English to Arabic machine translation of mathematical documents

This paper is about the development of a machine translation system tailored specifically for LATEX mathematical documents. The system focuses on translating English LATEX mathematical documents into Arabic LATEX, catering to the growing demand for multilingual accessibility in scientific and mathematical literature. With the vast proliferation of LATEX mathematical documents the need for an efficient and accurate translation system has become increasingly essential. This paper addresses the necessity for a robust translation tool that enables seamless communication and comprehension of complex mathematical content across language barriers. The proposed system leverages a Transformer model as the core of the translation system, ensuring enhanced accuracy and fluency in the translated Arabic LATEX documents. Furthermore, the integration of RyDArab, an Arabic mathematical TEX extension, along with a rule-based translator for Arabic mathematical expressions, contributes to the precise rendering of complex mathematical symbols and equations in the translated output. The paper discusses the architecture, methodology, of the developed system, highlighting its efficacy in bridging the language gap in the domain of mathematical documentatio

Anorexigen-induced pulmonary hypertension and the serotonin (5-HT) hypothesis: lessons for the future in pathogenesis

Epidemiological studies have established that fenfluramine, D-fenfluramine, and aminorex, but not other appetite suppressants, increase the risk of primary pulmonary hypertension (PH). One current hypothesis suggests that fenfluramine-like medications may act through interactions with the serotonin (5-hydroxytryptamine [5-HT]) transporter (5-HTT) located on pulmonary artery smooth muscle cells and responsible for the mitogenic action of 5-HT. Anorexigens may contribute to PH by boosting 5-HT levels in the bloodstream, directly stimulating smooth muscle cell growth, or altering 5-HTT expression. We suggest that individuals with a high basal level of 5-HTT expression related to the presence of the long 5-HTT gene promoter variant may be particularly susceptible to one or more of these potential mechanisms of appetite-suppressant-related PH

Oestrogen receptor alpha in pulmonary hypertension

Aims Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2+/− mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression. Methods and results: By immunohistochemistry, we showed that ERα, ERβ, and G-protein-coupled receptors are expressed in human pulmonary arteries localizing mainly to the smooth muscle layer which also expresses the serotonin transporter (SERT). Protein expression of ERα protein was higher in female PAH patient hPASMCs compared with male and serotonin also increased the expression of ERα. 17β-estradiol induced proliferation of hPASMCs via ERα activation and this engaged mitogen-activated protein kinase and Akt signalling. Female mice over-expressing SERT (SERT+ mice) develop PH and the ERα antagonist MPP attenuated the development of PH in normoxic and hypoxic female SERT+ mice. The therapeutic effects of MPP were accompanied by increased expression of BMPR2 in mouse lung. Conclusion: ERα is highly expressed in female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can increase ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent PH in the mouse and increases BMPR2 expression.</p

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Identification of a novel allosteric inhibitory site on tryptophan hydroxylase 1 enabling unprecedented selectivity over all related hydroxylases

Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements – SERT, 5-HT2A, 5HT2B, and combined 5-HT2A/B receptors, have all been tested clinically and failed. Thus, inhibition of tryptophan hydroxylase 1 (TPH1), the rate limiting step in 5-HT synthesis, has been suggested as a more broad, and thereby more effective, mode of 5-HT inhibition. However, selectivity over non-pathogenic enzyme family members, TPH2, phenylalanine hydroxylase, and tyrosine hydroxylase has hampered therapeutic development. Here we describe the site/sequence, biochemical, and biophysical characterization of a novel allosteric site on TPH1 through which selectivity over TPH2 and related aromatic amino acid hydroxylases is achieved. We demonstrate the mechanism of action by which novel compounds selectively inhibit TPH1 using surface plasma resonance and enzyme competition assays with both tryptophan ligand and BH4 co-factor. We demonstrate 15-fold greater potency within a human carcinoid cell line versus the most potent known TPH1/2 non-specific inhibitor. Lastly, we detail a novel canine in vivo system utilized to determine effective biologic inhibition of newly synthesized 5-HT. These findings are the first to demonstrate TPH1-selective inhibition and may pave the way to a truly effective means to reduce pathologic 5-HT and thereby treat complex remodeling diseases such as PAH

Circulating protein biomarkers in systemic sclerosis related pulmonary arterial hypertension: a review of published data

Pulmonary arterial hypertension (PAH) develops in 7-12% of patients with systemic sclerosis (SSc) and is associated with a 3 year survival of 52%. Early detection by screening is therefore recommended for all patients with SSc. Historically, screening has been performed using echocardiography and measurement of gas transfer. More recently the DETECT protocol, using a combination of biomarkers (including N-terminal pro-brain natriuretic peptide) and clinical parameters, has been developed. The optimal method of screening for PAH with high sensitivity and specificity is, however, not clear. Protein expression differences between different SSc disease phenotypes have been reported, and include alterations in concentration of NT-proBNP, endoglin, soluble vascular endothelial growth factor receptor 1, placenta growth factor, growth differentiation factor-15, vascular endothelial growth factor alpha, resistin-like molecule beta, and soluble thrombomodulin. This review summarizes the current knowledge of these protein changes in patients with SSc and PAH

Gene expression in lungs of mice lacking the 5-hydroxytryptamine transporter gene

<p>Abstract</p> <p>Background</p> <p>While modulation of the serotonin transporter (5HTT) has shown to be a risk factor for pulmonary arterial hypertension for almost 40 years, there is a lack of in vivo data about the broad molecular effects of pulmonary inhibition of 5HTT. Previous studies have suggested effects on inflammation, proliferation, and vasoconstriction. The goal of this study was to determine which of these were supported by alterations in gene expression in serotonin transporter knockout mice.</p> <p>Methods</p> <p>Eight week old normoxic mice with a 5-HTT knock-out (5HTT-/-) and their heterozygote(5HTT+/-) or wild-type(5HTT+/+) littermates had right ventricular systolic pressure(RVSP) assessed, lungs collected for RNA, pooled, and used in duplicate in Affymetrix array analysis. Representative genes were confirmed by quantitative RT-PCR and western blot.</p> <p>Results</p> <p>RVSP was normal in all groups. Only 124 genes were reliably changed between 5HTT-/- and 5HTT+/+ mice. More than half of these were either involved in inflammatory response or muscle function and organization; in addition, some matrix, heme oxygenase, developmental, and energy metabolism genes showed altered expression. Quantitative RT-PCR for examples from each major group confirmed changes seen by array, with an intermediate level in 5HTT +/- mice.</p> <p>Conclusion</p> <p>These results for the first time show the in vivo effects of 5HTT knockout in lungs, and show that many of the downstream mechanisms suggested by cell culture and ex vivo experiments are also operational in vivo. This suggests that the effect of 5HTT on pulmonary vascular function arises from its impact on several systems, including vasoreactivity, proliferation, and immune function.</p

ICAM-1 PROMOTES THE ABNORMAL ENDOTHELIAL CELLPHENOTYPE IN CHRONIC THROMBOEMBOLIC PULMONARYHYPERTENSION

International audienceBACKGROUND - Pulmonary endothelial cells play a key role in the pathogenesis of ChronicThromboembolic Pulmonary Hypertension (CTEPH). Increased synthesis and/or release ofIntercellular Adhesion Molecule 1 (ICAM-1) by pulmonary endothelial cells of patients withCTEPH has been recently reported, suggesting a potential role for ICAM-1 in CTEPH.METHODS - We studied pulmonary endarterectomy specimens from 172 patients with CTEPHand pulmonary artery specimens from 97 controls undergoing lobectomy for low-stage cancerwithout metastasis.RESULTS - ICAM-1 was overexpressed in vitro in isolated and cultured endothelial cells fromendarterectomy specimens. Endothelial cell (EC) growth and apoptosis resistance weresignificantly higher in CTEPH specimens than in controls (P<0.001). Both abnormalities wereabolished by pharmacological inhibition of ICAM-1 synthesis or activity. Overexpression ofICAM-1 contributed to the acquisition and maintenance of abnormal EC growth and apoptosisresistance via phosphorylation of SRC, p38 and ERK1/2 and overproduction of Survivin.Regarding the ICAM-1 E469K polymorphism, the KE heterozygote genotype was significantlymore frequent in CTEPH than in controls, but was not associated with disease severity amongpatients with CTEPH.CONCLUSIONS - ICAM-1 contributes to maintaining the abnormal endothelial cell phenotypein CTEPH

Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice

<p>Abstract</p> <p>Background</p> <p>Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH). Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6).</p> <p>Methods</p> <p>To determine whether endogenous IL-6 contributes to mediate hypoxic PH and lung inflammation, we studied IL-6-deficient (IL-6^-/-) and wild-type (IL-6^+/+) mice exposed to hypoxia for 2 weeks.</p> <p>Results</p> <p>Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels were decreased in IL-6^-/-mice compared to wild-type controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia was similar in IL-6^+/+and IL-6^-/-mice. Hypoxia exposure of IL-6^+/+mice led to marked increases in IL-6 mRNA and protein levels within the first week, with positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor and gp 130 (the IL-6 signal transducer) mRNA levels increased after 1 and 2 weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle-cells (PA-SMCs) and microvascular endothelial cells revealed prominent synthesis of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6^-/-mice showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild-type mice, as assessed by lung protein levels and immunostaining for the specific macrophage marker F4/80, with no difference in lung expression of adhesion molecules or cytokines.</p> <p>Conclusion</p> <p>These data suggest that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice.</p

Pulmonary Hypertension Associated with Use of Phentermine

Weight-control drugs (known as anorexigens) such as fenfluramine have been linked with pulmonary hypertension in previous reports. In our case, a 29 year old woman was admitted for shortness of breath and was diagnosed with pulmonary hypertension. Three months ago, she had been taking phentermine for five weeks. Other factors that might have contributed to the development of pulmonary hypertension were excluded. With treatment, her symptoms improved. This is the first case that can suggest a possible connection between phenermine single medication with pulmonary hypertension. Phentermine has been considered a relatively safe drug to treat obesity, and further investigation is needed to decide the safety and dosage of phentermine