Miracle-dz/UniFAR-FTUs huggingface dataset:
The aging patient with hemophilia

The prospects for many boys born with hemophilia today include a normal life expectancy and minimal to no joint disease. However, despite the availability of safe replacement clotting factor concentrates and effective antiviral treatment, the aging patient with hemophilia today faces many challenges. These include management of their hemophilia as well as the same age‐related health issues as experienced in the general population. While increasing, data on the prevalence of comorbidities and their management in the hemophilia population remain limited. This review will focus on issues related to management of hemophilia and complications of cardiovascular, musculoskeletal, hepatic, and renal disease. Available research is summarized and potential approaches to management are discussed. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Political connections in China : determinants and effects on firms' exporting behaviour and financial health

Using a comprehensive firm-level dataset from the National Bureau Statistics (NBS) of China over the period 2000-2007, this thesis studies political connections, intended as the \(lishu\) relationship between Chinese manufacturing firms and central, provincial or local governments. Although extensive studies have investigated firms’ political connections, the \(lishu\) relationship has not been explored. Besides, the literature has generally overlooked an important question: what are the determinants of political connections? To fill this gap, we firstly investigate the determinants of the \(lishu\) relationship. We find that firms’ characteristics, ownerships, financial variables, profitability, and sales growth significantly affect the probability of having a \(lishu\) relationship. We then examine the link between the \(lishu\) relationship and firms’ exporting propensity and intensity. By examining the unobserved firm heterogeneity and the initial conditions problem, we find that the \(lishu\) relationship has a negative impact on firms’ exporting. Furthermore, firm size, productivity, financial health and age are the significant determinants of firms’ exporting. Finally, we explore the links between the \(lishu\) relationship and financial constraints, demonstrating that firms’ financial constraints can be alleviated through a \(lishu\) relationship. This effect is pronounced for firms affiliated with high level of government, foreign firms and firms in financially constrained regions.
Individually dosed omalizumab: an effective treatment for severe peanut allergy

Treatment with omalizumab has shown a positive effect on food allergies, but no dosages are established. Basophil allergen threshold sensitivity (CD‐sens) can be used to objectively measure omalizumab treatment efficacy and correlates with the outcome of double‐blind placebo‐controlled food challenge to peanut.
Rapid Production of Platelet-activating Factor Is Induced by Protein Kinase Cα-mediated Phosphorylation of Lysophosphatidylcholine Acyltransferase 2 Protein

Background: The mechanism for rapid biosynthesis of platelet-activating factor (PAF), a potent proinflammatory lipid mediator, is unclear. Results: Phosphorylation of lysophosphatidylcholine acyltransferase 2 (LPCAT2) at Ser-34 via PKCα enhanced rapid PAF biosynthesis following PAF or ATP stimulation. Conclusion: The molecular basis for rapid PAF biosynthesis in response to inflammatory stimuli is elucidated. Significance: These data suggest a better understanding of PAF production in early-phase inflammation. Platelet-activating factor (PAF), a potent proinflammatory lipid mediator, is synthesized rapidly in response to extracellular stimuli by the activation of acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAFAT). We have reported previously that lyso-PAFAT activity is enhanced in three distinct ways in mouse macrophages: rapid activation (30 s) after PAF stimulation and minutes to hours after LPS stimulation. Lysophosphatidylcholine acyltransferase 2 (LPCAT2) was later identified as a Ca2+-dependent lyso-PAFAT. However, the mechanism of rapid lyso-PAFAT activation within 30 s has not been elucidated. Here we show a new signaling pathway for rapid biosynthesis of PAF that is mediated by phosphorylation of LPCAT2 at Ser-34. Stimulation by either PAF or ATP resulted in PKCα-mediated phosphorylation of LPCAT2 to enhance lyso-PAFAT activity and rapid PAF production. Biochemical analyses showed that the phosphorylation of Ser-34 resulted in augmentation of Vmax with minimal Km change. Our results offer an answer for the previously unknown mechanism of rapid PAF production.
Phosphorus and the ruminant

Phosphorus insufficiency in the ruminant is reflected in retarded growth, poor reproductive performance, reduced milk yield and wool growth, and impaired skeletal and dental health. Geographically widespread, it is associated with soils deficient in available phosphorus, with a preponderance of poorer grasses and a paucity of legumes in the herbage and in general with a low protein content in the food intake. Aphosphorosis may be corrected by supplementary feeding with phosphatic minerals.
Oxidative Stress and Abdominal Aneurysms: How Aortic Hemodynamic Conditions May Influence AAA Disease

Atherosclerosis and abdominal aortic aneurysm (AAA) disease are chronic inflammatory conditions, comparable in fundamental ways t~ ,inflamm~tory bowel diseases or rheumatoid arthritis. Seemingly independent arterial disease risk factors such ~s hypertension, cigarette smoking, diabe~es, chronic low-grade infections and obesity have In common ~e ability to increase vascular inflammation ,and Inflammatory cell signaling. The recently recognized Utility of the inflammatory biomarker C-reactive protein (CRP) in predicting adverse c~rdiovasc~lar events underscores the importance of Inflammation in vascular disease [1-4]. In the specific circumStance of AAAs, inflammation-mediated smooth muscle cell (SMC) apoptosis (or programmed cell death), progressive elastolysis and d,isorganized and dYsfunctional aortic remodeling directly promote aneurysmal degeneration [5,6]. AAA pathogenesis research to date has emphasIZed the significance and structural consequences of SMC apoptosis and dysfunctional, extracell~lar matrix (ECM) remodeling. Attention IS now being ~ocussed on "upstream" signals that modulate aortic Inflammation and ultimately regulate these events. Oxidative stress, or the production of reactive oxygen species (ROS) such as superoxide radicals and hYdrogen peroxide is one such modulating ,influen~e. ~enerated by resident aortic as well as Infiltrative Inflammatory cells, ROS activate extracellular pro~eolYtic matrix metalloproteinases, (MMPs) an~ Induce SMC apoptosis. The potential role for OXIdative stress in catalyzing aortic aneurysmal degene~­ ation was highlighted recently by Miller and associates [7], who found evidence of increased R~S­ generating enzyme activity, increased superoxide
Fertile Hypomorphic ARGONAUTE (ago1) Mutants Impaired in Post-Transcriptional Gene Silencing and Virus Resistance

Transgene-induced post-transcriptional gene silencing (PTGS) results from specific degradation of RNAs that are homologous with the transgene transcribed sequence. This phenomenon, also known as cosuppression in plants and quelling in fungi, resembles RNA interference (RNAi) in animals. Indeed, cosuppression/quelling/RNAi require related PAZ/PIWI proteins (AGO1/QDE-2/RDE-1), indicating that these mechanisms are related. Unlike Neurospora crassa qde-2 and Caenorhabditis elegans rde-1 mutants, which are morphologically normal, the 24 known Arabidopsis ago1 mutants display severe developmental abnormalities and are sterile. Here, we report the isolation of hypomorphic ago1 mutants, including fertile ones. We show that these hypomorphic ago1 mutants are defective for PTGS, like null sgs2, sgs3, and ago1 mutants, suggesting that PTGS is more sensitive than development to perturbations in AGO1. Conversely, a mutation in ZWILLE/PINHEAD, another member of the Arabidopsis AGO1 gene family, affects development but not PTGS. Similarly, mutations in ALG-1 and ALG-2, two members of the C. elegans RDE-1 gene family, affect development but not RNAi, indicating that the control of PTGS/RNAi and development by PAZ/PIWI proteins can be uncoupled. Finally, we show that hypomorphic ago1 mutants are hypersensitive to virus infection, confirming the hypothesis that in plants PTGS is a mechanism of defense against viruses.
Stress-induced and alcohol cue-induced craving in recently abstinent alcohol-dependent individuals.

BACKGROUND Research has shown that exposure to stress/negative affect and to alcohol cues can each increase alcohol craving and relapse susceptibility in alcohol-dependent individuals. However, whether the emotional and physiological states associated with stress-induced and alcohol cue-induced craving are comparable has not been well studied. Therefore, this study examined the craving, emotional, and physiological responses to stress and to alcohol cues in treatment-engaged, 4-week abstinent, alcohol-dependent individuals using analogous stress and alcohol cue imagery methods. METHOD Twenty treatment-seeking, alcohol-dependent participants (18 males/2 females) were exposed to a brief 5-minute guided imagery procedure that involved imagining a recent personal stressful situation, a personal alcohol cue-related situation, and a neutral-relaxing situation, 1 imagery per session presented in random order. Alcohol craving, anxiety and emotion rating scales, cardiovascular measures, and salivary cortisol were compared across the 3 conditions. RESULTS Exposure to stress and to alcohol cues each produced significant increases in alcohol craving, anxiety, and negative emotions and decreases in positive emotions. Stress-induced alcohol craving was significantly correlated with increases in sadness, anger, and anxiety ratings, but alcohol cue-induced craving was associated with decreases in positive affect (joy and neutral relaxed state) and increases in anxiety and fear ratings. Furthermore, stress increased systolic and diastolic blood pressure responses, but significant increases in salivary cortisol were only observed in the alcohol cue condition. CONCLUSIONS Although both stress and alcohol cues produce increases in anxiety associated with alcohol craving, each produced a dissociable psychobiological state involving subjective emotional, cardiovascular, and cortisol responses. These data could have significant implications for understanding the specific psychobiology associated with stress or alcohol cue exposure and their potential effects on alcohol relapse susceptibility.
Doppler assessment of hypoxic pulmonary vasoconstriction and susceptibility to high altitude pulmonary oedema.

BACKGROUND--Subjects with previous high altitude pulmonary oedema may have stronger than normal hypoxic pulmonary vasoconstriction. Susceptibility to high altitude pulmonary oedema may be detectable by echo Doppler assessment of the pulmonary vascular reactivity to breathing a hypoxic gas mixture at sea level. METHODS--The study included 20 healthy controls, seven subjects with a previous episode of high altitude pulmonary oedema, and nine who had successfully climbed to altitudes of 6000-8842 m during the 40th anniversary British expedition to Mount Everest. Echo Doppler measurements of pulmonary blood flow acceleration time (AT) and ejection time (ET), and of the peak velocity of the tricuspid regurgitation jet (TR), were obtained under normobaric conditions of normoxia (fraction of inspired oxygen, FIO2, 0.21), of hyperoxia (FIO2 1.0), and of hypoxia (FIO2 0.125). RESULTS--Hypoxia decreased AT/ET by mean (SE) 0.06 (0.01) in the control subjects, by 0.11 (0.01) in those susceptible to high altitude pulmonary oedema, and by 0.02 (0.02) in the successful high altitude climbers. Hypoxia increased TR in the three groups by 0.22 (0.06) (n = 14), 0.56 (0.13) (n = 5), and 0.18 (0.1) (n = 7) m/s, respectively. However, AT/ET and/or TR measurements outside the normal range, defined as mean +/- 2 SD of measurements obtained in the controls under hypoxia, were observed in only two of the subjects susceptible to high altitude pulmonary oedema and in five of the successful high altitude climbers. CONCLUSIONS--Pulmonary vascular reactivity to hypoxia is enhanced in subjects with previous high altitude pulmonary oedema and decreased in successful high altitude climbers. However, echo Doppler estimates of hypoxic pulmonary vaso-constriction at sea level cannot reliably identify subjects susceptible to high altitude pulmonary oedema or successful high altitude climbers from a normal control population.
Efficacy/Safety of Olmesartan Medoxomil versus Losartan Potassium in Patients by Stage 1 or 2 Hypertension

Abstract An exploratory subgroup analysis of a prospective, randomized, double–blind, forced–titration study comparing the efficacy and safety of once–daily olmesartan medoxomil (OM) and losartan potassium (LOS) in patients with stage 1 or stage 2 hypertension is reported. After a 3– to 4–week placebo run–in period, eligible patients received once–daily OM (weeks 1–4, 20 mg; weeks 5–8, 40 mg), placebo plus OM (weeks 1–2, placebo; weeks 3–4, OM 20 mg; weeks 5–8, OM 40 mg), or LOS (weeks 1–4, 50 mg; weeks 5–8, 100 mg). A subset of patients underwent ambulatory blood pressure (BP) monitoring. Efficacy endpoints by hypertension stage were mean change from baseline in seated cuff diastolic BP (SeDBP) at week 8 (primary); seated cuff systolic BP (SeSBP) at week 4 and week 8, and SeDBP at week 4 (secondary); and the change from baseline in mean 24–hour ambulatory BP at week 8, and BP target achievement (tertiary). At week 8, patients with stage 1 and stage 2 hypertension had least–squares mean SeDBP reductions from baseline of 9.9 and 9.5 mm Hg, respectively, for OM treatment, and 6.9 and 7.3 mm Hg for LOS treatment (P = 0.0095 and P = 0.0035, respectively). Overall, 63.6% of patients with stage 1 hypertension treated with OM versus 47.3% treated with LOS (P = 0.0095) achieved an SeBP of < 140/90 mm Hg, while 36.1% of patients with stage 2 hypertension treated with OM versus 25.2% treated with LOS (P = 0.0022) achieved an SeBP of < 140/90 mm Hg. At week 8, OM–treated patients with stage 2 hypertension had a significantly greater reduction in least–squares mean 24–hour ambulatory BP versus LOS–treated patients. Olmesartan and LOS were well tolerated, and the most common treatment–emergent adverse event was headache. Once–daily, maximum doses of OM in patients with stage 1 or stage 2 hypertension achieved superior BP reductions versus LOS, with similar tolerability.
Colloidal self-organization for nanoelectronics

The major part of the expenses in modern IC manufacturing process is nowadays devoted to the R & D needed to optimize chip size, wafer size, defectivity and interconnects- building up to keep Moore's law a reality. But the question is: Can circuits with sub-0.1 /spl mu/m dimensions be fabricated by the extension of current device production technologies? An interdisciplinary 'off the beaten path' approach is mandatory to overcome future limitations. One such approach is fabrication of devices (or at least parts of devices) by self-organization.
Isolation of a rat liver delta-aminolevulinate dehydrase (ALAD) cDNA clone: evidence for unequal ALAD gene dosage among inbred mouse strains.

We have isolated several cDNA clones encoding delta-aminolevulinate dehydrase [ALAD; porphobilinogen synthase; 5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing), EC 4.2. 1.24], the second enzyme in the heme biosynthetic pathway. We used a rabbit polyclonal antibody developed against the purified 35-kDa subunit of rat liver ALAD to screen a lambda gt11 cDNA expression library constructed from rat liver mRNA. A prototype clone (ALAD-1) contained a 680-base-pair insert and expressed a 140-kDa beta-galactosidase gene cDNA insert fusion protein immunoreactive with both polyclonal and monoclonal anti-ALAD. Identity of ALAD-1 was verified by hydridization to ALAD mRNA that had been enriched via immunopurification of rat liver polysomes with anti-ALAD. Intensity of such hybridization to a 1500-nucleotide-long mRNA was approximately equal to 200-fold greater than that realized with whole liver mRNA, a result consistent with the degree of immunoenrichment of ALAD mRNA found independently by analysis of cell-free translation products. A second ALAD cDNA clone (ALAD-3) was isolated when the rat liver cDNA expression library was rescreened with ALAD-1. The identity of both ALAD cDNA clones was established by correspondence between their nucleotide sequence and the reported amino-terminal protein sequence of bovine ALAD. Hybridization of ALAD cDNA to mouse genomic DNA indicates that the previously unexplained incremental differences in ALAD enzymatic activity among inbred mouse strains has arisen through alterations in ALAD gene dose.
Ammonium Homeostasis and Human Rhesus Glycoproteins

The brain ammonium production is detoxified by astrocytes, the gut ammonium production is detoxified by hepatic cells, and the renal ammonium production plays a major role in renal acid excretion. As a result of ammonium handling in these organs, the ammonium and pH values are strictly regulated in plasma. Up until recently, it was accepted that mammalian cell transmembrane ammonium transport was due to NH4+ transport by non-specific transporting systems, and to non-ionic NH3 diffusion, whereas lower organisms (such as bacteria, yeasts and plants) were endowed with specific ammonium transporters (Amts). Sequence homologies between Amts and human Rhesus (Rh) glycoproteins (RhAG, from erythroid cells, and RhBG and RhCG from epithelial cells) raised the hypothesis that Rh glycoproteins act as specific ammonium transporters, further sustained by the polarized distribution of RhBG and RhCG in gut, kidney and liver. Results from functional studies agree that Rh glycoproteins are the first ammonium transporters reported in mammals. However, the nature of the transported specie(s) is much debated: in particular, it is proposed that Rh glycoproteins mediate a direct NH3 transport, or that they mediate an indirect NH3 transport (resulting from NH4+ for H+ exchange). Direct NH3 transport (associated or not with NH4+ transport) raises the exciting hypothesis that Rh glycoproteins may also transport other gasses than NH3 (namely, CO2).
Catastrophizing and pain in arthritis, fibromyalgia, and other rheumatic diseases.

OBJECTIVE Pain is among the most frequently reported, bothersome, and disabling symptoms described by patients with osteoarthritis, rheumatoid arthritis, fibromyalgia, and other musculoskeletal conditions. This review describes a growing body of literature relating catastrophizing, a set of cognitive and emotional processes encompassing magnification of pain-related stimuli, feelings of helplessness, and a generally pessimistic orientation, to the experience of pain and pain-related sequelae across several rheumatic diseases. METHODS We reviewed published articles in which pain-related catastrophizing was assessed in the context of one or more rheumatic conditions. Because much of the available information on catastrophizing is derived from the more general chronic pain literature, seminal studies in other disease states were also considered. RESULTS Catastrophizing is positively related, in both cross-sectional and prospective studies across different musculoskeletal conditions, to the reported severity of pain, affective distress, muscle and joint tenderness, pain-related disability, poor outcomes of pain treatment, and, potentially, to inflammatory disease activity. Moreover, these associations generally persist after controlling for symptoms of depression. There appear to be multiple mechanisms by which catastrophizing exerts its harmful effects, from maladaptive influences on the social environment to direct amplification of the central nervous system's processing of pain. CONCLUSION Catastrophizing is a critically important variable in understanding the experience of pain in rheumatologic disorders as well as other chronic pain conditions. Pain-related catastrophizing may be an important target for both psychosocial and pharmacologic treatment of pain.
Fast rate coding in hippocampal CA3 cell ensembles

Environments with overlapping features are represented by distinct patterns of activity in the hippocampus, enabling information to be stored and retrieved with minimal interference. This orthogonalization of correlated inputs is thought to take place within the hippocampus itself. However, the orthogonalization process has been shown to take days to develop in CA1. This prolonged time course is in striking contrast to the fast encoding of behavioral memory by the hippocampus. To explore this apparent paradox, we asked whether orthogonalization depended on the type of remapping exhibited by the hippocampal network. We have previously distinguished two types of remapping, global remapping, which results in the activation of different assemblies of place fields, and rate remapping, which encodes differences between cue constellations by substantial changes in firing rate without a change in the place code. Global remapping has previously been shown to be expressed immediately at novel locations. Here we asked if rate remapping follows a slower time course. Ensemble activity was recorded simultaneously from CA3 and CA1 in rats exposed to two similar, novel environments. It was found that rate changes in response to novel sensory cue configurations can form immediately, just as during global remapping, in particular in CA3. The fast encoding of both spatial and nonspatial information in CA3 is consistent with a role for the autoassociative CA3 circuitry in the acquisition and expression of episodic memories. © 2006 Wiley‐Liss, Inc.
Integración de optimización evolutiva para el reconocimiento de emociones en voz

Resumen. En este articulo se presenta el desarrollo de un sistema de reconocimiento de emociones basado en la voz. Se consideraron las siguientes emociones basicas: Enojo, Felicidad, Neutro y Tristeza. Para este proposito una base de datos de voz emocional fue creada con ocho usuarios Mexicanos con 640 frases (8 usuarios × 4 emociones × 20 frases por emocion). Los Modelos Ocultos de Markov (Hidden Markov Models, HMMs) fueron usados para construir el sistema de reconocimiento. Basado en el concepto de modelado acustico de vocales especificas emotivas un total de 20 fonemas de vocales (5 vocales × 4 emociones) y 22 fonemas de consonantes fueron considerados para el entrenamiento de los HMMs. Un Algoritmo Genetico (Genetic Algorithm, GA) fue integrado dentro del proceso de reconocimiento para encontrar la arquitectura mas adecuada para el HMM para cada vocal especifica emotiva. Una tasa de reconocimiento total aproximada del 90.00 % fue conseguida con el reconocedor de voz construido con los HMMs optimizados.