Dynamics of gene expression and the regulatory inference problem

From the response to external stimuli to cell division and death, the dynamics of living cells is based on the expression of specific genes at specific times. The decision when to express a gene is implemented by the binding and unbinding of transcription factor molecules to regulatory DNA. Here, we construct stochastic models of gene expression dynamics and test them on experimental time-series data of messenger-RNA concentrations. The models are used to infer biophysical parameters of gene transcription, including the statistics of transcription factor-DNA binding and the target genes controlled by a given transcription factor.Comment: revised version to appear in Europhys. Lett., new titl

Emission-aware Energy Storage Scheduling for a Greener Grid

Reducing our reliance on carbon-intensive energy sources is vital for reducing the carbon footprint of the electric grid. Although the grid is seeing increasing deployments of clean, renewable sources of energy, a significant portion of the grid demand is still met using traditional carbon-intensive energy sources. In this paper, we study the problem of using energy storage deployed in the grid to reduce the grid's carbon emissions. While energy storage has previously been used for grid optimizations such as peak shaving and smoothing intermittent sources, our insight is to use distributed storage to enable utilities to reduce their reliance on their less efficient and most carbon-intensive power plants and thereby reduce their overall emission footprint. We formulate the problem of emission-aware scheduling of distributed energy storage as an optimization problem, and use a robust optimization approach that is well-suited for handling the uncertainty in load predictions, especially in the presence of intermittent renewables such as solar and wind. We evaluate our approach using a state of the art neural network load forecasting technique and real load traces from a distribution grid with 1,341 homes. Our results show a reduction of >0.5 million kg in annual carbon emissions -- equivalent to a drop of 23.3% in our electric grid emissions.Comment: 11 pages, 7 figure, This paper will appear in the Proceedings of the ACM International Conference on Future Energy Systems (e-Energy 20) June 2020, Australi

High Performance EVA Glove Collaboration: Glove Injury Data Mining Effort

Human hands play a significant role during Extravehicular Activity (EVA) missions and Neutral Buoyancy Lab (NBL) training events, as they are needed for translating and performing tasks in the weightless environment. Because of this high frequency usage, hand and arm related injuries are known to occur during EVA and EVA training in the NBL. The primary objectives of this investigation were to: 1) document all known EVA glove related injuries and circumstances of these incidents, 2) determine likely risk factors, and 3) recommend interventions where possible that could be implemented in the current and future glove designs. METHODS: The investigation focused on the discomforts and injuries of U.S. crewmembers who had worn the pressurized Extravehicular Mobility Unit (EMU) spacesuit and experienced 4000 Series or Phase VI glove related incidents during 1981 to 2010 for either EVA ground training or in-orbit flight. We conducted an observational retrospective case-control investigation using 1) a literature review of known injuries, 2) data mining of crew injury, glove sizing, and hand anthropometry databases, 3) descriptive statistical analyses, and finally 4) statistical risk correlation and predictor analyses to better understand injury prevalence and potential causation. Specific predictor statistical analyses included use of principal component analyses (PCA), multiple logistic regression, and survival analyses (Cox proportional hazards regression). Results of these analyses were computed risk variables in the forms of odds ratios (likelihood of an injury occurring given the magnitude of a risk variable) and hazard ratios (likelihood of time to injury occurrence). Due to the exploratory nature of this investigation, we selected predictor variables significant at p0.15. RESULTS: Through 2010, there have been a total of 330 NASA crewmembers, from which 96 crewmembers performed 322 EVAs during 1981-2010, resulting in 50 crewmembers being injured inflight and 44 injured during 11,704 ground EVA training events. Of the 196 glove related injury incidents, 106 related to EVA and 90 to EVA training. Over these 196 incidents, 277 total injuries (126 flight; 151 training) were reported and were then grouped into 23 types of injuries. Of EVA flight injuries, 65% were commonly reported to the hand (in general), metacarpophalangeal (MCP) joint, and finger (not including thumb) with fatigue, abrasion, and paresthesia being the most common injury types (44% of total flight injuries). Training injuries totaled to more than 70% being distributed to the fingernail, MCP joint, and finger crotch with 88% of the specific injuries listed as pain, erythema, and onycholysis. Of these training injuries, when reporting pain or erythema, the most common location was the index finger, but when reporting onycholysis, it was the middle finger. Predictor variables specific to increased risk of onycholysis included: female sex (OR=2.622), older age (OR=1.065), increased duration in hours of the flight or training event (OR=1.570), middle finger length differences in inches between the finger and the EVA glove (OR=7.709), and use of the Phase VI glove (OR=8.535). Differentiation between training and flight and injury reporting during 2002-2004 were significant control variables. For likelihood of time to first onycholysis injury, there was a 24% reduction in rate of reporting for each year increase in age. Also, more experienced crewmembers, based on number of EVA flight or training events completed, were less likely to report an onycholysis injury (3% less for every event). Longer duration events also found reporting rates to occur 2.37 times faster for every hour of length. Crewmembers with larger hand size reported onycholysis 23% faster than those with smaller hand size. Finally, for every 1/10th of an inch increase in difference between the middle finger length and the glove, the rate of reporting increased by 60%. DISCUSSION: One key finding was that the Series 4000 glove had a lower injury risk than the Phase VI, which provides a platform for further evaluation. General interventions that reduce hand overexertion and repetitive use exposure through tool development, procedural changes and shorter exposures may be one mitigation path, but due to the way the training event times were reported, we cannot provide a guideline for a specific event duration change. When the finger length was different from the glove length, the risk of injury increased indicating that the use of larger finger take-ups could be contributing to injury and therefore may not be recommended. Prior to this investigation, there was one previous investigation indicating hand anthropometry may be related to onycholysis. We found different hand anthropometry variables indicated by this investigation as compared to the prior, specifically differences in middle finger length compared to glove finger length, which point more towards a sizing issue than a specific anthropometry issue. Additionally, although this investigation has identified sizing as an issue, the force and environmental-related variables of the EVA glove that could also cause injury were not accounted for

The Potential and Challenges of CAD with Equational Constraints for SC-Square

Cylindrical algebraic decomposition (CAD) is a core algorithm within Symbolic Computation, particularly for quantifier elimination over the reals and polynomial systems solving more generally. It is now finding increased application as a decision procedure for Satisfiability Modulo Theories (SMT) solvers when working with non-linear real arithmetic. We discuss the potentials from increased focus on the logical structure of the input brought by the SMT applications and SC-Square project, particularly the presence of equational constraints. We also highlight the challenges for exploiting these: primitivity restrictions, well-orientedness questions, and the prospect of incrementality.Comment: Accepted into proceedings of MACIS 201

Activation of PKA via asymmetric allosteric coupling of structurally conserved cyclic nucleotide binding domains

Cyclic nucleotide-binding (CNB) domains allosterically regulate the activity of proteins with diverse functions, but the mechanisms that enable the cyclic nucleotide-binding signal to regulate distant domains are not well understood. Here we use optical tweezers and molecular dynamics to dissect changes in folding energy landscape associated with cAMP-binding signals transduced between the two CNB domains of protein kinase A (PKA). We find that the response of the energy landscape upon cAMP binding is domain specific, resulting in unique but mutually coordinated tasks: one CNB domain initiates cAMP binding and cooperativity, whereas the other triggers inter-domain interactions that promote the active conformation. Inter-domain interactions occur in a stepwise manner, beginning in intermediate-liganded states between apo and cAMP-bound domains. Moreover, we identify a cAMP-responsive switch, the N3A motif, whose conformation and stability depend on cAMP occupancy. This switch serves as a signaling hub, amplifying cAMP-binding signals during PKA activation

From Navas to Kaltoft: The European Court of Justice’s evolving definition of disability and the implications for HIV-positive individuals

This article will examine the definition of disability developed by the European Court of Justice for the purposes of the Employment Equality Directive and examine whether it is sufficient for the purpose of bringing People Living with HIV/AIDS within its scope. The article will argue that in order to adequately protect People Living with HIV/AIDS within the EU from discrimination, the European Court of Justice needs to ensure that a coherent EU wide definition of disability, based fully upon the social model of disability, is adopted. This is necessary in order to ensure adequate protection not only for People Living with HIV/AIDS but for all individuals with disabilities from discrimination throughout the EU. In addition to this central argument, this paper will argue that the lack of a coherent definition of disability grounded in the social model fragments protection for People Living with HIV/AIDS across the EU leading to a number of possible unintended consequences

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals