MCNPX-PoliMi Variance Reduction Techniques for Simulating Neutron Scintillation Detector Response.

Scintillation detectors have emerged as a viable He–3 replacement technology in the field of nuclear nonproliferation and safeguards. MCNPX–PoliMi is a Monte Carlo Code that has been used for simulating detailed scintillation physics; however, until now, simulations have only been done in analog mode. Analog Monte Carlo simulations can take long times to run. In this thesis, two nonanalog approaches to speed up MCNPX–PoliMi simulations of neutron scintillation detector response have been studied. In the first approach, a response matrix method (RMM) is used to efficiently calculate neutron pulse height distributions (PHDs). This method combines the neutron current incident on the detector face with an MCNPX–PoliMi–calculated response matrix to generate PHDs. The PHD calculations and their associated uncertainty are compared for three different techniques: fully analog MCNPX–PoliMi, the RMM, and the RMM with source biasing. The RMM with source biasing reduces computation time or increases the figure–of–merit on an average by a factor of 600 for polyethylene and 300 for lead shielding (when compared to the fully analog calculation). The simulated neutron PHDs show good agreement with the laboratory measurements, thereby validating the RMM. In the second approach, MCNPX–PoliMi simulations are performed with the aid of variance reduction techniques. This is done by separating the analog and nonanalog components of the simulations. Tally mechanisms are developed for PHDs, time–of–flight curves, and cross–correlations. Three laboratory measurements (bare, lead–shielded, and polyethylene shielded) are performed with a Cf–252 source to validate the nonanalog MCNPX–PoliMi cross–correlation simulations. For the bare cross–correlation case, the nonanalog simulation speedup was a factor of 3.4; for the lead–shielded case, the speedup was a factor of 16; and for the polyethylene–shielded case, the speedup was a factor of 2.6. The agreement of simulations with laboratory measurements was good. In summary, this thesis demonstrates that known variance reduction techniques, when properly applied to nonlinear scintillation detector response problems, can significantly increase the figure–of–merit (sometimes by 2 or 3 orders of magnitude). This can yield major reductions in computation times and analyses for important homeland security problems.PHDNuclear Engineering and Radiological SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/96118/1/shikhap_1.pd

Abruptio placentae: impact of early treatment on maternal and fetal outcomes

Background: Haemorrhage is the leading cause for maternal mortality in India as well as the world. Abruptio placenta is the second most common cause of antepartum haemorrhage and it is associated with sudden, severe and devastating maternal and fetal complications. The main objective of this study is to study the impact of early treatment on maternal and fetal outcomes.Methods: This single center retrospective study includes all patients admitted at Lokmanya Tilak Municipal General Hospital, a tertiary referral hospital, diagnosed to have abruptio placenta (grade II and grade III) from 01 July 2019 to 31 December 2019. In this study a total of 48 cases were included and data regarding time duration between onset of symptoms and initiation of treatment, clinical course and maternal and fetal outcomes was noted.Results: A total of 5059 deliveries occurred over six months. The incidence of placental abruption was found to be 0.94%. Patients receiving early care (30 cases, 62.5%) were found to have significantly better maternal outcomes (p=0.006, Chi square test) as well as fetal outcomes (p=0.007, Fischer’s exact test) than patients who received delayed care (18 cases, 37.5%).Conclusions: Abruptio placentae is an obstetric emergency and early diagnosis as well as initiation of treatment plays an important role in curbing complications. Strengthening of peripheral centers, availability of multi-disciplinary approach and educating health care staff as well as patients form the cornerstones of improved maternal and fetal outcomes

Financial and energy exchange traded funds futures: an evidence of spillover and portfolio hedging

This paper examines spillover from financial exchange-traded funds (ETF) futures to energy ETF futures using adjusted daily data extending from April 2, 2009, to November 23, 2020. We also explore the portfolio hedging-based conditional variance and co-variance derived from dynamic conditional correlation. The proxies for the financial ETF futures are financial select sector SPDR fund (XLF) and generic 1st S&P 500 index futures (SP1) while generic 1st crude oil WTI futures (CL1), generic 1st natural gas futures (NG1), and energy select SPDR fund (XLE) are proxies of energy ETF futures. The results obtained from Granger causality indicate that there is unidirectional causality from RXLF to RSP1 while bidirectional causality between RXLF and RCL1 at a 5% significance level. Further, dynamic conditional correlation indicates the spillover effect from RXLF to RCL1, RXLF to RXLE, RSP1 to RCL1, and RSP1 to RXLE both in the short-run and long run. The spillover from RXLF to RNG1 is witnessed only in the short run while the spillover from RSP1 to RNG1 is present in long run. The present study corroborates with the studies of Chang et al. (Int J Finan Stud 6(2): 1–24, 2018) and Lau et al. (Int Rev Finan Anal 52: 316-332, 2017). We notice that the average optimal hedge ratio of the RXLF/RNG1 pair is the most expensive while the cheapest hedging strategy is of RSP1/RCL1 pair

Oxidative and pro-inflammatory impact of regular and denicotinized cigarettes on blood brain barrier endothelial cells: is smoking reduced or nicotine-free products really safe?

Background: Both active and passive tobacco smoke (TS) potentially impair the vascular endothelial function in a causative and dose-dependent manner, largely related to the content of reactive oxygen species (ROS), nicotine, and pro-inflammatory activity. Together these factors can compromise the restrictive properties of the blood–brain barrier (BBB) and trigger the pathogenesis/progression of several neurological disorders including silent cerebral infarction, stroke, multiple sclerosis and Alzheimer’s disease. Based on these premises, we analyzed and assessed the toxic impact of smoke extract from a range of tobacco products (with varying levels of nicotine) on brain microvascular endothelial cell line (hCMEC/D3), a well characterized human BBB model. Results: Initial profiling of TS showed a significant release of reactive oxygen (ROS) and reactive nitrogen species (RNS) in full flavor, nicotine-free (NF, “reduced-exposure” brand) and ultralow nicotine products. This release correlated with increased oxidative cell damage. In parallel, membrane expression of endothelial tight junction proteins ZO-1 and occludin were significantly down-regulated suggesting the impairment of barrier function. Expression of VE-cadherin and claudin-5 were also increased by the ultralow or nicotine free tobacco smoke extract. TS extract from these cigarettes also induced an inflammatory response in BBB ECs as demonstrated by increased IL-6 and MMP-2 levels and up-regulation of vascular adhesion molecules, such as VCAM-1 and PECAM-1. Conclusions: In summary, our results indicate that NF and ultralow nicotine cigarettes are potentially more harmful to the BBB endothelium than regular tobacco products. In addition, this study demonstrates that the TS-induced toxicity at BBB ECs is strongly correlated to the TAR and NO levels in the cigarettes rather than the nicotine conten

Early transcriptome profile of goat peripheral blood mononuclear cells (PBMCs) infected with peste des petits ruminant's vaccine virus (Sungri/96) revealed induction of antiviral response in an interferon independent manner

Sungri/96 vaccine strain is considered the most potent vaccine providing long-term immunity against peste des petits ruminants (PPR) in India. Previous studies in our laboratory highlighted induction of robust antiviral response in an interferon independent manner at 48 h and 120 h post infection (p.i.). However, immune response at the earliest time point 6 h p.i. (time taken to complete one PPRV life cycle), in PBMCs infected with Sungri/96 vaccine virus has not been investigated. This study was taken up to understand the global gene expression profiling of goat PBMCs after Sungri/96 PPRV vaccine strain infection at 6 h post infection (p.i.). A total of 1926 differentially expressed genes (DEGs) were identified with 616 - upregulated and 1310 - downregulated. TLR7/TLR3, IRF7/IRF1, ISG20, IFIT1/IFIT2, IFITM3, IL27 and TREX1 were identified as key immune sensors and antiviral candidate genes. Interestingly, type I interferons (IFNα/β) were not differentially expressed at this time point as well. TREX1, an exonuclease which inhibits type I interferons at the early stage of virus infection was found to be highly upregulated. IL27, an important antiviral host immune factor was significantly upregulated. ISG20, an antiviral interferon induced gene with exonuclease activity specific to ssRNA viruses was highly expressed. Functional profiling of DEGs showed significant enrichment of immune system processes with 233 genes indicating initiation of immune defense response in host cells. Protein interaction network showed important innate immune molecules in the immune network with high connectivity. The study highlights important immune and antiviral genes at the earliest time point

Comparative and temporal transcriptome analysis of peste des petits ruminants virus infected goat peripheral blood mononuclear cells

Peste des petits ruminanats virus (PPRV), a morbillivirus causes an acute, highly contagious disease – peste des petits ruminants (PPR), affecting goats and sheep. Sungri/96 vaccine strain is widely used for mass vaccination programs in India against PPR and is considered the most potent vaccine providing long-term immunity. However, occurrence of outbreaks due to emerging PPR viruses may be a challenge. In this study, the temporal dynamics of immune response in goat peripheral blood mononuclear cells (PBMCs) infected with Sungri/96 vaccine virus was investigated by transcriptome analysis. Infected goat PBMCs at 48 h and 120 h post infection revealed 2540 and 2000 differentially expressed genes (DEGs), respectively, on comparison with respective controls. Comparison of the infected samples revealed 1416 DEGs to be altered across time points. Functional analysis of DEGs reflected enrichment of TLR signaling pathways, innate immune response, inflammatory response, positive regulation of signal transduction and cytokine production. The upregulation of innate immune genes during early phase (between 2-5 days) viz. interferon regulatory factors (IRFs), tripartite motifs (TRIM) and several interferon stimulated genes (ISGs) in infected PBMCs and interactome analysis indicated induction of broad-spectrum anti-viral state. Several Transcription factors – IRF3, FOXO3 and SP1 that govern immune regulatory pathways were identified to co-regulate the DEGs. The results from this study, highlighted the involvement of both innate and adaptive immune systems with the enrichment of complement cascade observed at 120 h p.i., suggestive of a link between innate and adaptive immune response. Based on the transcriptome analysis and qRT-PCR validation, an in vitro mechanism for the induction of ISGs by IRFs in an interferon independent manner to trigger a robust immune response was predicted in PPRV infection

Evaluation and comparison of the constitutive expression levels of Toll-like receptors 2, 3 and 7 in the peripheral blood mononuclear cells of Tharparkar and crossbred cattle

Aim: This study was undertaken to assess the differential expression levels of toll-like receptors (TLRs) 2, 3 and 7 in peripheral blood mononuclear cells (PBMCs) isolated from Tharparkar and Crossbred cattle belonging to different regions of India. Materials and Methods: PBMCs were isolated from blood samples of Tharparkar cattle from Indian Veterinary Research Institute (IVRI) farm (n=30); Suratgarh farm (n=61); Jaipur farm (n=8) and cross breed cattle from Jaipur (n=47). RNA was isolated from PBMCs and cDNA was synthesized using random hexamers. The expression profiles of TLR 2, 3 and 7 were estimated by real-time PCR and normalized to the expression of β-actin. Results: PBMCs of Tharparkar cattle from Suratgarh, exhibited a significantly higher (p<0.05) constitutive expression levels of TLR2, TLR3 and TLR7 genes as compared to Tharparkar cattle from IVRI or Jaipur as well as the crossbred cattle from Jaipur. PBMCs of crossbred cattle from Jaipur showed higher expression profiles of all the TLRs than Tharparkar cattle from Jaipur and IVRI. Conclusion: Our study indicates, expression levels of TLR2, TLR3 and TLR7 are significantly higher for Tharparkar cattle from Suratgarh than the cattle from Jaipur and IVRI and crossbred cattle from Jaipur. However, crossbred cattle from Jaipur showed higher basal expression levels of all the three TLRs than Tharparkar cattle from Jaipur and IVRI. Results also indicate that PBMCs of Tharparkar cattle show a regional variation in the expression pattern of TLRs

Association of water spectral indices with plant and soil water relations in contrasting wheat genotypes

Spectral reflectance indices can be used to estimate the water status of plants in a rapid, non-destructive manner. Water spectral indices were measured on wheat under a range of water-deficit conditions in field-based yield trials to establish their relationship with water relations parameters as well as available volumetric soil water (AVSW) to indicate soil water extraction patterns. Three types of wheat germplasm were studied which showed a range of drought adaptation; near-isomorphic sister lines from an elite/elite cross, advanced breeding lines, and lines derived from interspecific hybridization with wild relatives (synthetic derivative lines). Five water spectral indices (one water index and four normalized water indices) based on near infrared wavelengths were determined under field conditions between the booting and grain-filling stages of crop development. Among all water spectral indices, one in particular, which was denominated as NWI-3, showed the most consistent associations with water relations parameters and demonstrated the strongest associations in all three germplasm sets. NWI-3 showed a strong linear relationship (r2 >0.6–0.8) with leaf water potential (ψleaf) across a broad range of values (–2.0 to –4.0 MPa) that were determined by natural variation in the environment associated with intra- and inter-seasonal affects. Association observed between NWI-3 and canopy temperature (CT) was consistent with the idea that genotypes with a better hydration status have a larger water flux (increased stomatal conductance) during the day. NWI-3 was also related to soil water potential (ψsoil) and AVSW, indicating that drought-adapted lines could extract more water from deeper soil profiles to maintain favourable water relations. NWI-3 was sufficiently sensitive to detect genotypic differences (indicated by phenotypic and genetic correlations) in water status at the canopy and soil levels indicating its potential application in precision phenotyping

Cell-Free DNA and Active Rejection in Kidney Allografts

Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P1% indicate a probability of active rejection

Dysregulated miRNAome and Proteome of PPRV Infected Goat PBMCs Reveal a Coordinated Immune Response

In this study, the miRNAome and proteome of virulent Peste des petits ruminants virus (PPRV) infected goat peripheral blood mononuclear cells (PBMCs) were analyzed. The identified differentially expressed miRNAs (DEmiRNAs) were found to govern genes that modulate immune response based on the proteome data. The top 10 significantly enriched immune response processes were found to be governed by 98 genes. The top 10 DEmiRNAs governing these 98 genes were identified based on the number of genes governed by them. Out of these 10 DEmiRNAs, 7 were upregulated, and 3 were downregulated. These include miR-664, miR-2311, miR-2897, miR-484, miR-2440, miR-3533, miR-574, miR-210, miR-21-5p, and miR-30. miR-664 and miR-484 with proviral and antiviral activities, respectively, were upregulated in PPRV infected PBMCs. miR-210 that inhibits apoptosis was downregulated. miR-21-5p that decreases the sensitivity of cells to the antiviral activity of IFNs and miR-30b that inhibits antigen processing and presentation by primary macrophages were downregulated, indicative of a strong host response to PPRV infection. miR-21-5p was found to be inhibited on IPA upstream regulatory analysis of RNA-sequencing data. This miRNA that was also highly downregulated and was found to govern 16 immune response genes in the proteome data was selected for functional validation vis-a-vis TGFBR2 (TGF-beta receptor type-2). TGFBR2 that regulates cell differentiation and is involved in several immune response pathways was found to be governed by most of the identified immune modulating DEmiRNAs. The decreased luciferase activity in Dual Luciferase Reporter Assay indicated specific binding of miR-21-5p and miR-484 to their target thus establishing specific binding of the miRNAs to their targets.This is the first report on the miRNAome and proteome of virulent PPRV infected goat PBMCs