Miracle-dz/UniFAR-FTUs huggingface dataset:
Ex vivo acidic preconditioning enhances bone marrow ckit+ cell therapeutic potential via increased CXCR4 expression

Aims The chemokine receptor CXCR4 modulates endothelial progenitor cell migration, homing, and differentiation, and plays a key role in cardiovascular regeneration. Here we examined the effect of ex vivo acidic preconditioning (AP) on CXCR4 expression and on the regenerative potential of mouse bone marrow (BM) ckit+ cells. Methods and results Acidic preconditioning was achieved by exposing BM ckit+ cells to hypercarbic acidosis (pH 7.0) for 24 h; control cells were kept at pH 7.4. Acidic preconditioning enhanced CXCR4 and stromal cell-derived factor 1 (SDF-1) mRNA levels, as well as CXCR4 phosphorylation. Acidic preconditioning ability to modulate CXCR4 expression depended on cytosolic calcium [Ca2+]i mobilization and on nitric oxide (NO), as determined by [Ca2+]i buffering with BAPTA, and by treatment with the NO donor (DETA/NO) and the NO synthase inhibitor (L-NAME). Further, AP increased SDF-1-driven chemotaxis, transendothelial migration, and differentiation toward the endothelial lineage in vitro. In a mouse model of hindlimb ischaemia, control and AP ckit+ cells were transplanted into the ischaemic muscle; AP cells accelerated blood flow recovery, increased capillary, and arteriole number as well as the number of regenerating muscle fibres vs. control. These effects were abolished by treating AP cells with L-NAME. Conclusion Acidic preconditioning represents a novel strategy to enhance BM ckit+ cell therapeutic potential via NO-dependent increase in CXCR4 expression.
Measurements of tidal flow around a headland with a shipboard acoustic Doppler current profiler

A shipboard acoustic Doppler current profiler (ADCP) and moored current meters were used to obtain detailed measurements of the spatial structure of the tidal flow around a headland in Vineyard Sound, Massachusetts, where tidal currents typically range from 50 to 70 cm s−1. Eight shipboard surveys were conducted, each of which followed one of five trapezoidal tracks in the vicinity of the headland, completing 11–12 circuits in the course of the tidal cycle (12.4 hours). The measurements from the ADCP compare favorably with moored velocity measurements at two locations (rms deviations of ±3 cm s−1), but the comparison showed more scatter at two other sites (rms deviations of ±7 cm s−1). The ADCP measurements from separate cruises were merged to form a composite spatial representation of the tidal and residual currents, providing resolution of the spatial structure of the flow around the headland at scales from several hundred meters to 10 km. The semidiurnal tidal flow is relatively uniform in space, roughly following the bathymetry around the headland, while a residual current field consists of counterrotating eddies on either side of the headland, with spatial scales of 5–8 km and velocities as high as 25 cm s−1. The instantaneous current field indicates the formation of transient eddies on the downstream side of the headland during flood and ebb, with clear evidence of flow separation near the tip of the headland.
Proof-producing translation of higher-order logic into pure and stateful ML

Abstract The higher-order logic found in proof assistants such as Coq and various HOL systems provides a convenient setting for the development and verification of functional programs. However, to efficiently run these programs, they must be converted (or ‘extracted’) to functional programs in a programming language such as ML or Haskell. With current techniques, this step, which must be trusted, relates similar looking objects that have very different semantic definitions, such as the set-theoretic model of a logic and the operational semantics of a programming language. In this paper, we show how to increase the trustworthiness of this step with an automated technique. Given a functional program expressed in higher-order logic, our technique provides the corresponding program for a functional language defined with an operational semantics, and it provides a mechanically checked theorem relating the two. This theorem can then be used to transfer verified properties of the logical function to the program. We have implemented our technique in the HOL4 theorem prover, translating functions to a subset of Standard ML, and have applied the implementation to examples including functional data structures, a parser generator, cryptographic algorithms, a garbage collector and the 500-line kernel of the HOL light theorem prover. This paper extends our previous conference publication with new material that shows how functions defined in terms of a state-and-exception monad can be translated, with proofs, into stateful ML code. The HOL light example is also new.
Southern San Andreas Fault Evaluation Field Activity: Approaches to Measuring Small Geomorphic Offsets—Challenges and Recommendations for Active Fault Studies

In southern California, where fast slip rates and sparse vegetation contribute to crisp expression of faults and microtopography, field and high‐resolution topographic data (<1 m/pixel) increasingly are used to investigate the mark left by large earthquakes on the landscape (e.g., Zielke et al. , 2010; Zielke et al. , 2012; Salisbury, Rockwell, et al. , 2012, Madden et al. , 2013). These studies measure offset streams or other geomorphic features along a stretch of a fault, analyze the offset values for concentrations or trends along strike, and infer that the common magnitudes reflect successive surface‐rupturing earthquakes along that fault section. Wallace (1968) introduced the use of such offsets, and the challenges in interpreting their “unique complex history” with offsets on the Carrizo section of the San Andreas fault; these were more fully mapped by Sieh (1978) and followed by similar field studies along other faults (e.g., Lindvall et al. , 1989; McGill and Sieh, 1991). Results from such compilations spurred the development of classic fault behavior models, notably the characteristic earthquake and slip‐patch models, and thus constitute an important component of the long‐standing contrast between magnitude–frequency models (Schwartz and Coppersmith, 1984; Sieh, 1996; Hecker et al. , 2013). The proliferation of offset datasets has led earthquake geologists to examine the methods and approaches for measuring these offsets, uncertainties associated with measurement of such features, and quality ranking schemes (Arrowsmith and Rockwell, 2012; Salisbury, Arrowsmith, et al. , 2012; Gold et al. , 2013; Madden et al. , 2013). In light of this, the Southern San Andreas Fault Evaluation (SoSAFE) project at the Southern California Earthquake Center (SCEC) organized a combined field activity and workshop (the “Fieldshop”) to measure offsets, compare techniques, and explore differences in interpretation. A thorough analysis of the measurements from the field activity will be provided separately; this …
Processing of auditory location changes after horizontal head rotation

Under natural conditions, our sound localization capabilities enable us to move constantly while keeping a stable representation of our auditory environment. However, since most auditory studies focus on head-restrained conditions, it is still unclear whether neurophysiological markers of auditory spatial processing reflect representation in a head-centered or an allocentric coordinate system. Therefore, we used human electroencephalography to test whether the spatial mismatch negativity (MMN) as a marker of spatial change processing is elicited by changes of sound source position in terms of a head-related or an allocentric coordinate system. Subjects listened to a series of virtually localized band-passed noise tones and were occasionally cued visually to conduct horizontal head movements. After these head movements, we presented deviants either in terms of a head-centered or an allocentric coordinate system. We observed significant MMN responses to the head-related deviants only but a change-related novelty P3-like component for both head-related and allocentric deviants. These results thus suggest that the spatial MMN is associated with a representation of auditory space in a head-related coordinate system and that the integration of motor output and auditory input possibly occurs at later stages of the auditory “where” processing stream.
Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans- activation

Expression of human immunodeficiency virus type 1 (HIV-1) structural proteins requires the presence of the viral trans-activator protein Rev. Rev is localized in the nucleus and binds specifically to the Rev response element (RRE) sequence in viral RNA. Furthermore, the interaction of the Rev activation domain with a cellular cofactor is essential for Rev function in vivo. Using cross-linking experiments and Biospecific Interaction Analysis (BIA) we identify eukaryotic initiation factor 5A (eIF-5A) as a cellular factor binding specifically to the HIV-1 Rev activation domain. Indirect immunofluorescence studies demonstrate that a significant fraction of eIF-5A localizes to the nucleus. We also provide evidence that Rev transactivation is functionally mediated by eIF-5A in Xenopus oocytes. Furthermore, we are able to block Rev function in mammalian cells by antisense inhibition of eIF-5A gene expression. Thus, regulation of HIV-1 gene expression by Rev involves the targeting of RRE-containing RNA to components of the cellular translation initiation complex.
Lagrangian models of reactive transport in heterogeneous porous media with uncertain properties

We consider multi-component reactive transport in heterogeneous porous media with uncertain hydraulic and chemical properties. This parametric uncertainty is quantified by treating relevant flow and transport parameters as random fields, which renders the governing equations stochastic. We adopt a stochastic Lagrangian framework to replace a three-dimensional advection–reaction transport equation with a one-dimensional equation for solute travel times. We derive approximate expressions for breakthrough curves and their temporal moments. To illustrate our general theory, we consider advective transport of dissolved species undergoing an irreversible bimolecular reaction.
The effect of saddle design on stresses in the perineum during cycling.

PURPOSE Repetitive internal stress in the perineum has been associated with soft-tissue trauma in bicyclists. Using an engineering approach, the purpose of this study was to quantify the amount of compression exerted in the perineum for a range of saddle widths and orientations. METHODS Computer tomography was used to create a three-dimensional voxel-based finite element model of the right side of the male perineum-pelvis. For the creation of the saddle model, a commercially available saddle was digitized and the surface manipulated to represent a variety of saddle widths and orientations. The two models were merged, and a static downward load of 189 N was applied to the model at the region representing the sacroiliac joint. For validation purposes, external stresses along the perineum-saddle interface were compared with the results of pressure sensitive film. Good agreement was found for these external stresses. The saddles were then stretched and rotated, and the magnitude and location of maximum stresses within the perineum were both recorded. In all cases, the model of the pelvis-perineum was held in an upright position. RESULTS Stresses within the perineum were reduced when the saddle was sufficiently wide to support both ischial tuberosities. This supporting mechanism was best achieved when the saddle was at least two times wider than the bi-ischial width of the cyclist. Stresses in the anterior of the perineum were reduced when the saddle was tilted downward, whereas stresses in the posterior were reduced when the saddle was tilted upward. CONCLUSIONS Recommendations that saddles should be sufficiently wide to support the ischial tuberosities appear to be well founded. Recommendations that saddles be tilted downward (i.e., nose down) are supported by the model, but with caution, given the limitations of the model.
Microarray image analysis based on an evolutionary approach

Biological conclusions reached during microarray experiments can be greatly affected by human intervention, which is currently required in microarray image analysis. Therefore, accurate and automatic analysis of cDNA microarray images becomes crucial. In this paper, an automatic approach to microarray image analysis is presented. The proposed approach is based on the concept of evolution in order to process the microarray images. Conducted experiments in a set of real microarray images confirm the effectiveness of the proposed approach.
Angiotensin-converting enzyme inhibitors. Relationship between pharmacodynamics and pharmacokinetics.

The inter-relationship between the pharmacokinetic and pharmacodynamic behaviour of ACE inhibitors is reviewed. First, some of the methods which have been used to assess the pharmacodynamics of ACE inhibitors in humans are presented. They include humoral assays (e.g. ACE activity in plasma, renin activity, etc.), haemodynamic changes (blood pressure, total peripheral resistance, etc.) and agonist challenges (angiotensin I infusions). Subsequently a pharmacokinetic-dynamic model is described, based on biochemical processes obtained after ACE inhibition, which seems to be useful for the interpretation of the complex processes. The various correlations between plasma drug concentration on the one hand and plasma ACE activity, angiotensin II concentration in plasma or blood pressure on the other, are discussed on the basis of this model. From the model obtained it becomes obvious that under many circumstances the release of the inhibitor from ACE binding is the step which in fact determines the pharmacodynamically relevant elimination rate of the drug at low concentrations, whereas at high concentrations the elimination of the drug is mainly dependent on kidney (and/or liver) elimination rate. The dynamic-kinetic correlations are then presented for some ACE inhibitors in various disease states: arterial hypertension, heart failure, old age, renal failure, liver disease. In a final section the kinetic and dynamic relevance of interactions of ACE inhibitors with food and other drugs is described (e.g. prostaglandin inhibitors, diuretics, digoxin and cimetidine). Despite the great body of literature which deals with the kinetic and/or dynamic properties of ACE inhibitors, precise knowledge of the relationship between their kinetic and dynamic behaviour is rather limited and there is a clear need for further studies to elucidate this complex topic, thereby improving therapeutic possibilities with these useful new compounds.
Fairness via Source Throttling: A Configurable and High-Performance Fairness Substrate for Multicore Memory Systems

Cores in chip-multiprocessors (CMPs) share multiple memory subsystem resources. If resource sharing is unfair, some applications can be delayed significantly while others are unfairly prioritized. Previous research proposed separate fairness mechanisms for each resource. Such resource-based fairness mechanisms implemented independently in each resource can make contradictory decisions, leading to low fairness and performance loss. Therefore, a coordinated mechanism that provides fairness in the entire shared memory system is desirable. This article proposes a new approach that provides fairness in the entire shared memory system, thereby eliminating the need for and complexity of developing fairness mechanisms for each resource. Our technique, Fairness via Source Throttling (FST), estimates unfairness in the entire memory system. If unfairness is above a system-software-set threshold, FST throttles down cores causing unfairness by limiting the number of requests they create and the frequency at which they do. As such, our source-based fairness control ensures fairness decisions are made in tandem in the entire memory system. FST enforces thread priorities/weights, and enables system-software to enforce different fairness objectives in the memory system. Our evaluations show that FST provides the best system fairness and performance compared to three systems with state-of-the-art fairness mechanisms implemented in both shared caches and memory controllers.
Oxidative Stress Induced by Fumonisin B1 in Continuous Human and Rodent Neural Cell Cultures

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticillioides, which is a common infectant of corn and other cereal grains. Of concern to human health is also a possible airborne exposure to FB1-producing strains of F. verticillioides, which may grow in moisture-damaged buildings. In this study, we have characterized oxidative stress-related parameters induced by FB1 in three different neural cell lines, human SH-SY5Y neuroblastoma, rat C6 glioblastoma and mouse GT1-7 hypothalamic cells. The cells were exposed to graded doses of FB1 between 0.1 and 100 μM for 0-144 h after which the production of reactive oxygen species (ROS), lipid peroxidation, intracellular glutathione (GSH) levels and cell viability were measured. FB1 caused a dose-dependent increase of ROS production in C6 glioblastoma and GT1-7 hypothalamic cells but was without an effect in SH-SY5Y cells. Decreased GSH levels, increased MDA-formation, indicative of lipid peroxidation and necrotic cell death were observed in all cell lines after incubation with FB1. These findings indicate that FB1 induces oxidative stress in human, rat and mouse neural cell cultures.
Blood Vessel Density in Basal Cell Carcinomas and Benign Trichogenic Tumors as a Marker for Differential Diagnosis in Dermatopathology

In order to get insight into the density of blood vessels in the stroma of benign and malignant trichogenic neoplasms, immunohistological quantification of CD 31 positive vessels was performed in 112 tumors, comprised of 50 BCCs of nodular (35) or morphoeic (15) growth patterns, 17 Pinkus' tumors, as well as 17 trichoepitheliomas of which 6 were desmoplastic, 8 trichofolliculomas, and 20 trichoblastomas. Methods. Vessel density was counted within the tumors, in the tumor-surrounding stroma, and, as a control, in the normal skin of the operation specimen. The results were compared using statistical methods. Results. Whereas, irrespective of the patients' age and location of tumors, the vessel density in normal skin showed no significant differences (8.8 ± 2.7), the counts in the peritumoral stroma revealed significant differences between the different tumors investigated. The highest counts were obtained in BCC (24.7 ± 6.7) and the lowest in benign trichogenic neoplasms (around 14) Pinkus' tumors revealed intermediate counts (19.7 ± 6.6). The vessel densities within the tumors were generally low, and no correlation to the dignity was found. Conclusion. Determination of blood vessel density in the peritumoral stroma may be an additional parameter for differential diagnosis of trichogenic tumors of uncertain dignity.
Adolescents Demonstrate Greater Gait Balance Control Deficits After Concussion Than Young Adults

Background: Age has been described as a factor that affects recovery after concussion. The recommended management protocol is to treat adolescents in a more cautious manner than adults. However, few studies have prospectively and longitudinally assessed the way these age groups perform on motor tasks after concussion. Purpose: To examine dual-task gait balance control deficits after concussion in a group of adolescents and young adults in reference to matched control subjects within 72 hours of injury and throughout 2 months after injury. Study Design: Cohort study; Level of evidence, 2. Methods: Adolescents and young adults who sustained a concussion and individually matched controls completed a whole-body motion gait analysis while simultaneously performing a cognitive task. Subjects with concussion reported to the laboratory within 72 hours after injury and at the following time points: 1 week, 2 weeks, 1 month, and 2 months after injury. Control subjects completed the same protocol at similar time points. Gait balance control measurements included whole-body center-of-mass (COM) medial-lateral displacement/velocity and anterior velocity. Results: A total of 38 subjects with concussion, 19 young adults (mean ± SD age, 20.3 ± 2.4 years) and 19 adolescents (mean ± SD age, 15.1 ± 1.1 years), and 38 individually matched control subjects were tested. Within 72 hours of injury, adolescents displayed significantly greater COM medial-lateral displacement (P = .001) and peak velocity (P = .001) relative to their control group, and the young adult concussion group displayed significantly less peak COM anterior velocity than their control group (P = .01). Across the 2 months of testing, adolescents with concussion displayed significantly greater total COM medial-lateral displacement than did adolescent controls (P = .001), while young adults with concussion did not significantly differ from their matched controls (P = .07). Conclusion: An examination of gait balance control during dual-task walking revealed that after concussion, in reference to matched controls, adolescents demonstrated greater gait balance control deficits than did young adults initially and throughout the 2-month postinjury period, supporting the recommendation of conservative management for adolescents after concussion.
Reinvestigation of the Oxidative Folding Pathways of Hen Egg White Lysozyme: Switching of the Major Pathways by Temperature Control

It has been well established that in the oxidative folding of hen egg white lysozyme (HEL), which has four SS linkages in the native state (N), three des intermediates, i.e., des[76–94], des[64–80], and des [6–127], are populated at 20 °C and N is dominantly formed by the oxidation of des[64–80] and des[6–127]. To elucidate the temperature effects, the oxidative folding pathways of HEL were reinvestigated at 5–45 °C in the presence of 2 M urea at pH 8.0 by using a selenoxide reagent, DHSox. When reduced HEL was reacted with 1–4 equivalents of DHSox, 1S, 2S, 3S, and 4S intermediate ensembles with 1–4 SS linkages, respectively, were produced within 1 min. After the oxidation, 3S was slowly converted to the des intermediates with formation of the native structures through SS rearrangement. At 5 °C, des[76–94] was populated in the largest amount, but the oxidation to N was slower than that of des[64–80] and des[6–127]. At 35 °C, on the other hand, des[64–80] and des[6–127] were no longer stable, and only des[76–94] was populated. The results suggested that the major folding pathways of HEL can be switched from one to the other by temperature control.
Open-Domain Question Answering from Large Text Collections

This book is a revised version of Marius Paşca’s 2001 dissertation at Southern Methodist University, supervised by Sanda Harabagiu. Paşca, Harabagiu, and Dan Moldovan are members of a Texas-based research team that has achieved considerable success in the question answering (QA) track of TREC, the major annual text retrieval conference. Open-domain QA involves retrieving relevant passages from large text collections (e.g., newswire or the WWW) in hopes of finding answers to specific factual questions on arbitrary topics. Queries are not lists of keywords, but rather full sentences, such as “Who was Secretary of State during the Nixon administration? ” Paşca focuses on extraction-based QA, in which answer strings (typically NPs or named entities) are not generated, but rather extracted verbatim from relevant text passages. Extractionbased QA is appropriate for simple “factoid” questions but, as Paşca acknowledges, usually fails on why and how questions, as well as complex but decomposable questions such as “How far is it from the largest alpine lake in North America to the largest city in Nevada? ” The book’s introductory chapters present background information that newcomers to QA will find useful. Here, Paşca analyzes the extraction-based QA task and breaks it down into three main subproblems: