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This research focuses on a quantum model created using an entirely novel nanosheet FET. The standard model describes the performance of a Gate-all-around (GAA) Junction-less (JL) nanosheet device with a gate dielectric of SiO2 and HfO2, each having a thickness of 1 nm. The performance of both the classical and quantum models of the GAA nanosheet device is evaluated using the visual TCAD tool, which measures the ION, IOFF, ION/ IOFF, threshold voltage, DIBL, gain parameters (gm, gd, Av), gate capacitance, and cut-off frequency (fT). The device is suited for applications needing rapid switching since it has a low gate capacitance of the order of 10–18, according to the simulation results. A transconductance (gm) value of 21 µS and an impressive cut-off frequency of 9.03 GHz are displayed during device analysis. A detailed investigation has also been done into the P-type device response for the same device. Finally, the proposed GAA nanosheet device is used in the inverter model. The NSFET-based inverter, although having higher gate capacitance, has the shortest propagation latency.

This work investigates the effect of single and dual-k spacer materials consisting of different dielectric constants (k) in optimized nano-channel gate-stack nanosheet (NS-FET) employing hafnium oxide and silicon dioxide as gate insulator to improve its sub-threshold performance. The effect of the external low-k spacer modification in the dual-k spacer has been shown by adjusting the inner high-k spacer. The drain-induced barrier lowering (DIBL) in this modification with dual-k spacer is 14 mV/V, a significant improvement above single spacer NS-FET. The Visual TCAD 3D Cogenda tool is used to examine the performance of the developed NS-FET with air, single, dual-k, and hybrid spacers. The CADENCE platform is used to perform circuit aspects. Additionally, a comparison of the device architecture’s performance study with respect to DC characteristics is made. DC parameters of the proposed device are established: $I_{ON}$ to $I_{OFF}$ ratio of approximately $10^{5}$ , DIBL of approximately 14 mV/V, sub-threshold swing (SS) of approximately 62 mV/dec, and low threshold voltage (Vth) of 0.38 V. The analysis on power consumption for advanced NS-FET is also analyzed with single-k and dual-k spacers. The performance of single-k and dual-k spacer dielectric variation for CMOS inverter is also shown. Furthermore, low power consumption by this NS-FET ensures improved device performance suitable for nanoscale semiconductor industries.

A robust image encryption process is still one of the most challenging tasks in image security owing to massive degree and sensitivity nature of information in the form of pixels. The hurdles include greater computational difficulty, information loss during encryption, universality, applicability of the approach, and less scalability. Many image encryption methods existing in literature merely encrypt a portion of the data. Therefore, we propose a robust, dynamic, and sophisticated technique to enhance the encryption process to make it difficult for an attacker to gain unauthorized access to the pixel data. The proposed system uses a novel analytical research methodology through dynamically harnessing the potential of neural network that offers better forward and backward secrecy, dynamic control, and automatic management unlike any existing system. The encryption procedure comprises of two levels, first level is confusion- permutation of input image and second level is diffusion by Bit XOR operation for secure transmission and storage of images. Finally, the encrypted image is used as a target for training the Artificial Neural Network (ANN) model. ANN trained values are used for final level of encryption to develop a Neural Network (NN)-based cryptosystem, where the crypto analyst or the cracker need to know the number of adaptive iterations and the final weights for the encryption and decryption systems to crack the system which offers higher degree of resiliency towards potential threats. Results and security analysis show that our algorithm has good encryption effect, ability of resisting exhaustive attack, statistical attack, and differential attack. The system performance after implementing the proposed method is compared with existing methods present in literature with respect to processing time and Structural Similarity Index Measure (SSIM). Our proposed method offers significant reduction in encryption time and is approximately 10-15% faster than others with SSIM of 0.002165, close to zero after encryption. It also successfully balances the image quality with higher image security and lower computational complexity.

This paper carries out a brief study of the impact of Covid-19 on seven indices of the Indian economy. For the analysis, risk, covariance, and Capital Market Line (CML) formulas have been applied to the same set of stocks belonging to two different time periods, i.e., pre- and post-Covid. Using these formulas and two tools, namely, the Granger Causality Test and the Augmented Dickey-Fuller Model (ADF), the impact of Covid-19 on the stocks has been analyzed. After a thorough analysis, it is concluded that the impact of the pandemic has been drastic on the selected stocks and the performance of the stocks has been highly fluctuating post Covid-19. [ABSTRACT FROM AUTHOR]

Presents corrections to the paper, Corrections to “A Faster and Robust Artificial Neural Network Based Image Encryption Technique With Improved SSIM”.

Tropical dry-deciduous forests comprise more than 45% of the tiger (Panthera tigris) habitat in India. However, in the absence of rigorously derived estimates of ecological densities of tigers in dry forests, critical baseline data for managing tiger populations are lacking. In this study tiger densities were estimated using photographic capture–recapture sampling in the dry forests of Panna Tiger Reserve in Central India. Over a 45-day survey period, 60 camera trap sites were sampled in a well-protected part of the 542-km2 reserve during 2002. A total sampling effort of 914 camera-trap-days yielded photo-captures of 11 individual tigers over 15 sampling occasions that effectively covered a 418-km2 area. The closed capture–recapture model Mh, which incorporates individual heterogeneity in capture probabilities, fitted these photographic capture history data well. The estimated capture probability/sample, $\hat{p} = 0.04$, resulted in an estimated tiger population size and standard error ( $\hat{N}(S\hat{E}\hat{N}$)) of 29 (9.65), and a density ( $\hat{D}(S\hat{E}\hat{D}$)) of 6.94 (3.23) tigers/100 km2. The estimated tiger density matched predictions based on prey abundance. Our results suggest that, if managed appropriately, the available dry forest habitat in India has the potential to support a population size of about 9000 wild tigers. [ABSTRACT FROM AUTHOR]

Conservation practices are supposed to get refined by advancing scientific knowledge. We study this phenomenon in the context of monitoring tiger populations in India, by evaluating the ‘pugmark census method’ employed by wildlife managers for three decades. We use an analytical framework of modern animal population sampling to test the efficacy of the pugmark censuses using scientific data on tigers and our field observations. We identify three critical goals for monitoring tiger populations, in order of increasing sophistication: (1) distribution mapping, (2) tracking relative abundance, (3) estimation of absolute abundance. We demonstrate that the present census-based paradigm does not work because it ignores the first two simpler goals, and targets, but fails to achieve, the most difficult third goal. We point out the utility and ready availability of alternative monitoring paradigms that deal with the central problems of spatial sampling and observability. We propose an alternative sampling-based approach that can be tailored to meet practical needs of tiger monitoring at different levels of refinement. [ABSTRACT FROM AUTHOR]

Exosomes are secreted vesicles of ~30 to 150 nm diameter that play important roles in human health and disease. To better understand how cells release these vesicles, we examined the biogenesis of the most highly enriched human exosome marker proteins, the exosomal tetraspanins CD81, CD9, and CD63. We show here that endocytosis inhibits their vesicular secretion and, in the case of CD9 and CD81, triggers their destruction. Furthermore, we show that syntenin, a previously described exosome biogenesis factor, drives the vesicular secretion of CD63 by blocking CD63 endocytosis and that other endocytosis inhibitors also induce the plasma membrane accumulation and vesicular secretion of CD63. Finally, we show that CD63 is an expression-dependent inhibitor of endocytosis that triggers the vesicular secretion of lysosomal proteins and the clathrin adaptor AP-2 mu2. These results suggest that the vesicular secretion of exosome marker proteins in exosome-sized vesicles occurs primarily by an endocytosis-independent pathway.

Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD ('ocGVHD'), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. We performed a secondary analysis of data from the ABA2 trial (N = 185), in which detailed GVHD data were collected prospectively and systematically adjudicated. Analyses included cumulative incidence of classic versus ocGVHD, their specific organ manifestations, global disease severity scores, non-relapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in these two cGVHD subtypes. Of 92 patients who developed cGVHD, 35 were classified as ocGVHD. The 1-year cumulative incidence, organ involvement, and global severity of classic and ocGVHD were similar between ABA2 patients receiving CNI/MTX+placebo and CNI/MTX+abatacept; thus, cohorts were combined for ocGVHD evaluation. This analysis identified ocGVHD as having significantly higher severity at presentation and at maximum global severity compared to classic cGVHD. OS and DFS were significantly lower for ocGVHD versus classic cGVHD. OcGVHD is associated with increased cGVHD severity scores, and is associated with decreased OS and DFS compared to classic cGVHD, underscoring the high risks with this cGVHD subtype., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Congenital central hypoventilation syndrome (CCHS), a rare disease caused by paired-like homeobox 2B variants, affects control of breathing. We report on a 21-month-old boy with CCHS caused by a novel nonpolyalanine repeat mutation, neuroblastoma, severe obstructive and central sleep apnea, and sleep-related hypoxemia without hypoventilation. At 10 months, due to persistent central sleep apnea during serial polysomnography, bilevel positive airway pressure therapy was initiated despite the absence of hypoventilation. Nonpolyalanine repeat mutations are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and neural crest tumors; however, our patient had a relatively milder respiratory phenotype requiring sleep-only assisted ventilation without tracheostomy. Although alveolar hypoventilation is the hallmark of CCHS, our patient lacked hypoventilation. Bilevel positive airway pressure could be considered in some infants with CCHS requiring sleep-only assisted ventilation for tracheostomy avoidance. Our case demonstrates the expanding phenotypic spectrum in CCHS and the importance of formulating an individualized care plan., Citation: Fain ME, Raghunandan S, Pencheva B, Leu RM, Kasi AS. Images: atypical presentation of congenital central hypoventilation syndrome in an infant with central and obstructive sleep apnea. J Clin Sleep Med . 2024;20(3):478-481., (© 2024 American Academy of Sleep Medicine.)

Exosomes are small extracellular vesicles important in health and disease. Syntenin is thought to drive the biogenesis of CD63 exosomes by recruiting Alix and the ESCRT machinery to endosomes, initiating an endosome-mediated pathway of exosome biogenesis. Contrary to this model, we show here that syntenin drives the biogenesis of CD63 exosomes by blocking CD63 endocytosis, thereby allowing CD63 to accumulate at the plasma membrane, the primary site of exosome biogenesis. Consistent with these results, we find that inhibitors of endocytosis induce the exosomal secretion of CD63, that endocytosis inhibits the vesicular secretion of exosome cargo proteins, and that high-level expression of CD63 itself also inhibits endocytosis. These and other results indicate that exosomes bud primarily from the plasma membrane, that endocytosis inhibits their loading into exosomes, that syntenin and CD63 are expression-dependent regulators of exosome biogenesis, and that syntenin drives the biogenesis of CD63 exosomes even in Alix knockout cells.

Hematopoietic cell transplantation (HCT) is the only readily available cure for many life-threatening pediatric nonmalignant diseases (NMD), but most patients lack a matched related donor and are at higher risk for graft-versus-host disease (GVHD). Use of abatacept (Aba) to target donor T-cell activation has been safe and effective in preventing GVHD after unrelated donor (URD) HCT for malignant diseases (Aba2 trial). Our primary objective was to evaluate the tolerability of Aba added to standard GVHD prophylaxis (cyclosporine and mycophenolate mofetil) in pediatric patients with NMD undergoing URD HCT. In this single-arm, single-center phase 1 trial, 10 patients receiving reduced intensity or nonmyeloablative conditioning underwent URD HCT. Immune reconstitution was assessed longitudinally via flow cytometry and compared to pediatric patients on Aba2. Nine patients successfully engrafted, with 1 primary graft rejection in the setting of inadequate cell dose; secondary graft rejection occurred in 1 patient with concurrent cytomegalovirus viremia. Two deaths occurred, both unrelated to Aba. One patient developed probable posttransplant lymphoproliferative disease, responsive to rituximab and immune suppression withdrawal. No patients developed severe acute or chronic GVHD, and 8 patients were off systemic immunosuppression at 1 year. Immune reconstitution did not appear to be impacted by Aba, and preservation of naïve relative to effector memory CD4+ T cells was seen akin to Aba2. Thus, 4 doses of Aba were deemed tolerable in pediatric patients with NMD following URD HCT, with encouraging preliminary efficacy and supportive immune correlatives in this NMD cohort., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Plasmablastic lymphoma (PBL) is a rare subtype of aggressive large B-cell lymphoma, with a dismal prognosis despite aggressive therapies. New approaches are needed for those with refractory disease. PBL expresses antigens similar to multiple myeloma (MM), including B-cell maturation antigen (BCMA). Chimeric antigen receptor T-cell (CAR-T) therapy directed against BCMA has shown efficacy for the treatment of heavily pretreated MM with low rates of grades 3 and 4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in a phase Ib/II trial (A Study of JNJ-68284528, a CAR-T Directed Against BCMA in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1), NCT03548207). However, data for the use of BCMA CAR-T for treating PBL are lacking.We report a challenging case of multiple refractory PBL that emerged from B-cell acute lymphoblastic leukemia in an adolescent who failed to respond to an allogeneic hematopoietic cell transplant. The patient developed rapidly advancing disease despite withdrawal of immunosuppression, treatment with etoposide, ibrutinib, and daratumumab, prompting consideration of BCMA CAR-T (under emergency investigational new drug (eIND)). The patient achieved a complete remission (CR), without recurrent acute graft versus host disease (GVHD), CRS or ICANS after BCMA CAR-T therapy. BCMA CAR-T expansion was detected in vivo, peaking on day 15. The patient remains in CR for more than a year post CAR-T therapy, supporting consideration of immunotherapy for future patients with refractory PBL, a disease with few treatment options., Competing Interests: Competing interests: MQ reports honoraria from Vertex and Novartis. MVD is on the advisory board for Janssen, Sanofi, and Lava Therapeutics. SC is on the science advisory board of SOBI. JLK reports consulting for Abbvie, BMS, and DSnC for Incyte. JMS reports employment, equity and stock options at Janssen. DM reports employment at Janssen Research & Development, being adjunct assistant professor at Mount Sinai Hospital, Icahn School of Medicine, and being on the consultancy/advisory board at Takeda, Celgene, BMS, GlaxoSmithKline, Legend, Janssen, Kinevant, and Foundation Medicine. CCJ is an employee of Janssen Research & Development and physician consultant at Memorial Sloan Kettering Cancer Center. EZ is an employee of Janssen Research & Development. AT-M is an employee of Janssen Research & Development and an adjunct assistant professor at Los Angeles County/University of Southern California. AB is an employee of Janssen Research & Development. MV is an employee of Janssen-Cilag GmbH. TN reports being an employee of Caribou Biosciences, Inc., in Berkeley, California. NL reports being a full-time employee of Janssen. LP is an employee at Legend Biotech., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Endothelial cells (ECs) form the inner lining of blood vessels and are central to sensing chemical perturbations that can lead to oxidative stress. The degree of stress is correlated with divergent phenotypes such as quiescence, cell death, or senescence. Each possible cell fate is relevant for a different aspect of endothelial function, and hence, the regulation of cell fate decisions is critically important in maintaining vascular health. This study examined the oxidative stress response (OSR) in human ECs at the boundary of cell survival and death through longitudinal measurements, including cellular, gene expression, and perturbation measurements. 0.5 mM hydrogen peroxide (HP) produced significant oxidative stress, placed the cell at this junction, and provided a model to study the effectors of cell fate. The use of systematic perturbations and high-throughput measurements provide insights into multiple regimes of the stress response. Using a systems approach, we decipher molecular mechanisms across these regimes. Significantly, our study shows that heme oxygenase-1 (HMOX1) acts as a gatekeeper of cell fate decisions. Specifically, HP treatment of HMOX1 knockdown cells reversed the gene expression of about 51% of 2,892 differentially expressed genes when treated with HP alone, affecting a variety of cellular processes, including anti-oxidant response, inflammation, DNA injury and repair, cell cycle and growth, mitochondrial stress, metabolic stress, and autophagy. Further analysis revealed that these switched genes were highly enriched in three spatial locations viz., cell surface, mitochondria, and nucleus. In particular, it revealed the novel roles of HMOX1 on cell surface receptors EGFR and IGFR, mitochondrial ETCs (MTND3, MTATP6), and epigenetic regulation through chromatin modifiers (KDM6A, RBBP5, and PPM1D) and long non-coding RNA (lncRNAs) in orchestrating the cell fate at the boundary of cell survival and death. These novel aspects suggest that HMOX1 can influence transcriptional and epigenetic modulations to orchestrate OSR affecting cell fate decisions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Raghunandan, Ramachandran, Ke, Miao, Lal, Chen and Subramaniam.)

Most children with COVID-19 have asymptomatic or mild illness. Those who become critically ill suffer from acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). The rapid deterioration of lung function has been linked to microangiopathic and immune-mediated processes seen in the lungs of adult patients with COVID-19. The role of complement-mediated acute lung injury is supported by animal models of SARS-CoV, evaluation of lung tissue in those who died from COVID-19 and response of COVID-19 ARDS to complement inhibition. We present a summary of a child with COVID-19 disease treated with convalescent plasma and eculizumab and provide a detailed evaluation of the inflammatory pathways., Competing Interests: CJ receives research funds from Terumo BCT, Octapharma and Medtronics. SC is a scientific advisor to Alexion, Novartis and Agios pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Raghunandan, Josephson, Verkerke, Linam, Ingram, Zerra, Arthur, Stowell, Briones and Chonat.)

M2 polarization of macrophages is predominant in case of tumors and some other infectious diseases for disease progression. Repolarization of the M2 phenotype to the M1 state may be required to cure diseases. Hence, it is of great interest to find out a material that would repolarize the M2 phenotype to the M1 state. Herein, the arabinogalactan protein from Andrographis paniculata (ApAGP) was used to prepare a silver nanoparticle-ApAGP (SNP-ApAGP) bioconjugate, which was characterized via UV-vis spectroscopy, zeta potential analysis, FT-IR spectroscopy, and HR-TEM. Studies suggest that SNP-ApAGP (2.5 μg mL -1 ) up-regulates ROS generation, NO generation, and pro-inflammatory cytokine release (IL-12, IFN-γ, TNF-α, and IL-6). SNP-ApAGP also down-regulates the arginase-1 activity and anti-inflammatory cytokine release (IL-4 & IL-10) in M0, M1, and M2-polarized peritoneal macrophages in vitro. Therefore, SNP-ApAGP induces M1 polarization in M0 macrophages, enhances the pro-inflammatory activity of the M1 phenotype, and can also repolarize M2 macrophages into the M1 phenotype. Therefore, SNP-ApAGP could be used for treating various infectious diseases and cancers where repolarization of M2 macrophages may be required to cure the disease.

Hepatic stellate cells (HSCs) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSCs inhibits liver inflammation and fibrosis. We found that p62/SQSTM1, a protein upregulated in liver parenchymal cells but downregulated in HCC-associated HSCs, negatively controls HSC activation. Total body or HSC-specific p62 ablation potentiates HSCs and enhances inflammation, fibrosis, and HCC progression. p62 directly interacts with VDR and RXR promoting their heterodimerization, which is critical for VDR:RXR target gene recruitment. Loss of p62 in HSCs impairs the repression of fibrosis and inflammation by VDR agonists. This demonstrates that p62 is a negative regulator of liver inflammation and fibrosis through its ability to promote VDR signaling in HSCs, whose activation supports HCC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

p62 is a ubiquitin-binding autophagy receptor and signaling protein that accumulates in premalignant liver diseases and most hepatocellular carcinomas (HCCs). Although p62 was proposed to participate in the formation of benign adenomas in autophagy-deficient livers, its role in HCC initiation was not explored. Here we show that p62 is necessary and sufficient for HCC induction in mice and that its high expression in non-tumor human liver predicts rapid HCC recurrence after curative ablation. High p62 expression is needed for activation of NRF2 and mTORC1, induction of c-Myc, and protection of HCC-initiating cells from oxidative stress-induced death., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Caring is a fundamental issue in the rehabilitation of a person with mental illness and more so for people with severe mental illness. The lack of adequate manpower resources in the country is adding and enlisting the responsibility of providing care on the families to provide physical, medical, social and psychological care for their severely unwell mentally ill people., Aim of the Study: To examine the load of caregiving with reference to the types of care during the symptomatic and remission phases of severe mental illness and the various ways in which caregivers adapt their lives to meet the needs of people with severe mental illness., Materials and Methods: The present research draws its data from the 200 families with mental illness in Andra Pradesh and Karnataka in India. The data presented in the study was collected from interviews using an interview schedule with open-ended questions., Results: The study diffuses the notion of 'care' as 'physical', 'medical, 'psychological' and 'social' care. The present article focuses on the caregiving roles of the caregivers of people with schizophrenia, affective disorders and psychosis not otherwise specified (NOS) and found that the caregiving does not differ much between the different diagnosis, but caregiving roles changes from active involvement in physical and medical care to more of social and psychological care during the remission., Conclusion: The study records the incredulous gratitude of caregivers at being acknowledged for the work they do. In that regard, the study itself provides a boost to the morale of tired, unacknowledged caregivers.

The retroviral Gag polyprotein mediates viral assembly. The Gag protein has been shown to interact with other Gag proteins, with the viral RNA, and with the cell membrane during the assembly process. Intrinsically disordered regions linking ordered domains make characterization of the protein structure difficult. Through small-angle scattering and molecular modeling, we have previously shown that monomeric human immunodeficiency virus type 1 (HIV-1) Gag protein in solution adopts compact conformations. However, cryo-electron microscopic analysis of immature virions shows that in these particles, HIV-1 Gag protein molecules are rod shaped. These differing results imply that large changes in Gag conformation are possible and may be required for viral formation. By recapitulating key interactions in the assembly process and characterizing the Gag protein using neutron scattering, we have identified interactions capable of reversibly extending the Gag protein. In addition, we demonstrate advanced applications of neutron reflectivity in resolving Gag conformations on a membrane. Several kinds of evidence show that basic residues found on the distal N- and C-terminal domains enable both ends of Gag to bind to either membranes or nucleic acid. These results, together with other published observations, suggest that simultaneous interactions of an HIV-1 Gag molecule with all three components (protein, nucleic acid, and membrane) are required for full extension of the protein., (Published by Elsevier Ltd.)