Multiagent Simulators for Social Networks

Multiagent social network simulations are an avenue that can bridge the communication gap between the public and private platforms in order to develop solutions to a complex array of issues relating to online safety. While there are significant challenges relating to the scale of multiagent simulations, efficient learning from observational and interventional data to accurately model micro and macro-level emergent effects, there are equally promising opportunities not least with the advent of large language models that provide an expressive approximation of user behavior. In this position paper, we review prior art relating to social network simulation, highlighting challenges and opportunities for future work exploring multiagent security using agent-based models of social network

Characterisation of Na/K-ATPase, its isoforms, and the inotropic response to ouabain in isolated failing human hearts

Objective: The aim was to determine whether failing human hearts have increased sensitivity to the inotropic and toxic effects of ouabain, and to examine alterations in Na/K-ATPase that might explain the observed higher ouabain sensitivity. Methods: For contractility studies, a total of 57 trabeculae were isolated from two non- failing (death from head injury) and 10 terminally failing, explanted human hearts. After the experiment, each trabecula was inspected under the light microscope for morphological alterations consistent with heart failure. Samples for biochemical and molecular studies were obtained from five non-failing and 13 failing hearts. Total Na/K-ATPase was measured in desoxycholate treated homogenates and expressed per unit of tissue wet or dry weight, DNA, protein, or myosin. Interference from residual bound digoxin due to previous therapy was excluded. The expression of the three α isoforms was studied at both the mRNA level using northern blots and the protein level by analysis of dissociation kinetics of the [3H]ouabain-enzyme complex. Results: Trabeculae showing morphological alterations and decreased contractility were sensitive to lower concentrations of ouabain (3-100 nM) than control trabeculae (100-1000 nM); the inotropic EC50 and the minimum toxic concentration were both reduced. [3H]Ouabain binding was significantly lower (p≪0.001) in failing than in non-failing hearts, at 293(SD 74) v 507(48) pmol·g−1 wet weight. No significant change was observed in maximum ATPase turnover rate, or in sensitivities to Na+, K+, vanadate, and dihydro-ouabain. All three α isoforms were expressed at the mRNA level in both normal and failing hearts. Conclusions: This study shows conclusively, for the first time, that failing human hearts are more sensitive to ouabain. This may be at least partly due to a mean reduction of 42% (95% confidence interval, 26 to 56%) in the concentration of Na/K-ATPase (decrease in Na,K pump reserve), but not to an alteration in its catalytic properties or in its isoform composition. Cardiovascular Research 1993;27:2229-223

Body composition in coronary artery disease in KONKAN region of India-Is non- obesity an indicator of Coronary Artery Disease?

 Background India is witnessing a rising prevalence of non communicable diseases like diabetes, hypertension, coronary artery disease. This is attributed to rapid nutrition and lifestyle transition taking place since last 2 decades. Obesity is a well known independent risk factor   but very little information is available about role of leanness (low BMI). We investigated whether non-obesity could be an independent risk factor for Coronary artery disease in a rural clinic in KONKAN.    Methods  In a cross sectional study we studied body composition of 300 patients (207 men) who underwent Coronary angiography in a rural hospital in KONKAN region.  History of diabetes, hypertension and history smoking, tobacco chewing was recorded. Body composition was estimated using bio-impedance analyser. Based on results of coronary angiography, we generated a SYNTAX score derived by number of vessels involved and classified them into groups of severity of coronary artery disease (CAD).     Results There were 95 (31 %) diabetes and 189 (63%) hypertensive patients in the sample and 60% of them smoked or chewed tobacco. There were 43 (28 males) patients with SYNTAX score of zero. Among those with coronary artery disease (n=257) increasing severity of CAD   was associated with lower body weight, BMI, body fat percentage, and body fat mass and ejection fraction as against positive trend for lean mass and visceral fat.   Conclusion BMI, fat mass decreased with severity of CAD while lean mass and visceral fat increased. We observed high proportion of CAD in underweight and lean KONKAN adults. These findings need further investigations

Na+, K+-ATPase Subunit Composition in a Human Chondrocyte Cell Line; Evidence for the Presence of α1, α3, β1, β2 and β3 Isoforms

Membrane transport systems participate in fundamental activities such as cell cycle control, proliferation, survival, volume regulation, pH maintenance and regulation of extracellular matrix synthesis. Multiple isoforms of Na+, K+-ATPase are expressed in primary chondrocytes. Some of these isoforms have previously been reported to be expressed exclusively in electrically excitable cells (i.e., cardiomyocytes and neurons). Studying the distribution of Na+, K+-ATPase isoforms in chondrocytes makes it possible to document the diversity of isozyme pairing and to clarify issues concerning Na+, K+-ATPase isoform abundance and the physiological relevance of their expression. In this study, we investigated the expression of Na+, K+-ATPase in a human chondrocyte cell line (C-20/A4) using a combination of immunological and biochemical techniques. A panel of well-characterized antibodies revealed abundant expression of the α1, β1 and β2 isoforms. Western blot analysis of plasma membranes confirmed the above findings. Na+, K+-ATPase consists of multiple isozyme variants that endow chondrocytes with additional homeostatic control capabilities. In terms of Na+, K+-ATPase expression, the C-20/A4 cell line is phenotypically similar to primary and in situ chondrocytes. However, unlike freshly isolated chondrocytes, C-20/A4 cells are an easily accessible and convenient in vitro model for the study of Na+, K+-ATPase expression and regulation in chondrocytes

Innovations in Fixed-Target Serial X-ray Crystallography

Over the last decade, brilliant, coherent femtosecond X-ray free-electron lasers (XFELs) have revolutionized structural biology by enabling ultrafast, room-temperature (RT) protein structure and dynamics studies. Using a diffract-before-destroy approach, even weakly-diffracting micro or nanocrystals of hard-to-crystallize proteins can be studied using multi-crystal or “serial” data collection. But challenges exist in efficiently delivering hundreds to thousands of crystals to the X-ray beam while maintaining crystal integrity and maximizing signal-to-noise in ambient or vacuum environments. Microfabricated fixed-target supports are an exciting alternative to widely used liquid jet-based technologies as they offer distinct advantages like clog-free delivery, significantly lower sample consumption, control over sample distribution, and the ability to incorporate stimuli like ligands, caged reactants, or electric fields “on-chip” for dynamic time-resolved experiments.The works compiled in this dissertation focus on the development of two fixed-target sample delivery devices, (1) silicon micropatterned grids with ultra-thin graphene-polymer enclosing layers for structural characterization of weakly-diffracting, two-dimensional (2D) nanocrystals, or three-dimensional (3D) microcrystals where background scatter from the device can limit diffraction resolution attained, and (2) polymer microfluidic chips that enable direct on-chip crystallization and stable, long-term storage, for plug-and-play in situ diffraction measurements. Experiments on model proteins were used to benchmark the performance of these devices to demonstrate high-resolution data collection, paving the way for reliable, user-friendly protein structure studies on more scientifically interesting targets in the future