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Considering the exceptional growth of Cyber Physical Systems (CPSs), multiple and potentially grave security challenges have emerged in this field. Different vulnerabilities and attacks are present in front of new generation CPSs, such as Industrial CPS (I-CPS). The underlying non-uniform standards, device heterogeneity, network complexity, etc., make it difficult to offer a systematized coverage on CPS security in an industrial environment. This work considers the security perspective of I-CPSs, and offers a decade-wide survey including different vulnerabilities, attacks, CPS components, and various other aspects. The comparative year-wise analysis of the existing works w.r.t objective, approach referred, testbed used and derived inference, is also presented over a decade. Additionally, the work details different security issues and research challenges present in I-CPS. This work attempts to offer a concise and precise literature study focused on the state-of-the-art I-CPS security. This work also encourages the young researchers to explore the wide possibilities present in this emerging field. • Analyzes the security perspectives of Industrial Cyber Physical Systems (I-CPSs). • Offers a year-wise analysis of the existing works w.r.t objective, approach, etc. • Details different security issues and research challenges present in I-CPS. • Attempts to offer a precise literature study focused on the I-CPS security. • Encourages the researchers to explore the wide possibilities in I-CPS. [ABSTRACT FROM AUTHOR]

Abstract To strengthen the security of access control protocols for mobile cloud environment, dynamic attributes of mobile devices are used. The weak or disconnection issue of the mobile network is a critical task to deal with. The proposed approach provides access control as well as data confidentiality using dynamic attributes encryption. The pairs of mobile agents are used to deal with the issue of network connection. The secret key is distributed using the anonymous key-issuing protocol which preserves the anonymity of the user. The approach is implemented in a real mobile cloud environment, and the performance under various parameters is evaluated. [ABSTRACT FROM AUTHOR]

Summary Incomplete understanding of mechanisms involved in the host–pathogen interactions constrains our efforts to eliminate tuberculosis. In many individuals, resulting from immune response to mycobacterial infection organised structures called granulomas are formed. To identify host responses that may control at least the early stages of infection, we employed an in vitro granuloma model. Here, human PBMCs were infected with live Mycobacterium tuberculosis in culture, and the appearance of granuloma-like structures was monitored over the next several days. Production of cytokines and chemokines in culture supernatants was monitored at various times, and the resulting temporal profiles were examined for possible correlations with either granuloma formation, or bacterial growth. While a positive association of TNF-α and IFN-γ secretion levels with extent of granuloma formation could clearly be identified, we were, however, unable to detect any statistically significant relationship between any cytokine/chemokine and bacterial growth. Examination of specific host cellular biochemical pathways revealed that either modulation of neutral lipid homeostasis through inhibition of the G i -protein coupled receptor GPR109A, or regulation of host metabolic pathways through addition of vitamin D, provided a more effective means of controlling infection. A subsequent genotypic analysis for a select subset of genes belonging to pathways known to be significant for TB pathology revealed associations of polymorphisms with cytokine secretions and bacterial growth independently. Collectively therefore, the present study supports that key metabolic pathways of the host cell, rather than levels of relevant cytokines/chemokines might be more critical for regulating the intracellular mycobacterial load, in the context of granuloma formation. [ABSTRACT FROM AUTHOR]

Summary Adaptation of organisms to ever-changing nutritional environments relies on sensor tissues and systemic signals. Identification of these signals would help understand the physiological crosstalk between organs contributing to growth and metabolic homeostasis. Here we show that Eiger, the Drosophila TNF-α, is a metabolic hormone that mediates nutrient response by remotely acting on insulin-producing cells (IPCs). In the condition of nutrient shortage, a metalloprotease of the TNF-α converting enzyme (TACE) family is active in fat body (adipose-like) cells, allowing the cleavage and release of adipose Eiger in the hemolymph. In the brain IPCs, Eiger activates its receptor Grindelwald, leading to JNK-dependent inhibition of insulin production. Therefore, we have identified a humoral connexion between the fat body and the brain insulin-producing cells relying on TNF-α that mediates adaptive response to nutrient deprivation. [ABSTRACT FROM AUTHOR]

Graphite (G) and its nano form Graphene (nG) are one of the most admirable fillers for incorporating multifunctional attributes in polymer/elastomer matrix. Use of such fillers in polymers/elastomers has enhanced their several properties and applicabilities. Acrylo Nitrile Butadiene Rubber (NBR) is a workhorse of the several industrial applications especially for automotive rubber products and in hydraulic area. Enhanced tribological properties of NBR are one of the crucial requirements for sealing applications. In this field we are first to report the anti wear study on NBR filled with Graphite and graphene layers. Sliding wear test showed that the wear parameters of NBR nanocomposites have significantly improved. The incorporation of graphene in NBR has reduced coefficient of friction 2.3 times more than that of graphite incorporated NBR. The reason for the same is proposed that the homogeneous distribution of nano layers in the elastomer matrix, the enhanced self lubrication of graphene, the favourable interface stability of composite contributed together to the improved wear properties of NBR nanocomposites. Along with it we have also investigated the effect of applied load, revolution per minute i.e., sliding speed on wear properties. The incorporation of fillers (G &nG) in NBR has also improved the hardness and tensile properties other than tribological properties. Electrical conductivity of graphene filled NBR has also been reported in comparison to graphite filled NBR and pristine NBR. The prepared graphene and the nanocomposites have also been fully characterized by different sophisticated techniques viz HR-TEM, FEG-SEM, Micro Raman, FT-IR. Improvement in such properties of NBR will definitely widen its role in multiple applications. [ABSTRACT FROM AUTHOR]

Summary The tuberculin skin test (TST) and interferon-gamma release assays (IGRA), namely, the QuantiFERON-TB Gold test (QFT), remain the standard immunological diagnostic tools for latent tuberculosis (TB) infection (LTBI). However, the sub-optimal detection rates of both of these tests are major impediments in recognizing the population at risk. This study was aimed at evaluating additional cytokines besides interferon-gamma (IFN-γ) as biomarkers for improving LTBI diagnosis in the tribal population of Melghat, India. Seventy-four close TB contacts were stratified by QFT and TST results into: (i) QFT+/TST+ ( n = 26), (ii) QFT+/TST− ( n = 12), (iii) QFT−/TST− ( n = 35) and (iv) QFT−/TST+ ( n = 1) groups. A panel of cytokines (IL-6, IL-10, TNF-α and IL-2R) was then evaluated in antigen-stimulated QFT cell-free culture supernatants using IMMULITE-1000, an automated immunoassay analyzer. Cytokine estimation showed significantly higher levels of IL-6 in the QFT+/TST+ group, while significantly higher levels of IL-10 were found in the QFT−/TST− group. Correlation analysis identified a positive correlation between IL-6 and the QFT response ( r = 0.6723, P < 0.0001), while a negative correlation was seen between QFT and IL-10 expression ( r = −0.3271, P = 0.0044). Similarly, IL-6 was positively correlated with TST levels ( r = 0.6631, P < 0.0001), and conversely, a negative correlation was found between TST and IL-10 expression ( r = −0.5698, P < 0.0001). The positive and negative predictive values of IL-6 were found to be 92.59 and 93.33%, respectively, and the positive and negative predictive values of IL-10 were 96.55 and 91.18%, respectively. No significant impact of the demographic characteristics on cytokine positivity was observed. Our preliminary results suggest that the evaluation of additional cytokines in QFT cell-free culture supernatants may be valuable for the identification of LTBI. Combining IL-6 and IL-10 with QFT and/or TST could markedly improve the detection accuracy of LTBI. Our observations require investigation in larger well-characterized cohorts along with follow-up studies to further confirm the study outcome. [ABSTRACT FROM AUTHOR]

MPS II is an X linked recessive lysosomal storage disorder with multi-system involvement and marked molecular heterogeneity. In this study, we explored the clinical and molecular spectrum of 144 Indian patients with MPS II from 130 unrelated families. Clinical information was collected on a predesigned clinical proforma. Sanger method was employed to sequence all the exons and exon/intron boundaries of the IDS gene. In cases where causative variation was not detected by Sanger sequencing, MLPA and RFLP were performed to identify large deletions/duplications and complex rearrangements. Cytogenetic microarray was done in one patient to see the breakpoints and extent of deletion. In one patient with no detectable likely pathogenic or pathogenic variation, whole-genome sequencing was also performed. Novel variants were systematically assessed by in silico prediction software and protein modelling. The pathogenicity of variants was established based on ACMG criteria. An attempt was also made to establish a genotype-phenotype correlation. Positive family history was present in 31% (41/130) of patients. Developmental delay and intellectual disability were the main reasons for referral. Macrocephaly, coarse facies and dysostosis were present in almost all patients. Hepatosplenomegaly, joint contractures and short stature were the characteristic features, seen in 87% (101/116), 67.8% (74/109) and 41.4% (41/99) patients respectively. Attenuated phenotype was seen in 32.6% (47/144) patients, while severe phenotype was seen in 63% (91/144) patients. The detection rate for likely pathogenic or pathogenic variants in our cohort is 95.5% (107/112) by Sanger sequencing, MLPA and RFLP. We also found two variants of unknown significance, one each by Sanger sequencing and WGS. Total of 71 variants were identified by Sanger sequencing and 29 of these variants were found to be novel. Amongst the novel variants, there was a considerable proportion (51%) of frameshift variants (15/29). Almost half of the causative variants were located in exon 3,8 and 9. A significant genotype-phenotype correlation was also noted for both known and novel variants. This information about the genotype spectrum and phenotype will be helpful for diagnostic and prognostic purposes. [ABSTRACT FROM AUTHOR]

With rising incidence of acquired drug resistance among life-threatening pathogens, alternative approaches to improve therapy and vaccination have taken center stage. To this end, genome-wide and pathway-specific siRNA libraries are being employed increasingly to identify genes that regulate immune responses against a number of pathogens. In this study using calcium and cysteine protease pathway-specific siRNA libraries, we identified genes that play critical roles in modulating diverse functions of dendritic cells (DCs) during Mycobacterium tuberculosis infection. Knockdown of many of these genes in the two pathways resulted in reduced bacterial burden within DCs. These included genes that regulated activation of transcription factors, ubiquitin-specific peptidases, and genes that are involved in autophagy and neddylation. Knockdown of certain genes increased the expression of IL-12p40 and surface densities of costimulatory molecules in an antigen- and receptor-specific manner. Increased IL-12p40 and costimulatory molecules on DCs also promoted the development of Th1 responses from a Th2 inducing antigen. Furthermore, modulation of autophagy and oxidative burst appeared to be one of the mechanisms by which these genes regulated survival of M. tuberculosis within DCs. Although some genes regulated specific responses, others regulated multiple responses that included IL-12 production, T cell priming, as well as intracellular survival of M. tuberculosis. Further dissection of the mechanisms such as neddylation, by which these genes regulate immune responses, would improve our understanding of host parameters that are modulated during M. tuberculosis infection. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The aim of this retrospective study was to determine the prevalence of three-rooted mandibular permanent first molars among the Indian population by using periapical radiographs. Methods: Five hundred eighty-six patients (320 females and 266 males) were selected, with at least 1 mandibular first molar. A total of 1054 periapical radiographs of mandibular first molars, comprising 526 right side and 528 left side, were included. The radiographs were taken at 30-degree mesial angulation and were evaluated by using the magnifying lens. The incidence, gender, and symmetry of three-rooted mandibular first molars were recorded and analyzed by using the χ2 test. Results: The prevalence of three-rooted mandibular first molars was 5.97% for all patients and 4.55% for all teeth, respectively. The incidence of bilateral symmetrical distribution was 37.14%. The incidence was 6.88% for female patients and 4.89% for male patients (χ2 = 1.02, P > .05) and 4.94% for the right side and 4.17% for the left side, respectively (χ2 = 0.36, P > .05). No statistically significant differences were found between female and male patients and between the right-side and left-side occurrences. Conclusions: Clinicians should be aware of the high racial prevalence of this unusual root morphology in mandibular first molars among the Indian population before and during the root canal treatment of three-rooted mandibular first molars. [Copyright &y& Elsevier]

Error-free progression through mitosis is critical for proper cell division and accurate distribution of the genetic material. The anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase regulates the progression from metaphase to anaphase and its activation is controlled by the cofactors Cdc20 and Cdh1. Additionally, genome stability is maintained by the spindle assembly checkpoint (SAC), which monitors proper attachment of chromosomes to spindle microtubules prior to cell division. We had shown a role for Tank Binding Kinase 1 (TBK1) in microtubule dynamics and mitosis and here we describe a novel role of TBK1 in regulating SAC in breast and lung cancer cells. TBK1 interacts with and phosphorylates Cdc20 and Cdh1 and depletion of TBK1 elevates SAC components. TBK1 inhibition increases the association of Cdc20 with APC/C and BubR1 indicating inactivation of APC/C; similarly, interaction of Cdh1 with APC/C is also enhanced. TBK1 and TTK inhibition reduces cell viability and enhances centrosome amplification and micronucleation. These results indicate that alterations in TBK1 will impede mitotic progression and combining TBK1 inhibitors with other regulators of mitosis might be effective in eliminating cancer cells. • Tank Binding Kinase 1 (TBK1) regulates mitotic spindle assembly checkpoint. • TBK1 interacts with and phosphorylates Cdc20 and Cdh1. • Association of Cdc20 and Ch1 with APC is affected by TBK1. • Inhibition of TBK1 can lead to centrosome amplification and growth arrest. • Inhibitors TBK1 and the mitotic kinase TTK co-operate to induce growth arrest. [ABSTRACT FROM AUTHOR]

The brain provides a sanctuary site for HIV due, in part, to poor penetration of antiretroviral agents at the blood-brain barrier. This lack of penetration is partially attributed to drug efflux transporters such as P-glycoprotein (P-gp) and ABCG2. Inhibition of both ABCG2 and P-gp is critical for enhancing drug accumulation into the brain. In this work, we have developed a class of homodimers based on the HIV reverse transcriptase inhibitor azidothymidine (AZT) that effectively inhibits P-gp and ABCG2. These agents block transporter mediated efflux of the P-gp substrate calcein-AM and the ABCG2 substrate mitoxantrone. The homodimers function by interacting with the transporter drug binding sites as demonstrated by competition studies with the photo-affinity agent and P-gp/ABCG2 substrate [ 125 I]iodoarylazidoprazosin. As such, these dual inhibitors of both efflux transporters provide a model for the future development of delivery vehicles for antiretroviral agents to the brain. [ABSTRACT FROM AUTHOR]

• We report a FRET-based nanosensor for monitoring the levels tungsten in living cells. • This probe is nontoxic and non-invasive. • Highly selective pH sensing in wide pH range. • This nanosensor is applicable for prokaryotic and eukaryotic cellular environments. • The advantages of this sensor is simplicity, low-cost, high accuracy and good precision. Tungsten is considered a critical metal due to its unique properties and economic importance. Recent research has linked high tungsten concentrations to pulmonary diseases and increased cancer risk. Tungsten is on the list of critical metals at high risk maintained by the European Union. We have developed a genetically encoded fluorescence resonance energy transfer (FRET)-based nanosensor for the first time to determine tungsten ion efflux mechanisms and measure its concentration and distribution within living cells in real-time. For the construction of the nanosensor, TupA (tungsten binding protein), a highly selective protein, was sandwiched between ECFP and Venus, a FRET pair. SENTUN (SENsor for TUNgsten) was the name given to the newly developed nanosensor. SENTUN was highly specific and selective for tungsten and stable at physiological pH levels. We also created three mutants: SENTUN-118D, SENTUN-118K, and SENTUN-178W, with SENTUN-118K exhibiting the highest affinity for tungsten and its comprehensive range detection. The novelty of this sensor is that it is genetically encoded and can be used for real-time measurement of tungsten levels in living cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Microcephaly is a frequent feature of neurodevelopmental disorders (NDDs). Our study presents the heterogeneous spectrum of genetic disorders in patients with microcephaly either in isolated form or in association with other neurological and extra-neural abnormalities. We present data of 91 patients from 87 unrelated families referred to our clinic during 2016–2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations in autosomal recessive genes were identified 31 were homozygotes (including 16 from non-consanguineous families). The study added 28 novel pathogenic/likely pathogenic variations. The study also calls attention to phenotypic variability and expansion in spectrum as well as uncovers genes where microcephaly is not reported previously or is a rare finding. We here report phenotypes associated with the genes for ultra-rare NDDs with microcephaly namely ATRIP , MINPP1 , PNPLA8 , AIMP2 , ANKLE2 , NCAPD2 and TRIT1. [ABSTRACT FROM AUTHOR]