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Abstract Background Pneumococcal disease caused by Streptococcus pneumoniae is an important cause of morbidity and mortality across all ages, particularly in younger children and older adults. Here, we describe pneumococcal disease hospitalizations at Ministry of Health (MoH) facilities in Malaysia between 2013 and 2015. Methods This was a retrospective databases analysis. Tabular data from the Malaysian Health Data Warehouse (MyHDW) were used to identify microbiologically confirmed, pneumococcal disease hospitalizations and deaths during hospitalization, using hospital-assigned ICD-10 codes (i.e., classified as meningitis, pneumonia, or non-meningitis non-pneumonia). Case counts, mortality counts, and case fatality rates were reported by patient age group and by Malaysian geographic region. Results A total of 683 pneumococcal disease hospitalizations were identified from the analysis: 53 pneumococcal meningitis hospitalizations (5 deaths and 48 discharges), 413 pneumococcal pneumonia hospitalizations (24 deaths and 389 discharges), and 205 non-meningitis non-pneumonia pneumococcal disease hospitalizations (58 deaths and 147 discharges). Most hospitalizations occurred in children aged

Ferroptosis is a caspase-independent, iron-dependent form of regulated necrosis extant in traumatic brain injury, Huntington disease, and hemorrhagic stroke. It can be activated by cystine deprivation leading to glutathione depletion, the insufficiency of the antioxidant glutathione peroxidase-4, and the hemolysis products hemoglobin and hemin. A cardinal feature of ferroptosis is extracellular signal-regulated kinase (ERK)1/2 activation culminating in its translocation to the nucleus. We have previously confirmed that the mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor U0126 inhibits persistent ERK1/2 phosphorylation and ferroptosis. Here, we show that hemin exposure, a model of secondary injury in brain hemorrhage and ferroptosis, activated ERK1/2 in mouse neurons. Accordingly, MEK inhibitor U0126 protected against hemin-induced ferroptosis. Unexpectedly, U0126 prevented hemin-induced ferroptosis independent of its ability to inhibit ERK1/2 signaling. In contrast to classical ferroptosis in neurons or cancer cells, chemically diverse inhibitors of MEK did not block hemin-induced ferroptosis, nor did the forced expression of the ERK-selective MAP kinase phosphatase (MKP)3. We conclude that hemin or hemoglobin-induced ferroptosis, unlike glutathione depletion, is ERK1/2-independent. Together with recent studies, our findings suggest the existence of a novel subtype of neuronal ferroptosis relevant to bleeding in the brain that is 5-lipoxygenase-dependent, ERK-independent, and transcription-independent. Remarkably, our unbiased phosphoproteome analysis revealed dramatic differences in phosphorylation induced by two ferroptosis subtypes. As U0126 also reduced cell death and improved functional recovery after hemorrhagic stroke in male mice, our analysis also provides a template on which to build a search for U0126's effects in a variant of neuronal ferroptosis.SIGNIFICANCE STATEMENT Ferroptosis is an iron-dependent mechanism of regulated necrosis that has been linked to hemorrhagic stroke. Common features of ferroptotic death induced by diverse stimuli are the depletion of the antioxidant glutathione, production of lipoxygenase-dependent reactive lipids, sensitivity to iron chelation, and persistent activation of extracellular signal-regulated kinase (ERK) signaling. Unlike classical ferroptosis induced in neurons or cancer cells, here we show that ferroptosis induced by hemin is ERK-independent. Paradoxically, the canonical MAP kinase kinase (MEK) inhibitor U0126 blocks brain hemorrhage-induced death. Altogether, these data suggest that a variant of ferroptosis is unleashed in hemorrhagic stroke. We present the first, unbiased phosphoproteomic analysis of ferroptosis as a template on which to understand distinct paths to cell death that meet the definition of ferroptosis.

The present investigation aims to evaluate the feasibility of using Persea americana (Avocado) biodiesel in compression ignition engines. Persea americana bio-oil was extracted through a soxhlet extraction process using n-hexane solvent after careful pre-processing of the feedstocks. Since the Free Fatty Acid content was 1.78% estimated through titration, single stage base-catalyzed transesterification technique was adopted using methanol and sodium hydroxide as catalysts in the molar ratio of 1:6. Gas Chromatography-Mass Spectrometry analysis revealed the presence of Oleic acid in major proportions. The Fourier transform Infra-Red analysis confirmed the presence of carbonyl group ester ions between 722.19 cm-1 and 1460 cm-1. The 13C NMR and 1H NMR studies supported the successful transformation of triglycerides into Fatty Acid Methyl Esters with distinct peaks at 3.369 ppm and 48.147 ppm, respectively.

PurposeTo evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites.DesignSecondary analysis of a randomized controlled trial.ParticipantsPatients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico.MethodsFrom 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests.Main outcome measuresVision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months).ResultsAmong 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P < 0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P > 0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively).ConclusionsAmong patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed. Moreover, translationally relevant aspects are increasingly recognized in basic science studies, which is believed to increase their predictive value and the relevance of obtained findings for clinical application.This review reports key results from some of the most remarkable and encouraging achievements in neurovascular research that have been reported at the 10th International Symposium on Neuroprotection and Neurorepair. Basic science topics discussed herein focus on aspects such as neuroinflammation, extracellular vesicles, and the role of sex and age on stroke recovery. Translational reports highlighted endovascular techniques and targeted delivery methods, neurorehabilitation, advanced functional testing approaches for experimental studies, pre-and post-conditioning approaches as well as novel imaging and treatment strategies. Beyond ischemic stroke, particular emphasis was given on activities in the fields of traumatic brain injury and cerebral hemorrhage in which promising preclinical and clinical results have been reported. Although the number of neutral outcomes in clinical trials is still remarkably high when targeting cerebrovascular diseases, we begin to evidence stepwise but continuous progress towards novel treatment options. Advances in preclinical and translational research as reported herein are believed to have formed a solid foundation for this progress.

The availability of generic direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has prompted many low-and-middle-income countries to launch HCV elimination programs. Because the efficacy of some of these generic DAAs varies by HCV viral subtype, information on subtype distribution can contribute important information to these elimination programs. We conducted a cross-sectional serosurvey to characterize HCV subtype diversity among HIV positive people who inject drugs (PWID) across 14 cities in India. Of 801 HIV positive PWID sampled, 639 tested HCV antibody positive (78.9%). Among 105 samples sequenced, genotype 3 (58.1%) was the most commonly observed followed by genotype 1 (36.2%) and genotype 6 (5.7%). Of the genotype 3 infections, 65% were subtype 3a and 35% were subtype 3b. Of the genotype 1 infections, 94% were subtype 1a and 6% were subtype 1b. All genotype 6 samples were subtype 6n. There was some variability in genotype diversity depending on geographic region and PWID epidemic stage with greater diversity observed in older PWID epidemics. One sequence, HY018, did not cluster with any known reference sequences in phylogenetic analysis. Nearly 80% of HIV infected PWID across India are co-infected with HCV, and subtype prevalence and genetic diversity varied by region and PWID epidemic stage. HCV elimination programs in India will need to consider HCV subtype.

In recent times, energy storage has been a major concern in the renewable energy sector. Traditional batteries are becoming less effective and sustainable as the world is moving towards renewable energy. Gravity battery, also known as Gravitricity is a new energy storage technology that is gaining popularity in the renewable energy sector. Gravity battery uses excess energy to hoist heavy objects, and when needed, the objects are released, generating energy. This paper highlights the need for alternative energy storage systems and the potential of gravity batteries to address the limitations of traditional batteries. This paper provides an in-depth analysis of gravity battery technology including the need analysis, problem Statement, product producers, advantages, disadvantages, and how it can replace the present batteries in power systems. The paper concludes that gravity battery technology is a promising alternative to traditional batteries and requires further research and development to accelerate its adoption in the renewable energy sector.

Ferroptosis, a non-apoptotic form of programmed cell death, is triggered by oxidative stress in cancer, heat stress in plants, and hemorrhagic stroke. A homeostatic transcriptional response to ferroptotic stimuli is unknown. We show that neurons respond to ferroptotic stimuli by induction of selenoproteins, including antioxidant glutathione peroxidase 4 (GPX4). Pharmacological selenium (Se) augments GPX4 and other genes in this transcriptional program, the selenome, via coordinated activation of the transcription factors TFAP2c and Sp1 to protect neurons. Remarkably, a single dose of Se delivered into the brain drives antioxidant GPX4 expression, protects neurons, and improves behavior in a hemorrhagic stroke model. Altogether, we show that pharmacological Se supplementation effectively inhibits GPX4-dependent ferroptotic death as well as cell death induced by excitotoxicity or ER stress, which are GPX4 independent. Systemic administration of a brain-penetrant selenopeptide activates homeostatic transcription to inhibit cell death and improves function when delivered after hemorrhagic or ischemic stroke.

The aim of this paper is to investigate the second order half-linear retarded difference equation Δ(μ(n)(Δη(n))α)+δ(n)ηα(σ(n))=0\Delta \left( {\mu \left( n \right){{\left( {\Delta \eta \left( n \right)} \right)}^\alpha }} \right) + \delta \left( n \right){\eta ^\alpha }\left( {\sigma \left( n \right)} \right) = 0 under the condition ∑n=n0∞μ−1α(n)

ObjectivesN-acetylcysteine (NAC) is a clinically approved thiol-containing redox modulatory compound currently in trials for many neurological and psychiatric disorders. Although generically labeled as an "antioxidant," poor understanding of its site(s) of action is a barrier to its use in neurological practice. Here, we examined the efficacy and mechanism of action of NAC in rodent models of hemorrhagic stroke.MethodsHemin was used to model ferroptosis and hemorrhagic stroke in cultured neurons. Striatal infusion of collagenase was used to model intracerebral hemorrhage (ICH) in mice and rats. Chemical biology, targeted lipidomics, arachidonate 5-lipoxygenase (ALOX5) knockout mice, and viral-gene transfer were used to gain insight into the pharmacological targets and mechanism of action of NAC.ResultsNAC prevented hemin-induced ferroptosis by neutralizing toxic lipids generated by arachidonate-dependent ALOX5 activity. NAC efficacy required increases in glutathione and is correlated with suppression of reactive lipids by glutathione-dependent enzymes such as glutathione S-transferase. Accordingly, its protective effects were mimicked by chemical or molecular lipid peroxidation inhibitors. NAC delivered postinjury reduced neuronal death and improved functional recovery at least 7 days following ICH in mice and can synergize with clinically approved prostaglandin E2 (PGE2 ).InterpretationNAC is a promising, protective therapy for ICH, which acted to inhibit toxic arachidonic acid products of nuclear ALOX5 that synergized with exogenously delivered protective PGE2 in vitro and in vivo. The findings provide novel insight into a target for NAC, beyond the generic characterization as an antioxidant, resulting in neuroprotection and offer a feasible combinatorial strategy to optimize efficacy and safety in dosing of NAC for treatment of neurological disorders involving ferroptosis such as ICH. Ann Neurol 2018;84:854-872.

The study aimed to determine the prevalence of occult hepatitis B virus infection among HIV-infected persons and to evaluate the use of a pooling strategy to detect occult HBV infection in the setting of HIV infection. Five hundred and two HIV-positive individuals were tested for HBV, occult HBV and hepatitis C and D with serologic and nucleic acid testing (NAT). We also evaluated a pooled NAT strategy for screening occult HBV infection among the HIV-positive individuals. The prevalence of HBV infection among HIV-positive individuals was 32 (6.4%), and occult HBV prevalence was 10%. The pooling HBV NAT had a sensitivity of 66.7% and specificity of 100%, compared to HBV DNA NAT of individual samples. In conclusion, this study found a high prevalence of occult HBV infection among our HIV-infected population. We also demonstrated that pooled HBV NAT is highly specific, moderately sensitive and cost-effective. As conventional HBV viral load assays are expensive in resource-limited settings such as India, pooled HBV DNA NAT might be a good way for detecting occult HBV infection and will reduce HBV-associated complications.

Six × six full diallel mating involving six parents viz., (P1) ADT 37, (P2) ADT 43, (P3) ADT 45, (P4) ASD 16, (P5) CO51 and (P6) CO47 was effected to evolve 30 hybrids in rice crop. The six parents along with their 30 F1 hybrids were evaluated for ten agronomic traits viz days to 50 per cent flowering, plant height at maturity, the number of productive tillers per plant, panicle length, the number of filled seeds per panicle, seed length, seed breadth, seed L/B ratio, hundred seed weight and seed yield per plant. The traits viz., seed length and seed L/B ratio were controlled by complete dominance. Incomplete dominance was found to operating in the expression of the traits viz., the number of filled seeds per panicle and seed yield per plant. Partial dominance can be had as semi additivity. On the other hand, the traits viz., days to 50 per cent flowering, plant height at maturity, panicle length, seed breadth and hundred seed weight were controlled by over dominance. Apart from this amphi directional dominance was well evidenced from the correlation coefficient of Yr and Wr – Vr as well as Vr – Wr graph. It is earnestly advised to inter-cross among the parents to evolve high heterotic lines and/or improved populations.

BackgroundPhenol is one of the most versatile and important organic compound. It is also a growing concern as water pollutants due to its high persistence and toxicity. Removal of Phenol from wastewaters was investigated using a novel nanoparticle adsorption and nanofiltration technique named as Nanoparticle Assisted Nano Filtration (NANF).MethodsThe nanoparticle used for NANF study were silver nanoparticles and synthesized to three distinct average particle sizes of 10 nm, 40 nm and 70 nm. The effect of nanoparticle size, their concentrations and their tri and diparticle combinations upon phenol removal were studied.ResultsTotal surface areas (TSA) for various particle size and concentrations have been calculated and the highest was 4710 × 10(12 )nm(2 )for 10 nm particles and 180 ppm concentration while the lowest was for 2461 × 10(11) for 70 nm and 60 ppm concentrations. Tri and diparticle studies showed more phenol removal % than that of their individual particles, particularly for using small particles on large membrane pore size and large particles at low concentrations. These results have also been confirmed with COD and toxicity removal studies.ConclusionsThe combination of nanoparticles adsorption and nanofiltration results in high phenol removal and mineralization, leading to the conclusion that NANF has very high potential for treating toxic chemical wastewaters.

This paper introduces extensions H4,p and X8,p of Horn’s double hypergeometric function H4 and Exton’s triple hypergeometric function X8, taking into account recent extensions of Euler’s beta function, hypergeometric function, and confluent hypergeometric function. Among the numerous extended hypergeometric functions, the primary rationale for choosing H4 and X8 is their comparable extension type. Next, we present various integral representations of Euler and Laplace types, Mellin and inverse Mellin transforms, Laguerre polynomial representations, transformation formulae, and a recurrence relation for the extended functions. In particular, we provide a generating function for X8,p and several bounding inequalities for H4,p and X8,p. We explore the utilization of the H4,p function within a probability distribution. Most special functions, such as the generalized hypergeometric function, the Beta function, and the p-extended Beta integral, exhibit natural symmetry.

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron, and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. We show that the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) family of iron-dependent, oxygen-sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in the mouse striatum improved functional recovery after ICH. A low-molecular-weight hydroxyquinoline inhibitor of the HIF-PHD enzymes, adaptaquin, reduced neuronal death and behavioral deficits after ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of activity of the prodeath factor ATF4 rather than activation of an HIF-dependent prosurvival pathway. Together, these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier-permeable inhibitor adaptaquin can improve functional outcomes after ICH in several rodent models.

The present investigation was undertaken to retrieve information on the nature and extent of genetic diversity among 110 mungbean genotypes for yield related traits by using Mahalanobis’s D2 statistics. One hundred and ten genotypes could be grouped under 15 clusters, cluster XV showed maximum intra-cluster distance while the highest inter-cluster distance was observed between cluster VI and XIII. Seed yield exhibited a maximum contribution to genetic divergence (72.02 per cent) followed by days to 50 per cent flowering (15.33 per cent) and plant height (4.24 per cent) while the other traits viz., the number of clusters per plant, the number of pods per cluster, pod length and seeds per pod exhibited insignificant values for contribution to genetic divergence. The maximum and minimum cluster value for seed yield ranged from 5.83 to 19.13. The greater the distance between two clusters, the wider the genetic diversity between the varieties. Keeping this in view, it is indicated that hybridization between the varieties (SML 171/1, AGG 11-013, FRM 1320, EC 396114 and SML 138) of cluster VI and cluster XIII (CO 4, VPM 50 and PLM 501), cluster VIII (V4, V2 and CO 7) and cluster VI (CO 4, VPM 50 and PLM 501), cluster II (AGG 10-850 and EC 396118) with cluster VI (SML 171/1, AGG 11-013, FRM 1320, EC 396114 and SML 138) would produce a better seed yield along with earliness in green gram.

Efficiency of Intrusion detection systems-IDS are evaluated using parameters like completeness, performance and accuracy. The first important parameter is the completeness, which occurs when the detection of attack fails. This is the most difficult parameter to evaluate compared to the other two parameters. The second one is performance, which indicates the audit events process. When the IDS doesn’t work properly or works poorly, the real time detection becomes impossible. Legitimate actions are flagged as anomalous which is termed as inaccuracy. This part needs attention to address the inaccuracies. Optimal solutions must take the inaccuracies into consideration for accuracy, thereby efficiency of IDS. There are different trends in IDS. Some of them are discussed below. Behavior and knowledge-based IDS: Misuse detection, appearance-based detection, behavior detection and anomaly detection etc. There are numerous stability and security issues as a result of the Internet’s and computer networks’ rapid proliferation. The present study reports the case study of image processing in a fruit grading plant with data safety over cloud with Original Equipment Manufacturer (OEM). How Artificial Neural Networks (ANN) architecture can help is discussed and recommendations are made for impending improvement.

Hypoxic adaptation mediated by HIF transcription factors requires mitochondria, which have been implicated in regulating HIF1α stability in hypoxia by distinct models that involve consuming oxygen or alternatively converting oxygen into the second messenger peroxide. Here, we use a ratiometric, peroxide reporter, HyPer to evaluate the role of peroxide in regulating HIF1α stability. We show that antioxidant enzymes are neither homeostatically induced nor are peroxide levels increased in hypoxia. Additionally, forced expression of diverse antioxidant enzymes, all of which diminish peroxide, had disparate effects on HIF1α protein stability. Moreover, decrease in lipid peroxides by glutathione peroxidase-4 or superoxide by mitochondrial SOD, failed to influence HIF1α protein stability. These data show that mitochondrial, cytosolic or lipid ROS were not necessary for HIF1α stability, and favor a model where mitochondria contribute to hypoxic adaptation as oxygen consumers.

Histone deacetylase (HDAC) inhibition improves function and extends survival in rodent models of a host of neurological conditions, including stroke, and neurodegenerative diseases. Our understanding, however, of the contribution of individual HDAC isoforms to neuronal death is limited. In this study, we used selective chemical probes to assess the individual roles of the Class I HDAC isoforms in protecting Mus musculus primary cortical neurons from oxidative death. We demonstrated that the selective HDAC8 inhibitor PCI-34051 is a potent neuroprotective agent; and by taking advantage of both pharmacological and genetic tools, we established that HDAC8 is not critically involved in PCI-34051's mechanism of action. We used BRD3811, an inactive ortholog of PCI-34051, and showed that, despite its inability to inhibit HDAC8, it exhibits robust neuroprotective properties. Furthermore, molecular deletion of HDAC8 proved insufficient to protect neurons from oxidative death, whereas both PCI-34051 and BRD3811 were able to protect neurons derived from HDAC8 knock-out mice. Finally, we designed and synthesized two new, orthogonal negative control compounds, BRD9715 and BRD8461, which lack the hydroxamic acid motif and showed that they stably penetrate cell membranes but are not neuroprotective. These results indicate that the protective effects of these hydroxamic acid-containing small molecules are likely unrelated to direct epigenetic regulation via HDAC inhibition, but rather due to their ability to bind metals. Our results suggest that hydroxamic acid-based HDAC inhibitors may mediate neuroprotection via HDAC-independent mechanisms and affirm the need for careful structure-activity relationship studies when using pharmacological approaches.

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed. Moreover, translationally relevant aspects are increasingly recognized in basic science studies, which is believed to increase their predictive value and the relevance of obtained findings for clinical application.This review reports key results from some of the most remarkable and encouraging achievements in neurovascular research that have been reported at the 10th International Symposium on Neuroprotection and Neurorepair. Basic science topics discussed herein focus on aspects such as neuroinflammation, extracellular vesicles, and the role of sex and age on stroke recovery. Translational reports highlighted endovascular techniques and targeted delivery methods, neurorehabilitation, advanced functional testing approaches for experimental studies, pre-and post-conditioning approaches as well as novel imaging and treatment strategies. Beyond ischemic stroke, particular emphasis was given on activities in the fields of traumatic brain injury and cerebral hemorrhage in which promising preclinical and clinical results have been reported. Although the number of neutral outcomes in clinical trials is still remarkably high when targeting cerebrovascular diseases, we begin to evidence stepwise but continuous progress towards novel treatment options. Advances in preclinical and translational research as reported herein are believed to have formed a solid foundation for this progress.

A major thrust of our laboratory has been to identify how physiological stress is transduced into transcriptional responses that feed back to overcome the inciting stress or its consequences, thereby fostering survival and repair. To this end, we have adopted the use of an in vitro model of ferroptosis, a caspase-independent, but iron-dependent form of cell death (Dixon et al., 2012; Ratan, 2020). In this review, we highlight three distinct epigenetic targets that have evolved from our studies and which have been validated in vivo studies. In the first section, we discuss our studies of broad, pan-selective histone deacetylase (HDAC) inhibitors in ferroptosis and how these studies led to the validation of HDAC inhibitors as candidate therapeutics in a host of disease models. In the second section, we discuss our studies that revealed a role for transglutaminase as an epigenetic modulator of proferroptotic pathways and how these studies set the stage for recent elucidation of monoamines as post-translation modifiers of histone function. In the final section, we discuss our studies of iron-, 2-oxoglutarate-, and oxygen-dependent dioxygenases and the role of one family of these enzymes, the HIF prolyl hydroxylases, in mediating transcriptional events necessary for ferroptosis in vitro and for dysfunction in a host of neurological conditions. Overall, our studies highlight the importance of epigenetic proteins in mediating prodeath and prosurvival responses to ferroptosis. Pharmacological agents that target these epigenetic proteins are showing robust beneficial effects in diverse rodent models of stroke, Parkinson's disease, Huntington's disease, and Alzheimer's disease.

Traumatic spinal cord injury (SCI) is a devastating neurological condition that involves both primary and secondary tissue loss. Various cytotoxic events including hypoxia, hemorrhage and blood lysis, bioenergetic failure, oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation contribute to secondary injury. The HIF prolyl hydroxylase domain (PHD/EGLN) family of proteins are iron-dependent, oxygen-sensing enzymes that regulate the stability of hypoxia inducible factor-1α (HIF-1α) and also mediate oxidative stress caused by free iron liberated from the lysis of blood. PHD inhibition improves outcome after experimental intracerebral hemorrhage (ICH) by reducing activating transcription factor 4 (ATF4)-driven neuronal death. As the ATF4-CHOP (CCAAT-enhancer-binding protein homologous protein) pathway plays a role in the pathogenesis of contusive SCI, we examined the effects of PHD inhibition in a mouse model of moderate T9 contusive SCI in which white matter damage is the primary driver of locomotor dysfunction. Pharmacological inhibition of PHDs using adaptaquin (AQ) moderately lowers acute induction of Atf4 and Chop mRNAs and prevents the acute decline of oligodendrocyte (OL) lineage mRNAs, but does not improve long-term recovery of hindlimb locomotion or increase chronic white matter sparing. Conditional genetic ablation of all three PHD isoenzymes in OLs did not affect Atf4, Chop or OL mRNAs expression levels, locomotor recovery, and white matter sparing after SCI. Hence, PHDs may not be suitable targets to improve outcomes in traumatic CNS pathologies that involve acute white matter injury.

INTRODUCTION: Deep learning-based Image compression achieves a promising result in recent years as compared with the traditional transform coding methodology. Autoencoder, an unsupervised learning algorithm with the input value as same as that of the output value, is considered in this research work for effective medical image reconstruction. OBJECTIVES: Medical data needs to be reconstructed without distorting the details present over it. A deep neural network that accepts the data and processes it to the other several layers and reconstructs that data is achieved by autoencoder. METHODS: Deep Autoencoder is implemented in this methodology as it has been considered for high dimensionality reduction. Layer by layer pretraining is achieved using an approximate inference algorithm called Deep Boltzmann Machine. RESULTS: The proposed method proves to be efficient when compared with the performance of the other autoencoders such as Deep Autoencoder with multiple Backpropagation (DA-MBP), Deep Autoencoder with RBM (DA-RBM) and Deep Convolutional Autoencoder with RBM (DCA-RBM). CONCLUSION: Performance metrics are measured in terms of Mean Square Error, Structural similarity Index and PSNR.

Identifying disease-causing pathways and drugs that target them in Parkinson's disease (PD) has remained challenging. We uncovered a PD-relevant pathway in which the stress-regulated heterodimeric transcription complex CHOP/ATF4 induces the neuron prodeath protein Trib3 that in turn depletes the neuronal survival protein Parkin. Here we sought to determine whether the drug adaptaquin, which inhibits ATF4-dependent transcription, could suppress Trib3 induction and neuronal death in cellular and animal models of PD. Neuronal PC12 cells and ventral midbrain dopaminergic neurons were assessed in vitro for survival, transcription factor levels and Trib3 or Parkin expression after exposure to 6-hydroxydopamine or 1-methyl-4-phenylpyridinium with or without adaptaquin co-treatment. 6-hydroxydopamine injection into the medial forebrain bundle was used to examine the effects of systemic adaptaquin on signaling, substantia nigra dopaminergic neuron survival and striatal projections as well as motor behavior. In both culture and animal models, adaptaquin suppressed elevation of ATF4 and/or CHOP and induction of Trib3 in response to 1-methyl-4-phenylpyridinium and/or 6-hydroxydopamine. In culture, adaptaquin preserved Parkin levels, provided neuroprotection and preserved morphology. In the mouse model, adaptaquin treatment enhanced survival of dopaminergic neurons and substantially protected their striatal projections. It also significantly enhanced retention of nigrostriatal function. These findings define a novel pharmacological approach involving the drug adaptaquin, a selective modulator of hypoxic adaptation, for suppressing Parkin loss and neurodegeneration in toxin models of PD. As adaptaquin possesses an oxyquinoline backbone with known safety in humans, these findings provide a firm rationale for advancing it towards clinical evaluation in PD.

In the present study, we report the synthesis of Au nanoparticles (Au NPs) on molybdenum sulfide@reduced graphene oxide (MoS2@rGO)-based hetero-photocatalytic nanohybrids through a one pot hydrothermal method. Variety of characterization was performed to support this hypothesis including X-ray diffraction (XRD), transmission electron microscope (TEM), X-ray photoelectron spectra (XPS), Raman, Ultra violet, photoluminescence and N2 adsorption analysis. BET surface area and BJH pore size of Au/MoS2@rGO was found to be 128 m2g−1 and 10.5 nm, which is higher than bare MoS2 (43 m2/g and 3.5 nm). Electrochemical impedance spectroscopy (EIS) results indicate that Au/MoS2@rGO performed a faster charge-transfer in comparison to MoS2@rGO hybrid. The calculated optical bandgap values are 2.78, 2.51 and 2.23 eV for MoS2, MoS2@rGO and Au/MoS2@rGO composite samples, respectively. Moreover, the lowest PL intensity of Au/MoS2@rGO indicates that less recombination of electron-hole pair and can be useful for the generation of H2 activity under light illumination. Furthermore, the resulting Au/MoS2@rGO catalyst has a reduced overpotential of 60 mV and a low Tafel slope of 32 mV decade−1, indicating increased electrocatalytic activity towards HER. The improved performance is attributed to the increased active sites and a synergistic effect between Au and molybdenum, leading to electronic structure change and charge redistribution of MoS2. The results provide a low-cost countermeasure for the preparation of rGO-supported MoS2 catalysts, and have broad application prospects. [ABSTRACT FROM AUTHOR]

In recent years, fault diagnosis in the Induction Motor Drive (IMD) has been a popular and important field in the motor-drive research area. The development of control circuits for induction motors has prompted the attention of both researchers and industrialists. This paper proposes a broken bar fault diagnosis using Hilbert Transform (HT) and Artificial Neural Networks (ANN), with the drive regulated through the Indirect Field Orientation Control (IFOC). The HT obtains the spectrum of stator current, which is utilized to identify the Broken Rotor Bar (BRB) failure. The magnitude and side-band frequency of the drive are extracted using the Fast Fourier Transform (FFT), and these parameters are fed into the ANN inputs. The fault severity is computed by the ratio of mean side-band frequency amplitude to the main frequency amplitude for finding the impact of failure in the drive. ANN is used to diagnose failure with high accuracy. The tested and training results are used to attain the minimum Mean Square Errors (MSEs). The IFOC is involved in this proposed system to ensure high performance under the variable speed drives. The proposed scheme is validated in both MATLAB/Simulink and experimental platforms. [ABSTRACT FROM AUTHOR]

Exercise induces beneficial responses in the brain, which is accompanied by an increase in BDNF, a trophic factor associated with cognitive improvement and the alleviation of depression and anxiety. However, the exact mechanisms whereby physical exercise produces an induction in brain Bdnf gene expression are not well understood. While pharmacological doses of HDAC inhibitors exert positive effects on Bdnf gene transcription, the inhibitors represent small molecules that do not occur in vivo. Here, we report that an endogenous molecule released after exercise is capable of inducing key promoters of the Mus musculus Bdnf gene. The metabolite β-hydroxybutyrate, which increases after prolonged exercise, induces the activities of Bdnf promoters, particularly promoter I, which is activity-dependent. We have discovered that the action of β-hydroxybutyrate is specifically upon HDAC2 and HDAC3, which act upon selective Bdnf promoters. Moreover, the effects upon hippocampal Bdnf expression were observed after direct ventricular application of β-hydroxybutyrate. Electrophysiological measurements indicate that β-hydroxybutyrate causes an increase in neurotransmitter release, which is dependent upon the TrkB receptor. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF.

In the present work, an attempt was made to reduce the NOx emission of crude rice bran oil methyl ester without any considerable increase in smoke density, when used as a fuel in a stationary CI engine. Three factors namely, fuel injection timing, Exhaust Gas Recirculation (EGR) and fuel injection pressure were chosen and their combined effect in controlling the NOx emission of a stationary Diesel engine fuelled with crude rice bran oil methyl ester was investigated. Three levels were chosen in each factor and NOx emission, smoke density and brake thermal efficiency were taken as the response variables. Experiments were designed by employing design of experiments method and Taguchi’s L9 orthogonal array was used to conduct the engine tests with different levels of the chosen factors. Multi Response Signal-to-Noise ratio (MRSN) was calculated for the response variables and the optimum combination level of factors was obtained simultaneously using Taguchi’s parametric design. Confirmation experiment was conducted for the obtained optimum combination level of factors and the results were compared with normal operating conditions and significant improvement was observed in the response variables. Dans la présente étude, il a été tenté de réduire les émissions de NOx de l'ester méthylique d'huile de riz brut sans accroissement considérable de la densité de fumée lorsqu'il est utilisé comme carburant dans un moteur stationnaire à allumage par compression. Trois facteurs, à savoir le calage d'injection de carburant, le pourcentage de recirculation des gaz d'échappement (EGR ; Exhaust Gas Recirculation) et la pression d'injection de carburant ont été choisis, et leur effet combiné a été examiné en matière de maîtrise des émissions de NOx d'un moteur Diesel stationnaire alimenté avec de l'ester méthylique d'huile de riz brut. Trois niveaux ont été choisis pour chaque facteur et les émissions de NOx, la densité de fumée ainsi que le rendement thermique au frein ont été retenus en tant que variables de réponse. Les expériences ont été conçues en employant la méthode des plans d'expériences et la table orthogonale L9 de Taguchi a été utilisée pour conduire les essais moteurs selon différents niveaux des facteurs choisis. Le Rapport Signal-Bruit de Réponses Multiples (RSBRM) a été calculé pour les variables de réponse et le niveau de combinaison optimum des facteurs a été obtenu en utilisant simultanément la conception paramétrique de Taguchi. Une expérience de confirmation a été menée pour le niveau de combinaison optimum des facteurs, puis les résultats ont été comparés avec les conditions de fonctionnement normal et une amélioration significative des variables de réponse a été observée.

In the nearshore zone of present study area, the movement of sand alongshore is due to the action of waves and currents. The sediment movement along the shoreline of study area is mainly governed by the forces associated with the incoming waves and the availability of sediments within the area. Thepresent investigation has beenmadeas an attempt to appreciate the sediment movement in relation to wave activity along the coast. The longshore sediment transport is higher in the northerly direction as compared to southerly direction. The normal condition is for and to be moved annually or more frequently in the shallows and on the beach. Waves and wave-driven currents cause longshore drift of sand along the beach and offshore. The net erosive nature of the study area (except Kanyakumari) from March to October is due to the prevalence of high waves from S and SE directions.