Data-driven optimization for microgrid control under distributed energy resource variability.

The integration of renewable energy resources into the smart grids improves the system resilience, provide sustainable demand-generation balance, and produces clean electricity with minimal leakage currents. However, the renewable sources are intermittent in nature. Therefore, it is necessary to develop scheduling strategy to optimise hybrid PV-wind-controllable distributed generator based Microgrids in grid-connected and stand-alone modes of operation. In this manuscript, a priority-based cost optimization function is developed to show the relative significance of one cost component over another for the optimal operation of the Microgrid. The uncertainties associated with various intermittent parameters in Microgrid have also been introduced in the proposed scheduling methodology. The objective function includes the operating cost of CDGs, the emission cost associated with CDGs, the battery cost, the cost of grid energy exchange, and the cost associated with load shedding. A penalty function is also incorporated in the cost function for violations of any constraints. Multiple scenarios are generated using Monte Carlo simulation to model uncertain parameters of Microgrid (MG). These scenarios consist of the worst as well as the best possible cases, reflecting the microgrid's real-time operation. Furthermore, these scenarios are reduced by using a k-means clustering algorithm. The reduced procedures for uncertain parameters will be used to obtain the minimum cost of MG with the help of an optimisation algorithm. In this work, a meta-heuristic approach, grey wolf optimisation (GWO), is used to minimize the developed cost optimisation function of MG. The standard LV Microgrid CIGRE test network is used to validate the proposed methodology. Results are obtained for different cases by considering different priorities to the sub-objectives using GWO algorithm. The obtained results are compared with the results of Jaya and PSO (particle swarm optimization) algorithms to validate the efficacy of the GWO method for the proposed optimization problem.

Prostate cancer biomarkers: from early diagnosis to precision treatment.

Prostate cancer (PCa) is the second most prevalent cancer in men. In 2020, approximately 1,414,259 new cases were reported that accounted for 3,75,324 deaths (Sung et al. in CA 71:209-249, 2021). PCa is often asymptomatic at early stages; hence, routine screening and monitoring based on reliable biomarkers is crucial for early detection and assessment of cancer progression. Early diagnosis of disease is key step in reducing PCa-induced mortality. Biomarkers such as PSA have played vital role in reducing recent PCa deaths. Recent research has identified many other biomarkers and also refined PSA-based tests for non-invasive diagnosis of PCa in patients. Despite progress in screening methods, an important issue that influences treatment is heterogeneity of the cancer in different individuals, necessitating personalized treatment. Currently, focus is to identify biomarkers that can accurately diagnose PCa at early stage, indicate the stage of the disease, metastatic nature and chances of survival based on individual patient profile (Fig. 1). Fig. 1 Graphical abstract.

Unveiling stress markers: A systematic review investigating psychological stress biomarkers.

Psychological stress is a ubiquitous facet of modern life, impacting individuals across diverse contexts and demographics. Understanding its physiological manifestations through biomarkers has gained substantial attention within the scientific community. A comprehensive search was conducted across multiple databases for peer-reviewed articles published within the past decade. Preliminary findings reveal many biomarkers associated with psychological stress across different biological systems, including the hypothalamic-pituitary-adrenal axis, immune system, cardiovascular system, and central nervous system. This systematic review explores psychological, physiological, and biochemical biomarkers associated with stress. Analyzing recent literature, it synthesizes findings across these three categories, elucidating their respective roles in stress response mechanisms. Psychological markers involve subjective assessments like self-reported stress levels, perceived stress scales, or psychometric evaluations measuring anxiety, depression, or coping mechanisms. Physiological markers include heart rate variability, blood pressure, and immune system responses such as cytokine levels or inflammatory markers. Biochemical markers involve hormones or chemicals linked to stress. It includes cortisol, catecholamines, copeptin, salivary amylase, IL-6, and C-reactive protein.

Rare fatal effect of combined use of sildenafil and alcohol leading to Cerebrovascular Accident.

Sildenafil is the first internationally approved drug for erectile dysfunction. Unsupervised and non-prescribed use of sildenafil among young Indian population has increased in last few years. Sildenafil helps in erection of penis by inhibiting the action of Phosphodiesterase-5 (PDE-5) enzyme, present in the vasculature of corpus cavernosum muscle and lengthens the duration of erection. Documented adverse effects of sildenafil are headache, flushing, nasal congestion, dyspepsia, and slight decrease in systolic and diastolic blood pressure. We present a rare case of sudden death due to cerebrovascular hemorrhage after sildenafil use and concomitant alcohol intake. The history is that a 41-year-old male with no significant past medical and surgical history was staying at a hotel room with a female friend; he had consumed 2 tablets of sildenafil (50 mg each) and alcohol at night. Next morning, he developed uneasiness following which he was taken to the Hospital where he was declared dead on arrival. The important autopsy findings include edematous brain with about 300 g of clotted blood in the right basal ganglia extending to bilateral ventricles, and in pons region. Other significant findings on microscopic examination were hypertrophic ventricular wall of heart, fatty changes in liver and acute tubular necrosis and hypertensive changes in the kidney. The findings are discussed in the light of the literature about the lethal complications of combined use of sildenafil and alcohol including cerebrovascular accidents. As a forensic pathologist it is the duty of the doctor to execute meticulous autopsy along with ancillary investigations including toxicological analysis and to correlate all these findings to determine the possible effects of drugs when present, so as to gather knowledge about potentially fatal drugs and further create public awareness regarding the same.

Association between serum vitamin D level and uterine fibroid in premenopausal women in Indian population.

We aim to evaluate the association between serum 25-hydroxyvitamin D3 levels and total number, volume and location of uterine fibroids (UFs) in premenopausal women in North Indian population. This case control study was undertaken in 310 women between 18 years and 45 years of age. Cases comprised of 102 women with fibroid lesion and the control group included 208 women with normal uterine morphology on ultrasonography. Blood samples were taken for measuring 25-hydroxyvitamin D3 levels. The mean serum 25-hydroxyvitamin D3 level in the study and control group was 14.52 ± 7.89 ng/mL and 26.6 ± 14.36 ng/mL respectively (p < 0.05). There was significant inverse correlation between serum 25-hydroxyvitamin D3 levels and total volume of fibroids (p = 0.000) while none between 25-hydroxyvitamin D3 levels with location, number of fibroids. 25-hydroxyvitamin D3 deficiency was more common in the study group (54.90%) compared to healthy controls (6.7%) while sufficiency was more common among controls (67.8% vs. 27.45) (p < 0.05). Women with deficient 25-hydroxyvitamin D3 levels have an odds of 18.36 for developing uterine fibroid. Women with low parity, those belonging to higher socioeconomic status and having less than 1-hour sun exposure per day were independently found to have high risk for development of UFs. Vitamin D may have a role in growth of UFs. Women not able to get adequate sun exposure due to indoor working conditions may need evaluation and supplementation as prophylaxis for development of fibroid.

Simultaneous expression of MMB-FOXM1 complex components enables efficient bypass of senescence.

Cellular senescence is a stable cell cycle arrest that normal cells undergo after a finite number of divisions, in response to a variety of intrinsic and extrinsic stimuli. Although senescence is largely established and maintained by the p53/p21WAF1/CIP1 and pRB/p16INK4A tumour suppressor pathways, the downstream targets responsible for the stability of the growth arrest are not known. We have employed a stable senescence bypass assay in conditionally immortalised human breast fibroblasts (CL3EcoR) to investigate the role of the DREAM complex and its associated components in senescence. DREAM is a multi-subunit complex comprised of the MuvB core, containing LIN9, LIN37, LIN52, LIN54, and RBBP4, that when bound to p130, an RB1 like protein, and E2F4 inhibits cell cycle-dependent gene expression thereby arresting cell division. Phosphorylation of LIN52 at Serine 28 is required for DREAM assembly. Re-entry into the cell cycle upon phosphorylation of p130 leads to disruption of the DREAM complex and the MuvB core, associating initially to B-MYB and later to FOXM1 to form MMB and MMB-FOXM1 complexes respectively. Here we report that simultaneous expression of MMB-FOXM1 complex components efficiently bypasses senescence with LIN52, B-MYB, and FOXM1 as the crucial components. Moreover, bypass of senescence requires non-phosphorylated LIN52 that disrupts the DREAM complex, thereby indicating a central role for assembly of the DREAM complex in senescence.

Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype.

Cellular senescence is a stable cell cycle arrest that can be triggered in normal cells in response to various intrinsic and extrinsic stimuli, as well as developmental signals. Senescence is considered to be a highly dynamic, multi-step process, during which the properties of senescent cells continuously evolve and diversify in a context dependent manner. It is associated with multiple cellular and molecular changes and distinct phenotypic alterations, including a stable proliferation arrest unresponsive to mitogenic stimuli. Senescent cells remain viable, have alterations in metabolic activity and undergo dramatic changes in gene expression and develop a complex senescence-associated secretory phenotype. Cellular senescence can compromise tissue repair and regeneration, thereby contributing toward aging. Removal of senescent cells can attenuate age-related tissue dysfunction and extend health span. Senescence can also act as a potent anti-tumor mechanism, by preventing proliferation of potentially cancerous cells. It is a cellular program which acts as a double-edged sword, with both beneficial and detrimental effects on the health of the organism, and considered to be an example of evolutionary antagonistic pleiotropy. Activation of the p53/p21WAF1/CIP1 and p16INK4A/pRB tumor suppressor pathways play a central role in regulating senescence. Several other pathways have recently been implicated in mediating senescence and the senescent phenotype. Herein we review the molecular mechanisms that underlie cellular senescence and the senescence associated growth arrest with a particular focus on why cells stop dividing, the stability of the growth arrest, the hypersecretory phenotype and how the different pathways are all integrated.

KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell.

Endocytic recycling is a complex itinerary, critical for many cellular processes. Membrane tubulation is a hallmark of recycling endosomes (REs), mediated by KIF13A, a kinesin-3 family motor. Understanding the regulatory mechanism of KIF13A in RE tubulation and cargo recycling is of fundamental importance but is overlooked. Here, we report a unique mechanism of KIF13A dimerization modulated by Rab22A, a small guanosine triphosphatase, during RE tubulation. A conserved proline between neck coil-coiled-coil (NC-CC1) domains of KIF13A creates steric hindrance, rendering the motors as inactive monomers. Rab22A plays an unusual role by binding to NC-CC1 domains of KIF13A, relieving proline-mediated inhibition and facilitating motor dimerization. As a result, KIF13A motors produce balanced motility and force against multiple dyneins in a molecular tug-of-war to regulate RE tubulation and homeostasis. Together, our findings demonstrate that KIF13A motors are tuned at a single-molecule level to function as weak dimers on the cellular cargo.

Isolation and Characterization of Cross-Neutralizing Human Anti-V3 Single-Chain Variable Fragments (scFvs) Against HIV-1 from an Antigen Preselected Phage Library.

Recently conducted human phase- I trials showed protective effect of anti-HIV-1 broadly neutralizing antibodies (bnAbs). The V3 region of the HIV-1 envelope is highly conserved as it is the co-receptor binding site, and is highly immunogenic. Recombinant single-chain antibody fragments (scFvs) can serve as potential tools for construction of chimeric/bispecific antibodies that can target different epitopes on the HIV-1 envelope. Previously, we have constructed a V3 specific human scFv phage recombinant library by a combinational approach of Epstein-Barr virus (EBV) transformation and antigen (V3) preselection, using peripheral blood mononuclear cells (PBMCs), from a subtype C HIV-1 infected antiretroviral naive donor. In the present study, by biopanning this recombinant scFv phage library with V3B (subtype B) and V3C (subtype C) peptides, we identified unique cross reactive anti-V3 scFv monoclonals. These scFvs demonstrated cross-neutralizing activity when tested against subtype A, subtype B, and subtype C viruses. Further, molecular modeling of the anti-V3 scFvs with V3C and V3B peptides predicted their sites of interaction with the scFvs, providing insights for future immunogen design studies. A large collection of such monoclonal antibody fragments with diverse epitope specificities can be useful immunotherapeutic reagents along with antiretroviral drugs to prevent HIV-1 infection and disease progression.

Free radical scavenging potential of sericin obtained from various ecoraces of tasar cocoons and its cosmeceuticals implication.

Tropical tasar silkworm Antheraea mylitta is a wild sericigenous insect which is distributed in different geographical regions and named as different ecoraces. In the present study, we investigated the molecular characterisation and cosmeceutical properties of sericin extracted from different ecoraces of tasar cocoons. The surface morphology and molecular weight of cocoons were determined by scanning electron microscope (SEM) and SDS-PAGE, respectively. Characterisation of sericin was performed by various methods such as FTIR, CHNS, TGA and amino acid analyzer. The anti-tyrosinase, anti-elastase, glutathione-S-transferase inhibition, free radical scavenging potential and inhibition of oxidative damages were measured in tasar ecoraces sericin. SEM images have revealed the removal of sericin from the surface of cocoons. SDS-PAGE of sericin depicted the presence of diverse molecular weight of proteins. Structural determination by FTIR revealed the presence of both α-helical and ß-sheet structures. Thermal properties of sericin were studied by TGA which showed a 50% weight loss at temperature 410 °C-430 °C. Additionally, ecoraces sericin contains 17 amino acids in which serine, aspartic acid and glycine are predominantly present (55.68-59.61%). Further, anti-tyrosinase, anti-elastase, inhibition of glutathione-S-transferase activity, free radical scavenging potential and inhibition of lipid peroxidation were also observed in ecoraces sericin. Our findings suggest that the present study appear to be helpful in exploiting sericin as potential biomaterial in cosmeceutical and allied field.

Tasar silk fiber waste sericin: New source for anti-elastase, anti-tyrosinase and anti-oxidant compounds.

The present study investigates the properties of sericin extracted from tasar silk fiber waste (TSFW). The surface morphology of TSFW was observed by scanning electron microscope (SEM). SEM images revealed the removal of residual sericin over the surface of TSFW. The molecular weight distribution of sericin was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results suggested that TSFW sericin represented a family of proteins with wide-ranging molecular weight distribution (11-245 kDa). Structural determination by FTIR revealed the presence of both α-helical and ß-sheet structures. The colour was studied by colorimeter indicating less brightness, more red and yellow colour intensities. The carbon: nitrogen ratio (C:N) was studied by CHNS element analyzer and the ratio is 5.15-7.85. Thermal properties of TSFW sericin have been studied by thermogravimetric analysis (TGA) method. TGA curve showed higher thermal stability and variable degradation profiles. Furthermore, TSFW sericin contains 17 amino acids where serine, aspartic acid and glycine are the more significant compounds (54.34-60.49%). In addition, sericin was found to inhibit tyrosinase, elastase and glutathione-S-transferase activity, and had apparent radical scavenging impacts on 2.2­diphenyl­1­picryl­hydrazil (DPPH), hydrogen peroxide and inhibition of lipid peroxidation. Result suggested that TSFW sericins might be a valuable ingredient for cosmoceutical products.