Miracle-dz/UniFAR-FTUs huggingface dataset:
Cerebral Microembolism Is Blocked by Tirofiban, a Selective Nonpeptide Platelet Glycoprotein IIb/IIIa Receptor Antagonist

Background—Microembolic signals (MES) as detected by transcranial Doppler ultrasound define an individual stroke risk in patients with carotid artery disease. To study the composition of MES in vivo, we used the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist tirofiban, a highly selective platelet aggregation inhibitor. Methods and Results—Twenty-four patients with recent cerebral or retinal embolism of arterial origin and a MES rate >6 per hour on initial transcranial Doppler ultrasonography recording received the short-acting GPIIb/IIIa antagonist tirofiban. With tirofiban, the MES rate dropped from a median (range) of 38 (9 to 324) to zero in all patients. After cessation of infusion, the inhibitory effect of tirofiban was reversible, with a significant increase of MES (median 13.5; range, 0 to 35; n=16;P =0.001). Six patients received overlapping oral antiplatelet agents and remained MES-negative. Conclusions—Cerebral microembolism of arterial origin has the property of solid emboli, with platelet-fibrinogen units as predominant constituent parts. GPIIb/IIIa antagonists may have the potential to bridge the ischemic risk in patients with unstable carotid disease.
The key role of nitric oxide in hypoxia: hypoxic vasodilation and energy supply-demand matching.

SIGNIFICANCE A mismatch between energy supply and demand induces tissue hypoxia with the potential to cause cell death and organ failure. Whenever arterial oxygen concentration is reduced, increases in blood flow--hypoxic vasodilation--occur in an attempt to restore oxygen supply. Nitric oxide (NO) is a major signaling and effector molecule mediating the body's response to hypoxia, given its unique characteristics of vasodilation (improving blood flow and oxygen supply) and modulation of energetic metabolism (reducing oxygen consumption and promoting utilization of alternative pathways). RECENT ADVANCES This review covers the role of oxygen in metabolism and responses to hypoxia, the hemodynamic and metabolic effects of NO, and mechanisms underlying the involvement of NO in hypoxic vasodilation. Recent insights into NO metabolism will be discussed, including the role for dietary intake of nitrate, endogenous nitrite (NO₂⁻) reductases, and release of NO from storage pools. The processes through which NO levels are elevated during hypoxia are presented, namely, (i) increased synthesis from NO synthases, increased reduction of NO₂⁻ to NO by heme- or pterin-based enzymes and increased release from NO stores, and (ii) reduced deactivation by mitochondrial cytochrome c oxidase. CRITICAL ISSUES Several reviews covered modulation of energetic metabolism by NO, while here we highlight the crucial role NO plays in achieving cardiocirculatory homeostasis during acute hypoxia through both vasodilation and metabolic suppression. FUTURE DIRECTIONS We identify a key position for NO in the body's adaptation to an acute energy supply-demand mismatch.
Overview of speech enhancement techniques for automatic speaker recognition

Real world conditions differ from ideal or laboratory conditions, causing mismatch between training and testing phases, and consequently, inducing performance degradation in automatic speaker recognition systems. Many strategies have been adopted to cope with acoustical degradation; in some applications of speaker identification systems a clean sample of speech, prior to the recognition stage, is needed. This has justified the use of procedures that may reduce the impact of acoustical noise on the desired signal, giving rise to techniques involved in the enhancement of noisy speech. A comparative performance analysis of single-channel (based in classical spectral subtraction and some derived alternatives), dual-channel (based in adaptive noise cancelling) and multi-channel (using microphone arrays) speech enhancement techniques, with different types of noise at different SNRs, as a pre-processing stage to an ergodic HMM-based speaker recognizer, is presented.
The Monty Python method for generating random variables

We suggest an interesting and fast method for generating normal, exponential, t, von Mises, and certain other important random variables used in Monte Carlo studies. The right half of a symmetric density is cut into pieces, then, using simple area-preserving transformations, reassembled into a rectangle from which the x-coordinate—or a linear function of the x-coordinate—of a random point provides the required variate. To illustrate the speed and simplicity of the Monty Python method, we provide a small C program, self-contained, for rapid generation of normal (Gaussian) variables. It is self-contained in the sense that required uniform variates are generated in-line, as pairs of 16-bit integers by means of the remarkable new multiply-with-carry method.
Electrooculogram based detection of visual memory recall process

Detection of visual memory recall finds applications in context aware ubiquitous computing systems capable of assisting people with memory oblivion. The present work is aimed at identification of visual memory recall of human beings from the analysis of their eye movements through Electrooculogram signals. These signals are represented through Adaptive Autoregressive Parameters, Power Spectral Density, Hjorth Parameters and Wavelet Coefficients as signal features. Classification of the obtained feature spaces is carried out using Support Vector Machine with Radial Basis Function Kernel, K-Nearest Neighbour and Naïve Bayes classifiers to distinctly identify previously seen and new images from a series of images presented as visual stimuli. Performance of classification is evaluated in terms of classification accuracy, sensitivity and specificity. A maximum accuracy of 89.50% is obtained on an average over ten participating subjects using SVM-RBF classifier on a combined feature space comprising all four signal features.
A Novel Role for Mc1r in the Parallel Evolution of Depigmentation in Independent Populations of the Cavefish Astyanax mexicanus

The evolution of degenerate characteristics remains a poorly understood phenomenon. Only recently has the identification of mutations underlying regressive phenotypes become accessible through the use of genetic analyses. Focusing on the Mexican cave tetra Astyanax mexicanus, we describe, here, an analysis of the brown mutation, which was first described in the literature nearly 40 years ago. This phenotype causes reduced melanin content, decreased melanophore number, and brownish eyes in convergent cave forms of A. mexicanus. Crosses demonstrate non-complementation of the brown phenotype in F2 individuals derived from two independent cave populations: Pachón and the linked Yerbaniz and Japonés caves, indicating the same locus is responsible for reduced pigmentation in these fish. While the brown mutant phenotype arose prior to the fixation of albinism in Pachón cave individuals, it is unclear whether the brown mutation arose before or after the fixation of albinism in the linked Yerbaniz/Japonés caves. Using a QTL approach combined with sequence and functional analyses, we have discovered that two distinct genetic alterations in the coding sequence of the gene Mc1r cause reduced pigmentation associated with the brown mutant phenotype in these caves. Our analysis identifies a novel role for Mc1r in the evolution of degenerative phenotypes in blind Mexican cavefish. Further, the brown phenotype has arisen independently in geographically separate caves, mediated through different mutations of the same gene. This example of parallelism indicates that certain genes are frequent targets of mutation in the repeated evolution of regressive phenotypes in cave-adapted species.
Oxidative Responses of Human and Murine Macrophages During Phagocytosis of Leishmania chagasi1

Leishmania chagasi, the cause of South American visceral leishmaniasis, must survive antimicrobial responses of host macrophages to establish infection. Macrophage oxidative responses have been shown to diminish in the presence of intracellular leishmania. However, using electron spin resonance we demonstrated that murine and human macrophages produce O2− during phagocytosis of opsonized promastigotes. Addition of the O2− scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl to cultures resulted in increased infection, suggesting that O2− enhances macrophage leishmanicidal activity. The importance of NO· produced by inducible NO synthase (iNOS) in controlling murine leishmaniasis is established, but its role in human macrophages has been debated. We detected NO· in supernatants from murine, but not human, macrophages infected with L. chagasi. Nonetheless, the iNOS inhibitor NG-monomethyl-l-arginine inhibited IFN-γ-mediated intracellular killing by both murine and human macrophages. According to RNase protection assay and immunohistochemistry, iNOS mRNA and protein were expressed at higher levels in bone marrow of patients with visceral leishmaniasis than in controls. The iNOS protein also increased upon infection of human macrophages with L. chagasi promastigotes in vitro in the presence of IFN-γ. These data suggest that O2− and NO· each contribute to intracellular killing of L. chagasi in human and murine macrophages.
A effective SINR link to system mapping method for CQI feedback in TD-LTE system

This paper gives an overview of the so-called link performance model used in TD-LTE (Time Division-Long Term Evolution) system level simulations to determine the link CQI (channel quality Indicator) at reduced complexity of UE (User Equipment). Mainly, effective SINR methods including EESM and MIESM account for the instantaneous channel realization and other configurations and utilize the post processing SINR to compute the effective SNR (Signal to Noise Ratio). Then UE reports CQI values, depending on a linear mapping function from effective SNR to a corresponding CQI value. The simulation shows that EESM and MIESM algorithms bring a similar throughput performance comparing to the ideal CQI choice, but mapping function of EESM method is simpler than MIESM method. Also, EESM method requires all subcarriers to apply the same MCS, which is suitable for TD-LTE system. Therefore, TD-LTE wireless integrated testing instrument adopts EESM method to realize effective SINR link to system mapping.
Use of the HPRT gene to study nuclease-induced DNA double-strand break repair

Understanding the mechanisms of chromosomal double-strand break repair (DSBR) provides insight into genome instability, oncogenesis and genome engineering, including disease gene correction. Research into DSBR exploits rare-cutting endonucleases to cleave exogenous reporter constructs integrated into the genome. Multiple reporter constructs have been developed to detect various DSBR pathways. Here, using a single endogenous reporter gene, the X-chromosomal disease gene encoding hypoxanthine phosphoribosyltransferase (HPRT), we monitor the relative utilization of three DSBR pathways following cleavage by I-SceI or CRISPR/Cas9 nucleases. For I-SceI, our estimated frequencies of accurate or mutagenic non-homologous end-joining and gene correction by homologous recombination are 4.1, 1.5 and 0.16%, respectively. Unexpectedly, I-SceI and Cas9 induced markedly different DSBR profiles. Also, using an I-SceI-sensitive HPRT minigene, we show that gene correction is more efficient when using long double-stranded DNA than single- or double-stranded oligonucleotides. Finally, using both endogenous HPRT and exogenous reporters, we validate novel cell cycle phase-specific I-SceI derivatives for investigating cell cycle variations in DSBR. The results obtained using these novel approaches provide new insights into template design for gene correction and the relationships between multiple DSBR pathways at a single endogenous disease gene.
Tumour spectrum in hereditary non‐polyposis colorectal cancer (HNPCC) and in families with “suspected hnpcc”. A population‐based study in northern Italy

Hereditary non‐polyposis colorectal cancer (HNPCC or Lynch syndrome) is characterized by the early onset of colorectal neoplasms, frequently localized in the right colon, increased occurrence of multiple primaries, vertical transmission and aggregation of tumours in families in accordance to a Mendelian dominant type of inheritance. The syndrome accounts for approximately 5% of all colorectal cancers. The purpose of the present study was to describe the tumour spectrum and the most relevant clinical features of 28 kindreds with HNPCC, classified according to the guidelines of the International Collaborative Study Group, and of 61 “suspected” HNPCC. These families were observed during a 6‐year registration of colorectal neoplasms in a health‐care district of Northern Italy. Colorectal cancer was by far the most frequent malignancy; gastric cancer was the second. Uterine carcinoma was only slightly more frequent than expected. Lung‐ and breast‐tumour rates were lower than expected. Cancer distribution in the large bowel showed that about two fifths of the tumours developed in the right colon. The occurrence of cancer before the age of 50 to 60 was much more frequent in HNPCC. Multiple tumours developed in 25 patients with HNPCC and in 32 with “suspected” HNPCC. Pancolonoscopy remains the procedure of choice for surveillance; other examinations, such as gastroscopy, gynaecological investigations, urography and cholangiography, are suggested only to selected families. One of the main features of the study was the inclusion of 61 “suspected” HNPCC, a heterogeneous group of families which nonetheless deserves careful follow‐up.
Mechanisms of Increased Vascular Superoxide Production in Human Diabetes Mellitus: Role of NAD(P)H Oxidase and Endothelial Nitric Oxide Synthase

Background—Increased superoxide production contributes to reduced vascular nitric oxide (NO) bioactivity and endothelial dysfunction in experimental models of diabetes. We characterized the sources and mechanisms underlying vascular superoxide production in human blood vessels from diabetic patients with coronary artery disease compared with nondiabetic patients. Methods and Results—Vascular superoxide production was quantified in both saphenous veins and internal mammary arteries from 45 diabetic and 45 matched nondiabetic patients undergoing coronary artery bypass surgery. NAD(P)H-dependent oxidases were important sources of vascular superoxide in both diabetic and nondiabetic patients, but both the activity of this enzyme system and the levels of NAD(P)H oxidase protein subunits (p22phox, p67phox, and p47phox) were significantly increased in diabetic veins and arteries. In nondiabetic vessels, endothelial NO synthase produced NO that scavenged superoxide. However, in diabetic vessels, the endothelium was an additional net source of superoxide production because of dysfunctional endothelial NO synthase that was corrected by intracellular tetrahydrobiopterin supplementation. Furthermore, increased superoxide production in diabetes was abrogated by the protein kinase C inhibitor chelerythrine. Conclusions—These observations suggest important roles for NAD(P)H oxidases, endothelial NO synthase uncoupling, and protein kinase C signaling in mediating increased vascular superoxide production and endothelial dysfunction in human diabetes mellitus.
Extracellular matrix-associated molecules collaborate with ciliary neurotrophic factor to induce type-2 astrocyte development

O-2A progenitor cells give rise to both oligodendrocytes and type-2 astrocytes in vitro. Whereas oligodendrocyte differentiation occurs constitutively, type-2 astrocyte differentiation requires extracellular signals, one of which is thought to be ciliary neurotrophic factor (CNTF). CNTF, however, is insufficient by itself to induce the development of stable type-2 astrocytes. In this report we show the following: (a) that molecules associated with the extracellular matrix (ECM) cooperate with CNTF to induce stable type-2 astrocyte differentiation in serum-free cultures. The combination of CNTF and the ECM-associated molecules thus mimics the effect of FCS, which has been shown previously to induce stable type-2 astrocyte differentiation in vitro. (b) Both the ECM-associated molecules and CNTF act directly on O- 2A progenitor cells and can induce them to differentiate prematurely into type-2 astrocytes. (c) ECM-associated molecules also inhibit oligodendrocyte differentiation, even in the absence of CNTF, but this inhibition is not sufficient on its own to induce type-2 astrocyte differentiation. (d) Whereas the effect of ECM on oligodendrocyte differentiation is mimicked by basic fibroblast growth factor (bFGF), the effect of ECM on type-2 astrocyte differentiation is not. (e) The ECM-associated molecules that are responsible for inhibiting oligodendrocyte differentiation and for cooperating with CNTF to induce type-2 astrocyte differentiation are made by non-glial cells in vitro. (f) Molecules that have these activities and bind to ECM are present in the optic nerve at the time type-2 astrocytes are thought to be developing.
Modulation of mitochondrial membrane potential and reactive oxygen species production by copper in astrocytes

In monolayers of cultured rat astrocytes a number of agents that induce oxidative stress act synergistically with exposure to copper leading to rapid depolarization of the mitochondrial membrane potential (Ψm) and increased reactive oxygen species (ROS) production. Copper sensitized astrocytes to the action of menadione, an intracellular generator of superoxide anion radical, exogenous hydrogen peroxide (H2O2) and rotenone, an inhibitor of mitochondrial electron transport chain complex I. However, significant differences were observed in the ability to modulate the copper‐enhanced oxidative stress depending on which stressor was used. The inhibitor of mitochondrial permeability transition cyclosporin A attenuated the effect of copper and rotenone, but had no protective action in the case of H2O2/copper and menadione/copper combinations. The H2O2 scavenger pyruvate was effective at protecting mitochondria against damage associated with the combined exposure to H2O2/copper and menadione/copper but not to the rotenone/copper combination. The antioxidant Trolox was ineffective at protecting against any of these actions and indeed had a damaging effect when combined with copper. The membrane‐permeable copper chelator neocuproine combined with sensitizing concentrations of menadione caused a decrease in Ψm, mimicking the action of copper. Penicillamine, a membrane‐impermeable copper chelator, was effective at reducing copper sensitization. Endogenous copper, mobilized during periods of oxidative stress, may play a role in the pathophysiology of brain injury. Our results suggest that this might be particularly dangerous in dysfunctional conditions in which the mitochondrial electron transport chain is compromised.
Urinary cotinine and exposure to parental smoking in a population of children with asthma.

BACKGROUND Studies of the effects of tobacco smoke often rely on reported exposure to cigarette smoke, a measure that is subject to bias. We describe here the relationship between parental smoking exposure as assessed by urinary cotinine excretion and lung function in children with asthma. METHODS We studied 90 children 4-14 years of age, who reported a confirmed diagnosis or symptoms of asthma. In each child, we assessed baseline pulmonary function (spirometry) and bronchial responsiveness to carbachol stimulation. Urinary cotinine was measured by HPLC with ultraviolet detection. RESULTS Urinary cotinine concentrations in the children were significantly correlated (P <0.001) with the number of cigarettes the parents, especially the mothers, smoked. Bronchial responsiveness to carbachol (but not spirometry test results) was correlated (P <0.03) with urinary cotinine in the children. CONCLUSION Passive smoke exposure increases the bronchial responsiveness to carbachol in asthmatic children.
A new approach for target coverage in wireless sensor networks using fuzzy logic

The use of wireless sensor networks for monitoring and surveillance has gained attention in the past few years. The main challenge experienced in these network applications is how to guarantee a suitable level of coverage such that every target or event is observed. In this paper, a new fuzzy logic based scheme is proposed in order to build the set covers. The computations of this centralized scheme are done on the Base Station. The main goal is to determine a portion of the sensor nodes that must go into active mode to satisfy the coverage requirement. All other nodes will switch to sleep mode until the next round.
Sublethal Concentrations of Antibiotics Cause Shift to Anaerobic Metabolism in Listeria monocytogenes and Induce Phenotypes Linked to Antibiotic Tolerance

The human pathogenic bacterium Listeria monocytogenes is exposed to antibiotics both during clinical treatment and in its saprophytic lifestyle. As one of the keys to successful treatment is continued antibiotic sensitivity, the purpose of this study was to determine if exposure to sublethal antibiotic concentrations would affect the bacterial physiology and induce antibiotic tolerance. Transcriptomic analyses demonstrated that each of the four antibiotics tested caused an antibiotic-specific gene expression pattern related to mode-of-action of the particular antibiotic. All four antibiotics caused the same changes in expression of several metabolic genes indicating a shift from aerobic to anaerobic metabolism and higher ethanol production. A mutant in the bifunctional acetaldehyde-CoA/alcohol dehydrogenase encoded by lmo1634 did not have altered antibiotic tolerance. However, a mutant in lmo1179 (eutE) encoding an aldehyde oxidoreductase where rerouting caused increased ethanol production was tolerant to three of four antibiotics tested. This shift in metabolism could be a survival strategy in response to antibiotics to avoid generation of ROS production from respiration by oxidation of NADH through ethanol production. The monocin locus encoding a cryptic prophage was induced by co-trimoxazole and repressed by ampicillin and gentamicin, and this correlated with an observed antibiotic-dependent biofilm formation. A monocin mutant (ΔlmaDCBA) had increased biofilm formation when exposed to increasing concentration of co-trimoxazole similar to the wild type, but was more tolerant to killing by co-trimoxazole and ampicillin. Thus, sublethal concentrations of antibiotics caused metabolic and physiological changes indicating that the organism is preparing to withstand lethal antibiotic concentrations.
Vertebroplasty and Kyphoplasty for Osteolytic Vertebral Collapse

As many as 70% of patients with cancer and multiple myeloma initially present with osteolytic involvement of the spine. These vertebral fractures are associated with significant morbidity and mortality and represent a tremendous personal and societal burden. Traditional medical and surgical options often are inadequate or too invasive for this population debilitated by cancer. Vertebroplasty involves the injection of polymethylmethaerylate to strengthen a vertebra. This minimally invasive method, which has been adopted by practitioners during the past decade to treat symptomatic osteoporotic compression fractures is reported to provide quick pain relief in 90% of patients, with only infrequent, mostly minor, complications. In patients with osteolytic fractures, vertebroplasty is associated with an increased rate of cement leak and less predictable pain relief. Kyphoplasty is an extension of vertebroplasty that uses an inflatable bone tamp to restore the vertebral body toward its original height while creating a cavity to be filled with bone cement. Preliminary data indicate that kyphoplasty is a safe procedure associated with a lower risk of cement leak, restoration of vertebral body height, and sagittal spinal alignment. In patients with osteolytic fractures secondary to multiple myeloma, kyphoplasty yields quick pain relief, and is associated with a statistically significant improvement in generic health outcome measures.