Miracle-dz/UniFAR-FTUs huggingface dataset:
Daily use of smokeless tobacco: systemic effects.

STUDY OBJECTIVE To compare exposure to nicotine and related cardiovascular effects as well as urinary mutagenicity (a potential marker of systemic absorption of carcinogenic compounds) during use of oral snuff, chewing tobacco, and cigarettes, as desired. DESIGN Crossover sequential treatments, balanced-order experimental study. SETTING Clinical research center. PARTICIPANTS Eight healthy men who regularly smoked cigarettes and had previous experience with the use of both oral snuff and chewing tobacco. INTERVENTIONS Four 3- or 4-day blocks during which participants used oral snuff, chewing tobacco, and cigarettes as desired, or abstained from all tobacco. Concentrations of nicotine and cotinine (the primary metabolite of nicotine), cardiovascular effects, and urine sodium, catecholamine and mutagenicity were measured over 24 hours at the end of each treatment block. MEASUREMENTS AND MAIN RESULTS Circadian exposure to nicotine and cardiovascular effects, including urinary catecholamine excretion, were similar for all forms of tobacco use. Urine sodium excretion was greater while using smokeless tobacco than while smoking, probably due to absorption of sodium from the smokeless tobacco. Urine mutagenicity was markedly increased while smoking cigarettes and tended to be increased (P less than 0.10) while chewing tobacco but not while using oral snuff. CONCLUSIONS Systemic absorption of nicotine, sodium, and carcinogenic chemicals from smokeless tobacco may cause or aggravate human illness in addition to the known adverse effects on the oral cavity.
Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: The Role of Abnormal Peripheral Oxygen Extraction

Background—Exercise capacity as measured by peak oxygen uptake (VO2) is similarly impaired in patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). However, characterization of how each component of VO2 changes in response to incremental exercise in HFpEF versus HFrEF has not been previously defined. We hypothesized that abnormally low peripheral o2 extraction (arterio-mixed venous o2 content difference, [C(a-v)o2]) during exercise significantly contributes to impaired exercise capacity in HFpEF. Methods and Results—We performed maximum incremental cardiopulmonary exercise testing with invasive hemodynamic monitoring on 104 patients with symptomatic NYHA II to IV heart failure (HFpEF, n=48, peak VO2=13.9±0.5 mL kg−1 min−1, mean±SEM, and HFrEF, n=56, peak VO2=12.1±0.5 mL kg−1 min−1) and 24 control subjects (peak VO2 27.0±1.7 mL kg−1 min−1). Peak exercise C(a-v)o2 was lower in HFpEF compared with HFrEF (11.5±0.27 versus 13.5±0.34 mL/dL, respectively, P<0.0001), despite no differences in age, hemoglobin level, peak respiratory exchange ratio, CaO2, or cardiac filling pressures. Peak C(a-v)o2 and peak heart rate emerged as the leading predictors of peak VO2 in HFpEF. Impaired peripheral o2 extraction was the predominant limiting factor to exercise capacity in 40% of patients with HFpEF and was closely related to elevated systemic blood pressure during exercise (r=0.49, P=0.0005). Conclusions—In the first study to directly measure C(a-v)o2 throughout exercise in HFpEF, HFrEF, and normals, we found that peak C(a-v)o2 was a major determinant of exercise capacity in HFpEF. The important functional limitation imposed by impaired o2 extraction may reflect intrinsic abnormalities in skeletal muscle or peripheral microvascular function, and represents a potential target for therapeutic intervention.
Molecular Basis of Hb H Disease in Southwest Iran

Although α0-thalassemia (thal) defects are not very frequent in the Iranian population, Hb H disease does occur in the country. We have analyzed the α gene cluster of 13 patients showing the presence of Hb H to establish the molecular background of this disease in southwest Iran (Shiraz and Hormozgan provinces). Using gap-polymerase chain reaction (gap-PCR) and direct DNA sequencing we have found the − −MED-I deletion, the polyadenylation signal (poly A) mutations αT-Saudiα and αT-Turkishα, and Hb Constant Spring (Hb CS) in association with the common − α3. 7 deletion. This study has revealed that: 1) at least six genotypes are responsible for Hb H disease in the area: − α3. 7/− −MED-I; − α3. 7/αT-Saudiα; αT-Saudiα/αT-Saudiα; αCSα/− −MED-I; − −MED-I/αT-Turkishα; and the atypical forms of Hb H disease − α3. 7/αCSα. 2) The molecular background of Hb H disease in the southwest area of Iran is more similar to the Mediterranean type than to the Southeast Asian. 3) Hb Bart's hydrops fetalis syndrome and mild, intermediate or severe postnatal Hb H disease conditions can be expected, but at a relatively low incidence. 4) The diagnostic flowchart for patients with microcytic hypochromic anemia should include iron deficiency, β-thal, α+- and α0-thal analyses.
A model for damage analysis of concrete

The damage level in structures (global scale), elements (intermediate scale) and sections (local scale) can be evaluated using a single parameter called the "Damage Index". Part of the damage attributed to the local scale relates to the damage sustained by the materials of which the section is made. This study investigates the damage of concrete subjected to monotonic compressive loading using four different damage models - one proposed here for the first time and three other well-known models. The analytical results show that the proposed model is promising yet simple and effective for evaluating the damage of concrete. The proposed damage model of concrete with its promising characteristics indicated, appears to be a useful tool in the damage assessment of structures made of concrete.
The Impact of Hemolysis on Cell-Free microRNA Biomarkers

Cell-free microRNAs in plasma and serum have become a promising source of biomarkers for various diseases. Despite rapid progress in this field, there remains a lack of consensus regarding optimal quantification methods, reference genes, and quality control of samples. Recent studies have shown that hemolysis occurring during blood collection has substantial impact on the microRNA content in plasma/serum. To date, the impact of hemolysis has only been investigated for a limited number of microRNAs, mainly the red blood cell (RBC)-enriched miRs-16 and -451. In contrast, the effect of hemolysis on other microRNAs – in particular those proposed as biomarkers – has not been addressed. In this study we profiled the microRNA content of hemolyzed and non-hemolyzed plasma as well as RBCs to obtain a profile of microRNAs in the circulation affected or unaffected by hemolysis. Profiling by TaqMan Array Microfluidic Cards was used to compare three pairs of hemolyzed and non-hemolyzed plasma (with varying degrees of hemolysis) and one RBC sample. A total of 136 microRNAs were detectable in at least two of the samples, and of those 15 were at least twofold elevated in all three hemolyzed samples. This number increased to 88 microRNAs for the sample with the highest level of hemolysis, with all of these also detected in the RBC profile. Thus these microRNAs represent a large proportion of detectable microRNAs and those most likely to be affected by hemolysis. Several of the hemolysis-susceptible microRNAs (e.g., miRs-21, -106a, -92a, -17, -16) have also been previously proposed as plasma/serum biomarkers of disease, highlighting the importance of rigorous quality control of plasma/serum samples used for measurement of circulating microRNAs. As low-level hemolysis is a frequent occurrence during plasma/serum collection it is critical that this is taken into account in the measurement of any candidate circulating microRNA.
An Elitist Selection Adaptive Genetic Algorithm for Resource Allocation in Multiuser Packet-based OFDM Systems

This paper presents a new cross-layer resource allocation model for multiuser packet-based Orthogonal Frequency Division Multiplexing (OFDM) systems, where the packet arrival process, delay QoS in the application layer and the subcarrier conditions for all users in the physical layer are considered in the MAC layer design. The objective of the proposed cross-layer resource allocation is formulated into a constrained optimization problem, which incorporates the three layers into an integrated framework. To solve the problem effectively, we propose an elitist selection adaptive genetic algorithm (ESAGA), in which the probabilities of crossover and mutation are varied depending on the diversity of population. Numerical examples demonstrate the effectiveness of our proposed algorithm. Due to its low computational complexity, our proposed algorithm is very suitable for implementation in a practical system.
A New Model of Speech Motor Control Based on Task Dynamics and State Feedback

We present a new model of speech motor control (TD-SFC) based on articulatory goals that explicitly incorporates acoustic sensory feedback using a framework for state-based control. We do this by combining two existing, complementary models of speech motor control – the Task Dynamics model [1] and the State Feedback Control model of speech [2]. We demonstrate the effectiveness of the combined model by simulating a simple formant perturbation study, and show that the model qualitatively reproduces the behavior of online compensation for unexpected perturbations reported in human subjects.
Sodium Acts as a Potassium Analog on Gastric H,K-ATPase (*)

The effects of Na+ on gastric H,K-ATPase were investigated using leaky and ion-tight H,K-ATPase vesicles. Na+ activated the total ATPase activity in the absence of K+, reaching levels of 15% relative to those in the presence of K+. The Na+ activation, which takes place at the luminal side of the membrane, depended on the ATP concentration and the type of buffer used. The steady-state ATP phosphorylation level, studied with leaky vesicles, was reduced by Na+ due to both activation of the dephosphorylation reaction and a shift to E2 in the E1⤔E2 equilibrium. By studying this equilibrium in ion-tight H,K-ATPase vesicles, it was found that Na+ drives the enzyme via a cytosolic site to the nonphosphorylating E2 conformation. No H+-like properties of cytosolic Na+ could be detected. We therefore conclude that Na+ behaves like K+ rather than like H+ in the H,K-ATPase reaction.
Differences between Human Plasma and Serum Metabolite Profiles

Background Human plasma and serum are widely used matrices in clinical and biological studies. However, different collecting procedures and the coagulation cascade influence concentrations of both proteins and metabolites in these matrices. The effects on metabolite concentration profiles have not been fully characterized. Methodology/Principal Findings We analyzed the concentrations of 163 metabolites in plasma and serum samples collected simultaneously from 377 fasting individuals. To ensure data quality, 41 metabolites with low measurement stability were excluded from further analysis. In addition, plasma and corresponding serum samples from 83 individuals were re-measured in the same plates and mean correlation coefficients (r) of all metabolites between the duplicates were 0.83 and 0.80 in plasma and serum, respectively, indicating significantly better stability of plasma compared to serum (p = 0.01). Metabolite profiles from plasma and serum were clearly distinct with 104 metabolites showing significantly higher concentrations in serum. In particular, 9 metabolites showed relative concentration differences larger than 20%. Despite differences in absolute concentration between the two matrices, for most metabolites the overall correlation was high (mean r = 0.81±0.10), which reflects a proportional change in concentration. Furthermore, when two groups of individuals with different phenotypes were compared with each other using both matrices, more metabolites with significantly different concentrations could be identified in serum than in plasma. For example, when 51 type 2 diabetes (T2D) patients were compared with 326 non-T2D individuals, 15 more significantly different metabolites were found in serum, in addition to the 25 common to both matrices. Conclusions/Significance Our study shows that reproducibility was good in both plasma and serum, and better in plasma. Furthermore, as long as the same blood preparation procedure is used, either matrix should generate similar results in clinical and biological studies. The higher metabolite concentrations in serum, however, make it possible to provide more sensitive results in biomarker detection.
Clinical Safety , CorrelativeMarkers , andClinical Results of Adjuvant Nivolumab in Combination with Vaccine in Resected High-Risk Metastatic Melanoma

Purpose: The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IVmelanoma patients. Experimental Design: HLA-A 0201 positive patients with HMB-45, NY-ESO-1, and/or MART-1 positive resected tumors received nivolumab (1 mg/kg, 3 mg/kg, or 10 mg/kg i.v.) with a multi-peptide vaccine (gp100, MART-1, and NY-ESO-1 with Montanide ISA 51 VG) every 2 weeks for 12 doses followed by nivolumab maintenance every 12 weeks for 8 doses. Primary objective was safety and determination of a maximum tolerated dose (MTD). Secondary objectives included relapse-free survival (RFS), overall survival (OS), and immunologic correlative studies. Results: Thirty-three patients were enrolled. Median age was 47 years; 55% were male. Two patients had stage IIIC disease; 31 patients had stage IV disease. Median follow-up was 32.1 months. MTD was not reached. Most common related adverse events (>40%) were vaccine injection site reaction, fatigue, rash, pruritus, nausea, and arthralgias. Five related grade 3 adverse events [hypokalemia (1), rash (1), enteritis (1), and colitis (2)] were observed. Ten of 33 patients relapsed. Estimated median RFS was 47.1 months; median OS was not reached. Increases in CTLA-4þ/CD4þ, CD25þTreg/CD4þ, and tetramer specific CD8þ T-cell populations were observed with treatment (P < 0.05). Trends for lower baseline myeloid-derived suppressor cell and CD25þTreg/CD4þ populations were seen in nonrelapsing patients; PD-L1 tumor status was not significantly associated with RFS. Conclusions: Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study. Clin Cancer Res; 21(4); 712–20. 2014 AACR.
Effects of simulated weathering on the toxicity 1 of selected crude oils and their components to sea urchin 2 embryos 3 AUTHOR NAMES

17 Artificial weathering of Angolan crude and a Heavy Fuel Oil (HFO) was performed by evaporation and 18 photooxidation. The aliphatic, aromatic, polar and asphaltene fractions of the fresh and weathered oils 19 were isolated. The toxicity of the water accommodated fraction or an oil/fraction dissolved in DMSO 20 was assessed using the sea urchin embryo test. Photooxidation was observed to decrease the aromatics 21 content and increase polar compounds. A slight reduction in the toxicity of Angolan crude was observed 22 following weathering for the water-accommodated fraction and the extract in DMSO, but no effect was 23 seen for the Heavy Fuel Oil. For aliphatic compounds, the toxicity decreased in the order 24 Fresh>Evaporated>Photooxidated for both Angolan crude and HFO. Weathering slightly increased the 25 toxicity of the aromatic and polar fractions of the oil. The aromatic fractions were responsible for most 26 of the toxicity and the polar compounds were the second most important toxic components, despite 27 having less or similar abundance than the aliphatic fraction. The toxic contribution of the aromatic 28 compounds was higher for the HFO than for the Angolan crude. A decrease in the toxicity of Angolan 29 crude following weathering correlated with a reduction in the toxicity of the aliphatic fraction. 30
A Behavioral Study of TCP Linux Variants over Satellite Networks

The Transmission Control Protocol (TCP) is used by the vast majority of Internet applications. Since its introduction in the 70s, a lot of variants have been proposed to cope with the different network conditions we can have (e.g., wired networks, wireless networks, satellite links) and nowadays Linux OS includes 13 different TCP variants. The aim of this paper is to offer a detailed comparative analysis of the behavior offered by these variants over satellite networks, in terms of congestion window behavior and achieved throughput.
Beam Search Strategies for Neural Machine Translation

The basic concept in Neural Machine Translation (NMT) is to train a large Neural Network that maximizes the translation performance on a given parallel corpus. NMT is then using a simple left-to-right beam-search decoder to generate new translations that approximately maximize the trained conditional probability. The current beam search strategy generates the target sentence word by word from left-to-right while keeping a fixed amount of active candidates at each time step. First, this simple search is less adaptive as it also expands candidates whose scores are much worse than the current best. Secondly, it does not expand hypotheses if they are not within the best scoring candidates, even if their scores are close to the best one. The latter one can be avoided by increasing the beam size until no performance improvement can be observed. While you can reach better performance, this has the drawback of a slower decoding speed. In this paper, we concentrate on speeding up the decoder by applying a more flexible beam search strategy whose candidate size may vary at each time step depending on the candidate scores. We speed up the original decoder by up to 43% for the two language pairs German to English and Chinese to English without losing any translation quality.
Intestinal Master Transcription Factor CDX2 Controls Chromatin Access for Partner Transcription Factor Binding

ABSTRACT Tissue-specific gene expression requires modulation of nucleosomes, allowing transcription factors to occupy cis elements that are accessible only in selected tissues. Master transcription factors control cell-specific genes and define cellular identities, but it is unclear if they possess special abilities to regulate cell-specific chromatin and if such abilities might underlie lineage determination and maintenance. One prevailing view is that several transcription factors enable chromatin access in combination. The homeodomain protein CDX2 specifies the embryonic intestinal epithelium, through unknown mechanisms, and partners with transcription factors such as HNF4A in the adult intestine. We examined enhancer chromatin and gene expression following Cdx2 or Hnf4a excision in mouse intestines. HNF4A loss did not affect CDX2 binding or chromatin, whereas CDX2 depletion modified chromatin significantly at CDX2-bound enhancers, disrupted HNF4A occupancy, and abrogated expression of neighboring genes. Thus, CDX2 maintains transcription-permissive chromatin, illustrating a powerful and dominant effect on enhancer configuration in an adult tissue. Similar, hierarchical control of cell-specific chromatin states is probably a general property of master transcription factors.
Experimental Apparatuses for the Determination of Pavement Material Thermal Properties

Degradation due to temperature fluctuation is the predominant deterioration mechanism affecting many asphalt and cementitious pavement systems. Reduced durability, in turn, limits the sustainability of a materials system: maintenance and replacement are almost always energy and resource intensive. As such, accurate quantification of the thermal properties of any given pavement material is necessary to determine durability and evaluate the effectiveness of novel technologies. Two somewhat inexpensive apparatuses have been developed for this purpose. The first, a Guarded Longitudinal Calorimeter (GLC), measures heat flow through a specimen sandwiched between standards of known thermal properties during either heating or cooling; from the measured heat flow data, many useful thermal properties (apparent thermal conductivity, etc.) can be obtained. The second device, a Solar Simulator, measures the temperature at different depths in multiple well-insulated specimens as they are heated or cooled by halogen lamps or cooled air blowers. The theory, construction, and operation of these devices will be detailed, and the results of analyzing pavement materials in each will be discussed.
Antithrombotic Effects of FK419, a Novel Nonpeptide Platelet GPIIb/IIIa Antagonist, in a Guinea Pig Photochemically Induced Middle Cerebral Artery Thrombosis Model: Comparison with Ozagrel and Argatroban

Platelet activation and subsequent aggregation play a key role in the pathogenesis of ischemic brain damage. Recent studies revealed that enhanced platelet activation is also observed after ischemia, suggesting that secondary thrombus formation might participate in the development of cerebral infarction. The binding of platelet glycoprotein GPIIb/IIIa (integrin αIIbβ3) to fibrinogen is the final common pathway in platelet aggregation. Therefore, GPIIb/IIIa antagonists might be useful in acute ischemic stroke as well as in the secondary prevention of ischemic stroke. In the present study, we evaluated the effect of three compounds, FK419 ((S)-2-acetylamino-3-[(R)-[1-[3-(piperidin-4-yl) propionyl] piperidin-3-ylcarbonyl] amino] propionic acid trihydrate), a novel nonpeptide GPIIb/IIIa antagonist, ozagrel, a selective thromboxane A2 synthase inhibitor, and argatroban, a thrombin inhibitor, on middle cerebral artery (MCA) patency and ischemic brain damage using photochemically induced MCA thrombosis model in guinea pigs. FK419, ozagrel, or argatroban was administered 5 min after the termination of photoirradiation. FK419 dose-dependently improved MCA patency by decreasing the total occlusion time, time to continuous reperfusion, and the number of cyclic flow reductions, at doses that inhibited ADP-induced platelet aggregation ex vivo. In contrast, ozagrel only improved total occlusion time, and argatroban showed no improvement in MCA patency. FK419 also reduced ischemic brain damage in a dose-dependent fashion, whereas ozagrel and argatroban did not. Finally, FK419 ameliorated neurological deficits, whereas ozagrel and argatroban did not. These results indicate that FK419, a GPIIb/IIIa antagonist, ameliorates ischemic brain damage by improving MCA patency after occlusion and that FK419 is a promising candidate for the treatment of acute ischemic stroke.