Reliability and Quality Assurance Experience in Launcher Hold and Release System used in GSLV

The launcher hold and release system (LHRS) was successfully used, for the first time, for GSLV-DI mission after thorough test and evaluation, in line with reliability and quality assurance (R&QA) requirements. Various R&QA techniques are applied to make LHRS failure-free. Failure mode effect and criticality analysis (FMECA) was used as a tool for identifying critical failure modes. Single-point failure modes (SPFMs) identified from FMECA are strengthened by design modifications and the same are verified by testing. Testing philosophy is tailored to have more number of tests at the system level. Capability demonstration tests and failure mode simulation tests were carried out during system qualification phase. Acceptance tests are done on the flight hardware at launch pad to demonstrate better confidence on the system. This paper illustrates how R&QA techniques complimented and added value at different stages in the development cycle of LHRS, by means of few case studies. Testing methodologies adopted and problems encountered during the development and qualification phases are described in brief. Various problems surfaced during preparation for flight are also discussed

Prospecting for scarabid specific Bacillus thuringiensis crystal toxin cry8 gene in sugarcane ecosystem of Tamil Nadu, India

In the present study, we report the occurrence of cry8 positive isolates of Bacillus thuringiensis (Bt) in selected white grub, Holotrichia serrata F. (Coleoptera: Scarabaeidae), endemic soils of sugarcane ecosystem and other places in Tamil Nadu. Out of the 66 soil samples collected and screened for white grub specific Bt, 74 isolates of the bacterium, all containing only spherical crystal toxin, were identified. PCR screening of these isolates with cry8 gene universal primer revealed six isolates to be positive. Further, the amplicon of a 370 bp band, amplified with another set of degenerate primer designed based on the conserved sequence of cry8 genes, was sequenced from four isolates. Multiple sequence alignment revealed the gene sequences to be the same for all the isolates. The present report of the availability of cry8 positive Bt isolates opens the avenue for controlling white grubs through transgenic research

Low-loss, compact, spot-size-converter based vertical couplers for photonic integrated circuits

Funding: (i) European Union Horizon H2020 Programme (H2020-ICT27-2015, COSMICC No. 688516). (ii) European Union Research Council (ERC) starting grant 337508.In recent years, the monolithic integration of new materials such as SiN, Ge and LiNbO3 on silicon (Si) has become important to the Si photonics community due to the possibility of combining the advantages of both material systems. However, efficient coupling between the two different layers is challenging. In this work, we present a spot size converter based on a two-tier taper structure to couple the optical mode adiabatically between Si and SiN. The fabricated devices show a coupling loss as low as 0.058 dB  ±  0.01 dB per transition at 1525 nm. The low coupling loss between the Si to SiN, and vice versa, reveals that this interlayer transition occurs adiabatically for short taper lengths (<200 µm). The high refractive index contrast between the Si and SiN is overcome by matching the optical impedance. The proposed two-tier taper structure provides a new platform for optoelectronic integration and a route towards 3D photonic integrated circuits.PostprintPeer reviewe

Prospecting in Western Ghats of Karnataka for indigenous Bacillus thuringiensis isolates harbouring novel crystal toxin genes for sugarcane pest management

Prospecting for potential novel Bacillus thuringiensis with new holotype crystal toxins was carried out in the Western ghats hill range of Karnataka state, India. From the soil samples collected three Bt isolates SBIKWG 12, SBIKWG 24 and SBIKWG 70 were isolated. Of these while the two isolates, namely SBIKWG 12 and SBIKWG 24 produced bipyramidal crystal toxins, the third isolate produced spherical crystal. PCR screening of the isolates revealed the presence of lepidopteran and coleopteran active cry genes. Partial sequences obtained from these isolates revealed the presence of multiple crystal toxin genes. BlastX analysis of the partial gene sequences indicated the potential for the occurrence of new holotype crystal toxin genes in SBIKWG 24 and SBIKWG 70

Evaluation of tools for identifying large copy number variations from ultra-low-coverage whole-genome sequencing data

BackgroundDetection of copy number variations (CNVs) from high-throughput next-generation whole-genome sequencing (WGS) data has become a widely used research method during the recent years. However, only a little is known about the applicability of the developed algorithms to ultra-low-coverage (0.0005–0.8×) data that is used in various research and clinical applications, such as digital karyotyping and single-cell CNV detection.ResultHere, the performance of six popular read-depth based CNV detection algorithms (BIC-seq2, Canvas, CNVnator, FREEC, HMMcopy, and QDNAseq) was studied using ultra-low-coverage WGS data. Real-world array- and karyotyping kit-based validation were used as a benchmark in the evaluation. Additionally, ultra-low-coverage WGS data was simulated to investigate the ability of the algorithms to identify CNVs in the sex chromosomes and the theoretical minimum coverage at which these tools can accurately function. Our results suggest that while all the methods were able to detect large CNVs, many methods were susceptible to producing false positives when smaller CNVs (< 2 Mbp) were detected. There was also significant variability in their ability to identify CNVs in the sex chromosomes. Overall, BIC-seq2 was found to be the best method in terms of statistical performance. However, its significant drawback was by far the slowest runtime among the methods (> 3 h) compared with FREEC (~ 3 min), which we considered the second-best method.ConclusionsOur comparative analysis demonstrates that CNV detection from ultra-low-coverage WGS data can be a highly accurate method for the detection of large copy number variations when their length is in millions of base pairs. These findings facilitate applications that utilize ultra-low-coverage CNV detection.</div

Whole genome analysis and functional characterization of a novel Bacillus thuringiensis (Bt 62) isolate against sugarcane white grub Holotrichia serrata (F)

In this study, we report the whole genome assembly of Bt 62, a novel isolate harbouring cry8 holotype gene identified by us earlier. Sequencing was carried out using a combination of Illumina NextSeq 500 and Oxford Nanopore sequencing Technologies (ONT). The final assembled genome was 6.13 Mb comprising a circular chromosome and four plasmids. The bioassay studies against Holotrichia serrata (F.) (Coleoptera: Scarabaeidae), a polyphagous pest infesting sugarcane and other crops, indicated significant toxicity to first instar grubs over untreated larvae achieving a highest mean mortality of 91.11% for various doses tested. In vitro proteolytic assay and histopathological studies of the midgut of infected white grubs revealed proteolytic processing of the protoxin and extensive degeneration of larval midgut epithelial cells. The results demonstrate that this novel isolate could be used as a biopesticide or its crystal toxin genes could be expressed in sugarcane and other crops for resistance against H. serrata

Hyperoxic Treatment Induces Mesenchymal-to-Epithelial Transition in a Rat Adenocarcinoma Model

Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (∼16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the “switches” of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects

Human Bone Marrow-Derived Stem Cells Acquire Epithelial Characteristics through Fusion with Gastrointestinal Epithelial Cells

Bone marrow-derived mesenchymal stem cells (MSC) have the ability to differentiate into a variety of cell types and are a potential source for epithelial tissue repair. Several studies have demonstrated their ability to repopulate the gastrointestinal tract (GIT) in bone marrow transplanted patients or in animal models of gastrointestinal carcinogenesis where they were the source of epithelial cancers. However, mechanism of MSC epithelial differentiation still remains unclear and controversial with trans-differentiation or fusion events being evoked. This study aimed to investigate the ability of MSC to acquire epithelial characteristics in the particular context of the gastrointestinal epithelium and to evaluate the role of cell fusion in this process. In vitro coculture experiments were performed with three gastrointestinal epithelial cell lines and MSC originating from two patients. After an 8 day coculture, MSC expressed epithelial markers. Use of a semi-permeable insert did not reproduce this effect, suggesting importance of cell contacts. Tagged cells coculture or FISH on gender-mismatched cells revealed clearly that epithelial differentiation resulted from cellular fusion events, while expression of mesenchymal markers on fused cells decreased over time. In vivo cell xenograft in immunodeficient mice confirmed fusion of MSC with gastrointestinal epithelial cells and self-renewal abilities of these fused cells. In conclusion, our results indicate that fusion could be the predominant mechanism by which human MSC may acquire epithelial characteristics when in close contact with epithelial cells from gastrointestinal origin . These results could contribute to a better understanding of the cellular and molecular mechanisms allowing MSC engraftment into the GIT epithelium

Reciprocal influence of the p53 and the hypoxic pathways

When cells sense a decrease in oxygen availability (hypoxia), they develop adaptive responses in order to sustain this condition and survive. If hypoxia lasts too long or is too severe, the cells eventually die. Hypoxia is also known to modulate the p53 pathway, in a manner dependent or not of HIF-1 (hypoxia-inducible factor-1), the main transcription factor activated by hypoxia. The p53 protein is a transcription factor, which is rapidly stabilised by cellular stresses and which has a major role in the cell responses to these stresses. The aim of this review is to compile what has been reported until now about the interconnection between these two important pathways. Indeed, according to the cell line, the severity and the duration of hypoxia, oxygen deficiency influences very differently p53 protein level and activity. Conversely, p53 is also described to affect HIF-1α stability, one of the two subunits of HIF-1, and HIF-1 activity. The direct and indirect interactions between HIF-1α and p53 are described as well as the involvement in this complex network of their respective ubiquitin ligases von Hippel Lindau protein and murine double minute 2. Finally, the synergistic or antagonistic effects of p53 and HIF-1 on some important cellular pathways are discussed