Miracle-dz/UniFAR-FTUs huggingface dataset:
Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.
PhyResSE: a Web Tool Delineating Mycobacterium tuberculosis Antibiotic Resistance and Lineage from Whole-Genome Sequencing Data

ABSTRACT Antibiotic-resistant tuberculosis poses a global threat, causing the deaths of hundreds of thousands of people annually. While whole-genome sequencing (WGS), with its unprecedented level of detail, promises to play an increasingly important role in diagnosis, data analysis is a daunting challenge. Here, we present a simple-to-use web service (free for academic use at http://phyresse.org). Delineating both lineage and resistance, it provides state-of-the-art methodology to life scientists and physicians untrained in bioinformatics. It combines elaborate data processing and quality control, as befits human diagnostics, with a treasure trove of validated resistance data collected from well-characterized samples in-house and worldwide.
Spatiotemporal Dynamics of Perfusion and Oximetry during Ictal Discharges in the Rat Neocortex

Epileptic events elicit a large focal increase in cerebral blood flow (CBF) to perfuse metabolically active neurons in the focus. Conflicting data exists, however, on whether hemoglobin saturation increases or decreases in the focus and surrounding cortex, and whether CBF increases globally or is decreased in adjacent areas. How these hemodynamic events correlate with actual changes in tissue oxygenation is also not known. Using laser Doppler flowmetry, oxygen microsensors and intrinsic optical imaging spectroscopy, we demonstrate that the dip in hemoglobin in the focus correlates with a profound but temporary decrease in tissue oxygenation despite a large increase in CBF. Furthermore, CBF simultaneously decreases in the cortex immediately adjacent to the focus. These events are then replaced with a longer duration, less focal increase in CBF, cerebral blood volume, and hyperoxygenation, the duration of which correlates with the duration of the seizure. These findings raise the question of whether transient focal hypoxia and vascular steal might contribute to progressive deleterious effects of chronic epilepsy on the adult and developing brain. Possible mechanisms based on recent astrocyte-based models of neurovascular coupling are discussed.
Genetic explorations of recent human metabolic adaptations: hypotheses and evidence

Since humans and chimpanzees split from a common ancestor over 6 million years ago, human metabolism has changed dramatically. This change includes adaptations to a high‐quality diet, the evolution of an energetically expensive brain, dramatic increases in endurance abilities, and capacity for energy storage in white adipose tissue. Human metabolism continues to evolve in modern human populations in response to local environmental and cultural selective forces. Understanding the nature of these selective forces and the physiological responses during human evolution is a compelling challenge for evolutionary biologists. The complex genetic architecture surrounding metabolic phenotypes indicates that selection probably altered allelic frequencies across many loci in populations experiencing adaptive metabolic change to fit their environment. A recent analysis supports this hypothesis, finding that classic selective sweeps at single loci were rare during the past 250 000 years of human evolution. Detection of selective signatures at multiple loci, as well as exploration of physiological adaptation to environment in humans, will require cross‐disciplinary collaboration, including the incorporation of biological pathway analysis. This review explores the Thrifty Genotype Hypothesis, high‐altitude adaptation, cold‐resistance adaptation, and genetic evidence surrounding these proposed metabolic adaptations in an attempt to clarify current challenges and avenues for future progress.
Functional alteration in frontolimbic systems relevant to moral judgment in cocaine‐dependent subjects

Cocaine addiction is characterized by persistent decision‐making deficits, which are linked to structural and functional abnormalities in frontolimbic systems. Moral judgment is as a special instance of decision making, in which both cognitive and emotional signals must be adequately integrated to decide how to resolve moral dilemmas. Here, we employed a moral dilemmas functional magnetic resonance imaging (fMRI) task to explore possible alterations of frontolimbic systems in cocaine‐dependent subjects. We also explored if these alterations relate to more basic deficits in functional connectivity within these systems during spontaneous resting‐state activation. Ten cocaine‐dependent subjects and 14 non‐drug‐using controls participated in the study. Cocaine‐dependent subjects were carefully selected to discard potentially confounding co‐morbidities, and they underwent a uniform supervised abstinence period of 10 days. Both groups were scanned, and fMRI maps were generated to identify (1) brain response to moral dilemmas; and (2) the strength of functional connectivity within frontolimbic systems during resting‐state. During the moral dilemmas task, cocaine‐dependent subjects showed reduced activation involving frontolimbic structures as the anterior cingulate cortex (ACC), left insula and brain stem. Connectivity analyses showed that cocaine users had less resting‐state functional connectivity between ACC, thalamus, insula and brain stem. These results demonstrate that cocaine‐dependent subjects have functional alterations in the frontolimbic systems that support moral judgment and social decision making.
Tight Bounds For Random MAX 2-SAT

For a conjunctive normal form formula F with n variables andm = cn 2-variable clauses (c is called thedensity), denote bymaxF is the maximum number of clauses satisfiable by a single assignment of the variables. For the uniform random formula F with densityc = 1 + ε, ε À n−1/3, we prove that maxF is in (1 + ε−Θ(ε3))n with high probability. This improves the known upper bound(1 + ε − Ω(ε3/ ln(1/ε))) due to [6]. The algorithm for the lower bound is also simpler. In addition, we present a simple unified algorithm which not only yields bounds mentioned above for c = 1+ε, but also provides a tight lower bound (3/4c+Θ( √ c))n for large enoughc’s. To obtain the bounds for c = 1 + ε, we use the Poisson cloning model and analyze the pure literal algorithm, which is simpler than that of the unit clause algorithm used in [6] (Actually, in [6], it is conjectured that the “pure-literal” rule should give the same result using an alternative analysis.). The Poisson cloning model has been introduced in [13] to simplify analysis of certain algorithms with branching process natures. The model turns out to be almost the same as the uniform model with the same (mean) density. ∗MIT Computer Science and Artificial Intelligence Laboratory, 32 Vassar Street, Cambridge, Massachusetts 02139, USA, E-mail:hajiagha@mit.edu . This work was done when the author visited the Microsoft Research. †Microsoft Research, One Microsoft Way, Redmond, WA 98052, USA and Department of Mathematics, Yonsei University, Seoul 120-749, South Korea, E-mail: jehkim@microsoft.com , jehkim@yonsei.ac. kr .
Exploring the Use of Mobile Data Services in Europe: The Cases of Denmark and Greece

Mobile data services seem a promising revenue source for the stakeholders that have heavily invested in mobile communications infrastructures. However, in the Western world those services have not reached the mass markets yet. This chapter focuses on two markets that are representative of the European socioeconomic environment, Greece and Denmark, with the aim to investigate and compare mobile data services use through the means of an online survey. We depict two user groups and observe their behaviors in both countries. The results indicate differences in locations and frequency of services use that can be attributed to specific socioeconomic characteristics. However, certain similarities exist in the experience derived from mobile data service use since users believe that services cannot cater to their specific needs. We conclude by underlining the current challenges faced by mobile service providers in order to increase mobile data services use and summarizing user groups’ characteristics.
Endogenous steroids measured by high-specificity liquid chromatography-tandem mass spectrometry and prevalent cardiovascular disease in 70-year-old men and women.

CONTEXT There is a need for increased knowledge about endogenous sex hormone levels and clinical outcomes of risk/benefit. Immunoassays have poor specificity to reliably measure low steroid concentrations in elderly. OBJECTIVE The objective of the study was to evaluate plasma steroid concentrations with regard to prevalent cardiovascular disease (CVD) in elderly, using mass spectrometry. SETTING The study was conducted at a university hospital research unit. DESIGN AND METHODS Plasma samples were analyzed from 202 70-yr-olds as part of a large population-based study, Prospective Investigation of the Vasculature in Uppsala Seniors. Twenty-eight of these had prevalent CVD. Eleven steroids were quantified, using liquid chromatography-tandem mass spectrometry. Women with current/previous menopausal hormone therapy (n = 35) were excluded. RESULTS Men without prevalent CVD had higher plasma 17beta-estradiol (E2), compared with women. Men with prevalent CVD, compared with those without, had lower 17-hydroxypregnenolone (17OHPregn), 17-hydroxyprogesterone, and higher estrone/androstenedione and E2/testosterone (T) (aromatase activity). Women with prevalent CVD had lower pregnenolone, 17OHPregn, and dehydroepiandrosterone (DHEA) but higher DHEA/17OHPregn, androstenedione/DHEA, E2/T, E2/estrone, and E2/SHBG. The aromatase index, E2/T, was higher for prevalent CVD in both sexes. Adjustment for statin use, smoking, and body mass index yielded additional significant differences in men, whereas some were lost in women. Logistic regression indicated strong associations between prevalent CVD and low 17OHPregn, adjusted odds ratio of 0.18, 95% confidence interval (0.06-0.61); P = 0.006, in women and low 17-hydroxyprogesterone, 0.45 (0.25-0.80); P = 0.007 in men, most likely caused by increased throughput (consumption) toward estrogen synthesis. CONCLUSIONS Prevalent CVD was associated with indications of lower androgen precursors, increased aromatase activity, and higher estrogen levels in both sexes. Results might represent an endogenous response to a condition of developing atherosclerosis, rather than a causative relationship. Furthermore studies are needed.
Compile-time decided instruction cache locking using worst-case execution paths

Caches are notorious for their unpredictability. It is difficult or even impossible to predict if a memory access results in a definite cache hit or miss. This unpredictability is highly undesired for real-time systems. The Worst-Case Execution Time (WCET) of a software running on an embedded processor is one of the most important metrics during real-time system design. The WCET depends to a large extent on the total amount of time spent for memory accesses. In the presence of caches, WCET analysis must always assume a memory access to be a cache miss if it can not be guaranteed that it is a hit. Hence, WCETs for cached systems are imprecise due to the overestimation caused by the caches. Modern caches can be controlled by software. The software can load parts of its code or of its data into the cache and lock the cache afterwards. Cache locking prevents the cache's contents from being flushed by deactivating the replacement. A locked cache is highly predictable and leads to very precise WCET estimates, because the uncertainty caused by the replacement strategy is eliminated completely. This paper presents techniques exploring the lockdown of instruction caches at compile-time to minimize WCETs. In contrast to the current state of the art in the area of cache locking, our techniques explicitly take the worst-case execution path into account during each step of the optimization procedure. This way, we can make sure that always those parts of the code are locked in the I-cache that lead to the highest WCET reduction. The results demonstrate that WCET reductions from 54% up to 73% can be achieved with an acceptable amount of CPU seconds required for the optimization and WCET analyses themselves.
Avian Endogenous Retrovirus EAV-HP Shares Regions of Identity with Avian Leukosis Virus Subgroup J and the Avian Retrotransposon ART-CH

ABSTRACT The existence of novel endogenous retrovirus elements in the chicken genome, designated EAV-HP, with close sequence identity to theenv gene of avian leukosis virus (ALV) subgroup J has been reported (L. M. Smith, A. A. Toye, K. Howes, N. Bumstead, L. N. Payne, and K. Venugopal, J. Gen. Virol. 80:261–268, 1999). To resolve the genome structure of these retroviral elements, we have determined the complete sequence of two proviral clones of EAV-HP from a line N chicken genomic DNA yeast artificial chromosome library and from a meat-type chicken line 21 lambda library. The EAV-HP sequences from the two lines were 98% identical and had a typical provirus structure. The two EAV-HP clones showed identical large deletions spanning part of the gag, the entirepol, and part of the env genes. Theenv region of the EAV-HP clones was 97% identical to theenv sequence of HPRS-103, the prototype subgroup J ALV. The 5′ region of EAV-HP comprising the R and U5 regions of the long terminal repeat (LTR), the untranslated leader, and the 5′ end of the putative gag region were 97% identical to the avian retrotransposon sequence, ART-CH. The remaining gagsequence shared less than 60% identity with other ALV sequences. The U3 region of the LTR was distinct from those of other retroviruses but contained some of the conserved motifs required for functioning as a promoter. To examine the ability of this endogenous retroviral LTR to function as a transcriptional promoter, the EAV-HP and HPRS-103 LTR U3 regions were compared in a luciferase reporter gene assay. The low luciferase activity detected with the EAV-HP LTR U3 constructs, at levels close to those observed for a control vector lacking the promoter or enhancer elements, suggested that these elements function as a weak promoter, possibly accounting for their low expression levels in chicken embryos.
A Two-Phase Switching Hybrid Supply Modulator for RF Power Amplifiers With 9% Efficiency Improvement

A hybrid supply modulator consisting of a parallel operation of a high-drive, low output impedance, wideband class-AB linear amplifier and a high-efficiency, wideband, low-ripple switching amplifier is presented for the application of polar transmitters. At system level, a two-phase switching is employed to lower the inductor current ripple so that both the output ripple and power loss are reduced. On-chip feed-forward bandpass filter is used to extend the tracking bandwidth of the switching amplifier, without hurting the stability of parallel control loop or the need to increase switching frequency. At circuit level, the output impedance of the linear amplifier is lowered by optimizing the design of super source-follower output stage. Inductor current sharing and two-phase ramp generator are implemented for realizing the two-phase switching scheme. Fabricated in a 0.35-μm CMOS process, the prototype chip measures 9 % static efficiency improvement over the conventional single-phase switching design in the back-off power level. Dynamic efficiency is enhanced by 8-12% by enabling the bandpass filter. Successful tracking of a 4 MHz 0.4-2.8 V full-wave rectified sine wave and a WCDMA envelope signal is demonstrated.
Monosynaptic projections of single muscle spindle afferents to neck motoneurons in the cat

Monosynaptic connections to dorsal neck motoneurons of the cat from single afferents supplying primary endings of neck muscle spindles were studied using spike-triggered averaging techniques. Single-fiber EPSPs were detected in only 11 of the 112 afferent-motoneuron pairs examined. The average amplitude of single-fiber EPSPs recorded in motoneurons with a membrane potential of greater than -40 mV was 49 microV. Motoneurons receiving functional contacts from a single afferent were confined to a small rostrocaudal zone within the motor nucleus. The low frequency of single-fiber EPSPs in neck motoneurons could not be attributed to the absence of projections to the ventral horn or to damage to either the afferents or motoneurons. Our results suggest, therefore, that single afferents from neck muscle spindles make functional contacts with a small fraction of neck motoneurons, unlike the arrangement seen in more commonly studied hindlimb muscle systems (Henneman and Mendell, 1981).
Factors associated with a low HIV reservoir in patients with prolonged suppressive antiretroviral therapy.

OBJECTIVES The relevance of low-level HIV DNA in patients who have undergone prolonged therapy is not well understood. The objective of this study was to determine factors that influence the establishment of low-level HIV DNA in long-term treated patients (excluding treatment since acute infection). METHODS This was a cross-sectional study involving 243 patients receiving highly active antiretroviral therapy (HAART) for ≥6 months (median: 9 years of treatment) with plasma HIV RNA <50 copies/mL at the study timepoint, for whom total DNA measurements were performed. Patients treated since early acute infection or receiving cancer chemotherapeutic/immunosuppressive agents were excluded from the study. RESULTS Overall, the median HIV DNA was 372 copies/10(6) peripheral blood mononuclear cells (PBMCs). Forty-seven patients had levels of HIV DNA below the limit of detection and 58 patients had low-level HIV DNA (<100 copies/10(6) PBMCs). In multivariate analysis, a low total HIV DNA in HAART-treated patients was clearly associated with a low HIV RNA pre-therapeutic viral load (P < 0.0001), regardless of the cut-off used. CONCLUSIONS These results may be helpful to identify candidates for future trials aiming at a functional cure of HIV infection, since low total HIV DNA levels will most likely be a prerequisite of successful immunological control of HIV replication.
Youla-Like Parametrizations Subject to QI Subspace Constraints

Consider that a linear time-invariant (LTI) plant is given and that we wish to design a stabilizing controller for it. Admissible controllers are LTI and must belong to a pre-selected subspace that may impose structural restrictions, such as sparsity constraints. The subspace is assumed to be quadratically invariant (QI) with respect to the plant, which, from prior results, guarantees that there is a convex parametrization of all admissible stabilizing controllers provided that an initial admissible stable stabilizing controller is provided. This paper addresses the previously unsolved problem of extending Youla's classical parametrization so that it admits QI subspace constraints on the controller. In contrast with prior parametrizations, the one proposed here does not require initialization and it does not require the existence of a stable stabilizing controller. The main idea is to cast the stabilizability constraint as an exact model-matching problem with stability restrictions, which can be tackled using existing methods. Furthermore, we show that, when it exists, the solution of the exact model-matching problem can be used to compute an admissible stabilizing controller. Applications of the proposed parametrization on the design of norm-optimal controllers via convex methods are also explored. An illustrative example is provided, and a special case is discussed for which the exact model matching problem has a unique and easily computable solution.
Prosodic factors that affect the accentedness of L2 Japanese utterances: What matters most?

This study aims to identify the crucial prosodic factor for native speakers' accentedness judgement of L2 pronunciation. Prosodic features are known to have more impact on the accentedness of L2 learners' pronunciation than segmental features do. Among prosodic features, timing and pitch are looked at in this study as major prosodic factors that affect native speakers' accentedness judgement of L2 pronunciation. To examine the relative importance of timing and pitch, two types of speech samples - natural speech and prosody-modified speech - were used, as these two types of speech compensate each other's shortcomings: Natural speech contains genuine speech errors, whereas in synthesised speech, the number and degree of errors are rigidly controlled. In two experiments, native Japanese listeners assessed the accentedness of these stimuli and the results were compared. Both experiments obtained the same result: that timing is more important than pitch in improving the naturalness of L2 Japanese speech.
Optimal energy management of HEVs with consideration of battery aging

This paper presents an optimal control-based energy management strategy for a parallel hybrid electric vehicle (HEV). This strategy not only seeks to minimize fuel consumption while maintaining the state-of-charge of the battery within reasonable bounds, but also seeks to minimize wear of the battery and extend its life. This multi-objective optimal control problem is solved numerically using Pontryagin's Minimum Principle (PMP).