Miracle-dz/UniFAR-FTUs huggingface dataset:
High performance DNA sequencing, and the detection of mutations and polymorphisms, on the Clipper sequencer

The Visible Genetics Clipper sequencer is a new platform for automated DNA sequencing which employs disposable MicroCel cassettes and 50 μm thick polyacrylamide gels. Two DNA ladders can be analyzed simultaneously in each of 16 lanes on a gel, after labeling with far‐red absorbing dyes such as Cy5 and Cy5.5. This allows a simultaneous bidirectional sequencing of four templates. We have evaluated the Clipper sequencer, by cycle‐sequencing of an M13 single‐stranded DNA standard, and by coupled amplification and sequencing (CLIP) of reverse‐transcribed human immunodeficiency virus (HIV‐1) RNA standards and clinical patient samples. (i) Limitations of instrument. We have examined basic instrument parameters such as detector stability, background, digital sampling rate, and gain. With proper usage, the optical and electronic subsystems of the Clipper sequencer do not limit the data collection or sequence‐determination processes. (ii) Limitations of gel performance. We have also examined the physics of DNA band separation on 50 μm thick MicroCel gels. We routinely obtain well‐resolved sequence which can be base‐called with 98.5% accuracy to position ˜450 on an 11 cm gel, and to position ˜900 on a 25 cm gel. Resolution on 5 and 11 cm gels ultimately is limited by a sharp decrease in spacing between adjacent bands, in the biased reptation separation regime. Fick's (thermal) diffusion appears to be of minor importance on 6 cm or 11 cm gels, but becomes an additional resolution‐limiting factor on 25 cm gels. (iii) Limitations of enzymology. Template quality, primer nesting, choice of DNA polymerase, and choice between dye primers and dye terminators are key determinants of the ability to detect mutations and polymorphisms on the Clipper sequencer, as on other DNA sequencers. When CLIP is used with dye‐labeled primers and a DNA polymerase of the F667Y, Δ(5′ → 3′ exo) class, we can routinely detect single‐nucleotide mutations and polymorphisms over the 0.35—0.65 heterozygosity range. We present an example of detecting therapeutically relevant mutations in a clinical HIV‐1 RNA isolate.
The Blacklisting Memory Scheduler: Achieving high performance and fairness at low cost

In a multicore system, applications running on different cores interfere at main memory. This inter-application interference degrades overall system performance and unfairly slows down applications. Prior works have developed application-aware memory request schedulers to tackle this problem. State-of-the-art application-aware memory request schedulers prioritize memory requests of applications that are vulnerable to interference, by ranking individual applications based on their memory access characteristics and enforcing a total rank order. In this paper, we observe that state-of-the-art application-aware memory schedulers have two major shortcomings. First, ranking applications individually with a total order based on memory access characteristics leads to high hardware cost and complexity. Second, ranking can unfairly slow down applications that are at the bottom of the ranking stack. To overcome these shortcomings, we propose the Blacklisting Memory Scheduler (BLISS), which achieves high system performance and fairness while incurring low hardware cost and complexity. BLISS design is based on two new observations. First, we find that, to mitigate interference, it is sufficient to separate applications into only two groups, one containing applications that cause interference and another containing applications vulnerable to interference, instead of ranking individual applications with a total order. Vulnerable-to-interference group is prioritized over the interference-causing group. Second, we show that this grouping can be efficiently performed by simply counting the number of consecutive requests served from each application - an application that has a large number of consecutive requests served is dynamically classified as interference-causing. We evaluate BLISS across a wide variety of workloads and system configurations and compare its performance and complexity with five state-of-the-art memory schedulers. Our evaluations show that BLISS achieves 5% better system performance and 25% better fairness than the best-performing previous memory scheduler while greatly reducing critical path latency and hardware area cost of the memory scheduler (by 79% and 43%, respectively).
Control Strategies for Wide Output Voltage Range LLC Resonant DC–DC Converters in Battery Chargers

In this paper, a control strategy is presented for a high-performance capacitively loaded loop (LLC) multiresonant dc-dc converter in a two-stage smart charger for neighborhood electric vehicle (NEV) applications. It addresses several aspects and limitations of LLC resonant dc-dc converters in battery charging applications, such as very wide output voltage range while keeping the efficiency maximized, implementation of the current mode control at the secondary side, and optimization of burst mode operation for current regulation at very low output voltage. The proposed control scheme minimizes both low- and high-frequency current ripples on the battery while maintaining stability of the dc-dc converter, thus maximizing battery life without penalizing the volume of the charger. Experimental results are presented for a prototype unit converting 390 V from the input dc link to an output voltage range of 3-72 V dc at 650 W. The prototype achieves a peak efficiency value of 96%.
Social Embeddedness and Agent Development

Two different reasons for using agents are distinguished: the `engineering' perspective and the `social simulation' perspective. It is argued that this entails some differences in approach. In particular the former will want to prevent unpredictable emergent features of their agent populations whilst the later will want to use simulation to study precisely this phenomena. A concept of `social embeddedness' is explicated which neatly distinguishes the two approaches. It is argued that such embedding in a society is an essential feature of being a truly social agent. This has the consequence that such agents will not sit well within an `engineering' methodology.
Nanoparticle‐Templated Molecular Recognition Platforms for Detection of Biological Analytes

Molecular recognition of biological analytes with optical nanosensors provides both spatial and temporal biochemical information. A recently developed sensing platform exploits near‐infrared fluorescent single‐wall carbon nanotubes combined with electrostatically pinned heteropolymers to yield a synthetic molecular recognition technique that is maximally transparent through biological matter. This molecular recognition technique is known as corona phase molecular recognition (CoPhMoRe). In CoPhMoRe, the specificity of a folded polymer toward an analyte does not arise from a pre‐existing polymer‐analyte chemical affinity. Rather, specificity is conferred through conformational changes undergone by a polymer that is pinned to the surface of a nanoparticle in the presence of an analyte and the subsequent modifications in fluorescence readout of the nanoparticles. The protocols in this article describe a novel single‐molecule microscopy tool (near‐infrared fluorescence and total internal reflection fluorescence [nIRF TIRF] hybrid microscope) to visualize the CoPhMoRe recognition process, enabling a better understanding of synthetic molecular recognition. We describe this requisite microscope for simultaneous single‐molecule visualization of optical molecular recognition and signal transduction. We elaborate on the general procedures for synthesizing and identifying single‐walled carbon nanotube‐based sensors that employ CoPhMoRe via two biologically relevant examples of single‐molecule recognition for the hormone estradiol and the neurotransmitter dopamine. © 2016 by John Wiley & Sons, Inc.
Fas and Fas-Ligand in Eutopic and Ectopic Endometrium of Women With Endometriosis

The Fas/Fas-Ligand system is an important mediator of apoptosis. We analyzed their expression in tissue specimens obtained from 33 women with severe endometriosis and 18 women without endometriosis. Immunostaining for Fas-Ligand in the eutopic endometrium was stronger in the epithelial cells of secretory phase, while the epithelial cells of endometriotic lesions showed a significantly stronger staining for Fas-Ligand independently from the menstrual phase (P < 0.01). Immunostaining for Fas in the eutopic endometrium showed a reduced staining during the proliferative phase, whereas it was strong in the secretory phase. The epithelial cells of the ectopic endometrium showed a reduced staining for Fas independently from the menstrual phase with respect to the eutopic tissue (P < 0.01). The reduced expression of Fas in the ectopic endometrium with the contemporary higher expression of Fas-Ligand in the corresponding cells suggests a possible immune privilege of this tissue.
Immediate and early loading of SLA ITI single-tooth implants: an in vivo study.

PURPOSE The purpose of this investigation was to determine whether early and immediate loading of dental implants resulted in adverse consequences as determined clinically, radiographically, and histologically. MATERIALS AND METHODS In a canine model, 48 sand-blasted, large-grit, acid-etched (SLA) surfaced implants were placed at 4 different times before definitive restoration and loading. These times were 3 months (group A), 21 days (group B), 10 days (group C), and 2 days (immediately) (group D) before loading. Each implant was restored at the same time with a single gold screw-retained crown. Immediately after restoration all crowns were placed in function. Standardized periapical radiographs were made 1, 2, and 3 months after restoration. At the end of the study, block sections were obtained for histologic examination. Changes in crestal bone height on the mesial and distal aspects of each implant and the change in bone density of the coronal 3 mm of crestal bone were recorded. Primary, secondary, and total bone-to-implant contact; bone marrow-to-implant contact; and connective tissue-to-implant contact were evaluated histologically. RESULTS All implants were osseointegrated at the end of the study; no clinical failures of integration were noted. The changes in crestal bone heights for groups A, B, C, and D (means +/- SE) were 0.02 +/- 0.07 mm, 0.30 +/- 0.08 mm, 0.15 +/- 0.08 mm, and 0.35 +/- 0.18 mm, respectively. Total bone-to-implant contact for the 4 groups was 69.1%, 71.3%, 74.6%, and 75.2%, respectively (P > .57). DISCUSSION Under the conditions of this study no statistically significant differences were noted between the 4 different loading protocols for any of the parameters recorded. This finding is consistent with other recent studies and case reports. CONCLUSION The findings of this study indicate that early and immediate loading of single-unit SLA surfaced implants was possible in this model. (More than 50 references.)
E 2 F 1 inhibits circulating cholesterol clearance by regulating Pcsk 9 expression in the liver

Cholesterol accumulation in the liver is an early event in nonalcoholic fatty liver disease (NAFLD). Here, we demonstrate that E2F1 plays a crucial role in maintaining cellular cholesterol homeostasis by regulating cholesterol uptake via proprotein convertase subtilisin/kexin 9 (PCSK9), an enzyme that promotes low-density lipoprotein receptor (LDLR) degradation upon activation. E2f1–/– mice display reduced total plasma cholesterol levels and increased cholesterol content in the liver. In this study, we show that E2f1 deletion in cellular and mouse models leads to a marked decrease in Pcsk9 expression and an increase in LDLR expression. In addition to the upregulation of LDLR, we report that E2f1–/– hepatocytes exhibit increased LDL uptake. ChIP-Seq and PCSK9 promoter reporter experiments confirmed that E2F1 binds to and transactivates the PCSK9 promoter. Interestingly, E2f1–/– mice fed a high-cholesterol diet (HCD) display a fatty liver phenotype and liver fibrosis, which is reversed by reexpression of PCSK9 in the liver. Collectively, these data indicate that E2F1 regulates cholesterol uptake and that the loss of E2F1 leads to abnormal cholesterol accumulation in the liver and the development of fibrosis in response to an HCD. Research Article Hepatology Metabolism
Vitamin D and Human Skeletal Muscle

Vitamin D deficiency is an increasingly described phenomenon worldwide, with well‐known impacts on calcium metabolism and bone health. Vitamin D has also been associated with chronic health problems such as bowel and colonic cancer, arthritis, diabetes and cardiovascular disease. In recent decades, there has been increased awareness of the impact of vitamin D on muscle morphology and function, but this is not well recognized in the Sports Medicine literature. In the early 20th century, athletes and coaches felt that ultraviolet rays had a positive impact on athletic performance, and increasingly, evidence is accumulating to support this view. Both cross‐sectional and longitudinal studies allude to a functional role for vitamin D in muscle and more recently the discovery of the vitamin D receptor in muscle tissue provides a mechanistic understanding of the function of vitamin D within muscle. The identification of broad genomic and non‐genomic roles for vitamin D within skeletal muscle has highlighted the potential impact vitamin D deficiency may have on both underperformance and the risk of injury in athletes. This review describes the current understanding of the role vitamin D plays within skeletal muscle tissue.
Confidence measures for statistical machine translation

In this paper, we present several confidence measures for (statistical) machine translation. We introduce word posterior probabilities for words in the target sentence that can be determined either on a word graph or on an N best list. Two alternative confidence measures that can be calculated on N best lists are proposed. The performance of the measures is evaluated on two different translation tasks: on spontaneously spoken dialogues from the domain of appointment scheduling, and on a collection of technical manuals.
Factors Associated With Serum Albumin in Diabetes Mellitus Type 2 With Microalbuminuria Using Non-Normal Mixed Models: A Prospective Cohort Study

Background: The globally increasing epidemic of diabetes will lead to serious problems including diabetic nephropathy and kidney diseases in near future. The first clinical diagnosable stage in a diabetic kidney disease is microalbuminuria (urinary albumin excretion of 30 - 300 g/24 hours). Objectives: This prospective cohort study investigated the risk factors of microalbuminuria in patients with type 2 diabetes who had been registered in endocrine and metabolism research center in Isfahan city, Iran. Patients and Methods: This prospective cohort study was performed on 90 diabetic type 2 patients with microalbuminuria, who were selected according to the consecutive sample selection method during 6 years. Data were collected through regular and systematic measurements of serum albumin as the response variable and body mass index, systolic and diastolic blood pressure, the duration of diabetes, glycosylated hemoglobin (HbA1c), total cholesterol, triglyceride (TG), fasting blood sugar (FBS), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as the related factors. Non-normal mixed models were used to investigate the impact of effective factors on the amount of excreted serum albumin. Results: According to the deviance information criterion (DIC = 56.2), the non-normal mixed effects model with the skewed t distribution had a best fit and indicated that HbA1c, HDL and total cholesterol had a significant effect on the amount of albumin in urine (P < 0.05). Conclusions: Using nonnormal mixed models may lead to the best results as compared to common normality assumption.
Affibody-DyLight Conjugates for In Vivo Assessment of HER2 Expression by Near-Infrared Optical Imaging

Purpose Amplification of the HER2/neu gene and/or overexpression of the corresponding protein have been identified in approximately 20% of invasive breast carcinomas. Assessment of HER2 expression in vivo would advance development of new HER2-targeted therapeutic agents and, potentially, facilitate choice of the proper treatment strategy offered to the individual patient. We present novel HER2-specific probes for in vivo evaluation of the receptor status by near-infrared (NIR) optical imaging. Experimental Design Affibody molecules were expressed, purified, and labeled with NIR-fluorescent dyes. The binding affinity and specificity of the obtained probe were tested in vitro. For in vivo validation, the relationship of the measured NIR signal and HER2 expression was characterized in four breast cancer xenograft models, expressing different levels of HER2. Accumulation of Affibody molecules in tumor tissue was further confirmed by ex vivo analysis. Results Affibody-DyLight conjugates showed high affinity to HER2 (KD = 3.66±0.26). No acute toxicity resulted from injection of the probes (up to 0.5 mg/kg) into mice. Pharmacokinetic studies revealed a relatively short (37.53±2.8 min) half-life of the tracer in blood. Fluorescence accumulation in HER2-positive BT-474 xenografts was evident as soon as a few minutes post injection and reached its maximum at 90 minutes. On the other hand, no signal retention was observed in HER2-negative MDA-MB-468 xenografts. Immunostaining of extracted tumor tissue confirmed penetration of the tracer into tumor tissue. Conclusions The results of our studies suggest that Affibody-DyLight-750 conjugate is a powerful tool to monitor HER2 status in a preclinical setting. Following clinical validation, it might provide complementary means for assessment of HER2 expression in breast cancer patients (assuming availability of proper NIR scanners) and/or be used to facilitate detection of HER2-positive metastatic lesions during NIR-assisted surgery.
Mulitagent Reinforcement Learning in Stochastic Games with Continuous Action Spaces

We investigate the learning problem in stochastic games with continuous action spaces. We focus on repeated normal form games, and discuss issues in modelling mixed strategies and adapting learning algorithms in finite-action games to the continuous-action domain. We applied variable resolution techniques to two simple multi-agent reinforcement learning algorithms PHC and MinimaxQ. Preliminary experiments shows that our variable resolution partitioning method is successful at identifying important regions of the action space while keeping the total number of partitions low.
A price-based approach for voltage regulation and power loss minimization in power distribution networks

We present a price-based approach to deal with the challenges of the electrical power distribution systems with renewable generations. In specific, we address the power loss minimization and voltage regulation taking into account the actual grid capacity. Analogously, the cost function is reformulated to represent a social welfare maximization problem. Distributed optimization formulations, which bridge the physical power grid to the market-based approach, are presented and analyzed.
Childhood Metabolic Syndrome

The metabolic syndrome, also known as “syndrome X,” describes a cluster of cardiovascular risk factors that have been shown to predict the development of cardiovascular disease and type 2 diabetes (1). Some suggest that the cluster is driven by the consequences of peripheral insulin resistance (2), whereas others believe that obesity-related inflammation is the culprit (3). Many putative molecular mechanisms can provide excellent explanations for both theories regarding the primary driving mechanism of the clustering of cardiovascular risk factors (4) and how each one accelerates atherogenesis (5). Yet teasing inflammation and peripheral insulin resistance apart in individual patients or even in large cohorts is difficult because of their coexistence and possible vicious exacerbation of each other. The general paradigm regarding the evolvement of the syndrome is that adipocyte dysfunction in some obese individuals who are genetically prone or exposed to specific environmental signals leads to peripheral insulin resistance and subclinical inflammation culminating in accelerated atherosclerosis and overt clinical manifestations (6). The clinical utility of defining this syndrome in children and adolescents has been debated, since some propose that from a clinical standpoint, addressing each component of the cluster individually has comparable clinical and predictive outcomes, whereas others suggest such definitions are inappropriate for the pediatric age group. This debate has important implications from an epidemiological and public health standpoint. Yet it is imperative to indicate that the underlying pathophysiology that leads to the typical metabolic milieu characteristic of individuals with obesity-driven peripheral insulin resistance and/or subclinical inflammation has common features in all ages and is postulated to be the “driving force” of the development of accelerated atherogenesis and altered glucose metabolism in susceptible individuals. Several definitions of the metabolic syndrome in children have been proposed by various research groups (7,8) and expert consensus (9), and the use of …
Full Open Defects in Nanometric CMOS

Full open defects on the interconnect lines cause the broken wires to become floating. The voltage of a floating line depends on its topological characteristics, namely: parasitic capacitances to neighbouring structures, transistor capacitances of the downstream gate(s) and the trapped charge. However, in nanometric CMOS technologies, the oxide thickness is reduced below a few tens of Aring causing the gate tunnelling leakage to strongly impact the behaviour of defective circuits with full open defects. Floating lines can not be considered electrically isolated anymore and are subjected to transient evolutions until arriving at a quiescent state, determined by the technology and the downstream gate(s). The occurrence of full opens as well as the impact of the gate tunnelling leakage is expected to increase for future technologies. The analysis of full opens affecting basic CMOS gates is presented and their defective behaviour characterized. The prediction of the defective logic response of such basic gates is presented for nanometric technologies based on predictive technology models. The final steady state is found to be independent on the initial state of the floating node. Experimental evidence of this behaviour is presented for an industrial chip of 0.18 mum technology.
Towards Dynamic Green-Sizing for Database Servers

This paper presents two techniques for reducing the power consumed by database servers. Both techniques are intended primarily for transactional workloads on servers with memory-resident databases. The first technique is databasemanaged dynamic processor voltage and frequency scaling (DVFS). We show that a DBMS can exploit its knowledge of the workload and performance constraints to obtain power savings that are more than twice as large as the power savings achieved when DVFS is managed by the operating system. The second technique is rank-aware memory allocation, the goal of which is to power memory that the database system needs and avoid powering memory it does not need. We present experiments that show rank-aware allocation allows unneeded memory to move to low-power states, reducing memory power consumption.