Dynamic and Leakage Power-Composition Profile Driven Co-Synthesis for Energy and Cost Reduction

Recent research has shown that combining dynamic voltage scaling (DVS) and adaptive body bias (ABB) techniques achieve the highest reduction in embedded systems energy dissipation [1]. In this paper we show that it is possible to produce comparable energy saving to that obtained using combined DVS and ABB techniques but with reduced hardware cost achieved by employing processing elements (PEs) with separate DVS or ABB capability. A co-synthesis methodology which is aware of tasks’ power-composition profile (the ratio of the dynamic power to the leakage power) is presented. The methodology selects voltage scaling capabilities (DVS, ABB, or combined DVS and ABB) for the PEs, maps, schedules, and voltage scales applications given as task graphs with timing constraints, aiming to dynamic and leakage energy reduction at low hardware cost. We conduct detailed experiments, including a real-life example, to demonstrate the effectiveness of our methodology. We demonstrate that it is possible to produce designs that contain PEs with only DVS or ABB technique but have energy dissipation that are only 4.4% higher when compared with the same designs that employ PEs with combined DVS and ABB capabilities

HSF1 is a driver of leukemia stem cell self-renewal in acute myeloid leukemia

Acute myeloid leukemia (AML) is maintained by self-renewing leukemic stem cells (LSCs). A fundamental problem in treating AML is that conventional therapy fails to eliminate LSCs, which can reinitiate leukemia. Heat shock transcription factor 1 (HSF1), a central regulator of the stress response, has emerged as an important target in cancer therapy. Using genetic Hsf1 deletion and a direct HSF1 small molecule inhibitor, we show that HSF1 is specifically required for the maintenance of AML, while sparing steady-state and stressed hematopoiesis. Mechanistically, deletion of Hsf1 dysregulates multifaceted genes involved in LSC stemness and suppresses mitochondrial oxidative phosphorylation through downregulation of succinate dehydrogenase C (SDHC), a direct HSF1 target. Forced expression of SDHC largely restores the Hsf1 ablation-induced AML developmental defect. Importantly, the growth and engraftment of human AML cells are suppressed by HSF1 inhibition. Our data provide a rationale for developing efficacious small molecules to specifically target HSF1 in AML

Matrix Form of Deriving High Order Schemes for the First Derivative

بالنسبة للعديد من المشكلات في الفيزياء وديناميكا الموائع الحسابية (CFD) ، فإن الحصول على تقريب دقيق للمشتقات يعد مهمة صعبة. يقدم هذه البحث صنف من الطرق العددية عالية الرتبة لتقريب المشتقة الأولى. وتستند هذه التقريبات على أساس حل نظام خاص من المعادلات التي تحتوي على معاملات مجهولة. توفر طريقة الإنشاء أنواعاً متعددة من الطرق العددية برتب مختلفة الدقة. يتم تحليل دقة كل طريقة عددية باستخدام تحليل فورييه الذي يوضح تشتت وتبديد الطريقة العددية. يتم استخدام طريقة متعددة الحدود للتحقق من دقة رتب الطرق العددية المقترحة من خلال الحصول على حدود الخطأ. يتم حساب أخطاء التشتت والتبديد ومقارنتها لإظهار ميزات الطرق العددية عالية الرتبة.  علاوة على ذلك ، نخطط لدراسة خصائص الثبات والدقة للطرق العددية الحالية وتطبيقها على الأنظمة المعيارية للمعادلات التفاضلية الجزئية المعتمدة على الوقت في CFD.For many problems in Physics and Computational Fluid Dynamics (CFD), providing an accurate approximation of derivatives is a challenging task. This paper presents a class of high order numerical schemes for approximating the first derivative. These approximations are derived based on solving a special system of equations with some unknown coefficients. The construction method provides numerous types of schemes with different orders of accuracy. The accuracy of each scheme is analyzed by using Fourier analysis, which illustrates the dispersion and dissipation of the scheme. The polynomial technique is used to verify the order of accuracy of the proposed schemes by obtaining the error terms. Dispersion and dissipation errors are calculated and compared to show the features of high order schemes. Furthermore, there is a plan to study the stability and accuracy properties of the present schemes and apply them to standard systems of time dependent partial differential equations in CFD.  &nbsp

Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia

Low levels of high density lipoprotein-cholesterol (HDL-C) are associated with an elevated risk of arteriosclerotic coronary heart disease. Heritability of HDL-C levels is high. In this research discovery study, we used whole-exome sequencing to identify damaging gene variants that may play significant roles in determining HDL-C levels. We studied 204 individuals with a mean HDL-C level of 27.8 ± 6.4 mg/dl (range: 4-36 mg/dl). Data were analyzed by statistical gene burden testing and by filtering against candidate gene lists. We found 120 occurrences of probably damaging variants (116 heterozygous; four homozygous) among 45 of 104 recognized HDL candidate genes. Those with the highest prevalence of damaging variants were ABCA1 (n = 20), STAB1 (n = 9), OSBPL1A (n = 8), CPS1 (n = 8), CD36 (n = 7), LRP1 (n = 6), ABCA8 (n = 6), GOT2 (n = 5), AMPD3 (n = 5), WWOX (n = 4), and IRS1 (n = 4). Binomial analysis for damaging missense or loss-of-function variants identified the ABCA1 and LDLR genes at genome-wide significance. In conclusion, whole-exome sequencing of individuals with low HDL-C showed the burden of damaging rare variants in the ABCA1 and LDLR genes is particularly high and revealed numerous occurrences in HDL candidate genes, including many genes identified in genome-wide association study reports. Many of these genes are involved in cancer biology, which accords with epidemiologic findings of the association of HDL deficiency with increased risk of cancer, thus presenting a new area of interest in HDL genomics

Exome sequencing implicates impaired GABA signaling and neuronal ion transport in trigeminal neuralgia

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associate

Investigation of the Use of a Bio-Derived Solvent for Non-Solvent-Induced Phase Separation (NIPS) Fabrication of Polysulfone Membranes

Organic solvents, such as N-methyl-2-pyrrolidone (NMP) and dimethylacetamide (DMAc), have been traditionally used to fabricate polymeric membranes. These solvents may have a negative impact on the environment and human health; therefore, using renewable solvents derived from biomass is of great interest to make membrane fabrication sustainable. Methyl-5-(dimethylamino)-2-methyl-5-oxopentanoate (Rhodiasolv PolarClean) is a bio-derived, biodegradable, nonflammable and nonvolatile solvent. Polysulfone is a commonly used polymer to fabricate membranes due to its thermal stability, strong mechanical strength and good chemical resistance. From cloud point curves, PolarClean showed potential to be a solvent for polysulfone. Membranes prepared with PolarClean were investigated in terms of their morphology, porosity, water permeability and protein rejection, and were compared to membranes prepared with traditional solvents. The pores of polysulfone/PolarClean membranes were sponge-like, and the membranes displayed higher water flux values (176.0 ± 8.8 LMH) along with slightly higher solute rejection (99.0 ± 0.51%). On the other hand, PSf/DMAc membrane pores were finger-like with lower water flux (63.1 ± 12.4 LMH) and slightly lower solute rejection (96 ± 2.00%) when compared to PSf/PolarClean membrane