Small Scale ERP Engine Design

This project set out to create a 1) low-cost, 2) dynamic, and 3) user-friendly small scale ERP software tool. These three key attributes position this product against complex and expensive systems such as SAP or Oracle. While the product still retains the dynamic and financial capabilities any good ERP system should have, the biggest value proposition is its simple and user-friendly interface. The software has a dual product-market fit: for small businesses as a low-cost planning tool, and for universities as a teaching tool. In the design phase, the team kept a primary focus on ergonomic software development while maintaining a subsidiary focus on bringing the product to customers. Through the rapid prototyping process and one scope change, the team was able to meet software functional requirements and develop a go-to-market strategy for this ERP software solution

Provably stable numerical method for the anisotropic diffusion equation in toroidally confined magnetic fields

We present a novel numerical method for solving the anisotropic diffusion equation in toroidally confined magnetic fields which is efficient, accurate and provably stable. The continuous problem is written in terms of a derivative operator for the perpendicular transport and a linear operator, obtained through field line tracing, for the parallel transport. We derive energy estimates of the solution of the continuous initial boundary value problem. A discrete formulation is presented using operator splitting in time with the summation by parts finite difference approximation of spatial derivatives for the perpendicular diffusion operator. Weak penalty procedures are derived for implementing both boundary conditions and parallel diffusion operator obtained by field line tracing. We prove that the fully-discrete approximation is unconditionally stable and asymptotic preserving. Discrete energy estimates are shown to match the continuous energy estimate given the correct choice of penalty parameters. Convergence tests are shown for the perpendicular operator by itself, and the ``NIMROD benchmark" problem is used as a manufactured solution to show the full scheme converges even in the case where the perpendicular diffusion is zero. Finally, we present a magnetic field with chaotic regions and islands and show the contours of the anisotropic diffusion equation reproduce key features in the field.Comment: 33 pages, 8 figure

An efficient method for the anisotropic diffusion equation in magnetic fields

We solve the anisotropic diffusion equation in 2D, where the dominant direction of diffusion is defined by a vector field which does not conform to a Cartesian grid. Our method uses operator splitting to separate the diffusion perpendicular and parallel to the vector field. The slow time scale is solved using a provably stable finite difference formulation in the perpendicular to the vector field, and an integral operator for the diffusion parallel to it. Energy estimates are shown to for the continuous and semi-discrete cases. Numerical experiments are performed showing convergence of the method, and examples is given to demonstrate the capabilities of the method

Microenvironmental regulation of cancer cell metabolism: implications for experimental design and translational studies

Cancers have an altered metabolism, and there is interest in understanding precisely how oncogenic transformation alters cellular metabolism and how these metabolic alterations can translate into therapeutic opportunities. Researchers are developing increasingly powerful experimental techniques to study cellular metabolism, and these techniques have allowed for the analysis of cancer cell metabolism, both in tumors and in ex vivo cancer models. These analyses show that, while factors intrinsic to cancer cells such as oncogenic mutations, alter cellular metabolism, cell-extrinsic microenvironmental factors also substantially contribute to the metabolic phenotype of cancer cells. These findings highlight that microenvironmental factors within the tumor, such as nutrient availability, physical properties of the extracellular matrix, and interactions with stromal cells, can influence the metabolic phenotype of cancer cells and might ultimately dictate the response to metabolically targeted therapies. In an effort to better understand and target cancer metabolism, this Review focuses on the experimental evidence that microenvironmental factors regulate tumor metabolism, and on the implications of these findings for choosing appropriate model systems and experimental approaches. Keywords\: Cancer, Cancer models, Metabolism, Microenvironment, Nutrient availability, Nutrient sensingNational Institutes of Health (U.S.) (R01CA168653)National Cancer Institute (U.S.) (F32CA213810)National Cancer Institute (U.S.) (F32CA210421)Howard Hughes Medical InstituteLudwig Institute for Cancer ResearchStand Up To Cancer (SU2C-AACR-IRG 09-16)Lustgarten FoundationMIT Center for Precision Cancer Medicin

Anthrax lethal toxin induced lysosomal membrane permeabilization and cytosolic cathepsin release is Nlrp1b/Nalp1b-dependent.

NOD-like receptors (NLRs) are a group of cytoplasmic molecules that recognize microbial invasion or 'danger signals'. Activation of NLRs can induce rapid caspase-1 dependent cell death termed pyroptosis, or a caspase-1 independent cell death termed pyronecrosis. Bacillus anthracis lethal toxin (LT), is recognized by a subset of alleles of the NLR protein Nlrp1b, resulting in pyroptotic cell death of macrophages and dendritic cells. Here we show that LT induces lysosomal membrane permeabilization (LMP). The presentation of LMP requires expression of an LT-responsive allele of Nlrp1b, and is blocked by proteasome inhibitors and heat shock, both of which prevent LT-mediated pyroptosis. Further the lysosomal protease cathepsin B is released into the cell cytosol and cathepsin inhibitors block LT-mediated cell death. These data reveal a role for lysosomal membrane permeabilization in the cellular response to bacterial pathogens and demonstrate a shared requirement for cytosolic relocalization of cathepsins in pyroptosis and pyronecrosis

Non-invasive brain stimulation in Stroke patients (NIBS):A prospective randomized open blinded end-point (PROBE) feasibility trial using transcranial direct current stimulation (tDCS) in post-stroke hemispatial neglect

Up to 80% of people who experience a right-hemisphere stroke suffer from hemispatial neglect. This syndrome is debilitating and impedes rehabilitation. We carried out a clinical feasibility trial of transcranial direct current stimulation (tDCS) and a behavioural rehabilitation programme, alone or in combination, in patients with neglect. Patients >4 weeks post right hemisphere stroke were randomized to 10 sessions of tDCS, 10 sessions of a behavioural intervention, combined intervention, or a control task. Primary outcomes were recruitment and retention rates, with secondary outcomes effect sizes on measures of neglect and quality of life, assessed directly after the interventions, and at 6 months follow up. Of 288 confirmed stroke cases referred (representing 7% of confirmed strokes), we randomized 8% (0.6% of stroke cases overall). The largest number of exclusions (91/288 (34%)) were due to medical comorbidities that prevented patients from undergoing 10 intervention sessions. We recruited 24 patients over 29 months, with 87% completing immediate post-intervention and 67% 6 month evaluations. We established poor feasibility of a clinical trial requiring repeated hospital-based tDCS within a UK hospital healthcare setting, either with or without behavioural training, over a sustained time period. Future trials should consider intensity, duration and location of tDCS neglect interventions

Exposure to maternal obesity during suckling outweighs in utero exposure in programming for post-weaning adiposity and insulin resistance in rats

Exposure to maternal obesity during early development programmes adverse metabolic health in rodent offspring. We assessed the relative contributions of obesity during pregnancy and suckling on metabolic health post-weaning. Wistar rat offspring exposed to control (C) or cafeteria diet (O) during pregnancy were cross-fostered to dams on the same (CC, OO) or alternate diet during suckling (CO, OC) and weaned onto standard chow. Measures of offspring metabolic health included growth, adipose tissue mass, and 12-week glucose and insulin concentrations during an intraperitoneal glucose tolerance test (ipGTT). Exposure to maternal obesity during lactation was a driver for reduced offspring weight post-weaning, higher fasting blood glucose concentrations and greater gonadal adiposity (in females). Males displayed insulin resistance, through slower glucose clearance despite normal circulating insulin and lower mRNA expression of PIK3R1 and PIK3CB in gonadal fat and liver respectively. In contrast, maternal obesity during pregnancy up-regulated the insulin signalling genes IRS2, PIK3CB and SREBP1-c in skeletal muscle and perirenal fat, favouring insulin sensitivity. In conclusion exposure to maternal obesity during lactation programmes offspring adiposity and insulin resistance, overriding exposure to an optimal nutritional environment in utero, which cannot be alleviated by a nutritionally balanced post-weaning diet

A systematic review of the validity, reliability, and feasibility of measurement tools used to assess the physical activity and sedentary behaviour of pre-school aged children

Physical activity (PA) and sedentary behaviour (SB) of pre-school aged children are associated with important health and developmental outcomes. Accurate measurement of these behaviours in young children is critical for research and practice in this area. The aim of this review was to examine the validity, reliability, and feasibility of measurement tools used to assess PA and SB of pre-school aged children. Searches of electronic databases, and manual searching, were conducted to identify articles that examined the measurement properties (validity, reliability or feasibility) of measurement tools used to examine PA and/or SB of pre-school aged children (3–7 years old). Following screening, data were extracted and risk of bias assessment completed on all included articles. A total of 69 articles, describing 75 individual studies were included. Studies assessed measurement tools for PA (n = 27), SB (n = 5), and both PA and SB (n = 43). Outcome measures of PA and SB differed between studies (e.g. moderate to vigorous activity, step count, posture allocation). Most studies examined the measurement properties of one measurement tool only (n = 65). Measurement tools examined included: calorimetry, direct observation, combined heart rate and accelerometry, heart rate monitors, accelerometers, pedometers, and proxy report (parent, carer or teacher reported) measures (questionnaires or diaries). Studies most frequently assessed the validity (criterion and convergent) (n = 65), face and content validity (n = 2), test-retest reliability (n = 10) and intra-instrument reliability (n = 1) of the measurement tools. Feasibility data was abstracted from 41 studies. Multiple measurement tools used to measure PA and SB in pre-school aged children showed some degree of validity, reliability and feasibility, but often for different purposes. Accelerometers, including the Actigraph (in particular GT3X versions), Actical, ActivPAL and Fitbit (Flex and Zip), and proxy reported measurement tools used in combination may be useful for a range of outcome measures, to measure intensity alongside contextual information