria to remove dysfunctional mitochondria through the process of mitophagy. DJ-1 was also observed to modulate the viral replication and interferon responses along with low-density lipoprotein (LDL) receptor expression in neurons. Collectively these evidences reveal a comprehensive role for DJ-1 in neurotropic virus infection in the brain.

Hydrogeochemistry and Water Quality Index in the Assessment of Groundwater Quality for Drinking Uses.

The present investigation is aimed at understanding the hydrogeochemical parameters and development of a water quality index (WQI) to assess groundwater quality of a rural tract in the northwest of Bardhaman district of West Bengal, India. Groundwater occurs at shallow depths with the maximum flow moving southeast during pre-monsoon season and south in post-monsoon period. The physicochemical analysis of groundwater samples shows the major ions in the order of HCO3>Ca>Na>Mg>Cl>SO4 and HCO3>Ca>Mg>Na>Cl>SO4 in pre- and post-monsoon periods, respectively. The groundwater quality is safe for drinking, barring the elevated iron content in certain areas. Based on WQI values, groundwater falls into one of three categories: excellent water, good water, and poor water. The high value of WQI is because of elevated concentration of iron and chloride. The majority of the area is occupied by good water in pre-monsoon and poor water in post-monsoon period.

Combined inhalation and oral supplementation of Vitamin A and Vitamin D: a possible prevention and therapy for tuberculosis.

Tuberculosis is continuing as a problem of mankind. With evolution, MDR and XDR forms of tuberculosis have emerged from drug sensitive strain. MDR and XDR strains are resistant to most of the antibiotics, making the management more difficult. BCG vaccine is not providing complete protection against tuberculosis. Therefore new infections are spreading at a tremendous rate. At the present moment there is experimental evidence to believe that Vitamin A and Vitamin D has anti-mycobacterial property. It is in this context, we have hypothesized a host based approach using the above vitamins that can cause possible prevention and cure of tuberculosis with minimal chance of resistance or toxicity.

Retinoic acid and iron metabolism: a step towards design of a novel antitubercular drug.

The scenario of tuberculosis has gone deadly due to its high prevalence and emergence of widespread drug resistance. It is now high time to develop novel antimycobacterial strategies and to understand novel mechanisms of existing antimycobacterial compounds so that we are equipped with newer tuberculosis controlling molecules in the days to come. Iron has proven to be essential for pathogenesis of tuberculosis and retinoic acid is known to influence the iron metabolism pathway. Retenoic acid is also known to exhibit antitubercular effect in in vivo system. Therefore there is every possibility that retinoic acid by affecting the iron metabolism pathway exhibits its antimycobacterial effect. These aspects are reviewed in the present manuscript for understanding the antimycobacterial role of retinoic acid in the context of iron metabolism and other immunological aspects.