Coarse-graining intramolecular hydrodynamic interaction in dilute solutions of flexible polymers

We present a scheme for coarse-graining hydrodynamic interactions in an isolated flexible homopolymer molecule in solution. In contrast to the conventional bead-spring model that employs spherical beads of fixed radii to represent the hydrodynamic characteristics of coarse-grained segments, we show that our procedure leads naturally to a discrete model of a polymer molecule as a chain of orientable and stretchable Gaussian blobs. This model accounts for both intrablob and interblob hydrodynamic interactions, which depend on the instantaneous shapes of the blobs. In Brownian dynamics simulations of initially stretched chains relaxing under quiescent conditions, the transient evolution of the mean-square end-to-end distance and first normal stress difference obtained with the Gaussian-blob model are found to be less sensitive to the degree of coarse graining, in comparison with the conventional bead-spring model with Rotne-Prager-Yamakawa hydrodynamic interactions

Consistent, Durable, and Safe Memory Management for Byte-addressable Non Volatile Main Memory

This paper presents three building blocks for enabling the efficient and safe design of persistent data stores for emerging non-volatile memory technologies. Taking the fullest advantage of the low latency and high bandwidths of emerging memories such as phase change memory (PCM), spin torque, and memristor necessitates a serious look at placing these persistent storage technologies on the main memory bus. Doing so, however, introduces critical challenges of not sacrificing the data reliability and consistency that users demand from storage. This paper introduces techniques for (1) robust wear-aware memory allocation, (2) preventing of erroneous writes, and (3) consistency-preserving updates that are cacheefficient. We show through our evaluation that these techniques are efficiently implementable and effective by demonstrating a B+-tree implementation modified to make full use of our toolkit.

Fifty Years of ISCA: A data-driven retrospective on key trends

Computer Architecture, broadly, involves optimizing hardware and software for current and future processing systems. Although there are several other top venues to publish Computer Architecture research, including ASPLOS, HPCA, and MICRO, ISCA (the International Symposium on Computer Architecture) is one of the oldest, longest running, and most prestigious venues for publishing Computer Architecture research. Since 1973, except for 1975, ISCA has been organized annually. Accordingly, this year will be the 50th year of ISCA. Thus, we set out to analyze the past 50 years of ISCA to understand who and what has been driving and innovating computing systems thus far. Our analysis identifies several interesting trends that reflect how ISCA, and Computer Architecture in general, has grown and evolved in the past 50 years, including minicomputers, general-purpose uniprocessor CPUs, multiprocessor and multi-core CPUs, general-purpose GPUs, and accelerators.Comment: 17 pages, 11 figure

Hair follicle specific ACVR1/ALK2 critically affects skin morphogenesis and attenuates wound healing

The bone morphogenic protein signaling (BMP) is intricately involved in the quiescence and regulation of stem cells through activation of BMP receptors. Hair follicle stem cells play a critical role in cutaneous homeostasis and regeneration. Here, we utilize a novel mouse model with targeted overexpression of the BMP receptor ALK2/ACVR1 in hair follicle stem cells, to characterize its role in skin development and postnatal wound healing. Initial histologic evaluation demonstrated significant dysregulation in hair follicle morphogenesis in mutant mice. These demonstrated increased numbers of individual hair follicles with altered morphology and localization. Mutant follicles were found to exhibit elevated proliferative activity as well as increased prevalence of CD34 and ITGA6 positive follicle stem cells. Interestingly, constitutive overexpression of ALK2 resulted in attenuation of cutaneous wound healing. These findings demonstrate that hair follicle specific ALK2 is intricately involved in maintenance of the stem cell niche and wound healing.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138367/1/wrr12549_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138367/2/wrr12549.pd

The ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year: a cohort study

As there is limited knowledge regarding the longitudinal development and early ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naïve (thymic and central) and regulatory (resting and activated) CD4(+) T-cell populations during the first postnatal year. Blood samples were collected and analyzed at birth, 6 and 12 months of age from a population-derived sample of 130 infants. The proportion of naïve and regulatory CD4(+) T-cell populations was determined by flow cytometry, and the thymic and central naïve populations were sorted and their phenotype confirmed by relative expression of T cell-receptor excision circle DNA (TREC). At birth, the majority (94%) of CD4(+) T cells were naïve (CD45RA(+)), and of these, ~80% had a thymic naïve phenotype (CD31(+) and high TREC), with the remainder already central naïve cells (CD31(-) and low TREC). During the first year of life, the naïve CD4(+) T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naïve T regulatory cells (rTreg; CD4(+)CD45RA(+)FoxP3(+)) and activated Treg (aTreg, CD4(+)CD45RA(-)FoxP3(high)) increased markedly. The ratio of thymic to central naïve CD4(+) T cells was lower in males throughout the first postnatal year indicating early sexual dimorphism in immune development. This longitudinal study defines proportions of CD4(+) T-cell populations during the first year of postnatal life that provide a better understanding of normal immune development

Heracles: Improving Resource Efficiency at Scale

User-facing, latency-sensitive services, such as web-search, underutilize their computing resources during daily periods of low traffic. Reusing those resources for other tasks is rarely done in production services since the contention for shared resources can cause latency spikes that violate the service-level objectives of latency-sensitive tasks. The resulting under-utilization hurts both the affordability and energy-efficiency of large-scale datacenters. With technology scaling slowing down, it becomes important to address this opportunity. We present Heracles, a feedback-based controller that enables the safe colocation of best-effort tasks alongside a latency-critical service. Heracles dynamically manages multiple hardware and software isolation mechanisms, such as CPU, memory, and network isolation, to ensure that the latency-sensitive job meets latency targets while maximizing the resources given to best-effort tasks. We evaluate Heracles using production latency-critical and batch workloads from Google and demonstrate average server utilizations of 90% without latency violations across all the load and colocation scenarios that we evaluated

An inventory of supranational antimicrobial resistance surveillance networks involving low- and middle-income countries since 2000.

Low- and middle-income countries (LMICs) shoulder the bulk of the global burden of infectious diseases and drug resistance. We searched for supranational networks performing antimicrobial resistance (AMR) surveillance in LMICs and assessed their organization, methodology, impacts and challenges. Since 2000, 72 supranational networks for AMR surveillance in bacteria, fungi, HIV, TB and malaria have been created that have involved LMICs, of which 34 are ongoing. The median (range) duration of the networks was 6 years (1-70) and the number of LMICs included was 8 (1-67). Networks were categorized as WHO/governmental (n = 26), academic (n = 24) or pharma initiated (n = 22). Funding sources varied, with 30 networks receiving public or WHO funding, 25 corporate, 13 trust or foundation, and 4 funded from more than one source. The leading global programmes for drug resistance surveillance in TB, malaria and HIV gather data in LMICs through periodic active surveillance efforts or combined active and passive approaches. The biggest challenges faced by these networks has been achieving high coverage across LMICs and complying with the recommended frequency of reporting. Obtaining high quality, representative surveillance data in LMICs is challenging. Antibiotic resistance surveillance requires a level of laboratory infrastructure and training that is not widely available in LMICs. The nascent Global Antimicrobial Resistance Surveillance System (GLASS) aims to build up passive surveillance in all member states. Past experience suggests complementary active approaches may be needed in many LMICs if representative, clinically relevant, meaningful data are to be obtained. Maintaining an up-to-date registry of networks would promote a more coordinated approach to surveillance

The maternal diet, gut bacteria, and bacterial metabolites during pregnancy influence offspring asthma

This review focuses on the current evidence that maternal dietary and gut bacterial exposures during pregnancy influence the developing fetal immune system and subsequent offspring asthma. Part 1 addresses exposure to a farm environment, antibiotics, and prebiotic and probiotic supplementation that together indicate the importance of bacterial experience in immune programming and offspring asthma. Part 2 outlines proposed mechanisms to explain these associations including bacterial exposure of the fetoplacental unit; immunoglobulin-related transplacental transport of gut bacterial components; cytokine signaling producing fetomaternal immune alignment; and immune programming via metabolites produced by gut bacteria. Part 3 focuses on the interplay between diet, gut bacteria, and bacterial metabolites. Maternal diet influences fecal bacterial composition, with dietary microbiota-accessible carbohydrates (MACs) selecting short-chain fatty acid (SCFA)-producing bacteria. Current evidence from mouse models indicates an association between increased maternal dietary MACs, SCFA exposure during pregnancy, and reduced offspring asthma that is, at least in part, mediated by the induction of regulatory T lymphocytes in the fetal lung. Part 4 discusses considerations for future studies investigating maternal diet-by-microbiome determinants of offspring asthma including the challenge of measuring dietary MAC intake; limitations of the existing measures of the gut microbiome composition and metabolic activity; measures of SCFA exposure; and the complexities of childhood respiratory health assessment