Miracle-dz/UniFAR-FTUs huggingface dataset:
Fampridine-SR for multiple sclerosis and spinal cord injury

Fampridine-SR is a sustained-release tablet form of the K+ channel-blocking compound 4-aminopyridine that has been shown to restore conduction in focally demyelinated axons, to enhance synaptic transmission in many types of neurons and to potentiate muscle contraction. The present review describes the mechanism of action and chemistry of Fampridine-SR, its pharmacokinetics and safety, and the outcomes of clinical trials of its safety and efficacy for enhancing neuromuscular function in patients with multiple sclerosis or spinal cord injury. Randomized clinical trials completed to date indicate that this form of K+ channel blockade may be useful for the improvement of walking ability in patients with multiple sclerosis.
Motor Unit Discharge Characteristics during Voluntary Contraction in Patients with Incomplete Spinal Cord Injury

Synchronisation of motor unit discharges is commonly seen in hand muscles of normal man but is absent following neurologically complete spinal cord injury and reduced after stroke. These findings support the notion that some corticospinal inputs to motoneurones are shared and contribute to the observed synchrony of discharge. In this study we have examined motor unit discharge in hand muscles below the level of an incomplete spinal cord injury in an attempt to relate strength of synchrony to the integrity of the corticospinal tract. Eight patients with incomplete spinal cord injury (neurological level C3‐C7) and eight control subjects took part in the study. The patients had sustained injury 14‐191 weeks prior to the recordings and had since regained good motor function in their hands. Two concentric needle electrodes were inserted into the first dorsal interosseus muscle which subjects were instructed to contract weakly so that potentials from individual motor units could be reliably identified on both recordings. Synchrony was detected by constructing cross‐correlograms between the discharges of pairs of individual motor units. The amount of synchronous firing was determined from the magnitude of any peak in the cross‐correlogram, as the probability above chance (XP) of one motor unit firing with respect to the other and vice versa. The degree of synchrony was lower (P < 0.05) in the patient group (mean XP 0.06) than in the control group (mean XP 0.09). The incidence of significant synchrony was lower in the patient group (41.8%) than in the control group (92.9%). The mean (± S.E.M.) frequency of motor unit discharge was slightly lower (P < 0.05) in patients (9.7 ± 0.4 impulses s−1) than controls (10.8 ± 0.5 impulses s−1). The mean width of synchrony peaks was narrower (P < 0.05) in patients (11.4 ± 1.1 ms) than controls (13.2 ± 0.6 ms). We conclude that the weaker synchrony of motor unit discharge in incomplete spinal cord injury may reflect permanent damage to some corticospinal axons.
Contrasting effects of intrauterine growth retardation and premature delivery on adult cortisol secretion and metabolism in man

objective Among babies born at term, intrauterine growth retardation (IUGR) predicts adult hypertension and hyperglycaemia. This might be due to elevated circulating glucocorticoids in adulthood, as described in animal models and in several cohorts of men who were low birthweight at term. Recently, we found that premature low birthweight babies also have adult cardiovascular risk factors, irrespective of IUGR. We have now investigated cortisol secretion in this group.
Mapping of a Gene for Parkinson's Disease to Chromosome 4q21-q23

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.
Leakage power recovery in spare cells by using state dependent leakage tables from library models

As the technology continues to shrinks, leakage power is growing at exponential rate due to the aggressive scaling trends of channel lengths, gate oxide thickness, and doping profiles combined with an increasing number of transistors packaged in a single chip. During the physical implementation stages VLSI designs often needs be corrected due to the changes in specification or design rule constraints violations. This correction process is called Engineering Change Order (ECO). Spare cells are redundant cells introduced in the layout during early physical design stage whose inputs are traditionally tied to Power (VDD) or Ground (VSS) and will be used during ECO changes. However these spare or ECO cells in stand-by mode contributes to a significant subthreshold leakage power in lower technology nodes. In this paper we are proposing a method which involves assigning optimal standby at every input of spare cell gate based on state dependent leakage power tables to minimize leakage power of spare cells. The proposed method was tested on standard cell based LVDS layout created using Synopsys SAED 32/28nm and other available Synopsys Design Ware 65nm, 45nm, 40nm & 28nm standard cell libraries. With the proposed method we could observe 48% to 30% reduction in spare cell leakage power and 3.8% to 0.7% reduction in design leakage power.
An adaptive neural processing node

The design and test results for two analog adaptive VLSI processing chips are described. These chips use pulse coded signals for communication between processing nodes and analog weights for information storage. The weight modification rule, implemented on chip, uses concepts developed by E. Oja (1982) and later extended by T. Leen et al. (1989) and T. Sanger (1989). Experimental results demonstrate that the network produces linearly separable outputs that correspond to dominant features of the inputs. Such representations allow for efficient additional neural processing. Part of the adaptation rule also includes a small number of fixed inputs and a variable lateral inhibition mechanism. Experimental results from the first chip show the operation of function blocks that make a single processing node. These function blocks include forward transfer function, weight modification, and inhibition. Experimental results from the second chip show the ability of an array of processing elements to extract important features from the input data.
The caspase‐derived C‐terminal fragment of βAPP induces caspase‐independent toxicity and triggers selective increase of Aβ42 in mammalian cells

During its physiopathological maturation, the β‐amyloid precursor protein undergoes several distinct proteolytic events by activities called secretases. In Alzheimer's disease, the main histological hallmark called senile plaque is clearly linked to the overproduction of the amyloid peptides Aβ40 and Aβ42, two highly aggregable βAPP‐derived fragments generated by combined cleavages by β‐ and γ‐secretases. Recently, an alternative hydrolytic pathway was described, involving another category of proteolytic activities called caspases, responsible for the production of a 31 amino acids βAPP C‐terminal fragment called C31. C31 was reported to lower the viability of N2a cells but the exact mechanisms mediating C31‐toxicity remained to be established. Here we show that the transient transfection of pSV2 vector encoding C31 lowers by about 80% TSM1 neuronal cells viability. Arguing against a C31‐stimulated apoptotic response, we demonstrate by combined enzymatic and immunological approaches that C31 expression did not modulate basal or staurosporine‐induced caspase 3‐like activity and pro‐caspase‐3 activation. Furthermore, C31 did not modify Bax and p53 expressions, poly‐(ADP‐ribose)‐polymerase cleavage and cytochrome c translocation into the cytosol. However, we established that C31 overexpression triggers selective increase of Aβ42 but not Aβ40 production by HEK293 cells expressing wild‐type βAPP751. Altogether, our data demonstrate that C31 induces a caspase‐independent toxicity in TSM1 neurons and potentiates the pathogenic βAPP maturation pathway by increasing selectively Aβ42 species in wild type‐βAPP‐expressing human cells.
Evolution des composantes du niveau marin à partir d'observations de marégraphie effectuées depuis la fin du 18ème siècle en Charente-Maritime

Les estimations de la remontee generale du niveau de la mer, de l’ordre de 17 ± 2 cm sur le siecle dernier, masquent une realite tres variable d’une region a l’autre. Qu’en est-il du littoral charentais ? Des series temporelles de plus de 40-50 ans sont souvent indispensables pour tirer des tendances fiables a long terme sur les composantes du niveau marin : niveau moyen de la mer, ondes de maree et effets meteorologiques. Or, de nombreux lots de mesures maregraphiques du littoral charentais « sommeillaient » dans les centres d’archive francais, i.e. : La Rochelle-Vieux port (1775-1892), La Rochelle-La Pallice (1885-auj.), ile d’Aix (1824-auj.), fort Enet (1859-1873), fort Boyard(1873-1909) et Cordouan (1812-1994). Les objectifs de nos travaux de recherche etaient multiples : inventorier,sauvegarder et numeriser des lots de mesures historiques du niveau marin, puis construire des series temporelles recomposees a partir de ces lots de mesures heterogenes, temporellement et spatialement, et enfin les exploiter pour mieux decrire et comprendre l’evolution a long terme du niveau de la mer. La qualite des trois series construites (LaRochelle : 1775-auj. ; Aix-Enet-Boyard : 1824-auj. ; et Cordouan : 1812-1994) a ensuite ete eprouvee en detail afin d’evaluer le niveau de precision de notre reconstruction. A partir de ces series inedites, nous avons pu etudier l’evolution des composantes du niveau marin. Suite a ces travaux, nous fournissons un inventaire le plus exhaustif possible detaillant les mesures de 25 observatoires de Charente-Maritime, de 1775 a aujourd’hui. Les donnees des series temporelles ainsi que des elements permettant d’apprecier leur qualite seront bientot disponibles en ligne sur REFMAR (refmar.shom.fr), SONEL (www.sonel.org) et au PSMSL (www.psmsl.org). Nos resultats positifs nous ont permis de reconstruire une serie encore plus globale, celle du pertuis d’Antioche, a partir des moyennes mensuelles du niveau marin des series de La Rochelle et d’Aix-Enet-Boyard. Parmi les resultats marquants obtenus,le niveau moyen de la mer s’est eleve de +1,38 ± 0,08 mm/an dans le pertuis d’Antioche sur la periode 1860-2010.Ce resultat est coherent avec Liverpool (+1,2 ± 0,1 mm/an sur la periode 1858-1997 [Woodworth, 1999a]) et avec les recents resultats suggerant que l’elevation du niveau marin sur les cotes atlantiques europeennes est moins importante qu’au niveau mondial (+1,7 ± 0,3 mm/an sur la periode 1870-2004 [Church & White, 2006]).
Coronary Heart Disease and Physical Activity of Work

It has previously been shown that the drivers of London's double-decker buses are more likely to die suddenly from "coronary thrombosis" than the conductors, and that Government clerks suffer more often from rapidly fatal cardiac infarction than do postmen.43 On the basis of these and similar observations a hypothesis has been stated that nmen in physically active jobs have a lower incidence of coronary (ischaemic) heart disease in middle-age than men in physically inactive jobs. More important, the disease is not so severe in physically active workers, tending to present in them in relatively benign forms. It is a principle of epidemiological research of this type to seek evidence from as many, as various, and as independent sources as possible.40 The present report deals with the frequency, in relation to occupation, of ischaemic myocardial fibrosis in men dying from causes other than coronary heart disease itself. These myocardial scars are often evidence of early coronary heart disease and of less severe, or at any rate non-lethal, ischaemia. Thus the present study provides a picture of coronary heart disease in one of its simpler forms, and this may help in elucidating social connexions. At the same time another test of the hypothesis is made, using quite different data from the previous inquiries and upon quite another aspect of the condition. The inquiry it was hoped would provide some information on the pathological mechanisms of any differences with physical activity of work that were found; and in particular we sought to learn something about the relationships of occupation to coronary artery disease. In brief, Can the hearts of men be seen to vary with the kind of work they have done ? At what phases in the complex of coronary-myocardial disease as a whole can this particular " cause "-physical activity/inactivitybe seen to operate ? More generally the inquiry was intended to provide a statistical account of the coronary arteries of the middle-aged British male population, 1954-6.42
Bone density of women who have recovered from anorexia nervosa.

OBJECTIVE To examine bone density in 19 women who had previously experienced classical anorexia nervosa from which they had been fully recovered for a mean of 21 years (current characteristics: median age 40.2 years; Eating Attitudes Test [EAT] score 2; body mass index [BMI] 21.1; average 1.8 offspring). METHOD Probands were compared, blindly, in respect of bone density, with 13 control subjects matched for age and sex and with no history of eating disorders. Dual energy X-ray absorptiometry (DXA) was used to evaluate the bone mineral density (BMD) of the lumbar spine and the head of the femur. RESULTS Femur BMD was still significantly less among ex-anorectic sufferers. Two subjects had experienced pathological fractures while anorectic, both having been strenuous exercisers. None appeared to have suffered post illness fractures. BMD at follow-up did not relate to the severity or chronicity of previous anorexia nervosa. DISCUSSION Full clinical recovery from anorexia nervosa does not quite confer full establishment of normal bone density. However, pathological fractures are not a feature thereafter, within middle life.
Infantile Hemangiomas: How Common Are They? A Systematic Review of the Medical Literature

Abstract: No published prospective studies have been published for several decades examining the incidence of hemangiomas. Older studies were performed before the delineation of “hemangiomas” from other vascular birthmarks was well‐established. The objective of our study is to critically re‐examine the literature reporting the incidence of infantile hemangiomas to determine if the true incidence is actually known. We performed both an electronic database search and hand search of the medical literature on the natural history of hemangiomas in full‐term newborns and infants. A total of seven articles were found comprising two study populations: newborns <2 weeks of age and infants over the age of 2 weeks. All studies included samples sizes >500 patients including both hospital‐based and primary care settings. Study designs ranged from retrospective chart reviews to cross‐sectional cohort studies. Descriptive nomenclature was not uniform between studies, and all had methodologic limitations including problems of definition and study design. Studies estimating the true incidence of infantile hemangiomas are all many decades old and have significant methodologic issues limiting their ability to determine hemangioma incidence. Future studies in primary care settings using the currently accepted classification schema of vascular birthmarks may more accurately define the incidence and potential impact of this common vascular tumor of infancy.
Characterization of biodegradable polyurethane microfibers for tissue engineering

A polyurethane designed to be biodegradable via hydrolysis and enzyme-mediated chain cleavage, has been investigated for its use as a temporary scaffold in tissue-engineering applications. The phase-segregated nature of the polyurethane imparts elastomeric properties that are attractive for soft tissue engineering. This polyurethane has been electrospun in order to create scaffolds that incorporate several biomimetic features including small fiber diameter, large void volume, and an interconnected porous network. Material properties were evaluated via gel-permeation chromatography, differential scanning calorimetry and Raman spectroscopy before and after processing. Analysis by gel-permeation chromatography showed that the molecular weights were similar, indicating that the bulk of the polymer chains were not degraded during processing. Thermal analysis revealed that the glass transition temperature did not shift and Raman spectra of the bulk polyurethane film compared to the electrospun mat were identical, confirming that the conformation of the polymer was unaffected by the shear and electric field used in the electrospinning process. In addition, field emission scanning electron microscopy revealed that the morphology of the electrospun mats had a broad fiber diameter distribution, and mechanical analysis showed that the mats had an ultimate tensile stress of 1.33 MPa and ultimate tensile strain of 78.6%. The degradation profile was investigated in the presence of chymotrypsin. These results were compared to a previous study of thin films of this polyurethane, and it was found that the increase of surface area aided the surface-mediated erosion of the material. It is believed that an electrospun matrix of this biodegradable polyurethane shows promise for use in soft tissue engineering and regenerative medicine applications.
Changes in the Nerve Fiber Layer Thickness Following a Reduction of Intraocular Pressure After Trabeculectomy

Purpose: To assess changes in the nerve fiber layer thickness after trabeculectomy using scanning laser polarimetry. Methods: The authors prospectively enrolled 46 eyes from 46 patients with primary open‐angle glaucoma in whom intraocular pressure had been reduced by more than 30% after trabeculectomy without significant ophthalmic complications and from whom good quality images were obtained by a scanning laser polarimetry preoperatively and at 3 to 6 months after trabeculectomy. In each enrolled eye, changes in the nerve fiber layer thickness after surgery in the defined ring (1.8 disc diameters) around the optic disc were calculated in 10° intervals (36 sectors in total) and in the following 4 quadrants (the sum of 9 10° sectors): superior, nasal, inferior, and temporal. Results: The mean intraocular pressure was 22.6 ± 6.9 mm Hg preoperatively and 10.2 ± 3.7 mm Hg postoperatively (P < 0.01). According to the analyses in every 10°, the postoperative nerve fiber layer thickness was significantly greater than the preoperative nerve fiber layer thickness in the superotemporal region (10–50°) and inferotemporal region (290–340°) of the optic disc (P < 0.05). A stepwise multiple regression analysis showed that only the preoperative mean deviation in the Humphrey visual fields was a significant independent factor associated with changes in the nerve fiber layer thickness in the nasal and inferior quadrants. Conclusions: The thickness of the nerve fiber layer, as measured by scanning laser polarimetry, may increase after trabeculectomy, especially in the superotemporal and inferotemporal regions, and can be expected in cases in the early stage of glaucoma that have a better mean deviation.
MATE Transporters Facilitate Vacuolar Uptake of Epicatechin 3′-O-Glucoside for Proanthocyanidin Biosynthesis in Medicago truncatula and Arabidopsis[C][W]

Expression of the Arabidopsis thaliana MYB transcription factor TRANSPARENT TESTA 2 (TT2) in Medicago trunculata hairy roots induces both proanthocyanidin accumulation and the ATP-dependent vacuolar/vesicular uptake of epicatechin 3′-O-glucoside; neither process is active in control roots that do, however, possess anthocyanidin 3-O-glucoside vacuolar uptake activity. A vacuolar membrane-localized multidrug and toxic compound extrusion (MATE) transporter, Medicago MATE1, was identified at the molecular level and shown to preferentially transport epicatechin 3′-O-glucoside. Genetic evidence has implicated TT12, a tonoplastic MATE transporter from Arabidopsis, in the transport of precursors for proanthocyanidin biosynthesis in the seed coat. However, although Arabidopsis TT12 facilitates the transport of cyanidin 3-O-glucoside into membrane vesicles when expressed in yeast, there is no evidence that cyanidin 3-O-glucoside is converted to proanthocyanidins after transport into the vacuole. Here, we show that Arabidopsis TT12, like Medicago MATE1, functions to transport epicatechin 3′-O-glucoside as a precursor for proanthocyanidin biosynthesis, and Medicago MATE1 complements the seed proanthocyanidin phenotype of the Arabidopsis tt12 mutant both quantitatively and qualitatively. On the basis of biochemical properties, tissue-specific expression pattern, and genetic loss-of-function analysis, we conclude that MATE1 is an essential membrane transporter for proanthocyanidin biosynthesis in the Medicago seed coat. Implications of these findings for the assembly of oligomeric proanthocyanidins are discussed.
Risk of tuberculosis infection and disease associated with work in health care settings.

BACKGROUND Tuberculosis (TB) in health care workers (HCWs) was not considered a serious problem following the advent of effective antibiotic therapy. Interest was re-stimulated by the occurrence of several major nosocomial outbreaks. METHODS We have reviewed the available published literature regarding prevalence and incidence of TB infection and disease among HCWs in countries categorised by mean income. We included studies published in English since 1960 from low- and middle-income countries (LMICs) and since 1990 from high-income countries (HICs). We excluded outbreak reports and studies based only on questionnaires. RESULTS The median prevalence of latent TB infection (LTBI) in HCWs was 63% (range 33-79%) in LMICs and 24% in HICs (4-46%). Among HCWs from LMICs, LTBI was consistently associated with markers of occupational exposure, but in HICs it was more often associated with non-occupational factors. The median annual incidence of TB infection attributable to health care work was 5.8% (range 0-11%) in LMICs and 1.1% (0.2-12%) in HICs. Rates of active TB in HCWs were consistently higher than in the general population in all countries, although findings were variable in HICs. Administrative infection control measures had a modest impact in LMICs, yet seemed the most effective in HICs. CONCLUSIONS TB remains a very important occupational risk for HCWs in LMICs and for workers in some institutions in HICs. Risk appears particularly high when there is increased exposure combined with inadequate infection control measures.
Ex vivo expansion of human mobilized peripheral blood stem cells using epigenetic modifiers

Epigenetic modifications likely control the fate of hematopoietic stem cells (HSCs). The chromatin‐modifying agents (CMAs), 5‐aza‐2′‐deoxycytidine (5azaD) and trichostatin A (TSA), have previously been shown to expand HSCs from cord blood and marrow. Here we assessed whether CMA can also expand HSCs present in growth factor–mobilized human peripheral blood (MPB).