Jawaharlal Nehru University

Nanotechnology is a novel area that has exhibited various remarkable applications, mostly in medicine and industry, due to the unique properties coming with the nanoscale size. One of the notable medical uses of nanomaterials (NMs) that attracted enormous attention recently is their significant anticoagulant activity, preventing or reducing coagulation of blood, decreasing the risk of strokes, heart attacks, and other serious conditions. Despite successful in vitro experiments, in vivo analyses are yet to be confirmed and further research is required to fully prove the safety and efficacy of nanoparticles (NPs) and to introduce them as valid alternatives to conventional ineffective anticoagulants with various shortcomings and side-effects. NMs can be synthesized through two main routes, i.e., the bottom-up route as a more preferable method, and the top-down route. In numerous studies, biological fabrication of NPs, especially metal NPs, is highly suggested given its eco-friendly approach, in which different resources can be employed such as plants, fungi, bacteria, and algae. This review discusses the green synthesis and characterization of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) as two of the most useful metal NPs, and also their alloys in different studies focussing on their anticoagulant potential. Challenges and alternative approaches to the use of these NPs as anticoagulants have also been highlighted.

Malaria still threatens half the globe population despite successful Artemisinin-based combination therapy. One of the reasons for our inability to eradicate malaria is the emergence of resistance to current antimalarials. Thus, there is a need to develop new antimalarials targeting Plasmodium proteins. The present study reported the design and synthesis of 4, 6 and 7-substituted quinoline-3-carboxylates 9(a–o) and carboxylic acids 10(a–b) for the inhibition of Plasmodium N-Myristoyltransferases (NMTs) using computational biology tools followed by chemical synthesis and functional analysis. The designed compounds exhibited a glide score of −9.241 to −6.960 kcal/mol for PvNMT and −7.538 kcal/mol for PfNMT model proteins. Development of the synthesized compounds was established via NMR, HRMS and single crystal X-ray diffraction study. The synthesized compounds were evaluated for their in vitro antimalarial efficacy against CQ-sensitive Pf3D7 and CQ-resistant PfINDO lines followed by cell toxicity evaluation. In silico results highlighted the compound ethyl 6-methyl-4-(naphthalen-2-yloxy)quinoline-3-carboxylate (9a) as a promising inhibitor with a glide score of −9.084 kcal/mol for PvNMT and −6.975 kcal/mol for PfNMT with IC50 values of 6.58 µM for Pf3D7 line. Furthermore, compounds 9n and 9o exhibited excellent anti-plasmodial activity (Pf3D7 IC50 = 3.96, 6.71 µM, and PfINDO IC50 = 6.38, 2.8 µM, respectively). The conformational stability of 9a with the active site of the target protein was analyzed through MD simulation and was found concordance with in vitro results. Thus, our study provides scaffolds for the development of potent antimalarials targeting both Plasmodium vivax and Plasmodium falciparum. Communicated by Ramaswamy H. Sarma

Background: TGFB1 cytokine is involved in normal mammary epithelial development as well as in breast tumorigenesis. It has role in both breast tumor suppression and progression. TGFB1 gene has several single nucleotide polymorphisms (SNPs) many of which modulate the activity of TGFB1. Our aim in this study was to analyze TGFB1 + 29 polymorphism in breast cancer individuals from North Indian population. Methods: TGFB1 + 29 T/C polymorphism was analyzed using Sanger sequencing in 285 breast cancer patients and age matched 363 healthy controls from North Indian population. Next, transcript expression of 13 apoptotic genes, TRAIL, DR4, DR5, DcR1, DcR2, Bcl2, cytochrome c, Casp8L, Casp8, FlipS, FlipL, Casp3s and Casp3 were carried out in 77 breast tumor tissues obtained from 77 individuals. Results: TGFB1 + 29 CC genotype provided protection against the development of breast cancer (P = 0.012). This was mainly attributable to higher age group (> 45 years) women (P = 0.016). Individuals having CC protector genotype showed significantly higher expression of TGFB1 transcript compared to the TT and TC risk genotypes (P = 0.044). Furthermore, we observed that TGFB1 + 29 CC genotype showed increased TRAIL mediated apoptosis via the extrinsic pathway in breast tumor patients with age greater than 45 years (P = 0.027). Conclusion: TGFB1 + 29 homozygous mutant CC genotype is related to protection against breast cancer in North Indian women population greater than 45 years of age.

Lipstatin, natural inhibitor of pancreatic lipase produced by Streptomyces toxytricini and used as an anti-obesity drug. Chemical mutagenesis was performed with different concentrations of N-methyl-N′-nitro-N-nitrosoguanidine (NTG) for strain improvement to obtain high yield of lipstatin. It was observed that the potential of the wild type strain to produce lipstatin (1.09 g/L) was very low. Selected mutants produced lipstatin in the range of 1.20–2.23 g/L at the flask level where maximum amount of lipstatin was produced by M5 mutant. For comparative study, both the parent and M5 mutant strain of S. toxytricini were grown at the lab scale bioreactor with suitable sources of carbon and nitrogen. Significant increase in the production of lipstatin was observed at the bioreactor level where the wild type strain produced 2.4 g/L of lipstatin, while through the NTG mutation, the production of lipstatin was 5.35 g/L. However, Dry Cell Weight (DCW) of the mutant strain was less in comparison with wild type strain and significant morphological differences were observed. Nearly 5 times increase in the production of lipstatin was achieved through NTG mutation and bioreactor-controlled conditions. It was determined that the NTG treatment might be beneficial for strain improvement to get a better candidate for lipstatin production on commercial scale.

Urban spaces have become sink for metal-rich waste, particularly in unorganized industrial clusters and metro-cities. Geochemical distribution of metals in different forms and their mobility and bioavailability in topsoils of Bhiwadi Industrial Cluster (BIC) near New Delhi are studies following m-BCR-SEP. Contamination factor (Cf), risk assessment code (RAC), ecological risk assessment (Er), and carcinogenic and non-carcinogenic health risk (HRA) were calculated to assess health and environmental risks. Residual fraction (F4) contained considerable amounts of Cd (57.2%), Cr (81.5%), Fe (86.1%), Mn (62.5%), Ni (58.3%), and V (71.4%). Pb was present in reducible fraction (F2; 52.8%), whereas Cu was distributed in F2 (33.3%) and F4 (31.6%). Zn showed equal distribution in acid exchangeable (F1; 33.9%) and oxidizable fraction (F3; 32.5%). High Cf was observed for Zn (0.9–20.9), Cu (0.46–17) and Pb (0.2–9.9). RAC indicated high risk of Cd, Cu, Mn, Ni, and Zn due to their high mobility and toxicity. High potential bioavailability of Cu, Pb, and Zn (> 65%) was found in samples collected near to metal casting, electroplating, and automobile part manufacturing industries. Considerable to extremely high ecological risk was observed for Cd, low to high risk for Cu, low risk to moderate risk for Cr, Mn, Ni, Zn, and Pb. All topsoil samples were in low to very high-risk range for metals. Ingestion was major pathway of metals followed by dermal and inhalation. Children were more prone to non-carcinogenic risks (hazardous index: 3.6). Topsoils had high carcinogenic risk to exposed population for Cd, Cr, Ni, and Pb.

The existing literature is rich in plain cement concrete short columns, but it is deficient with respect to geopolymer concrete (GPC) short columns with the incorporation of fibers with hybridization. The current investigation focuses to identify and measure the structural performance and behavior of two grades of GPC viz., normal and high strength grade with and without hybrid fibers. Two types of fibers i.e., steel and polypropylene are utilized to prepare the hybrid fiber reinforced GPC (HFRGPC) ranging from 0–2% in the increments of 0.5% coupled with longitudinal reinforcement. A total of 20 short columns (10 circular and 10 square headed) having a height of 1000 mm and sizes of 150 mm dia. and 150x150 mm respectively are prepared and tested for uni axial compression loading. The study results indicated that the circular GPC short columns possess better structural performance at ultimate load in terms of ductility ratio than those of square headed GPC specimens with and without fibers. The significant impacts of fiber volume fraction are investigated and reported. The experimental results of the of short columns showed a good agreement with the theoretical results.

During coarsening, small structures disappear, leaving behind only large ones. Here we study the spectral energy transfers in Model A, where the order parameter ϕ evolves via nonconserved dynamics. We show that the nonlinear interactions dissipate fluctuations and facilitate energy transfers among the Fourier modes so that only ϕ(k=0), where k is the wave number, survives at the end and approaches the asymptotic value +1 or −1. We contrast the coarsening evolution for the initial conditions with ⟨ϕ(x,t=0)⟩=0 and with uniformly positive or negative ϕ(x,t=0).

This paper proposes a compact analytical model and comprehensively investigates the biosensing performance of a novel dielectric modulated triple surrounding gate germanium source metal–oxide–semiconductor field‐effect transistor with a step graded channel. Solving the 2D Poisson's equation yields an analytical expression of threshold voltage, channel potential, drain current and sub threshold swing. The sensitivity variation in the biosensor has been thoroughly studied by varying different device parameters to investigate its biosensing performance. Graded doping in channel offers enhanced sensitivity than a non‐graded doped channel when the doping of the channel is more near the drain end than source end which is due to stronger electric field and gate capacitance. Effect of fill‐in factor for different biomolecules on the sensitivity has been thoroughly discussed. Different analytical results show an excellent agreement with the simulations done on SILVACO ATLAS TCAD simulator.

Dalit women suffer from multiple forms of oppression and discrimination based on gender, caste and class prejudices. This article explores the context and ramifications of emigration to the Gulf by Dalit women hailing from the Indian state of Andhra Pradesh who are mostly employed as domestic workers. Given the scarce opportunities at the place of origin, transnational migration has a meagre effect on the lives of Dalit women even as it contributes to earnings and the sustenance of household financial needs. This marginal gain, however, has a telling cost in terms of exploitative working conditions, adverse repercussions on mental and physical health as well as intra-family relations. The impact of migration on their overall welfare appears to be insignificant in the absence of state support in both origin and destination countries. The empirical analysis highlights that families of Dalit women, despite emigration, continue to reel under poverty, lack of education and remain exposed to exploitation, discrimination and state apathy.

Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily. It is a primary regulator of calcium and phosphate homeostasis required for skeleton and bone mineralization. Vitamin D in active form 1α,25 dihydroxyvitamin-D3 mediates its cellular functions by binding to VDR. Active VDR forms heterodimers with partner RXR (retinoid X receptor) to execute its physiological actions. HVDRR (Hereditary Vitamin D-Resistant Rickets) is a rare genetic disorder that occurs because of generalized resistance to the 1α,25(OH)2D3. HVDRR is caused by the polymorphic variations in VDR gene leading to defective intestinal calcium absorption and mineralization of newly forming bones. Using point and deletion SNPs of VDR we have studied several HVDRR-associated SNP variants for their subcellular dynamics, transcriptional functions, ‘genome bookmarking’, heterodimeric interactions with RXR, and receptor stability. We previously reported that VDR is a ‘mitotic bookmarking factor’ that remains constitutively associated with the mitotic chromatin to inherit ‘transcriptional memory’, however the mechanistic details remained unclear. We document that ‘genome bookmarking’ property by VDR is critically impaired by naturally occurring HVDRR-associated point and deletion variants found in patients. Furthermore, these HVDRR-associated SNP variants of VDR were found to be compromised in transcriptional function, nuclear translocation, protein stability and intermolecular interactions with its heterodimeric partner RXR. Intriguingly, majority of these disease-allied functional defects failed to be rescued by RXR. Our findings suggest that the HVDRR-associated SNP variations influence the normal functioning of the receptor, and this derived understanding may help in the management of disease with precisely designed small molecule modulators.

Nipah virus (NiV) is an emerging zoonotic virus that caused several serious outbreaks in the south asian region with high mortality rates ranging from 40 to 90% since 2001. NiV infection causes lethal encephalitis and respiratory disease with the symptom of endothelial cell-cell fusion. No specific and effective vaccine has yet been reported against NiV. To address the urgent need for a specific and effective vaccine against NiV infection, in the present study, we have designed two Multi-Epitope Vaccines (MEVs) composed of 33 Cytotoxic T lymphocyte (CTL) epitopes and 38 Helper T lymphocyte (HTL) epitopes. Out of those CTL and HTL combined 71 epitopes, 61 novel epitopes targeting nine different NiV proteins were not used before for vaccine design. Codon optimization for the cDNA of both the designed MEVs might ensure high expression potential in the human cell line as stable proteins. Both MEVs carry potential B cell linear epitope overlapping regions, B cell discontinuous epitopes as well as IFN-γ inducing epitopes. Additional criteria such as sequence consensus amongst CTL, HTL and B Cell epitopes was implemented for the design of final constructs constituting MEVs. Hence, the designed MEVs carry the potential to elicit cell-mediated as well as humoral immune response. Selected overlapping CTL and HTL epitopes were validated for their stable molecular interactions with HLA class I and II alleles and in case of CTL epitopes with human Transporter Associated with antigen Processing (TAP) cavity. The structure based epitope cross validation for interaction with TAP cavity was used as another criteria choosing final epitopes for NiV MEVs. Finally, human Beta-defensin 2 and Beta-defensin 3 were used as adjuvants to enhance the immune response of both the MEVs. Molecular dynamics simulation studies of MEVs-TLR3 ectodomain (Human Toll-Like Receptor 3) complex indicated the stable molecular interaction. We conclude that the MEVs designed and in silico validated here could be highly potential vaccine candidates to combat NiV infections, with great effectiveness, high specificity and large human population coverage worldwide.

This article presents a novel semi-flexible two port multi-input-multi-output (MIMO) antenna with dual circular polarization (CP) in the millimeter-wave frequency band (24-31 GHz) for wearable applications in biotechnologies. The radiating circular patch and ground plane are embedded with multiple sectoral slots and moon-shaped slots, respectively, for broad impedance bandwidth and CP property. The E θ and E ϕ fields are also classified as RHCP and LHCP at 27.10 GHz and 29.53 GHz, respectively. The microstrip line feeds the MIMO antenna, which is printed on a semi-flexible substrate with an overall electrical length of 2.9λ 0 × 1.8λ 0 × 0.04λ 0 at 24 GHz. The antenna is designed for homogeneous space conditions (off-body) with a flat profile. Its on-body performance capability top-up with bending analysis is examined on the surface (chest, hand, and leg) of the anatomical Gustav human body model. Further, the MIMO diversity parameters are also evaluated in the CST Microwave Studio Simulator. Later on, the simulated radiation characteristics are testified through in-vitro measurement of the fabricated MIMO antenna in free-space and chest mimicking gel-based phantom. Lastly, to ensure human shielding, the SAR analysis is mapped with the communication link margin to select the input power.

Objective To explore a set of inflammation associated circulatory miRNAs with potential role in etiopathology of psoriasis as differential disease biomarker/s. Subjects and Methodology: Expression profiling of 15 immunologically relevant miRNA candidates was done on plasma samples from psoriasis vulgaris patients compared to healthy subjects by qRT-PCR. Receiver operating characteristic (ROC) curve was analyzed for significantly altered miRNAs to evaluate their disease diagnostic potential. Correlation analysis among significantly altered miRNAs and their association with disease severity (PASI) was done to validate the candidates as robust disease biomarker/s. Downstream targets and the pathways for each of the significant miRNAs were deciphered using miR target prediction tools and pathway enrichment to elucidate their functional relevance in disease pathogenesis. Results: 5 miRNAs exhibited a significant change in their expression level among the 15 candidates tested viz miR-215, miR-148a, miR-125b, miR-223 and miR-142-3p. ROCs for all the 5 miRNAs individually as well as in combination exhibited a significant disease discriminatory area under the curve, AUC = 0.762 and p< 0.0001 for all the miRNAs taken together. Statistically, all 5 miRNAs in combination depicted a robust model as disease severity correlate compared to individual miRNAs with highest R2 value = 0.94 and least AIC score =131.8. Each of the miRNA also exhibited a significant association with at least one of the other miRNAs in the panel. All the 5 miRNAs exhibited functional role in psoriasis immune-pathogenesis in terms of their downstream targets and signaling pathways. Conclusion: In summary our findings identify a panel of blood-based circulatory miRNAs comprising miR-215, miR-148a, miR-125b-5p, miR-223 and miR-142-3p that can differentiate psoriasis vulgaris patients from healthy individuals. In light of the role of each of these miRNAs in modulating immune-inflammatory pathways, the panel provides a rationalized combination of biomarkers that can be tested further on an expanded cohort of patients for its diagnostic value.

Uncontrolled waste generation and management difficulties are causing chaos in the ecosystem. Although it is vital to ease environmental pressures, right now there is no such practical strategy available for the treatment or utilisation of waste material. Because the Earth's resources are limited, a long-term, sustainable, and sensible solution is necessary. Currently waste material has drawn a lot of attention as a renewable resource. Utilisation of residual biomass leftovers appears as a green and sustainable approach to lessen the waste burden on Earth while meeting the demand for bio-based goods. Several biopolymers are available from renewable waste sources that have the potential to be used in a variety of industries for a wide range of applications. Natural and synthetic biopolymers have significant advantages over petroleum-based polymers in terms of cost-effectiveness, environmental friendliness, and user-friendliness. Using waste as a raw material through industrial symbiosis should be taken into account as one of the strategies to achieve more economic and environmental value through inter-firm collaboration on the path to a near-zero waste society. This review extensively explores the different biopolymers which can be extracted from several waste material sources and that further have potential applications in food packaging industries to enhance the shelf life of perishables. This review-based study also provides key insights into the different strategies and techniques that have been developed recently to extract biopolymers from different waste byproducts and their feasibility in practical applications for the food packaging business.

The monsoonal rainfall in North-East India, including the study region (Jalpaiguri district, located in the eastern Himalayan foothills), is decreasing, and heavy precipitation event days have been increasing. In this study, different climatic components, such as average monthly minimum temperature, maximum temperature, precipitation, and wet days’ frequency of Jalpaiguri district over a century (1901–2000), have been investigated in order to figure out the changing pattern of climate. For robust interpretation, the Mann-Kendall trend and Sen’s slope statistical methods were applied for trend analysis of each climatic component. At the same time, a hundred-year temperature anomalies (average, minimum, maximum) have also been calculated. The linear trend of the annual average temperature anomaly in Jalpaiguri has indicated that the temperature anomaly was increased by about 0.006 °C/year. It was highest in 1999 (+1.2 °C); simultaneously, the temperature has risen significantly by 0.01 °C in February and November in the last century. The Mann-Kendall test reveals a significant drop in the annual rainfall by 0.93 mm in June, followed by 0.18 mm in August during the last century (1901–2000). In 1955, July received a record-breaking rainfall (1105.93 mm), the highest monthly rainfall in the last century.

B. S. Sherin, Gendering Minorities: Muslim Women and the Politics of Modernity, Orient BlackSwan, 2021, 222 pp., ₹615, ISBN 9789352876693 (Paperback).

The Supreme Court’s recent judgment upholding the economically weaker sections (EWS) quota has given rise to the idea that reservations can be provided to economically vulnerable sections of the people. This expansion in the beneficiaries of affirmative action has triggered the perception that the reservation policy, which was earlier seen as promoting the principle of equal opportunity and providing compensation to historically marginalised castes, is now also a tool to overthrow poverty, unemployment and economic deprivation. This essay addresses this rebuttal by the court and clarifies that in the context of India, the implementation of reservation policies was based on the premise that the abolition of untouchability was not sufficient to secure equality of opportunity and the battle for social equality will remain as long as we are struggling to deal with caste discrimination. This essay explains why the EWS quota is likely to be a poor tool for achieving economic equality or redressing social discrimination.

This study focuses on determining significant controlling factors of chemical consequences, inverse geochemical modeling, water quality, and human health risk in the Varuna River basin of India. The study interprets that according to pH, total dissolved solids, and total hardness, the maximum number of groundwater samples are alkaline, fresh, and have substantial hardness. The abundance of major ions follows a pattern: Na > Ca > Mg > K, and HCO3 > Cl > SO4 > NO3 > F. Piper diagram shows that Ca–Mg–HCO3 facies are predominant during both seasons. Na-normalized molar ratios of HCO3/Na, Mg/Na, and Ca/Na are 0.62, 0.95, and 1.82 (pre-monsoon) and 0.69, 0.91, and 1.71 (post-monsoon), respectively, elucidating the coupled silicate and carbonate weathering (dolomite dissolution) sources. The Na/Cl molar ratio is 5.3 (pre-monsoon) and 3.2 (post-monsoon), indicating silicate alteration as the primary process rather than halite dissolution. The chloro-alkaline indices confirm the presence of reverse ion- exchange. Geochemical modeling using PHREEQC identifies the formation of secondary kaolinite minerals. The inverse geochemical modeling categorizes the groundwaters along the flow path from recharge area waters (Group I: Na–HCO3–Cl), transitional area waters (Group II: Na–Ca–HCO3), and discharge area waters (Group III: Na–Mg–HCO3). The model demonstrates the prepotency of water–rock interactions in pre-monsoon justified by the precipitation of Chalcedony and Ca-montmorillonite. The mixing analysis shows that in the alluvial plains, groundwater mixing is a significant hydrogeochemical process that affects groundwater quality. The Entropy Water Quality Index ranks 45% (pre-monsoon) and 50% (post-monsoon) of samples as an excellent category. However, the non-carcinogenic health risk assessment shows that children are more susceptible to fluoride and nitrate contamination.

Outlier analysis and data clustering both are important tasks in the data analysis domain. In this paper, we decompose data points at multiple levels of hierarchy to identify the presence of outliers at multiple levels. This approach creates a tree-like structure of outlier’s hierarchically. Experimenting on a real dataset gives us vital information about the characteristics of outliers and numerical results establish strong evidence for validating the proposed approach.KeywordsHierarchical clusteringDecompositionHierarchyOutlier

In many real-world scenarios such as fraud detection, phishing website classification, etc., the training datasets normally have skewed class distribution with majority (e.g., legitimate websites) class samples overwhelming the minority (e.g., phishing websites) class samples. The machine learning algorithms assume balanced class distributions and are biased towards the majority (uninteresting) class ignoring the minority (interesting) class (es). For handling class imbalance, researchers have proposed solutions both at the (i) data-level and (ii) algorithm-level. In this study we propose a dual approach for handling class imbalance in phishing website classification both at the data and algorithm. We propose a novel hybrid resampling approach KMeansSMOTENCR which balances the dataset by first oversampling the minority class using KMeans Synthetic Minority Oversampling Technique (KMeansSMOTE) (Douzas et al. in Inf Sci 465:1–20, 2018 [1]) followed by Neighborhood Clearing Rule (NCR) (Laurikkala in AIME, LNAI 2001. Springer, Berlin, pp 63–66, 2001 [2]) under sampling technique as the data cleaning approach to take care of the possibility of synthetic minority class samples invading the majority class samples. Finally, we employed Cost-Sensitive Random Forest (CS-RF), Cost-Sensitive Extreme Gradient Boosting (CS-XGB), Cost-Sensitive Support Vector Machine (CS-SVM), and Cost-Sensitive Logistic Regression (CS-LR) classifiers as algorithm-level balancing approach. We evaluated the performance of CS-RF, CS-XGBoost, CS-SVM, and CS-LR classifiers on (i) Original-(Imbalanced), (ii) NCR-(Balanced), (iii) KMeansSMOTE-(Balanced), and (iv) KMeansSMOTENCR-(Balanced) datasets. In Sect. 4 Result and Discussion we demonstrate that the highest ROC_AUC, F1 and GMean are obtained from our proposed method which outperforms the other three. To the best of our knowledge and belief our novel hybrid resampling approach ‘KMeansSMOTENCR’ has not been published in the existing studies as of now.