Unitarity violation in sequential neutrino mixing in a model of extra dimensions

We investigate the possibility of unitarity violation in the sequential neutrino mixing matrix in a scenario with extra compact spacelike dimensions. Gauge singlet neutrinos are assumed to propagate in one extra dimension, giving rise to an infinite tower of states in the effective four-dimensional theory. It is shown that this leads to small lepton-number violating entries in the neutrino mass matrix, which can violate unitarity on the order of one per cent.Comment: 16 pages, 2 table

Combinatorial Recruitment of CREB, C/EBPβ and c-Jun Determines Activation of Promoters upon Keratinocyte Differentiation

Background: Transcription factors CREB, C/EBPβ and Jun regulate genes involved in keratinocyte proliferation and differentiation. We questioned if specific combinations of CREB, C/EBPβ and c-Jun bound to promoters correlate with RNA polymerase II binding, mRNA transcript levels and methylation of promoters in proliferating and differentiating keratinocytes. Results: Induction of mRNA and RNA polymerase II by differentiation is highest when promoters are bound by C/EBP β alone, C/EBPβ together with c-Jun, or by CREB, C/EBPβ and c-Jun, although in this case CREB binds with low affinity. In contrast, RNA polymerase II binding and mRNA levels change the least upon differentiation when promoters are bound by CREB either alone or in combination with C/EBPβ or c-Jun. Notably, promoters bound by CREB have relatively high levels of RNA polymerase II binding irrespective of differentiation. Inhibition of C/EBPβ or c-Jun preferentially represses mRNA when gene promoters are bound by corresponding transcription factors and not CREB. Methylated promoters have relatively low CREB binding and, accordingly, those which are bound by C/EBPβ are induced by differentiation irrespective of CREB. Composite “Half and Half” consensus motifs and co localizing consensus DNA binding motifs are overrepresented in promoters bound by the combination of corresponding transcription factors. Conclusion: Correlational and functional data describes combinatorial mechanisms regulating the activation of promoters. Colocalization of C/EBPβ and c-Jun on promoters without strong CREB binding determines high probability of activation upon keratinocyte differentiation

Identification and characterization of EhCaBP2: a second member of the calcium-binding protein family of the protozoan parasite entamoeba histolytica

Entamoeba histolytica, an early branching eukaryote, is the etiologic agent of amebiasis. Calcium plays a pivotal role in the pathogenesis of amebiasis by modulating the cytopathic properties of the parasite. However, the mechanistic role of Ca2+ and calcium-binding proteins in the pathogenesis of E. histolytica remains poorly understood. We had previously characterized a novel calcium-binding protein (EhCaBP1) from E. histolytica. Here, we report the identification and partial characterization of an isoform of this protein, EhCaBP2. Both EhCaBPs have four canonical EF-hand Ca2+ binding domains. The two isoforms are encoded by genes of the same size (402 bp). Comparison between the two genes showed an overall identity of 79% at the nucleotide sequence level. This identity dropped to 40% in the 75-nucleotide central linker region between the second and third Ca2+ binding domains. Both of these genes are single copy, as revealed by Southern hybridization. Analysis of the available E. histolytica genome sequence data suggested that the two genes are non-allelic. Homology-based structural modeling showed that the major differences between the two EhCaBPs lie in the central linker region, normally involved in binding target molecules. A number of studies indicated that EhCaBP1 and EhCaBP2 are functionally different. They bind different sets of E. histolytica proteins in a Ca2+-dependent manner. Activation of endogenous kinase was also found to be unique for the two proteins and the Ca2+ concentration required for their optimal functionality was also different. In addition, a 12-mer peptide was identified from a random peptide library that could differentially bind the two proteins. Our data suggest that EhCaBP2 is a new member of a class of E. histolytica calcium-binding proteins involved in a novel calcium signal transduction pathway

Estimation of non-health gross domestic product (NHGDP) loss due to COVID-19 deaths in West Bengal, India

OBJECTIVES: The state of West Bengal witnessed a significant surge of COVID-19 in all three waves. However, there is a gap in understanding the economic loss associated with COVID-19. This study estimates future non-health gross domestic product (NHGDP) losses associated with COVID-19 deaths in West Bengal, India. SETTING: Various open domains were used to gather data on COVID-19 deaths in West Bengal and the aforementioned estimates. PRIMARY AND SECONDARY OUTCOME MEASURES: The NHGDP losses were evaluated using the cost-of-illness approach. Future NHGDP losses were discounted at 3%. Excess death estimates by the WHO and Global Burden of Disease (GBD) were used. Sensitivity analysis was carried out by varying discount rates and average age of death (AAD). RESULTS: 21 532 deaths in West Bengal from 17 March 2020 to 31 December 2022 decreased the future NHGDP by $0.92 billion. Nearly 90$55,171; however, the average loss/death declined with rise in age. Based on the GBD and WHO excess death estimates, the NHGDP loss increased to $9.38 billion and$9.42 billion, respectively. When the lower age interval is considered as AAD, the NHGDP loss increased to $1.3 billion. At 5$0.767 billion and $0.549 billion, respectively. CONCLUSIONS: Results from the study suggest that COVID-19 contributed to a major economic loss in West Bengal. The mortality and morbidity caused by COVID-19, the substantial economic costs at individual and population levels in West Bengal, and probably across India and other countries, is another economic argument for better infection control strategies across the globe to minimise the impact of COVID-19

Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer

Aberrant transcriptional activity of androgen receptor (AR) is one of the dominant mechanisms for developing of castration-resistant prostate cancer (CRPC). Analyzing AR-transcriptional complex related to CRPC is therefore important towards understanding the mechanism of therapy-resistance. While studying its mechanism, we observed that a transmembrane protein called neuropilin-2 (NRP2) plays a contributory role in forming a novel AR-transcriptional complex containing nuclear pore proteins. Using immunogold electron microscopy, high-resolution confocal microscopy, chromatin immunoprecipitation, proteomics, and other biochemical techniques, we delineated the molecular mechanism of how a specific splice variant of NRP2 becomes sumoylated upon ligand stimulation and translocates to the inner nuclear membrane. This splice variant of NRP2 then stabilizes the complex between AR and nuclear pore proteins to promote CRPC specific gene expression. Both full-length and splice variants of AR have been identified in this specific transcriptional complex. In vitro cell line-based assays indicated that depletion of NRP2 not only destabilizes the AR-nuclear pore protein interaction but also inhibits the transcriptional activities of AR. Using an in vivo bone metastasis model, we showed that the inhibition of NRP2 led to the sensitization of CRPC cells toward established anti-AR therapies such as enzalutamide. Overall, our finding emphasize the importance of combinatorial inhibition of NRP2 and AR as an effective therapeutic strategy against treatment refractory prostate cancer

Bearing capacity of interfering multiple strip footings by using lower bound finite elements limit analysis

The ultimate bearing capacity of a number of multiple strip footings, identically spaced and equally loaded to failure at the same time,is computed by using the lower bound limit analysis in combination with finite elements. The efficiency factor due to the component of soil unit weight, is computed with respect to changes in the clear spacing (xi(gamma)) between the footings. It is noted that the failure load for a footing in the group becomes always greater than that of a single isolated footing. The values of xi(gamma) for the smooth footings are found to be always lower than the rough footings. The values ofxi(gamma) are found to increase continuously with a decrease in the spacing between footings. As compared to the available theoretical and experimental results reported in literature, the present analysis provides generally a little lower values of xi(gamma). (C) 2010 Elsevier Ltd. All rights reserved

Pullout capacity of inclined plate anchors embedded in sand

The pullout capacity of an inclined strip plate anchor embedded in sand has been determined by using the lower bound theorem of the limit analysis in combination with finite elements and linear optimization. The numerical results in the form of pullout factors have been presented by changing gradually the inclination of the plate from horizontal to vertical. The pullout resistance increases significantly with an increase in the horizontal inclination (theta) of the plate especially for theta > 30 degrees. The effect of the anchor plate-soil interface friction angle (delta) on the pullout resistance becomes extensive for a vertical anchor but remains insignificant for a horizontal anchor. The development of the failure zone around the anchor plates was also studied by varying theta and delta. The results from the analysis match well with the theoretical and experimental results reported in literature

Uplift Capacity of Anchors in Layered Sand Using Finite-Element Limit Analysis: Formulation and Results

The vertical pullout capacity of strip and circular plate anchors embedded horizontally in a layered sandy medium was computed by using the plane strain and axisymmetric lower-bound limit analyses in combination with finite elements and linear optimization. The soil medium below the anchor plate was assumed to be comprised of loose sand. Two different sand layers were considered above the anchor with different combinations of their internal friction angles. For several embedment ratios (H/B), the variations of the pullout factors F-gamma and F-q due to the components of soil unit weight and surcharge, respectively, were computed as a function of H-dense/H for different cases; here, H and H-dense imply (1) the depth of the anchor plate from ground surface and (2) the thickness of the dense sand layer, respectively. The pullout resistance increased continuously with an increase in H-dense/H. For a given H/B, with the same value of H-dense/H, the uplift resistance became greater for a case when the dense sand layer was kept just above the plate rather than placing it close to ground surface. Compared with strip anchors, the uplift factors became considerably greater for circular anchors. The effect of the variation of the unit weights of the two layers above the anchor plate on its pullout resistance was also explored. The results obtained from the analysis compare well with the available theoretical and experimental data. (C) 2016 American Society of Civil Engineers

Seismic Pullout Capacity of Inclined Anchor Plates in Sand

By using the lower bound finite elements limit analysis, the pullout capacity of an inclined strip anchor plate embedded in a cohesionless soil medium has been computed with an inclusion of pseudo-static horizontal earthquake body forces. The variation of the pullout capacity factor (Fγ) with changes in horizontal earthquake acceleration co-efficient (αh) has been computed by varying the inclination angle (β) of the anchor plate between 0° and 90°. The results clearly reveal that the pullout capacity factor (Fγ) decreases significantly with an increase in the value of αh. The reduction in the pullout resistance due to seismic forces (1) becomes much more extensive for a vertical anchor plate as compared to the horizontal anchor, (2) decreases generally with increases in the soil friction angle (ϕ) and (3) increases with an increase in friction angle between soil and anchor plate (δ). The developments of the failure zone around the anchor plate were also examined by varying αh and β. The results obtained from the analysis compare well with the solutions reported in literature. © 2016, Springer International Publishing Switzerland