•A genetic algorithm (GA) is used to model the percentage shear force carried by floodplains depending on geometric and hydraulic parameters for predicting zonal and overall stage discharge.•The ...comprehensive study involves a data-driven model constituting wide spectrum of data of compound open channel flow.•The main focus of the derived mathematical model was to obtain a generalized unified solution, irrespective of the types of configuration of the open channels.•The current approach is more straightforward and capable of evaluating the intensity of momentum transfer across interfaces near the zero shear line using the percentage shear force, percentage area, and depth ratio of the compound channels for predicting discharge.•The proposed model predicts stage-discharge comparatively very well compared to conventional methods.
In this paper, a unified method has been proposed for the percentage shear force carried by floodplains using fewer non-dimensional parameters such as the floodplain's percentage area, the ratio of Manning’s roughness and the depth ratio. This new data-driven dynamic model for percentage shear force is obtained using a genetic algorithm (GA) program, a well-documented machine-learning software, which can examine the existing relationship among the variables and explore the influencing factors. GA facilitated a unified relationship between apparent shear force and the chosen parameters. The new proposed model is simple and accurate compared to the previous models, which were either complex or distinct for different configurations. The efficiency of the new model shows that the most predicted test case results are under the 5% error cap. The cohesive expression derived for smooth and roughened compound channels is the most significant advantage of the GA-based data-driven model, providing a simple and easy-use formula for engineers to apply for broad applications. Compared with the other available approaches, the model proposed provides the most accurate discharge prediction for various unique datasets.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ligand-mediated targeting of drugs especially in anticancer drug delivery is an effective approach. Dendrimers, due to unique surface topologies, can be a choice in this context. In the present ...study, PAMAM (polyamidoamine) dendrimers up to fourth generation were synthesized and characterized through infrared (IR), nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectrometric, and transmission electron microscopic (TEM) techniques. Primary amines present on the dendritic surface were conjugated through folic acid and folic acid−PEG (poly(ethylene glycol))−NHS (N-hydroxysuccinimide) conjugates. Tumor in mice was induced through the use of KB cell culture. Prepared dendritic conjugates were evaluated for the anticancer drug delivery potential using 5-FU (5-fluorouracil) in tumor-bearing mice. Approximately 31% of 5-FU was loaded in folate−PEG−dendritic conjugates. Results indicated that folate−PEG−dendrimer conjugate was significantly safe and effective in tumor targeting compared to a non-PEGylated formulation. Tailoring of dendrimers via PEG−folic acid reduced hemolytic toxicity, which led to a sustained drug release pattern as well as highest accumulation in the tumor area.
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IJS, KILJ, NUK, PNG, UL, UM
Mechanosensitive ion channels, Piezo1 and 2, are activated by pressure and involved in diverse physiological functions, including senses of touch and pain, proprioception and many more. Understanding ...their function is important for elucidating the mechanosensitive mechanisms of a range of human diseases. Recently, Piezo channels were suggested to be contributors to migraine pain generation. Migraine is typically characterized by allodynia and mechanical hyperalgesia associated with the activation and sensitization of trigeminal ganglion (TG) nerve fibers. Notably, migraine specific medicines are ineffective for other types of pain, suggesting a distinct underlying mechanism. To address, in a straightforward manner, the specificity of the mechanosensitivity of trigeminal vs. somatic nerves, we compared the activity of Piezo1 channels in mouse TG neurons vs. dorsal root ganglia (DRG) neurons. We assessed the functional expression of Piezo1 receptors using a conventional live calcium imaging setup equipped with a multibarrel application system and utilizing a microfluidic chip-based setup. Surprisingly, the TG neurons, despite higher expression of the
gene, were less responsive to Piezo1 agonist Yoda1 than the DRG neurons. This difference was more prominent in the chip-based setup, suggesting that certain limitations of the conventional approach, such as turbulence, can be overcome by utilizing microfluidic devices with laminar solution flow.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction
Trillium govanianum (Nag Chhatri and Teen Patra) is traditionally used for curing joint pains, wounds, and sexual disorders. Steroidal saponins are the main active components of this ...species. However, only a small amount of information is available about steroidal saponins of this plant.
Objective
To develop an ultra‐high‐performance liquid chromatography‐quadrupole time of flight tandem mass spectrometry (UHPLC‐QTOF‐MS/MS) and ultra‐high‐performance liquid chromatography‐evaporative light scattering detector (UHPLC‐ELSD) methods for the qualitative and quantitative determination of steroidal saponins in T. govanianum.
Method
The dried rhizomes of T. govanianum (100 mg) were extracted with ethanol–water (80:20, 10 mL) by ultrasonic treatment for 30 min at 40°C. The prepared sample was analysed by UHPLC‐QTOF‐MS/MS and UHPLC‐ELSD for the qualitative and quantitative determination of steroidal saponins.
Result
A total of 24 saponins were identified using UHPLC‐QTOF‐MS/MS; seven of them were characterised by comparing with standards. Furthermore, five saponins govanoside B (2), protodioscin (6), pennogenin tetraglycosides (11), borassoside E (21) and borassoside D (24) were quantified using UHPLC‐ELSD method in different extracts and fractions of T. govanianum. The method showed good linearity (R2 ≥ 0.993), limit of detection (0.92–4.09 μg/mL), limit of quantification (3.1–13.5 μg/mL), precision intra‐day relative standard deviations (RSDs) < 4.3% and inter‐day RSDs < 5.5%, and accuracy (84.0–110.3%). This is the first report on the quantification of 2, 6, 11, 21 and 24 in T. govanianum.
Conclusion
The present study provides an efficient analytical method for the identification and quantification of steroidal saponins and will be helpful for the quality evaluation of T. govanianum.
The systematic analysis of steroidal saponins in Trillium govanianum was performed. A total of 24 saponins were tentatively identified, and their characteristic fragmentations were also summarised. Furthermore, five saponins were quantified, among them borassoside E (21), protodioscin (6) and govanoside B (2) were found most abundant and could be used as marker compounds for quality control of T. govanianum.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The human sweat is a mixture of secretions from three types of glands: eccrine, apocrine, and sebaceous. Eccrine glands open directly on the skin surface and produce high amounts of water-based fluid ...in response to heat, emotion, and physical activity, whereas the other glands produce oily fluids and waxy sebum. While most body fluids have been shown to contain nucleic acids, both as ribonucleoprotein complexes and associated with extracellular vesicles (EVs), these have not been investigated in sweat. In this study we aimed to explore and characterize the nucleic acids associated with sweat particles. We used next generation sequencing (NGS) to characterize DNA and RNA in pooled and individual samples of EV-enriched sweat collected from volunteers performing rigorous exercise. In all sequenced samples, we identified DNA originating from all human chromosomes, but only the mitochondrial chromosome was highly represented with 100% coverage. Most of the DNA mapped to unannotated regions of the human genome with some regions highly represented in all samples. Approximately 5 % of the reads were found to map to other genomes: including bacteria (83%), archaea (3%), and virus (13%), identified bacteria species were consistent with those commonly colonizing the human upper body and arm skin. Small RNA-seq from EV-enriched pooled sweat RNA resulted in 74% of the trimmed reads mapped to the human genome, with 29% corresponding to unannotated regions. Over 70% of the RNA reads mapping to an annotated region were tRNA, while misc. RNA (18,5%), protein coding RNA (5%) and miRNA (1,85%) were much less represented. RNA-seq from individually processed EV-enriched sweat collection generally resulted in fewer percentage of reads mapping to the human genome (7-45%), with 50-60% of those reads mapping to unannotated region of the genome and 30-55% being tRNAs, and lower percentage of reads being rRNA, LincRNA, misc. RNA, and protein coding RNA. Our data demonstrates that sweat, as all other body fluids, contains a wealth of nucleic acids, including DNA and RNA of human and microbial origin, opening a possibility to investigate sweat as a source for biomarkers for specific health parameters.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•One-tissue format enables multiple tissue combinations on chip without design changes.•Tilting-based perfusion eliminates any tubing and ensures device robustness.•Perfusion leads to improved liver ...function on chip.•On-chip activation of the pro-drug cyclophosphamide leads to reduced tumor growth.•Chip design allows for biochemical and optical assays to assess drug response.
Rational development of more physiologic in vitro models includes the design of robust and flexible 3D-microtissue-based multi-tissue devices, which allow for tissue–tissue interactions. The developed device consists of multiple microchambers interconnected by microchannels. Pre-formed spherical microtissues are loaded into the microchambers and cultured under continuous perfusion. Gravity-driven flow is generated from on-chip reservoirs through automated chip-tilting without any need for additional tubing and external pumps. This tilting concept allows for operating up to 48 devices in parallel in order to test various drug concentrations with a sufficient number of replicates. For a proof of concept, rat liver and colorectal tumor microtissues were interconnected on the chip and cultured during 8 days in the presence of the pro-drug cyclophosphamide. Cyclophosphamide has a significant impact on tumor growth but only after bio-activation by the liver. This effect was only observed in the perfused and interconnected co-cultures of different microtissue types on-chip, whereas the discontinuous transfer of supernatant via pipetting from static liver microtissues that have been treated with cyclophosphamide did not significantly affect tumor growth. The results indicate the utility and multi-tissue functionality of this platform. The importance of continuous medium circulation and tissue interaction is highlighted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The role of the telomere repeat-binding factor 2 (TRF2) in telomere maintenance is well-established. However, recent findings suggest that TRF2 also functions outside telomeres, but relatively little ...is known about this function. Herein, using genome-wide ChIP-Seq assays of TRF2-bound chromatin from HT1080 fibrosarcoma cells, we identified thousands of TRF2-binding sites within the extra-telomeric genome. In light of this observation, we asked how TRF2 occupancy is organized within the genome. Interestingly, we found that extra-telomeric TRF2 sites throughout the genome are enriched in potential G-quadruplex–forming DNA sequences. Furthermore, we validated TRF2 occupancy at several promoter G-quadruplex motifs, which did adopt quadruplex forms in solution. TRF2 binding altered expression and the epigenetic state of several target promoters, indicated by histone modifications resulting in transcriptional repression of eight of nine genes investigated here. Furthermore, TRF2 occupancy and target gene expression were also sensitive to the well-known intracellular G-quadruplex–binding ligand 360A. Together, these results reveal an extensive genome-wide association of TRF2 outside telomeres and that it regulates gene expression in a G-quadruplex–dependent fashion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The gram pod borer is a major pest of chickpea, accounting for average annual yield losses to the tune of 40-50%. VIP3Aa, a class of insecticidal protein with different receptor binding site in the ...insect's midgut compared to Bt-crystal protein, offers an alternative protection strategy against Lepidopteran insects. Here, we report evaluation of genetically engineered chickpea lines harboring codon modified Vip3Aa (cmVip3Aa) against the Lepidopteran insect pest, gram pod borer. The synthetic codon modified, cmVip3Aa gene of 2,370 bp was sub-cloned in modified plant expression vector and used for direct transformation of embryonic axis explants of chickpea (cv. DCP 92-3), with transformation efficiency of 4.30%. Presence and transmission of transgene across two generations were confirmed by PCR and Southern blot analyses in the five selected transgenic chickpea lines. Real Time PCR analyses indicated variable levels of cmVip3Aa expression in the transgenic chickpea lines (average Cq values 15.01±0.86 to 19.32±0.10), which were absent in the non-transgenic counterpart. Detached leaf insect bioassay indicate larval mortality (up to 39.75%), reduced larval feeding (up to 82.91%) and reduced larval weight gain (up to 68.23%), compared to control lines. Evaluation of gene offers a platform to identify efficacious insecticidal gene that can be used for insect resistance management in chickpea.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the contemporary era of scientific and technical innovations, we are witnessing remarkable progress in the realm of quantum computing. Today's phase is referred to as the second quantum ...revolution, characterized by ongoing research and progress in the hardware, software, and applications of quantum computers. While the theoretical foundations of quantum computing have been in place for decades, the practical tools and technologies that have emerged in recent years have catapulted this field from theory into reality. This paper provides a brief overview of the fundamental principles of quantum computing and explores the various technologies that support them. From quantum programming languages and simulators to quantum hardware platforms and software development kits, these tools have paved the way for groundbreaking research, experimentation, and the exploration of quantum's boundless potential. Furthermore, it addresses the current developments, existing challenges, ongoing improvements, and future prospects in this dynamic field.
Variant peptides resulting from single nucleotide polymorphisms (SNPs) can lead to aberrant protein functions and have translational potential for disease diagnosis and personalized therapy. Variant ...peptides detected by proteogenomics are fraught with high number of false positives, but there is no uniform and comprehensive approach to assess variant quality across analysis pipelines. Despite class-specific FDR along with ad-hoc filters, the problem is far from solved. These protocols are typically manual and tedious, and thus not uniform across labs. We demonstrate that variant peptide rescoring, integrated with intensity, variant event information and search result features, allows better discrimination of correct variant peptides. Implemented into PgxSAVy - a tool for quality control of variant peptides, this method can tackle the high rate of false positives. PgxSAVy provides a rigorous framework for quality control and annotations of variant peptides on the basis of (i) variant quality, (ii) isobaric masses, and (iii) disease annotation. PgxSAVy demonstrated high accuracy by identifying true variants with 98.43% accuracy on simulated data. Large-scale proteogenomic reanalysis of ∼2.8 million spectra (PXD004010 and PXD001468) resulted in 12,705 variant peptide spectrum matches (PSMs), of which PgxSAVy evaluated 3028 (23.8%), 1409 (11.1%) and 8268 (65.1%) as confident, semi-confident and doubtful respectively. PgxSAVy also annotates the variants based on their pathogenicity and provides support for assisted manual validation. The analysis of proteins carrying variants can provide fine granularity in discovering important pathways. PgxSAVy will advance personalized medicine by providing a comprehensive framework for quality control and prioritization of proteogenomics variants. PgxSAVy is freely available at https://pgxsavy.igib.res.in/ as a webserver and https://github.com/anuragraj/PgxSAVy as a stand-alone tool.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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