Transferable neural networks for enhanced sampling of protein dynamics

Variational auto-encoder frameworks have demonstrated success in reducing complex nonlinear dynamics in molecular simulation to a single non-linear embedding. In this work, we illustrate how this non-linear latent embedding can be used as a collective variable for enhanced sampling, and present a simple modification that allows us to rapidly perform sampling in multiple related systems. We first demonstrate our method is able to describe the effects of force field changes in capped alanine dipeptide after learning a model using AMBER99. We further provide a simple extension to variational dynamics encoders that allows the model to be trained in a more efficient manner on larger systems by encoding the outputs of a linear transformation using time-structure based independent component analysis (tICA). Using this technique, we show how such a model trained for one protein, the WW domain, can efficiently be transferred to perform enhanced sampling on a related mutant protein, the GTT mutation. This method shows promise for its ability to rapidly sample related systems using a single transferable collective variable and is generally applicable to sets of related simulations, enabling us to probe the effects of variation in increasingly large systems of biophysical interest.Comment: 20 pages, 10 figure

Valuing certainty in a consensus-based water allocation mechanism

We present an interdisciplinary approach to attach economic value to model certainty. The central theme of this paper concerns valuing certainty in water resource management, specifically resource allocation. A conceptual framework is developed to study (1) a hypothetical scenario of three water users attempting to mutually agree on allocation of some fixed amount of water amongst themselves and (2) California water policy negotiations along the lines of Adams et al. (1996). We attempt to answer how uncertainty in a policy variable affects the "allocation solution" in such consensus-based decision-making processes. This study finally evolves into economic valuation of uncertainty reduction and willingness to pay for the same. Copyright 2007 by the American Geophysical Union

Enhancing electrochemical intermediate solvation through electrolyte anion selection to increase nonaqueous Li-O2_2 battery capacity

Among the 'beyond Li-ion' battery chemistries, nonaqueous Li-O$_2$ batteries have the highest theoretical specific energy and as a result have attracted significant research attention over the past decade. A critical scientific challenge facing nonaqueous Li-O$_2$ batteries is the electronically insulating nature of the primary discharge product, lithium peroxide, which passivates the battery cathode as it is formed, leading to low ultimate cell capacities. Recently, strategies to enhance solubility to circumvent this issue have been reported, but rely upon electrolyte formulations that further decrease the overall electrochemical stability of the system, thereby deleteriously affecting battery rechargeability. In this study, we report that a significant enhancement (greater than four-fold) in Li-O$_2$ cell capacity is possible by appropriately selecting the salt anion in the electrolyte solution. Using $^7$Li nuclear magnetic resonance and modeling, we confirm that this improvement is a result of enhanced Li$^+$ stability in solution, which in turn induces solubility of the intermediate to Li$_2$O$_2$ formation. Using this strategy, the challenging task of identifying an electrolyte solvent that possesses the anti-correlated properties of high intermediate solubility and solvent stability is alleviated, potentially providing a pathway to develop an electrolyte that affords both high capacity and rechargeability. We believe the model and strategy presented here will be generally useful to enhance Coulombic efficiency in many electrochemical systems (e.g. Li-S batteries) where improving intermediate stability in solution could induce desired mechanisms of product formation.Comment: 22 pages, 5 figures and Supporting Informatio

Anemia in Antiretroviral Naïve HIV/AIDS Patients: A Study from Eastern India

Background: Hematological manifestations are common throughout the course of HIV infection. Impact of anemia is the most significant among them. The present study was undertaken to evaluate the etiologies underlying anemia in HIV/AIDS. Methods This was a non randomized cross sectional observational study conducted in a tertiary care hospital of India over a period of 2 years. One hundred and fifty HIV patients were screened. Thorough clinical and laboratory evaluation was done in 50 randomly selected anemic cases. Results: Proper etiological diagnosis could be reached in 46 patients. Among them correlation between Hb% and CD4 count was statistically insignificant (p = 0.074, r = 0.47) whereas it was significant with absolute lymphocyte and CD4 count (p = 0.006, r = 0.41). There was better correlation of bone marrow iron status with percent saturation of transferrin (p = 0.003, r = 0.54) than with serum ferritin (p = 0.055, r = 0.09). Bone marrow iron status did not have any relationship with CD4 count. Anemia of chronic disease was the commonest etiology (37%) followed by HIV related myelodysplastic syndrome (31%), iron deficiency anemia (13%), bone marrow suppression due to direct involvement by some infective process (7%). Aplastic anemia, multiple myeloma, Hodgkin’s disease, pure red cell aplasia, hemophagocytic lymphohistiocytosis and vitamin B12 deficiency were detected in one case (2%) each. Conclusions: Etiologies of anemia in HIV/AIDS are multifactorial with anemia of chronic disease being the commonest. For screening of iron deficiency in this group, percent saturation is a better tool than serum ferritin. Absolute lymphocyte count can sometimes be used as a surrogate marker of immunological status in antiretroviral naïve HIV patients, particularly in resource poor areas