The Spontaneous Loss of Coherence Catastrophe in Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

The spontaneous loss of coherence catastrophe (SLCC) is a frequently observed, yet poorly studied, space-charge related effect in Fourier-transform ion cyclotron resonance mass spectrometry (FTICR-MS). This manuscript presents an application of the filter diagonalization method (FDM) in the analysis of this phenomenon. The temporal frequency behavior reproduced by frequency shift analysis using the FDM shows the complex nature of the SLCC, which can be explained by a combination of factors occurring concurrently, governed by electrostatics and ion packet trajectories inside the ICR cell

Machine learning for intrusion detection in industrial control systems : challenges and lessons from experimental evaluation

Abstract: Gradual increase in the number of successful attacks against Industrial Control Systems (ICS) has led to an urgent need to create defense mechanisms for accurate and timely detection of the resulting process anomalies. Towards this end, a class of anomaly detectors, created using data-centric approaches, are gaining attention. Using machine learning algorithms such approaches can automatically learn the process dynamics and control strategies deployed in an ICS. The use of these approaches leads to relatively easier and faster creation of anomaly detectors compared to the use of design-centric approaches that are based on plant physics and design. Despite the advantages, there exist significant challenges and implementation issues in the creation and deployment of detectors generated using machine learning for city-scale plants. In this work, we enumerate and discuss such challenges. Also presented is a series of lessons learned in our attempt to meet these challenges in an operational plant

Repurposing Lansoprazole and Posaconazole to treat Leishmaniasis: Integration of in vitro Testing, Pharmacological Corroboration, and Mechanisms of Action

Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing of compounds against Leishmania amastigotes and selected the most promising active compounds, Lansoprazole and Posaconazole. We identified possible Leishmania drug targets of Lansoprazole and Posaconazole using several available servers. Our in-silico screen identified likely Lansoprazole targets as the closely related calcium-transporting ATPases (LdBPK_352080.1, LdBPK_040010.1, and LdBPK_170660.1), and the Posaconazole target as lanosterol 14-alpha-demethylase (LdBPK_111100.1). Further validation showed LdBPK_352080.1 to be the most plausible target based on induced-fit docking followed by long (100ns) MD simulations to confirm the stability of the docked complexes. We present a likely ion channel-based mechanism of action of Lansoprazole against Leishmania calcium-transporting ATPases, which are essential for parasite metabolism and infectivity. The LdBPK_111100.1 interaction with Posaconazole is very similar to the known fungal orthologue. Herein, we present two novel anti-leishmanial agents, Posaconazole and Lansoprazole, already approved by the FDA for different indications and propose plausible mechanisms of action for their antileishmanial activity

Effectiveness of arts interventions to reduce mental-health-related stigma among youth: a systematic review and meta-analysis.

BACKGROUND: Educational interventions engage youth using visual, literary and performing arts to combat stigma associated with mental health problems. However, it remains unknown whether arts interventions are effective in reducing mental-health-related stigma among youth and if so, then which specific art forms, duration and stigma-related components in content are successful. METHODS: We searched 13 databases, including PubMed, Medline, Global Health, EMBASE, ADOLEC, Social Policy and Practice, Database of Promoting Health Effectiveness Reviews (DoPHER), Trials Register of Promoting Health Interventions (TRoPHI), EPPI-Centre database of health promotion research (Bibliomap), Web of Science, PsycINFO, Cochrane and Scopus for studies involving arts interventions aimed at reducing any or all components of mental-health-related stigma among youth (10-24-year-olds). Risk of bias was assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. Data were extracted into tables and analysed using RevMan 5.3.5. RESULTS: Fifty-seven studies met our inclusion criteria (n = 41,621). Interventions using multiple art forms are effective in improving behaviour towards people with mental health problems to a small effect (effect size = 0.28, 95%CI 0.08-0.48; p = 0.007) No studies reported negative outcomes or unintended harms. Among studies using specific art forms, we observed high heterogeneity among intervention studies using theatre, multiple art forms, film and role play. Data in this review are inconclusive about the use of single versus multiple sessions and whether including all stigma components of knowledge, attitude and behaviour as intervention content are more effective relative to studies focused on these stigma components, individually. Common challenges faced by school-based arts interventions included lack of buy-in from school administrators and low engagement. No studies were reported from low- and middle-income countries. CONCLUSION: Arts interventions are effective in reducing mental-health-related stigma to a small effect. Interventions that employ multiple art forms together compared to studies employing film, theatre or role play are likely more effective in reducing mental-health-related stigma

Bisindolylmaleimide IX: a Novel Anti-SARS-CoV2 Agent Targeting Viral Main Protease 3CLpro Demonstrated by Virtual Screening Pipeline and In-Vitro Validation Assays

SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2′-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = 5903). The screening was performed against viral targets using three sequential docking modes (i.e., HTVS, SP, and XP). Virtual screening identified ∼290 potential inhibitors based on the criteria of energy, docking parameters, ligand, and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. The top lead from each target pool was further subjected to molecular dynamics simulation using the Desmond module. The resulting top eight hits were tested for their SARS-CoV-2 anti-viral activity in-vitro. Among these, a known inhibitor of protein kinase C isoforms, Bisindolylmaleimide IX (BIM IX), was found to be a potent inhibitor of SARS-CoV-2. Further, target validation through enzymatic assays confirmed 3CLpro to be the target. This is the first study that has showcased BIM IX as a COVID-19 inhibitor thereby validating our pipeline

Challenges in machine learning based approaches for real-time anomaly detection in industrial control systems

Data-centric approaches are becoming increasingly common in the creation of defense mechanisms for critical infrastructure such as the electric power grid and water treatment plants. Such approaches often use well-known methods from machine learning and system identification, i.e., the Multi-Layer Perceptron, Convolutional Neural Network, and Deep Auto Encoders to create process anomaly detectors. Such detectors are then evaluated using data generated from an operational plant or a simulator; rarely is the assessment conducted in real time on a live plant. Regardless of the method to create an anomaly detector, and the data used for performance evaluation, there remain significant challenges that ought to be overcome before such detectors can be deployed with confidence in city-scale plants or large electric power grids. This position paper enumerates such challenges that the authors have faced when creating data-centric anomaly detectors and using them in a live plant

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D

Risk of high blood pressure in salt workers working near salt milling plants: A cross-sectional and interventional study

BACKGROUND: Workers working close to salt milling plants may inhale salt particles floating in the air, leading to a rise in plasma sodium, which, in turn, may increase the blood pressure and the risk of hypertension. METHODS: To test the above hypothesis, occupational health check-up camps were organized near salt manufacturing units and all workers were invited for a free health examination. The workers who worked with dry salt in the vicinity of salt milling plants were defined as "non-brine workers," while those working in brine pans located far away from milling plants were defined as "brine workers." Blood pressure (BP) was measured during each clinical examination. In all, 474 non-brine workers and 284 brine workers were studied. RESULTS: Mean systolic blood pressure of non-brine workers (122.1 ± 13.3 mm Hg) was significantly higher than that of brine workers (118.8 ± 12.8 mm Hg, p < 0.01). Mean diastolic blood pressure of non-brine workers (71.5 ± 10.4 mm Hg) was significantly higher than that of brine workers (69.7 ± 9.4 mm Hg, p = 0.02). The prevalence of hypertension was significantly higher in non-brine workers (12.2%) than in brine workers (7.0%, p = 0.02). Nineteen salt workers were monitored while they used face masks and spectacles, for six days. Systolic, as well as diastolic, blood pressure of these workers began declining on the third day and continued to decline on the fourth day, but remained stationary up to the sixth day. The concentration of salt particles in the breathing zone of these workers was 376 mg/m(3 )air. CONCLUSION: Inhalation of salt particles in non-brine workers may be an occupational cause of increased blood pressure

Global Oral Health Policies and Guidelines: Using Silver Diamine Fluoride for Caries Control

Silver diamine fluoride (SDF) was developed in Japan in the 1960s. It is a clear solution containing silver and fluoride ions. Because of its anti-bacterial and remineralizing effect, silver diamine fluoride has been used in managing dental caries for decades worldwide. This paper aims to summarize and discuss the global policies, guidelines, and relevant information on utilizing SDF for caries management. SDF can be used for treating dental caries in most countries. However, it is not permitted to be used in mainland China. Several manufacturers, mainly in Australia, Brazil, India, Japan, and the United States, produce SDF at different concentrations that are commercially available around the world. The prices differ between contents and brands. Different government organizations and dental associations have developed guidelines for clinical use of SDF. Dental professionals can refer to the specific guidelines in their own countries or territories. Training for using SDF is part of undergraduate and/or postgraduate curriculums in almost all countries. However, real utilization of SDF of dentists, especially in the private sector, remains unclear in most places because little research has been conducted. There are at least two ongoing regional-wide large-scale oral health programs, using SDF as one of the components to manage dental caries in young children (one in Hong Kong and one in Mongolia). Because SDF treatment does not require caries removal, and it is simple, non-invasive, and inexpensive, SDF is a valuable strategy for caries management in young children, elderly people, and patients with special needs. In addition, to reduce the risk of bacteria or virus transmission in dental settings, using SDF as a non-aerosol producing procedure should be emphasized under the COVID-19 outbreak.</p