Miracle-dz/UniFAR-FTUs huggingface dataset:
The structural basis of hypertension: vascular remodelling, rarefaction and angiogenesis/arteriogenesis.

The established phase of human essential hypertension is characterized by a normal cardiac output and an elevation in peripheral resistance. A considerable part of this increase in vascular resistance is determined by the structure of the microvasculature, in particular the small arteries and precapillary arterioles, where increases in the wall thickness : lumen ratios are frequently observed [1]. In addition, other abnormalities in the microvasculature are also known to occur, such as a reduction in microvessels. Rarefaction of capillaries and arterioles has been reported in many animal models of hypertension [2,3], and may also be involved in increasing peripheral resistance in essential hypertension [4]. Rarefaction of capillaries is caused by an absence of capillaries or a functional rarefaction, in which the capillaries are present but not perfused. Capillary rarefaction has not only been reported in established essential hypertension [4], but also in borderline essential hypertension [5] and young adults with a predisposition to high blood pressure [6]. This latter observation suggests that defective angiogenesis/ arteriogenesis may be an etiological component in the inheritance of high blood pressure, and raises the possibility that genetic factors may be responsible for at least a component of microvascular rarefaction.
Mint: realizing CUDA performance in 3D stencil methods with annotated C

We present Mint, a programming model that enables the non-expert to enjoy the performance benefits of hand coded CUDA without becoming entangled in the details. Mint targets stencil methods, which are an important class of scientific applications. We have implemented the Mint programming model with a source-to-source translator that generates optimized CUDA C from traditional C source. The translator relies on annotations to guide translation at a high level. The set of pragmas is small, and the model is compact and simple. Yet, Mint is able to deliver performance competitive with painstakingly hand-optimized CUDA. We show that, for a set of widely used stencil kernels, Mint realized 80% of the performance obtained from aggressively optimized CUDA on the 200 series NVIDIA GPUs. Our optimizations target three dimensional kernels, which present a daunting array of optimizations.
Progestin-inflammatory cytokine interactions affect matrix metalloproteinase-1 and -3 expression in term decidual cells: implications for treatment of chorioamnionitis-induced preterm delivery.

CONTEXT Chorioamnionitis (CAM)-elicited preterm delivery (PTD) is associated with elevated amniotic fluid levels of IL-1beta and TNF-alpha. We hypothesized that IL-1beta and TNF-alpha may induce matrix metalloproteinase (MMP)-1 and MMP-3 activity to promote PTD by degrading decidual and fetal membranes and cervical extracellular matrix. OBJECTIVE Our objective was to evaluate: 1) MMP-1 and MMP-3 expression in decidual sections from uncomplicated term, idiopathic preterm, and CAM-complicated deliveries, and 2) the separate and interactive effects of IL-1beta, TNF-alpha, medroxyprogesterone acetate (MPA), and a p38 MAPK inhibitor (SB203580) on MMP-1 and MMP-3 expression in term decidual cells (DCs). INTERVENTIONS AND MAIN OUTCOME MEASURES Decidua were immunostained for MMP-1 and MMP-3. Cultured term DCs were incubated with estradiol (E2) or E2 plus MPA with or without IL-1beta or TNF-alpha with or without SB203580. ELISA and Western blotting assessed secreted MMP-1 and MMP-3 levels, quantitative real-time RT-PCR assessed mRNA levels, and substrate gel zymography was used to determined MMP-1 and MMP-3 proteolytic activity. RESULTS MMP-1 and MMP-3 immunostaining was more prominent in CAM-complicated decidua vs. control preterm and term decidual specimens (P < 0.05). Compared with basal outputs by DCs incubated with E2, TNF-alpha enhanced MMP-1 and MMP-3 secretion by 14 +/- 3- and 9 +/- 2-fold, respectively, and IL-1beta increased MMP-1 and MMP-3 secretion by 13 +/- 3- and 19 +/- 2-fold, respectively (P < 0.05). Addition of MPA lowered basal MMP-1 and MMP-3 outputs by 70%, whereas the TNF-alpha- and IL-1beta-enhanced MMP-1 and MMP-3 levels were blunted by more than 50% (P < 0.05). SB203580 suppressed TNF-alpha- and IL-1beta-induced MMP-1 and MMP-3 secretion by severalfold. Western blotting confirmed the ELISA results, and mRNA levels corresponded with MMP-1 and MMP-3 protein levels. MMP-1 and MMP-3 proteolytic activity was confirmed by substrate gel zymography. CONCLUSION Augmented DC-expressed MMP-1 and MMP-3 in CAM-complicated pregnancies may promote PTD via decidual, fetal membrane, and cervical extracellular matrix degradation. Effects of progestin-p38 MAPK signaling inhibition on cytokine-enhanced MMP-1 and MMP-3 expression in term DCs suggest alternative mechanisms to prevent CAM-induced PTD.
Stabilization of Clay Using Woodash

The potential of woodash to stabilize clay soil was evaluated. The evaluation involved the determination of the geotechnical properties of clay soil in its natural state as well as when mixed with varying proportions of woodash. The parameters tested included the particle size distribution, specific gravity, Atterberg limits, compaction characteristics, California bearing ratio (CBR) and the compressive strength. The CBR and strength tests were repeated after 28-day curing of the treated samples. Results showed that the geotechnical parameters of clay soil are improved substantially by the addition of woodash; plasticity was reduced by 35% and CBR and strength increased by 23–50% and 49–67%, respectively, depending on the compactive energy used. The highest CBR and strength values were achieved at 10% woodash. Results also showed that curing improved the strength of the woodash-treated clay. However, the strength gain was short lived as the strength quickly decreased after 7–14 days of curing. These resul.
Mistimed sleep disrupts circadian regulation of the human transcriptome

Significance Disruption of the timing of the sleep–wake cycle and circadian rhythms, such as occurs during jet lag and shift work, leads to disordered physiological rhythms, but to what extent the molecular elements of circadian rhythm generation are affected is not known. Here, we show that delaying sleep by 4 h for 3 consecutive days leads to a sixfold reduction of circadian transcripts in the human blood transcriptome to just 1%, whereas, at the same time, the centrally driven circadian rhythm of melatonin is not affected. Genes and processes affected included those at the core of circadian rhythm generation and gene expression. The data have implications for understanding the negative health outcomes of disruption of the sleep–wake cycle. Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep–wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature is low and melatonin is synthesized. Desynchrony of sleep–wake timing and other circadian rhythms, such as occurs in shift work and jet lag, is associated with disruption of rhythmicity in physiology and endocrinology. However, to what extent mistimed sleep affects the molecular regulators of circadian rhythmicity remains to be established. Here, we show that mistimed sleep leads to a reduction of rhythmic transcripts in the human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony of sleep and centrally driven circadian rhythms. Transcripts affected are key regulators of gene expression, including those associated with chromatin modification (methylases and acetylases), transcription (RNA polymerase II), translation (ribosomal proteins, initiation, and elongation factors), temperature-regulated transcription (cold inducible RNA-binding proteins), and core clock genes including CLOCK and ARNTL (BMAL1). We also estimated the separate contribution of sleep and circadian rhythmicity and found that the sleep–wake cycle coordinates the timing of transcription and translation in particular. The data show that mistimed sleep affects molecular processes at the core of circadian rhythm generation and imply that appropriate timing of sleep contributes significantly to the overall temporal organization of the human transcriptome.
Inclusion of an informant yields strong associations between cognitive complaint and longitudinal cognitive outcomes in non-demented elders.

BACKGROUND The relation between the source of cognitive complaint and objective cognitive performance is not well understood. OBJECTIVE Examine self and informant cognitive complaint as predictors of objective cognitive and functional trajectory in non-demented elders. METHODS Participants from the National Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC; n = 6133, 72±8 years, 68% female) or mild cognitive impairment (MCI; n = 3010, 74±8 years, 55% female). Four independent groups defined cognitive complaint: no complaint, self-only complaint, informant-only complaint, or mutual complaint (both self and informant complaint). Linear mixed model regression analyses related complaint status (referent was no complaint) to cognitive and functional trajectories, adjusting for age, sex, race, education, and follow-up period. RESULTS Among NC participants, mutual complaint related to faster decline in global cognition (p < 0.0001), language (all p-values <0.0001), processing speed (p = 0.0002), and executive functioning (p = 0.0006). Informant-only complaint related to faster decline in global cognition (p = 0.0001) and processing speed (p = 0.0001). Self-only complaint related to greater decline in immediate (p < 0.0001) and delayed (p = 0.0005) episodic memory. In MCI, mutual complaint related to faster decline in global cognition (p < 0.0001), verbal episodic memory (all p-values <0.0001), language (all p-values <0.0001), and processing speed(all p-values <0.0006). Informant-only or self-only complaint associations with cognitive trajectory did not survive correction factor for multiple comparisons.Conclusion: Cognitive complaint appears to have clinical significance, as it is related to declines in objective cognitive performance over time. Mutual complaint was associated with the worst cognitive trajectory in both NC and MCI elders, highlighting the importance of incorporating an informant into evaluation of elders whenever feasible.
Locality analysis for parallel C programs

Many parallel architectures support a memory model where some memory accesses are local, and thus inexpensive, while other memory accesses are remote, and potentially quite expensive. In order to achieve good parallel performance, it is often necessary to reduce the number of remote memory accesses. This can be done by the programmer, the compiler, or a combination of both. The overall goal is to minimize the work required by the programmer, and have the compiler automate the process as much as possible. The paper reports on compiler techniques for decreasing the number of remote memory accesses using locality analysis for a parallel dialect of C called EARTH-C. The locality analysis uses an algorithm inspired by type inference algorithms for fast points-to analysis. The algorithm estimates when an indirect reference via a pointer can be safely assumed to be a local access. The locality inference algorithm is also used to guide the automatic specialization of functions in order to take advantage of locality scientific to particular calling contexts. The locality analysis and automatic specialization has been implemented in the EARTH-C compiler which produces low level threaded code for the EARTH-C multithreaded architecture. Experimental results are presented for a set of benchmarks that operate on irregular, dynamically allocated data structures. The techniques give moderate to significant speedups and they do lessen the burden on the programmer.
In Vivo Delta Opioid Receptor Internalization Controls Behavioral Effects of Agonists

Background GPCRs regulate a remarkable diversity of biological functions, and are thus often targeted for drug therapies. Stimulation of a GPCR by an extracellular ligand triggers receptor signaling via G proteins, and this process is highly regulated. Receptor activation is typically accompanied by desensitization of receptor signaling, a complex feedback regulatory process of which receptor internalization is postulated as a key event. The in vivo significance of GPCR internalization is poorly understood. In fact, the majority of studies have been performed in transfected cell systems, which do not adequately model physiological environments and the complexity of integrated responses observed in the whole animal. Methods and Findings In this study, we used knock-in mice expressing functional fluorescent delta opioid receptors (DOR-eGFP) in place of the native receptor to correlate receptor localization in neurons with behavioral responses. We analyzed the pain-relieving effects of two delta receptor agonists with similar signaling potencies and efficacies, but distinct internalizing properties. An initial treatment with the high (SNC80) or low (AR-M100390) internalizing agonist equally reduced CFA-induced inflammatory pain. However, subsequent drug treatment produced highly distinct responses. Animals initially treated with SNC80 showed no analgesic response to a second dose of either delta receptor agonist. Concomitant receptor internalization and G-protein uncoupling were observed throughout the nervous system. This loss of function was temporary, since full DOR-eGFP receptor responses were restored 24 hours after SNC80 administration. In contrast, treatment with AR-M100390 resulted in retained analgesic response to a subsequent agonist injection, and ex vivo analysis showed that DOR-eGFP receptor remained G protein-coupled on the cell surface. Finally SNC80 but not AR-M100390 produced DOR-eGFP phosphorylation, suggesting that the two agonists produce distinct active receptor conformations in vivo which likely lead to differential receptor trafficking. Conclusions Together our data show that delta agonists retain full analgesic efficacy when receptors remain on the cell surface. In contrast, delta agonist-induced analgesia is abolished following receptor internalization, and complete behavioral desensitization is observed. Overall these results establish that, in the context of pain control, receptor localization fully controls receptor function in vivo. This finding has both fundamental and therapeutic implications for slow-recycling GPCRs.
Postoperative Admission to a Dedicated Geriatric Unit Decreases Mortality in Elderly Patients with Hip Fracture

Background Elderly patients with hip fracture have a 5 to 8 fold increased risk of death during the months following surgery. We tested the hypothesis that early geriatric management of these patients focused on co-morbidities and rehabilitation improved long term mortality. Methods and Findings In a cohort study over a 6 year period, we compared patients aged >70 years with hip fracture admitted to orthopedic versus geriatric departments in a time series analysis corresponding to the creation of a dedicated geriatric unit. Co-morbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Each cohort was compared to matched cohorts extracted from a national registry (n = 51,275) to validate the observed results. Main outcome measure was 6-month mortality. We included 131 patients in the orthopedic cohort and 203 in the geriatric cohort. Co-morbidities were more frequent in the geriatric cohort (median CIRS: 8 vs 5, P<0.001). In the geriatric cohort, the proportion of patients who never walked again decreased (6% versus 22%, P<0.001). At 6 months, re-admission (14% versus 29%, P = 0.007) and mortality (15% versus 24%, P = 0.04) were decreased. When co-morbidities were taken into account, the risk ratio of death at 6 months was reduced (0·43, 95%CI 0·25 to 0·73, P = 0.002). Using matched cohorts, the average treatment effects on the treated associated to early geriatric management indicated a reduction in hospital mortality (−63%; 95% CI: −92% to −6%, P = 0.006). Conclusions Early admission to a dedicated geriatric unit improved 6-month mortality and morbidity in elderly patients with hip fracture.
abc: an extensible AspectJ compiler

Research in the design of aspect-oriented programming languages requires a workbench that facilitates easy experimentation with new language features and implementation techniques. In particular, new features for AspectJ have been proposed that require extensions in many dimensions: syntax, type checking and code generation, as well as data flow and control flow analyses.The AspectBench Compiler (abc) is an implementation of such a workbench. The base version of abc implements the full AspectJ language. Its frontend is built, using the Polyglot framework, as a modular extension of the Java language. The use of Polyglot gives flexibility of syntax and type checking. The backend is built using the Soot framework, to give modular code generation and analyses.In this paper, we outline the design of abc, focusing mostly on how the design supports extensibility. We then provide a general overview of how to use abc to implement an extension. Finally, we illustrate the extension mechanisms of abc through a number of small, but non-trivial, examples. abc is freely available under the GNU LGPL.
Optimal time and bandwidth allocation based on Nash bargaining solution for cooperative cognitive systems

In this paper, we propose a cooperative spectrum sharing strategy based on the Nash bargaining solution. Specifically, the primary system leases a fraction of its transmission time to the secondary system in exchange for cooperation to improve its transmission performance. To gain access to the spectrum of the primary system, the secondary system needs to split a fraction of its transmission bandwidth to help to forward the primary signal. As a reward, the secondary system can use the remaining bandwidth to transmit its own signal. We find a unique solution for this time and bandwidth allocation using the Nash bargaining solution. Simulation results demonstrate that the performance of the primary and secondary systems can both be improved by the proposed spectrum sharing strategy.
Dissemination of dynamic data

An increasing fraction of the data disseminated through the the internet is time-varying (i.e., changes frequently). Examples of such data include sports information, news, and financial information such as stock prices. An important issue then is the maintenance of their temporal coherency. A user may be willing to receive sports and news information that may be out-of-sync by a few minutes with respect to the server, but may desire to have stronger coherency requirements for data items such as stock prices. We assume that a user specifies a temporal coherency requirement (tcr) for each item of interest. The value of tcr denotes the maximum permissible deviation of the presented value from the value at the server and thus constitutes the user-specified tolerance. We consider temporal coherency requirements specified in terms of the value of the object (maintaining temporal coherency specified in units of time is a simpler problem that requires less sophisticated techniques). As shown in Figure 1, let S(t), P (t) and U(t) denote the value of the data item at the server, proxy cache and the user, respectively. Then, to maintain temporal coherency we should have jU(t) S(t)j c:
The movement of optically detectable organelles in myelinated axons of Xenopus laevis

1. Intra‐axonal organelles were detected by darkfield and Nomarski microscopy in isolated myelinated nerve fibres from Xenopus laevis. Nerve fibres from the 8th spinal roots, the sciatic nerve, and identified motor and sensory axons from other hind limb nerves were used. The movement of the organelles was recorded either on motion picture film or by noting the times at which they crossed the lines of an ocular grid.
Coupled climate model simulation of Holocene cooling events: oceanic feedback amplifies solar forcing

The coupled global atmosphere-ocean-vegetation model ECBilt-CLIO-VECODE is used to perform transient simulations of the last 9000 years, forced by variations in orbital parameters, atmospheric greenhouse gas concentrations and total solar irradiance (TSI). The objective is to study the impact of decadal-to-centennial scale TSI variations on Holocene climate variability. The simulations show that negative TSI anomalies increase the probability of temporary relocations of the site with deepwater formation in the Nordic Seas, causing an expansion of sea ice that produces additional cooling. The consequence is a characteristic climatic anomaly pattern with cooling over most of the North Atlantic region that is consistent with proxy evidence for Holocene cold phases. Our results thus suggest that the ocean is able to play an important role in amplifying centennial-scale climate variability.
Manifest Contracts for Datatypes

We study algebraic data types in a manifest contract system, a software contract system where contract information occurs as refinement types. We first compare two simple approaches: refinements on type constructors and refinements on data constructors. For example, lists of positive integers can be described by {l:int list | for_all (lambda y. y > 0) l} in the former, whereas by a user-defined datatype pos_list with cons of type {x:int | x > 0} X pos_list -> pos_list in the latter. The two approaches are complementary: the former makes it easier for a programmer to write types and the latter enables more efficient contract checking. To take the best of both worlds, we propose (1) a syntactic translation from refinements on type constructors to equivalent refinements on data constructors and (2) dynamically checked casts between different but compatible datatypes such as int list and pos_list. We define a manifest contract calculus to formalize the semantics of the casts and prove that the translation is correct.
Performance Analysis of Media Cloud-Based Multimedia Systems With Retrying Fault-Tolerance Technique

In this paper, the performance of a cloud-based multimedia system using retrying for fault tolerance is studied. Specifically, the response time of the cloud-based multimedia system is modeled and the probability distribution of the response time is derived considering the effect imposed by retrying tasks in case of service failures happening. As another important performance metric that can better reflect requirements of customers, the percentile of response time that characterizes a threshold response time so that a certain percentage of requests can be served in under the threshold value is also studied. Relationships among number of service resources, task arrival rate, service rate, and system performance are studied through numerical examples. In addition, the percentile of response time of cloud-based multimedia systems using the retrying technique is compared with that of systems using the check-pointing technique.