ABSTRACT
The remarkable spin-charge interconversion ability of transition metal dichalcogenides (TMDs) makes them promising candidates for spintronic applications. Nevertheless, their potential as spintronic terahertz (THz) emitters (STEs) remains constrained mainly due to their sizable resistivity and low spin Hall conductivity (SHC), which consequently result in modest THz emission. In this work, the TMD PtTe2, a type-II Dirac semimetal is effectively utilized to develop efficient STEs. This high efficiency primarily results from the large SHC of PtTe2, stemming from its low resistivity and significant spin-to-charge conversion efficiency, attributed to surface states and the local Rashba effect in addition to the inverse spin Hall effect. Remarkably, the peak THz emission from PtTe2/Co-STE exceeds that of Pt/Co-STE by â¼15% and is nearly double that of a similarly thick Pt/Co-STE. The efficient THz emission in the PtTe2/Co heterostructure opens new possibilities for utilizing the semimetal TMDs for developing THz emitters.
ABSTRACT
Understanding the spatial distribution of plant available soil nutrients and influencing soil properties and delineation soil nutrient management zones (MZs) are important for implementing precision nutrient management options (PNMO) in an area to achieve maintainable crop production. We assessed spatial distribution pattern of plant available sulphur (S) (PAS), boron (B) (PAB), zinc (PAZn), manganese (PAMn), iron (PAFe), and copper (PACu), and soil organic carbon (SOC), pH, and electrical conductivity (EC) to delineate soil nutrients MZs in northeastern region of India. A total of 17,471 representative surface (0-15 cm depth) soil samples were collected from the region, processed, and analysed for above-mentioned soil parameters. The values of PAS (0.22-99.2 mg kg-1), PAB (0.01-6.45 mg kg-1), PAZn (0.05-13.9 mg kg-1), PAMn (0.08-158 mg kg-1), PAFe (0.50-472 mg kg-1), PACu (0.01-19.2 mg kg-1), SOC (0.01-5.80%), pH (3.19-7.56) and EC (0.01-1.66 dS m-1) varied widely with coefficient of variation of 15.5-108%. The semivariogram analysis highlighted exponential, Gaussian and stable best fitted models for soil parameters with weak (PACu), moderate (PAB, PAZn, PAFe, SOC, pH, and EC) and strong (PAS, and PAMn) spatial dependence. The ordinary kriging interpolation revealed different distribution patterns of soil parameters. About 14.8, 27.5, and 3.40% area of the region had PAS of ≤15.0 mg kg-1, PAB of ≤0.50 mg kg-1, and PAZn of had ≤0.90 mg kg-1, respectively. About 67.5, and 32.5% area had SOC content >1.00 and < 1.00%, respectively. Soil pH was ≤5.50, and >5.50 to ≤6.50 in 41.7 and 40.3% area of the region, respectively. The techniques of principal component analysis and fuzzy c-mean algorithm clustering produced 6 MZs of the region with different areas and values of soil parameters. The MZs had different levels of deficiency pertaining to PAS, PAB, and PAZn. The produced MZ maps could be used for managing PAS, PAB, PAZn, SOC and soil pH in order to implement PNMO. The study highlighted the usefulness of MZ delineation technique for implementation of PNMO in different cultivated areas for sustainable crop production.
Subject(s)
Soil , Soil/chemistry , India , Zinc/analysis , Nutrients/analysis , Iron/analysis , Boron/analysis , Principal Component Analysis , Cluster Analysis , Fuzzy Logic , Manganese/analysisABSTRACT
Hallux amputations have long been performed for the definitive treatment of hallux osteomyelitis resulting from ulcerations. These amputations have been performed at various levels of the hallux. The aim of this study is to assess the long-term outcomes in patients with hallux amputations performed at these various levels and to determine whether there is an ideal anatomic level that would limit post-operative complications and need for revisional surgery. An Institutional Review Board (IRB)-approved retrospective chart review of 148 feet with hallux amputations performed at various levels from July 1, 2013 to July 16, 2020 at an academic medical center was conducted. A 2-year minimum follow up was required for inclusion in the study. Incidence of re-ulceration, need for further amputation, healing of index procedure, and revascularization status were evaluated. Statistical analysis utilizing chi square analysis was performed to calculate p-values where <.05 was statistically significant. In this retrospective study with a minimum of 2-year follow-up, there was a tendency for amputations performed at the level of the head of the proximal phalanx (21%) to have a lower rate of reulceration (24%) followed by amputations performed at the level of the metatarsophalangeal joint and interphalangeal joints (36%). However, neither proved to be statistically significant.
Subject(s)
Amputation, Surgical , Hallux , Humans , Retrospective Studies , Male , Female , Middle Aged , Hallux/surgery , Treatment Outcome , Aged , Osteomyelitis/surgery , Postoperative Complications/epidemiology , Follow-Up Studies , Reoperation/statistics & numerical data , AdultABSTRACT
BACKGROUND & AIMS: The utility of high-resolution anorectal manometry (HR-ARM) for diagnosing defecatory disorders (DDs) is unclear because healthy people may have features of dyssynergia. We aimed to identify objective diagnostic criteria for DD and to ascertain the utility of HR-ARM for diagnosing DD. METHODS: Constipated patients were assessed with HR-ARM and rectal balloon expulsion time (BET), and a subset underwent defecography. Normal values were established by assessing 184 sex-matched healthy individuals. Logistic regression models evaluated the association of abnormal HR-ARM findings with prolonged BET and reduced rectal evacuation (determined by defecography). RESULTS: A total of 474 constipated individuals (420 women) underwent HR-ARM and BET, and 158 underwent defecography. BET was prolonged, suggesting a DD, for 152 patients (32%). Rectal evacuation was lower for patients with prolonged vs normal BET. A lower rectoanal gradient during evacuation, reduced anal squeeze increment, and reduced rectal sensation were independently associated with abnormal BETs; the rectoanal gradient was 36% sensitive and 85% specific for prolonged BET. A lower rectoanal gradient and prolonged BET were independently associated with reduced evacuation. Among constipated patients, the probability of reduced rectal evacuation was 14% when the gradient and BET were both normal, 45% when either was abnormal, and 75% when both variables were abnormal. CONCLUSIONS: HR-ARM, BET, and defecography findings were concordant for constipated patients, and reduced rectoanal gradient was the best HR-ARM predictor of prolonged BET or reduced rectal evacuation. Prolonged BET, reduced gradient, and reduced evacuation each independently supported a diagnosis of DD in constipated patients. We propose the terms probable DD for patients with an isolated abnormal gradient or BET and definite DD for patients with abnormal results from both tests.
Subject(s)
Constipation , Defecography , Humans , Female , Constipation/diagnostic imaging , Health Status , Logistic Models , ManometryABSTRACT
Fragmentation is a major degradation pathway ubiquitous to all therapeutic monoclonal antibody (mAb) and therefore, monitored throughout the manufacturing process. Here, we describe a three-step approach to 1) detect, 2) confirm and 3) characterize partially reduced fragment species in an immunoglobulin G1 (IgG1) mAb with prolonged hold time of harvested cell culture fluid (HCCF). Microchip capillary electrophoresis (MCE) and high-performance size exclusion chromatography (HPSEC) were used as fast and efficient screening methods to detect fragmentation. HPSEC was found to be underestimating fragmentation levels. To confirm and characterize the fragments, capillary electrophoresis-sodium dodecyl sulphate (CE-SDS) was employed. Interestingly, the absence of fragments in the reduced CE-SDS analysis suggested partial reduction of disulphide bonds contributing to fragmentation in this mAb lot. This was further confirmed using reverse phase high performance liquid chromatography (RP-HPLC) coupled with mass spectrometry, which established the presence of heavy-heavy-light (HHL), heavy-heavy (HH), light-light dimer (LL), light chain (LC) and half antibody (HL) fragments with good mass accuracy. In this study, we demonstrated a readily applicable systematic strategy to support process development and investigate anomalous events in manufacturing. An additional highlight of this work is the data-driven comprehensive comparison of modern and conventional analytical techniques for fragment analysis.
Subject(s)
Antibodies, Monoclonal , Chromatography, Reverse-Phase , Antibodies, Monoclonal/chemistry , Workflow , Mass Spectrometry , Chromatography, GelABSTRACT
With improvement in survival after chronic lymphocytic leukemia (CLL) diagnosis, the real-world burden of second hematological malignancies (SHM) has not been comprehensively assessed in recent era. We analyzed risk, incidence, and outcomes of SHM in CLL patients between 2000 and 2019 using SEER database. CLL patients had greater risk for hematological malignancies than general population [SIR, standardized incidence ratio (95% CI):2.58 (2.46-2.70); p < 0.05]. The risk for subsequent lymphoma increased by 1.75 folds in 2015-2019 compared to 2000-2004. The duration, after CLL diagnosis, of maximum risk for SHM decreased as 60-119 months for time-period 2000-2004, 6-11 months for 2005-2009 to 2-5 months for 2010-2014 and 2015-2019. Incidence of SHM was 2.5% in CLL survivors (1736/70,346) with lymphoid SHM being more common than myeloid SHM, and DLBCL being the most common pathology (n = 610, 35% of all SHM). Male sex, age ≤65 years at CLL diagnosis, and chemotherapy treatment were associated with higher risk for SHM. The median gap between CLL and SHM diagnoses was 46 months. The median survival for de-novo-AML, t-MN, CML, and aggressive NHL was 63, 86, 95, and 96 months respectively. Although SHM remains rare, there is increased risk in recent era, likely due to improved survival in CLL patients, necessitating active surveillance strategies.
Subject(s)
Hematologic Neoplasms , Leukemia, Lymphocytic, Chronic, B-Cell , Leukemia, Myeloid, Acute , Lymphoma, Non-Hodgkin , Humans , Male , Aged , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Lymphoma, Non-Hodgkin/complications , Hematologic Neoplasms/therapy , Hematologic Neoplasms/complications , SurvivorsABSTRACT
Clinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant-eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)-based regimens before ASCT. Study endpoints included event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI-based regimens prior to ASCT. When adjusted for time to relapse, pre-ASCT response and use of BV maintenance, patients receiving CPI-based regimens had superior 2-year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p < .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI-based regimens were associated with superior 2-year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03-0.5, p < .0001). OS did not differ by pre-ASCT salvage regimen. In this large multicenter retrospective study, CPI-based regimens improved EFS and PFS compared to other salvage regimens independent of pre-ASCT response. These data support earlier sequencing of CPI-based regimens in R/R cHL in the pre-ASCT setting.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hodgkin Disease , Humans , Hodgkin Disease/drug therapy , Hodgkin Disease/pathology , Progression-Free Survival , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Brentuximab Vedotin/therapeutic use , Stem Cell Transplantation , Transplantation, Autologous , Salvage TherapyABSTRACT
Spintronics has been recently extended to neuromorphic computing because of its energy efficiency and scalability. However, a biorealistic spintronic neuron with probabilistic "spiking" and a spontaneous reset functionality has not been demonstrated yet. Here, we propose a biorealistic spintronic neuron device based on the heavy metal (HM)/ferromagnet (FM)/antiferromagnet (AFM) spin-orbit torque (SOT) heterostructure. The spintronic neuron can autoreset itself after firing due to the exchange bias of the AFM. The firing process is inherently stochastic because of the competition between the SOT and AFM pinning effects. We also implement a restricted Boltzmann machine (RBM) and stochastic integration multilayer perceptron (SI-MLP) using our proposed neuron. Despite the bit-width limitation, the proposed spintronic model can achieve an accuracy of 97.38% in pattern recognition, which is even higher than the baseline accuracy (96.47%). Our results offer a spintronic device solution to emulate biologically realistic spiking neurons.
Subject(s)
Models, Neurological , Neurons , Neurons/physiology , Neural Networks, Computer , Magnets , TorqueABSTRACT
There has been a widespread adoption of hypomethylating agents (HMA: 5-Azacytidine (5-Aza)/decitabine) and venetoclax (Ven) for the treatment of acute myeloid leukemia (AML); however, the mechanisms behind the combination's synergy are poorly understood. Monotherapy often encounters resistance, leading to suboptimal outcomes; however, the combination of HMA and Ven has demonstrated substantial improvements in treatment responses. This study elucidates multiple synergistic pathways contributing to this enhanced therapeutic effect. Key mechanisms include HMA-mediated downregulation of anti-apoptotic proteins, notably MCL-1, and the priming of cells for Ven through the induction of genes encoding pro-apoptotic proteins such as Noxa. Moreover, Ven induces sensitization to HMA, induces overcoming resistance by inhibiting the DHODH enzyme, and disrupts antioxidant pathways (Nrf2) induced by HMA. The combination further disrupts oxidative phosphorylation in leukemia stem cells, amplifying the therapeutic impact. Remarkably, clinical studies have revealed a favorable response, particularly in patients harboring specific mutations, such as IDH1/2, NPM1, CEBPA, or ASXL1. This prompts future studies to explore the nuanced underpinnings of these synergistic mechanisms in AML patients with these molecular signatures.
Subject(s)
Leukemia, Myeloid, Acute , Myeloproliferative Disorders , Humans , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Down-Regulation , Azacitidine , Leukemia, Myeloid, Acute/drug therapyABSTRACT
Carbon capture technologies have advanced in recent years to meet the ever-increasing quest to minimize excessive anthropogenic CO2 emissions. The most promising option for CO2 control has been identified as carbon capture and storage. Among the numerous sorbents, char generated from biomass thermal conversion has shown to be an efficient CO2 adsorbent. This study examines various characteristics that can be used to increase the yield of biochar suited for carbon sequestration. This review gives recent research progress in the area, stressing the variations and consequences of various preparation processes on textural features such as surface area, pore size and sorption performance with respect to CO2's sorption capacity. The adjoining gaps discovered in this field have also been highlighted herewith, which will serve as future work possibility. It aims to analyse and describe the possibilities and potential of employing pristine and modified biochar as a medium of CO2 capture. It also examines the parameters that influence biochar's CO2 adsorption ability and pertinent challenges regarding the production of biochar-based CO2 sorbent materials.
Subject(s)
Carbon Dioxide , Charcoal , Adsorption , CarbonABSTRACT
An optical switch with ultra high extinction ratio is proposed. Optical switching is realized using the resistive switching effect through the lateral coupling between the input nanophotonic waveguide and output waveguide at a wavelength of 1550 nm. The coupled waveguide system is engineered to increase the number of mode beats in a unit length of the device. An increase in the number of mode beats and controlled diffusion of metal ions through a thin dielectric layer with an applied electric field is responsible for a high optical extinction ratio of 27 dB for a 20 µm long device. Compared to electrical control by plasma dispersion in silicon, the resistive switching effect enables a reduction in the coupling length and an increase in the waveguide absorption, leading to an almost 100 times higher extinction ratio. The proposed compact on-chip silicon-based nanophotonic resistive device is a potential candidate for a large-scale integrated photonic circuit for applications in optical switching, modulation, memory, and computation.
ABSTRACT
A silicon-based engineered hybrid plasmonic waveguide with ultra-low dispersion is proposed. The ridge-shaped structure of the nanophotonic waveguide enables nano-scale confinement with electrically tunable characteristics using the plasma dispersion effect in silicon. The waveguide exhibits ultra-low dispersion of $1.28\;{{\rm ps}^2}/{\rm m}$ at telecommunication wavelength (1550 nm) in C band together with dual flatband dispersion over a wavelength range of 370 nm. The hybrid plasmonic mode is made to be confined in 15 nm thick ${{\rm SiO}_2}$ with a propagation loss of 15.3 dB/mm utilizing the engineered ridge structure comprising Si, ${{\rm SiO}_2}$, and gold. In addition, the proposed waveguide shows six zero-dispersion wavelengths. The imaginary and real parts of the effective refractive index of the guided hybrid plasmonic mode are reported to be tunable with the applied voltage. The reported numerical results can pave the way for achieving intensity modulators and other electrically tunable devices at telecommunication wavelengths. The ultra-low dispersion and electrical tuning make this nanophotonic waveguide an absolute contender for applications including efficient nonlinear signal processing such as wide wavelength conversion based on four-wave mixing, supercontinuum generation, and other nanoscale integrated photonic devices.
ABSTRACT
Spintronics relies on magnetization switching through current-induced spin torques. However, because spin transfer torque for ferromagnets is a surface torque, a large switching current is required for a thick, thermally stable ferromagnetic cell, and this remains a fundamental obstacle for high-density non-volatile applications with ferromagnets. Here, we report a long spin coherence length and associated bulk-like torque characteristics in an antiferromagnetically coupled ferrimagnetic multilayer. We find that a transverse spin current can pass through >10-nm-thick ferrimagnetic Co/Tb multilayers, whereas it is entirely absorbed by a 1-nm-thick ferromagnetic Co/Ni multilayer. We also find that the switching efficiency of Co/Tb multilayers partially reflects a bulk-like torque characteristic, as it increases with ferrimagnet thickness up to 8 nm and then decreases, in clear contrast to the 1/thickness dependence of ferromagnetic Co/Ni multilayers. Our results on antiferromagnetically coupled systems will invigorate research towards the development of energy-efficient spintronics.
ABSTRACT
BACKGROUND: Coronaviruses mainly affect the respiratory system; however, there are reports of SARS-CoV and MERS-CoV causing neurological manifestations. We aimed at discussing the various neurological manifestations of SARS-CoV-2 infection and to estimate the prevalence of each of them. METHODS: We searched the following electronic databases; PubMed, MEDLINE, Scopus, EMBASE, Google Scholar, EBSCO, Web of Science, Cochrane Library, WHO database, and ClinicalTrials.gov . Relevant MeSH terms for COVID-19 and neurological manifestations were used. Randomized controlled trials, non-randomized controlled trials, case-control studies, cohort studies, cross-sectional studies, case series, and case reports were included in the study. To estimate the overall proportion of each neurological manifestations, the study employed meta-analysis of proportions using a random-effects model. RESULTS: Pooled prevalence of each neurological manifestations are, smell disturbances (35.8%; 95% CI 21.4-50.2), taste disturbances (38.5%; 95%CI 24.0-53.0), myalgia (19.3%; 95% CI 15.1-23.6), headache (14.7%; 95% CI 10.4-18.9), dizziness (6.1%; 95% CI 3.1-9.2), and syncope (1.8%; 95% CI 0.9-4.6). Pooled prevalence of acute cerebrovascular disease was (2.3%; 95%CI 1.0-3.6), of which majority were ischaemic stroke (2.1%; 95% CI 0.9-3.3), followed by haemorrhagic stroke (0.4%; 95% CI 0.2-0.6), and cerebral venous thrombosis (0.3%; 95% CI 0.1-0.6). CONCLUSIONS: Neurological symptoms are common in SARS-CoV-2 infection, and from the large number of cases reported from all over the world daily, the prevalence of neurological features might increase again. Identifying some neurological manifestations like smell and taste disturbances can be used to screen patients with COVID-19 so that early identification and isolation is possible.
Subject(s)
Central Nervous System Diseases/epidemiology , Central Nervous System Diseases/virology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Betacoronavirus , COVID-19 , Humans , Pandemics , Prevalence , SARS-CoV-2ABSTRACT
RATIONALE: Goblet cell hyperplasia (GCH) is one of the cardinal features of chronic obstructive pulmonary disease (COPD) and contributes to airways obstruction. Rhinovirus (RV), which causes acute exacerbations in patients with COPD, also causes prolonged airways obstruction. Previously, we showed that RV enhances mucin gene expression and increases goblet cell number in a COPD mouse model. This study examines whether RV causes sustained GCH in relevant models of COPD. METHODS: Mucociliary-differentiated COPD and normal airway epithelial cell cultures and mice with normal or COPD phenotype were infected with RV or sham and examined for GCH by immunofluorescence and/or mucin gene expression. In some experiments, RV-infected COPD cells and mice with COPD phenotype were treated with γ-secretase inhibitor or interleukin-13 neutralising antibody and assessed for GCH. To determine the contribution of NOTCH1/3 in RV-induced GCH, COPD cells transduced with NOTCH1/3 shRNA were used. RESULTS: RV-infected COPD, but not normal cell cultures, showed sustained GCH and increased mucin genes expression. Microarray analysis indicated increased expression of NOTCH1, NOTCH3 and HEY1 only in RV-infected COPD cells. Blocking NOTCH3, but not NOTCH1, attenuated RV-induced GCH in vitro. Inhibition of NOTCH signalling by γ-secretase inhibitor, but not neutralising antibody to IL-13, abrogated RV-induced GCH and mucin gene expression. CONCLUSIONS: RV induces sustained GCH via NOTCH3 particularly in COPD cells or mice with COPD phenotype. This may be one of the mechanisms that may contribute to RV-induced prolonged airways obstruction in COPD.
Subject(s)
Goblet Cells/pathology , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/metabolism , Receptor, Notch3/genetics , Respiratory Mucosa/pathology , Rhinovirus , Actins/metabolism , Amyloid Precursor Protein Secretases/pharmacology , Animals , Antibodies, Neutralizing/pharmacology , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Cycle Proteins/metabolism , Cells, Cultured , Disease Models, Animal , ErbB Receptors/antagonists & inhibitors , Erlotinib Hydrochloride/pharmacology , Female , Gene Expression/drug effects , Gene Silencing , Goblet Cells/metabolism , Hepatocyte Nuclear Factor 3-gamma/genetics , Humans , Hyperplasia/metabolism , Hyperplasia/virology , Interleukin-13/immunology , Mice , Mucin 5AC/genetics , Mucin-5B/genetics , Pulmonary Disease, Chronic Obstructive/pathology , RNA, Messenger/metabolism , Receptor, Notch1/genetics , Receptor, Notch1/metabolism , Receptor, Notch3/metabolism , Respiratory Mucosa/metabolism , Signal Transduction/drug effectsABSTRACT
Rhinovirus (RV), which is associated with acute exacerbations, also causes persistent lung inflammation in patients with chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are not well-known. Recently, we demonstrated that RV causes persistent lung inflammation with accumulation of a subset of macrophages (CD11b+/CD11c+), and CD8+ T cells, and progression of emphysema. In the present study, we examined the mechanisms underlying the RV-induced persistent inflammation and progression of emphysema in mice with COPD phenotype. Our results demonstrate that at 14 days post-RV infection, in addition to sustained increase in CCL3, CXCL-10 and IFN-γ expression as previously observed, levels of interleukin-33 (IL-33), a ligand for ST2 receptor, and matrix metalloproteinase (MMP)12 are also elevated in mice with COPD phenotype, but not in normal mice. Further, MMP12 was primarily expressed in CD11b+/CD11c+ macrophages. Neutralization of ST2, reduced the expression of CXCL-10 and IFN-γ and attenuated accumulation of CD11b+/CD11c+ macrophages, neutrophils and CD8+ T cells in COPD mice. Neutralization of IFN-γ, or ST2 attenuated MMP12 expression and prevented progression of emphysema in these mice. Taken together, our results indicate that RV may stimulate expression of CXCL-10 and IFN-γ via activation of ST2/IL-33 signaling axis, which in turn promote accumulation of CD11b+/CD11c+ macrophages and CD8+ T cells. Furthermore, RV-induced IFN-γ stimulates MMP12 expression particularly in CD11b+/CD11c+ macrophages, which may degrade alveolar walls thus leading to progression of emphysema in these mice. In conclusion, our data suggest an important role for ST2/IL-33 signaling axis in RV-induced pathological changes in COPD mice.
Subject(s)
Interleukin-1 Receptor-Like 1 Protein/immunology , Interleukin-33/immunology , Picornaviridae Infections/immunology , Pulmonary Disease, Chronic Obstructive/immunology , Rhinovirus/physiology , Animals , Chemokine CCL3/genetics , Chemokine CCL3/immunology , Chemokine CXCL10/genetics , Chemokine CXCL10/immunology , Disease Models, Animal , Disease Progression , Female , Humans , Interferon-gamma/genetics , Interferon-gamma/immunology , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-33/genetics , Lung/immunology , Lung/pathology , Lung/virology , Macrophages/immunology , Male , Mice , Mice, Inbred C57BL , Neutrophils/immunology , Picornaviridae Infections/genetics , Picornaviridae Infections/pathology , Picornaviridae Infections/virology , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/virologyABSTRACT
The outer capsid spike protein VP4 of rotaviruses is a major determinant of infectivity and serotype specificity. Proteolytic cleavage of VP4 into 2 domains, VP8* and VP5*, enhances rotaviral infectivity. Interactions between the VP4 carbohydrate-binding domain (VP8*) and cell surface glycoconjugates facilitate initial virus-cell attachment and subsequent cell entry. Our saturation transfer difference nuclear magnetic resonance (STD NMR) and isothermal titration calorimetry (ITC) studies demonstrated that VP8*64-224 of canine rotavirus strain K9 interacts with N-acetylneuraminic and N-glycolylneuraminic acid derivatives, exhibiting comparable binding epitopes to VP8* from other neuraminidase-sensitive animal rotaviruses from pigs (CRW-8), cattle (bovine Nebraska calf diarrhoea virus, NCDV), and Rhesus monkeys (Simian rhesus rotavirus, RRV). Importantly, evidence was obtained for a preference by K9 rotavirus for the N-glycolyl- over the N-acetylneuraminic acid derivative. This indicates that a VP4 serotype 5A rotavirus (such as K9) can exhibit a neuraminic acid receptor preference that differs from that of a serotype 5B rotavirus (such as RRV) and the receptor preference of rotaviruses can vary within a particular VP4 genotype.
Subject(s)
Capsid Proteins/genetics , Neuraminic Acids/chemistry , Rotavirus/genetics , Viral Nonstructural Proteins/genetics , Animals , Capsid Proteins/chemistry , Carbohydrates/chemistry , Carbohydrates/genetics , Cattle , Dogs , Epitopes/genetics , Epitopes/immunology , Protein Binding/genetics , Protein Domains/genetics , Rotavirus/chemistry , Swine , Viral Nonstructural Proteins/chemistryABSTRACT
This study assessed caste differentials in family-level death clustering, linked survival prospects of siblings (scarring) and mother-level unobserved heterogeneity affecting infant mortality risk in the central and eastern Indian states of Jharkhand, Madhya Pradesh, Odisha and Chhattisgarh. Family-level infant death clustering was examined using bivariate analysis, and the linkages between the survival prospects of siblings and mother-specific unobserved heterogeneity were captured by applying a random effects logit model in the selected Indian states using micro-data from the National Family Health Survey-III (2005-06). The raw data clustering analysis showed the existence of clustering in all four states and among all caste groups with the highest clustering found in the Scheduled Castes of Jharkhand. The important factor from the model that increased the risk of infant deaths in all four states was the causal effect of a previous infant death on the risk of infant death of the subsequent sibling, after controlling for mother-level heterogeneity and unobserved factors. The results show that among the Scheduled Castes and Scheduled Tribes, infant death clustering is mainly affected by the scarring factor in Jharkhand and Madhya Pradesh, while mother-level unobserved factors were important in Odisha and both (scarring and mother-level unobserved factors) were key factors in Chhattisgarh. Similarly, the Other Caste Group was mainly influenced by the scarring factor only in Odisha, mother-level unobserved factors in Jharkhand and Chhattisgarh and both (scarring and mother-level unobserved factors) in Madhya Pradesh. From a government policy perspective, these results would help in identifying high-risk clusters of women among all caste groups in the four central and eastern Indian states that should be targeted to address maternal and child health related indicators.
Subject(s)
Developing Countries , Infant Mortality , Social Class , Adult , Cause of Death , Child , Cluster Analysis , Female , Humans , India , Infant , Male , Maternal Health , Risk , Siblings , Survival AnalysisABSTRACT
While current-induced spin-orbit torques have been extensively studied in ferromagnets and antiferromagnets, ferrimagnets have been less studied. Here we report the presence of enhanced spin-orbit torques resulting from negative exchange interaction in ferrimagnets. The effective field and switching efficiency increase substantially as CoGd approaches its compensation point, giving rise to 9 times larger spin-orbit torques compared to that of a noncompensated one. The macrospin modeling results also support efficient spin-orbit torques in a ferrimagnet. Our results suggest that ferrimagnets near compensation can be a new route for spin-orbit torque applications due to their high thermal stability and easy current-induced switching assisted by negative exchange interaction.
ABSTRACT
Rotavirus-cell binding is the essential first step in rotavirus infection. This binding is a major determinant of rotavirus tropism, as host cell invasion is necessary to initiate infection. Initial rotavirus-cell interactions are mediated by carbohydrate-recognizing domain VP8* of the rotavirus capsid spike protein VP4. Here, we report the first observation of significant structural rearrangement of VP8* from human and animal rotavirus strains upon glycan receptor binding. The structural adaptability of rotavirus VP8* delivers important insights into how human and animal rotaviruses utilize the wider range of cellular glycans identified as VP8* binding partners. Furthermore, our studies on rotaviruses with atypical genetic makeup provide information expected to be critical for understanding the mechanisms of animal rotavirus gene emergence in humans and support implementation of epidemiologic surveillance of animal reservoirs as well as future vaccination schemes.