Miracle-dz/UniFAR-FTUs huggingface dataset:
Dimethyl sulfoxide at 2.5% (v/v) alters the structural cooperativity and unfolding mechanism of dimeric bacterial NAD+ synthetase

Dimethyl sulfoxide (DMSO) is commonly used as a cosolvent to improve the aqueous solubility of small organic compounds. Its use in a screen to identify novel inhibitors of the enzyme NAD+ synthetase led to this investigation of its potential effects on the structure and stability of this 60‐kD homodimeric enzyme. Although no effects are observed on the enzyme's catalytic activity, as low as 2.5% (v/v) DMSO led to demonstrable changes in the stability of the dimer and its unfolding mechanism. In the absence of DMSO, the dimer behaves hydrodynamically as a single ideal species, as determined by equilibrium analytical ultracentrifugation, and thermally unfolds according to a two‐state dissociative mechanism, based on analysis by differential scanning calorimetry (DSC). In the presence of 2.5% (v/v) DMSO, an equilibrium between the dimer and monomer is now detectable with a measured dimer association constant, Ka, equal to 5.6 × 106/M. DSC curve analysis is consistent with this finding. The data are best fit to a three‐state sequential unfolding mechanism, most likely representing folded dimer ⇆ folded monomer ⇆ unfolded monomer. The unusually large change in the relative stabilities of dimer and monomer, e.g., the association equilibrium shifts from an infinitely large Ka down to ∼106/M, in the presence of relatively low cosolvent concentration is surprising in view of the significant buried surface area at the dimer interface, roughly 20% of the surface area of each monomer is buried. A hypothetical structural mechanism to explain this effect is presented.
Associated risk factors and management of chronic diabetic foot ulcers exceeding 6 months’ duration

Background The management of chronic diabetic foot ulcers (DFU) poses a great challenge to the treating physician and surgeon. The aim of this study was to identify the risk factors, clinical presentation, and outcomes associated with chronic DFU>6 months’ duration. Methods This prospective study was performed in Jabir Abu Eliz Diabetic Centre (JADC), Khartoum, Sudan. A total of 108 patients who had DFU for >6 months were included. Recorded data included patient's demographics, DFU presentation, associated comorbidities, and outcomes. DFU description included size, depth, protective sensation, perfusion, and presence of infection. Comorbidities assessed included eye impairment, renal and heart disease. All patients received necessary local wound care with sharp debridement of any concomitant necrotic and infected tissues and off-loading with appropriate shoe gear and therapeutic devices. Results The mean age of the studied patients was 56+SD 9 years with a male to female ratio of 3:3.3. The mean duration of DFU was 18±SD 17 months (ranging from 6 to 84 months). Ulcer healing was significantly associated with off-loading, mainly the use of total contact cast (TCC) (p=0.013). Non-healing ulcerations were significantly associated with longer duration of the chronic DFU>12 months (p=0.002), smoking (p=0.000), poor glycemic control as evidenced by an elevated HbA1c (>7%), large size (mean SD 8+4 cm), increased depth (p<0.001), presence of skin callus (p<0.000), impaired limb perfusion (p=0.001), impaired protective sensation as measured by 10 g monofilament (p=0.002), neuroischemia (p=0.002), and Charcot neuroarthropathy (p=0.017). Discussion Risk factors associated with chronic DFU of>6 months’ duration included the presentation of an ulcer with increased size and depth, with associated skin callus and neuroischemia, in a diabetic patient with a history of smoking and increased HbA1c >7%. Off-loading mainly with the use of TCC is an effective method of managing long-standing DFU.
Differential Control of Central Cardiorespiratory Interactions by Hypercapnia and the Effect of Prenatal Nicotine

Hypercapnia evokes a strong cardiorespiratory response including gasping and a pronounced bradycardia; however, the mechanism responsible for these survival responses initiated in the brainstem is unknown. To examine the effects of hypercapnia on the central cardiorespiratory network, we used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and inhibitory synaptic neurotransmission to cardioinhibitory vagal neurons (CVNs). Hypercapnia differentially modulated inhibitory neurotransmission to CVNs; whereas hypercapnia selectively depressed spontaneous glycinergic IPSCs in CVNs without altering respiratory-related increases in glycinergic neurotransmission, it decreased both spontaneous and inspiratory-associated GABAergic IPSCs. Because maternal smoking is the highest risk factor for sudden infant death syndrome (SIDS) and prenatal nicotine exposure is proposed to be the link between maternal smoking and SIDS, we examined the cardiorespiratory responses to hypercapnia in animals exposed to nicotine in the prenatal and perinatal period. In animals exposed to prenatal nicotine, hypercapnia evoked an exaggerated depression of GABAergic IPSCs in CVNs with no significant change in glycinergic neurotransmission. Hypercapnia altered inhibitory neurotransmission to CVNs at both presynaptic and postsynaptic sites. Although the results obtained in this study in vitro cannot be extrapolated with certainty to in vivo responses, the results of this study provide a likely neurochemical mechanism for hypercapnia-evoked bradycardia and the dysregulation of this response with exposure to prenatal nicotine, creating a higher risk for SIDS.
Post-saline infusion test aldosterone levels indicate severity and outcome in primary aldosteronism.

OBJECTIVE The saline infusion test (SIT) is widely used as a confirmatory test for primary aldosteronism (PA). SIT results are judged as follows: post-test aldosterone levels <50 ng/l exclude PA, whereas levels >50 ng/l confirm PA. We hypothesized that post-SIT aldosterone concentrations indicate the severity of PA and might predict outcome. DESIGN The study includes 256 PA patients of the German Conn's Registry who prospectively underwent SIT. The data of 126 patients with complete follow-up of 1.2±0.3 years after diagnosis were analyzed. The patients were divided into two groups with post-SIT aldosterone levels of 50-100 ng/l (group 1; n=38) and of >100 ng/l (group 2; n=88). RESULTS Patients in group 2 had a significantly shorter duration of hypertension (7.5 vs 11.7 years (median), P=0.014), higher systolic blood pressure (BP; 151±16 vs 143±17 mmHg, P=0.036), lower serum potassium (3.3±0.6 vs 3.5±0.4 mmol/l, P=0.006), higher 24-h urine protein excretion (7.4 vs 5.4 mg/dl (median), P=0.012), and were more often female (P=0.038). They showed more often unilateral disease (P<0.005) with larger tumors (14±10 vs 7±10 mm, P=0.021), underwent more often adrenalectomy (75% vs 37%, P<0.005), required a lower number of antihypertensive drugs after adrenalectomy (1.2±1.2 vs 2.5±1.4, P=0.001), had a faster normalization of urinary protein excretion (with medical treatment P=0.049; with Adx P<0.005) at follow-up, and more frequently underlying well-characterized mutation (P=0.047). CONCLUSIONS PA patients with post-SIT aldosterone levels of >100 ng/l have a more rapid development of PA caused more frequently by unilateral disease with larger aldosterone-producing adenomas. However, this group of patients may have a significantly better outcome following specific treatment.
A permutation approach for selecting the penalty parameter in penalized model selection

We describe a simple, computationally efficient, permutation‐based procedure for selecting the penalty parameter in LASSO‐penalized regression. The procedure, permutation selection, is intended for applications where variable selection is the primary focus, and can be applied in a variety of structural settings, including that of generalized linear models. We briefly discuss connections between permutation selection and existing theory for the LASSO. In addition, we present a simulation study and an analysis of real biomedical data sets in which permutation selection is compared with selection based on the following: cross‐validation (CV), the Bayesian information criterion (BIC), scaled sparse linear regression, and a selection method based on recently developed testing procedures for the LASSO.
Incidencia de factores personales y laborales en los salarios del sector hostelero: una visión de género

Este articulo aporta evidencia empirica sobre las diferencias en los rendimientos salariales desde una perspectiva de genero en el sector hostelero espanol, comparandolas con otros sectores de la economia espanola. Mediante la estimacion de una funcion minceriana, los resultados obtenidos revelan una significativa diferencia negativa del rendimiento del capital humano en la hosteleria frente al resto de sectores y una mayor penalizacion salarial asociada al rendimiento educativo para el caso de la mujer en la hosteleria, en contraposicicon a lo que ocurre en el resto de sectores analizados.
Fibronectin Binding to the Salmonella enterica Serotype Typhimurium ShdA Autotransporter Protein Is Inhibited by a Monoclonal Antibody Recognizing the A3 Repeat

ABSTRACT ShdA is a large outer membrane protein of the autotransporter family whose passenger domain binds the extracellular matrix proteins fibronectin and collagen I, possibly by mimicking the host ligand heparin. The ShdA passenger domain consists of ∼1,500 amino acid residues that can be divided into two regions based on features of the primary amino acid sequence: an N-terminal nonrepeat region followed by a repeat region composed of two types of imperfect direct amino acid repeats, called type A and type B. The repeat region bound bovine fibronectin with an affinity similar to that for the complete ShdA passenger domain, while the nonrepeat region exhibited comparatively low fibronectin-binding activity. A number of fusion proteins containing truncated fragments of the repeat region did not bind bovine fibronectin. However, binding of the passenger domain to fibronectin was inhibited in the presence of immune serum raised to one truncated fragment of the repeat region that contained repeats A2, B8, A3, and B9. Furthermore, a monoclonal antibody that specifically recognized an epitope in a recombinant protein containing the A3 repeat inhibited binding of ShdA to fibronectin.
An Economic Analysis of Personal Data Protection Obligations in the European Union

The collection, storage and processing of data have become easier and cheaper with the development of the Internet and the evolution of ICT technologies in general. This may be a cause (or a consequence) of new business models that rely on the exploitation of these stored data in order to try to extract some kind of value. If some value is found in personal data and in its processing in large volumes, this value would increase social welfare. In order for the value of an asset to be appraised, entrepreneurial activity is required. This is process of trial and error which may be hindered by regulation, due to the limits that this imposes on economic activity, for different reasons. In the European Union, the 1995 Data Protection Directive, the ePrivacy Directive and the more recent General Data Protection Regulation put limits to the exploitation of personal data. These limitations can be synthetized around the four rights that they grant individuals, the so-called ARCO rights: access, rectification, cancellation and objection. In this paper, the consequences of the data protection rights on entrepreneurial activity are analysed, and thus on the value that may be accrued from data related to individuals, and on social welfare. As a conclusion, some policy recommendations are proposed to achieve a balance between legal rights in the EU and possibilities for social welfare improvement.
A novel role for the Drosophila epsin (lqf): Involvement in autophagy

Screening P-element-induced mutant collections, 52 lines were selected as potentially defected ones in endocytosis or autophagy. After excluding those which were rescued by 20-hydroxyecdosone treatment, the exact position of the inserted P-element was determined in the remaining lines. In the case of l(3)S011027 stock, that liquid facets (lqf) gene was affected which codes an epsin-homolog protein in Drosophila. We reveal that Lqf is essential to the receptor-mediated endocytosis of larval serum proteins (LSPs) in the larval fat body cells of Drosophila. In l(3)S011027 line, lack of Lqf fails the formation of autophagosomes thus leading to the arrest of destroying of trophocytes. Transgenic larvae carrying Lqf-RNAi construct were unable to generate endocytic and autophagic vacuoles and led to a prolonged larval stage. On the other hand, GFP-tagged Lqf protein showed an exclusively co-localization with the LysoTracker Red- or GFP-Atg8a labeled autophagosomes. By using the antiserum generated against the fifth exon of lqf, we demonstrated that prior to the onset of developmental autophagy the Lqf protein was present in the nucleus of fat body cell, but thereafter the protein was localized in the territory of endocytic and autophagic vacuoles. The fact that the inhibition of the target of rapamycin (TOR) did not restore the autophagic process and the normal development in the case of lqf mutant larvae points to that the Lqf is downstream to the TOR, the central kinase of the autophagy pathway.
A closed-loop switched-capacitor interface for high-quality microaccelerometer

This paper presents a closed-loop switched-capacitor interface for high-quality bulk micro-mechanical accelerometer. Analogue force feedback is realized to establish an electromechanical closed-loop so as to improve the dynamic range. The feedback accuracy is guaranteed by applying bottom-plate-sampling structure in the feedback controller. A proportional derivative controller is introduced to compensate the instability derived from the high-quality accelerometer, while offset cancellation structure is inserted to further improve the dynamic range. The chip measures 2.5×2.5mm2 in Chartered 0. 18µm CMOS process. Simulation results show that the whole accelerometer system offers ±1.3g input range with 0.25% non-linearity from a single 6V supply, as well as a good degree of robustness.
Differential sensitivity of human monocytes and macrophages to ANP: a role of intracellular pH on reactive oxygen species production through the phospholipase involvement

Atrial natriuretic peptide (ANP), a cardiovascular hormone, elicits different biological actions in the immune system. The aim of the present work was to study the effect of ANP on the intracellular pH (pHi) of human monocytes and macrophages and to investigate whether pHi changes could play a role on phospholipase activities and reactive oxygen species (ROS) production. Human macrophages isolated by peripheral blood mononuclear cells and THP‐1 monocytes, which were shown to express all three natriuretic peptide receptors (NPR‐A, NPR‐B, and NPR‐C), were treated with physiological concentrations of ANP. A significant decrease of pHi was observed in ANP‐treated macrophages with respect to untreated cells; this effect was paralleled by enhanced phospholipase activity and ROS production. Moreover, all assessed ANP effects seem to be mediated by the NPR‐C. In contrast, no significant effect on pHi was observed in THP‐1 monocytes treated with ANP. Treatment of macrophages or THP‐1 monocytes with 5‐(N‐ethyl‐N‐isopropyl)amiloride, a specific Na+/H+ antiport inhibitor, decreases pHi in macrophages and monocytes. Our results indicate that only macrophages respond to ANP in terms of pHi and ROS production, through diacylglycerol and phosphatidic acid involvement, pointing to ANP as a new modulator of ROS production in macrophages.
Angiotensin II Decreases the Renal MRI Blood Oxygenation Level–Dependent Signal

Acute experimental reduction of renal blood flow decreases the renal blood oxygenation level–dependent (BOLD) MRI signal in animals. Angiotensin II also reduces renal blood flow, but the ability of BOLD MRI to dynamically detect this response has not yet been investigated in humans. Six healthy male volunteers underwent an individual dose-finding study to identify the intravenous doses of angiotensin II, norepinephrine, and sodium nitroprusside necessary to induce a 15-mm Hg peak mean arterial blood pressure change. MRI studies followed within 3 weeks, when angiotensin II (8.8±1.4 ng/kg), norepinephrine (52±12 ng/kg), and sodium nitroprusside (2.0±0.3 &mgr;g/kg) were given twice in an unblocked, randomized sequence while imaging experiments were performed on a 1.5-T Siemens Sonata. A multiecho echo-planar imaging sequence was used to acquire T2* maps with a temporal resolution of 1 respiratory cycle. Averaged over a renal cortex dominated region of interest, angiotensin II caused a shortening of T2* between 6% and 10%. Sodium nitroprusside and norepinephrine, although of equal potency concerning blood pressure responses, did not alter the renal BOLD signal. The renal BOLD response to angiotensin II appeared with short onset latency (as early as 10 seconds after peripheral intravenous angiotensin II bolus administration) suggesting that this response is a consequence of altered perfusion rather than increased renal oxygen consumption. The methods described here are suitable to assess renal responsiveness to angiotensin II and may, thus, be of great value in human hypertension research.
Molecular Cloning Of Human Paxillin, a Focal Adhesion Protein Phosphorylated by P210BCR/ABL(*)

Paxillin is a 68-kDa focal adhesion protein that is phosphorylated on tyrosine residues in fibroblasts in response to transformation by v-src, treatment with platelet-derived growth factor, or cross-linking of integrins. Paxillin has been shown to have binding sites for the SH3 domain of Src and the SH2 domain of Crk in vitro and to coprecipitate with two other focal adhesion proteins, vinculin and focal adhesion kinase (p125fak). After preliminary studies showed that paxillin was a substrate for the hematopoietic oncogene p210BCR/ABL, we investigated the role of this protein in hematopoietic cell transformation and signal transduction. A full-length cDNA encoding human paxillin was cloned, revealing multiple protein domains, including four tandem LIM domains, a proline-rich domain containing a consensus SH3 binding site, and three potential Crk-SH2 binding sites. The paxillin gene was localized to chromosome 12q24 by fluorescence in situ hybridization analysis. A chicken paxillin cDNA was also cloned and is predicted to encode a protein approximately 90% identical to human paxil-lin. Paxillin coprecipitated with p210BCR/ABL and mul-tiple other cellular proteins in myeloid cell lines, suggesting the formation of multimeric complexes. In normal hematopoietic cells and myeloid cell lines, tyrosine phosphorylation of paxillin and coprecipitation with other cellular proteins was rapidly and transiently induced by interleukin-3 and several other hematopoietic growth factors. The predicted structure of paxillin implicates this molecule in protein-protein interactions involved in signal transduction from growth factor receptors and the BCR/ABL oncogene fusion protein to the cytoskeleton.
PSM and Turnover Intention in Public Organizations

Not all employees contribute equally to the performance of their organizations, and the highest performers may have a disproportionate impact on organizational success. It is thus crucial for public organizations to retain top performers. Public service motivation (PSM) has been shown to be a differentiator of various types of individual job performance, and has also been linked to reduced turnover intention. This study examines the relationship between PSM, change-oriented organizational citizenship behavior (CO-OCB), and turnover intention using survey data from 16 central government ministries in South Korea. Analysis results suggest that CO-OCB plays a mediating role in the relationship between PSM and turnover intention, providing a creative outlet for the most intrinsically motivated employees that in turn strengthens their commitment to their organization. A number of implications of these findings are discussed.
Exoskeletons' design and usefulness evidence according to a systematic review of lower limb exoskeletons used for functional mobility by people with spinal cord injury

Abstract Purpose: Rehabilitation professionals have little information concerning lower limb exoskeletons for people with paraplegia. This study has four objectives: (1) Outline the characteristics of the exoskeletons’ design and their usefulness evidence as assistive mobility devices in the community for the Rewalk™, Mina, Indego®, Ekso™ (previously known as the eLEGS™) and Rex®; (2) document functional mobility outcomes of using these exoskeletons; (3) document secondary skills and benefits achieved with these exoskeletons, safety, user satisfaction and applicability in the community; and (4) establish level of scientific evidence of the selected studies. Method: A systematic review of the literature (January 2004 to April 2014) was done using the databases PubMed, CINAHL and Embase and groups of keywords associated with “exoskeleton”, “lower limb” and “paraplegia”. Results: Seven articles were selected. Exoskeleton use is effective for walking in a laboratory but there are no training protocols to modify identified outcomes over the term usage (ReWalk™: 3 months, Mina: 2 months and Indego®: 1 session). Levels of evidence of selected papers are low. Conclusions: The applicability and effectiveness of lower limb exoskeletons as assistive devices in the community have not been demonstrated. More research is needed on walking performance with these exoskeletons compared to other mobility devices and other training contexts in the community. Implications for rehabilitation Characteristics of the exoskeletons’ design and their usefulness evidence as assistive mobility devices in the community are addressed for the Rewalk™, Mina, Indego®, Ekso™ and Rex® ReWalk™, Indego® and Mina lower limb exoskeletons are effective for walking in a laboratory for individuals with complete lower-level SCI. The ReWalk™ has the best results for walking, with a maximum speed of 0.51 m/s after 45 sessions lasting 60 to 120 min; it is comparable to the average speed per day or per week in a manual wheelchair. The level of scientific evidence is low. Other studies are needed to provide more information about performance over the longer term when walking with an exoskeleton, compared to wheelchair mobility, the user’s usual locomotion, the use of different exoskeletons or the training context in which the exoskeleton is used.
Hepatic surgery for metastatic gastrointestinal neuroendocrine tumors.

Gastrointestinal neuroendocrine cancers are of significant interest to clinicians and basic scientists. Although accuracy of diagnosis has improved with advances in radioimmune and hormonal assays and in the diagnosis of earlier disease by computed tomography (CT) and magnetic resonance imaging (MRI), many patients still present with hepatic metastases. In contrast to most metastatic gastrointestinal cancers, which have rapid clinical progression with a general decrease in performance status or symptoms related to visceral obstruction and pain, the progression of gastrointestinal neuroendocrine cancers is often slow and associated with clinical endocrinopathies from overproduction of gut hormones. This small subgroup of patients with metastatic neuroendocrine malignancies to the liver has become the focus of intensive multimodality therapy.
Plasma and lipids from stored platelets cause acute lung injury in an animal model

BACKGROUND : Transfusion of PLT concentrates may cause TRALI, a life‐threatening reaction that has been linked to the infusion of anti‐WBC immunoglobulins or older, stored PLTs that contain bioactive lipids. We hypothesize that lipids generated during storage of PLTs cause TRALI in a two‐event animal model.