Miracle-dz/UniFAR-FTUs huggingface dataset:
The Soluble Catalytic Domain of Membrane Type 1 Matrix Metalloproteinase Cleaves the Propeptide of Progelatinase A and Initiates Autoproteolytic Activation

It has been proposed that the cell-mediated activation of progelatinase A requires binding of the C-terminal domain of the proenzyme to a membrane-associated complex of the membrane type matrix metalloproteinase MT1-MMP and TIMP-2. Subsequent sequential proteolysis of the propeptide by MT1-MMP and gelatinase A is thought to generate the active form of gelatinase A. We have prepared the proform of the catalytic domain of the MT1-MMP and demonstrated that this may be activated in vitro by trypsin proteolysis to yield a functional proteinase capable of cleaving typical metalloproteinase peptide substrates, gelatin and casein. The active catalytic domain of MT1-MMP was also shown to activate progelatinase A to a fully active form. Using the inactive mutant pro-E375A gelatinase A, we dissected the propeptide processing events that occur. MT1-MMP cleaves the propeptide at the sequence Asn37-Leu38 only. Further cleavage of the mutant enzyme propeptide at Asn80-Tyr81, equivalent to that of the active wild type gelatinase A, could only be effected by addition of gelatinase A to the system. TIMP-1 was essentially unable to prevent MT1-MMP processing of wild type or E375A progelatinase A, whereas TIMP-2 and TIMP-3 were good inhibitors of these events. Analysis of the rate of binding of TIMPs to the catalytic domain of MT1-MMP using kinetic methods showed that TIMP-1 is an extremely poor inhibitor of MT1-MMP. In comparison, TIMP-2 and TIMP-3 are excellent inhibitors, binding more rapidly to the catalytic domain of MT1-MMP than to the catalytic domain of gelatinase A. These data demonstrate the basic mechanism of MT1-MMP action on progelatinase A and the reason for the lack of inhibition by TIMP-1 previously demonstrated in cell-based activation studies.
Impact of multi-focused images on recognition of soft biometric traits

In video surveillance semantic traits estimation as gender and age has always been debated topic because of the uncontrolled environment: while light or pose variations have been largely studied, defocused images are still rarely investigated. Recently the emergence of new technologies, as plenoptic cameras, yields to deal with these problems analyzing multi-focus images. Thanks to a microlens array arranged between the sensor and the main lens, light field cameras are able to record not only the RGB values but also the information related to the direction of light rays: the additional data make possible rendering the image with different focal plane after the acquisition. For our experiments, we use the GUC Light Field Face Database that includes pictures from the First Generation Lytro camera. Taking advantage of light field images, we explore the influence of defocusing on gender recognition and age estimation problems. Evaluations are computed on up-to-date and competitive technologies based on deep learning algorithms. After studying the relationship between focus and gender recognition and focus and age estimation, we compare the results obtained by images defocused by Lytro software with images blurred by more standard filters in order to explore the difference between defocusing and blurring effects. In addition we investigate the impact of deblurring on defocused images with the goal to better understand the different impacts of defocusing and standard blurring on gender and age estimation.
Statin and Ezetimibe Combination Therapy Decreases Mean Platelet Volume Compared to Statin Monotherapy

permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. When platelets are activated, they increase in size and change from a quiescent disc to a swollen sphere. Large platelets are more reactive and likely aggregate more than small ones. 1 Mean platelet volume (MPV), an indicator of platelet size and activation , has been shown to predict ischemic stroke, myocardial in-farction, and overall vascular mortality. The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) study showed that ezetimibe added to statin therapy further decreases low density lipoprotein cholesterol (LDL-C) levels and prevented acute coronary syndromes. 4 In this study, we investigated the lowering effect of LDL-C and MPV changes in patients who are on statin-ezetimibe combination therapy and those who receive statin monotherapy. Patients with acute ischemic cerebral infarctions (n = 120) were divided into those who were on statin therapy (n= 60) and those on statin plus ezetimibe (n= 60). The statin group received either atorvastatin (20 mg; n = 13) or rosuvastatin (10 mg; n = 48). The statin plus ezetimibe group received ezetimibe (10 mg) on top of the same dose of statin (atorvastatin plus ezeti-mibe, n = 14; rosuvastatin plus ezetimibe, n = 47). Student's t-tests showed that MPV and serum LDL-C levels were more significantly decreased (MPV: P< 0.001; LDL-C: P= 0.017) by statin plus ezetimibe combination therapy (MPV: from 7.] mg/ dL). Total cholesterol and triglycerides, but not high-density lipo-protein-cholesterol, were more significantly altered with combination therapy than with statin monotherapy (Table 1). A multi-variate regression analysis showed that only LDL-C in the lipid profile correlated significantly with the MPV change. A Pearson correlation analysis showed a positive correlation between the post-treatment MPV and post-treatment LDL-C levels (r= 0.230, P= 0.012). Statin has pleiotrophic effects and modulates platelet function by direct interactions with platelet membranes or by influencing signaling pathways, irrespective of the cholesterol-lowering effects. Aydin et al. reported that high doses of statin decrease MPV and LDL-C levels in patients with diabetes, but the changes in LDL-C and MPV did not correlate. 5 Nevertheless, Marek et al. reported that MPV was correlated with small dense LDL-C. 6 The possible mechanisms through which small dense LDL-C increases MPV include easier oxidation and glycation, which enhances the mobilization of arachidonic acid from phospholipids and decreases membrane fluidity. However, small dense-LDL-C measurements are time consuming and expensive …
A dimensional approach to determine common and specific neurofunctional markers for depression and social anxiety during emotional face processing

Major depression disorder (MDD) and anxiety disorder are both prevalent and debilitating. High rates of comorbidity between MDD and social anxiety disorder (SAD) suggest common pathological pathways, including aberrant neural processing of interpersonal signals. In patient populations, the determination of common and distinct neurofunctional markers of MDD and SAD is often hampered by confounding factors, such as generally elevated anxiety levels and disorder‐specific brain structural alterations. This study employed a dimensional disorder approach to map neurofunctional markers associated with levels of depression and social anxiety symptoms in a cohort of 91 healthy subjects using an emotional face processing paradigm. Examining linear associations between levels of depression and social anxiety, while controlling for trait anxiety revealed that both were associated with exaggerated dorsal striatal reactivity to fearful and sad expression faces respectively. Exploratory analysis revealed that depression scores were positively correlated with dorsal striatal functional connectivity during processing of fearful faces, whereas those of social anxiety showed a negative association during processing of sad faces. No linear relationships between levels of depression and social anxiety were observed during a facial‐identity matching task or with brain structure. Together, the present findings indicate that dorsal striatal neurofunctional alterations might underlie aberrant interpersonal processing associated with both increased levels of depression and social anxiety.
How places matter: Telecare technologies and the changing spatial dimensions of healthcare

Dominant discourses on telecare technologies often celebrate the erasure of distance and place. This paper provides a critical intervention into these discourses by investigating how spaces still matter, despite the move from physical to virtual encounters between healthcare professionals and patients. I argue that science and technology studies (STS) research on telecare, as well as other technologies, can be enriched by including a focus on place to understand the dynamic interactions between people and things. Adopting insights of human geographers, I show how places in which technologies are used affect how technologies enable or constrain human actions and identities. Whereas some spaces may facilitate the incorporation of technologies, others may resist technologies. A focus on how places matter is important for understanding how telecare technologies reorder and redefine healthcare. Although other healthcare technologies are also important actors in transforming healthcare, telecare technologies do this in a very specific way: they redefine the spatial dimensions of healthcare. To capture and further explore this changing spatial configuration of healthcare, I introduce the notion of technogeography of care. This concept provides a useful heuristic to study how places matter in healthcare. Although telecare technologies introduce virtual encounters between healthcare providers and patients, the use of telecare devices still largely depends on locally grounded, situated care acts. Based on interviews with users of several cardiac telecare applications, including healthcare professionals and patients in Germany and the Netherlands, the paper shows how patients’ homes and public spaces are important for shaping the implementation and use of telecare technologies, and vice versa. Last, but not least, telecare devices are implicated as well. The paper emphasizes the place-dependency of the use and meaning of technical devices by showing how the same technological device can do and mean different things in different places.
Reconstitution and transphosphorylation of TGF‐beta receptor complexes.

Transforming growth factor‐beta (TGF‐beta) signals by contacting two distantly related transmembrane serine/threonine kinases called receptors I (T beta R‐I) and II (T beta R‐II). TGF‐beta binds to T beta R‐II, which is a constitutively active kinase and this complex recruits T beta R‐I, causing its phosphorylation and signal propagation to downstream substrates. The biochemical properties of this interaction were analyzed with reconstituted receptor systems. T beta R‐I and T beta R‐II baculovirally expressed at high levels in insect cells have the ligand binding properties of receptors expressed in mammalian cells, and form a complex in which T beta R‐I phosphorylation is dependent on the kinase activity of T beta R‐II. Furthermore, T beta R‐I and T beta R‐II can form a complex in vitro, and their cytoplasmic domains can specifically interact in a yeast two‐hybrid system. In vitro complex formation with catalytically active T beta R‐II is necessary and sufficient for T beta R‐I phosphorylation, which within this complex does not require the catalytic activity of T beta R‐I, thus mimicking T beta R‐I phosphorylation in intact cells. In addition, T beta R‐I phosphorylated in vitro remains associated with T beta R‐II. These results suggest that T beta R‐I and T beta R‐II have affinity for each other, however, the ligand is required for stable complex formation under physiological conditions. Once formed, this complex is sufficient for T beta R‐I phosphorylation by T beta R‐II.
Effect of oligochaete worm body fluids on biological phosphorus removal in a bench-scale EBPR system

During waste sludge reduction by oligochaetes, phosphorus (P) concentrations in the effluent have been noticed to increase. In the current study, batch experiments were carried out in order to provide explanations for this phosphorus release. The results indicated that increase in effluent phosphorus concentration might not be directly linked to the phosphorus in worm body fluids, as the phosphorus concentration in the system at the start of each operational period did not change significantly. However, the phosphorus removal efficiency rapidly dropped from 93.9%±1.9% to 62.2%±1.3% with increasing addition of oligochaete worm body fluids. Furthermore, an increase in worm body fluids induced a remarkable enhancement of anaerobic phosphorus release rate as well as anaerobic storage of poly-β-hydroxyalkanoate (PHA). At a worm density (wet weight) of 14.4 g/L, the anaerobic phosphorus release rate was elevated by 31.1%±2.8% and 57.3%±4.6% at 2.5% and 5.0% worm death rate, respectively, compared with the control. The contribution of worm body fluids to PHA production was 39.3–67.7 mg/g of dead worm (wet weight), which was mainly attributed to the extra synthesis of poly-β-hydroxyvalerate (PHV). Unfortunately, in the concomitant aerobic stage, inhibition of 3-hydroxybutyric acid (PHB) oxidation and ammonia utilization was observed along with the increasing addition of worm body fluids. Meanwhile, nitrite elevation was found at the beginning of the aerobic stage, which might be negative to the aerobic metabolic processes performed by phosphate-accumulating organisms (PAOs), namely PHB oxidation, phosphate uptake and ammonia utilization for biomass growth.
Evaluation of a modified prescription form to address prescribing errors.

PURPOSE The impact of a modified paper prescription form on the occurrence of prescribing errors was evaluated. METHODS Rural primary care providers practicing in the United States who wrote paper prescriptions in English were eligible for study participation. The prescribers agreed to use only the prescription pads provided to them during the study. The study prescription pads contained 50 prescription forms, each with a duplicate. Each prescription and duplicate contained a unique serial number for data identification purposes. When a prescriber wrote a prescription, the original was provided to the patient per usual practice, and the duplicate was retained as the study data. Two prescription pads contained modified forms and two prescription pads were similar to the prescription pads the prescriber had been using. Providers completed 100 standard and 100 modified prescriptions. Pharmacist consultants reviewed each prescription for the presence or absence of errors. The primary outcome measure was the number of errors. Secondary outcomes were risk differences between standard and modified prescription forms for various error types. RESULTS Of the 327 prescribers who were eligible and expressed interest in the study, 111 started the study and 84 completed the study. A total of 16,061 prescriptions were eligible for analysis. Pharmacists identified at least one prescribing problem in 987 prescriptions (6.1%). Modified prescription forms were associated with significantly more prescribing problems than standard prescription forms (odds ratio, 1.85; 95% confidence interval, 1.5-2.2; p < 0.001). CONCLUSION Modified prescription forms were associated with more errors than were standard prescription forms in a sample of rural prescribers.
Visibility-Driven Depth Determination of Surface Patches in Direct Volume Rendering

This paper presents an algorithm called surfseek for selecting surfaces on the most visible features in direct volume rendering (DVR). The algorithm is based on a previously published technique (WYSIWYP) for picking 3D locations in DVR. The new algorithm projects a surface patch on the DVR image, consisting of multiple rays. For each ray the algorithm uses WYSIWYP or a variant of it to find the candidates for the most visible locations along the ray. Using these candidates the algorithm constructs a graph and computes a minimum cut on this graph. The minimum cut represents a very visible but relatively smooth surface. In the last step the selected surface is displayed. We provide examples for the results in real-world dataset as well as in artificially generated datasets.
Development and evaluation of an extra chromosomal DNA-based PCR test for diagnosing bovine babesiosis.

Subclinical infections of bovine babesiosis, caused primarily by Babesia bigemina or Babesia bovis are a challenge to current diagnostic methods. In this study, the development and evaluation of a PCR test for sensitive and specific detection of B. bigemina or B. bovis is described. The target selected for amplification is part of the apocytochrome b gene, conserved in both Babesia spp. and located on the linear approximately 6.0 kb extra chromosomal DNA. The test was evaluated to detect the parasites over a period of 5 (B. bigemina) and 10 months (B. bovis) post infection in experimentally infected cattle. Analysis of DNA extracted from blood samples drawn from the experimental cattle in a blind study revealed an overall sensitivity of 85 and 64% for B. bovis and B. bigemina respectively, while the specificity was 97% for B. bovis and 91% for B. bigemina. The test results were compared with the recently developed ribosomal DNA-based polymerase chain reaction (PCR) test and to the complement fixation test for both Babesia spp. The extra chromosomal DNA-based test was 20% more sensitive than that of ribosomal DNA-based tests. This test may be a more desirable alternative to the currently used, complement fixation test.
BCL2 mutation spectrum in B‐cell non‐Hodgkin lymphomas and patterns associated with evolution of follicular lymphoma

BCL2 is a target of somatic hypermutation in t(14;18) positive and also in a small fraction of t(14;18) negative diffuse large B‐cell lymphoma (DLBCL), suggesting an aberrant role of somatic hypermutation (ASHM). To elucidate the prevalence of BCL2 mutations in lymphomas other than DLBCL, we Sanger‐sequenced the hypermutable region of the BCL2 gene in a panel of 69 mature B‐cell lymphomas, including Richter's syndrome DLBCL, marginal‐zone lymphomas, post‐transplant lymphoproliferative disorders, HIV‐associated and common‐variable immunodeficiency‐associated DLBCL, all known to harbour ASHM‐dependent mutations in other genes, as well as 16 t(14,18) negative and 21 t(14;18) positive follicular lymphomas (FLs). We also investigated the pattern of BCL2 mutations in longitudinal samples from 10 FL patients relapsing to FL or transforming to DLBCL (tFL). By direct sequencing, we found clonally represented BCL2 mutations in 2/16 (13%) of t(14;18) negative FLs, 2/16 (13%) HIV‐DLBCLs, 1/9 (11%) of Richter's syndrome DLBCL, 1/17 (6%) of post‐transplant lymphoproliferative disorders and 1/2 (50%) common‐variable immunodeficiency‐associated DLBCL. The proportion of mutated cases was significantly lower than in FLs carrying the t(14;18) translocation (15/21, 71%). However, the absence of t(14;18) by FISH or PCR and the molecular features of the mutations strongly suggest that BCL2 represents an additional target of ASHM in these entities. Analysis of the BCL2 mutation pattern in clonally related FL/FL and FL/tFL samples revealed two distinct scenarios of genomic evolution: (i) direct evolution from the antecedent FL clone, with few novel clonal mutations acquired by the tFL major clone, and (ii) evolution from a common mutated long‐lived progenitor cell, which subsequently acquired distinct mutations in the FL and in the relapsed or transformed counterpart. Copyright © 2014 John Wiley & Sons, Ltd.
Variation in microbial community structure in two boreal peatlands as determined by analysis of phospholipid Fatty Acid profiles

Analyses of phospholipid fatty acids (PLFAs) were used to assess variation in community structure and total microbial biomass in two boreal peatlands in Sweden. The total PLFA concentration in peat ranged from 0.16 to 7.0 nmol g of wet peat(sup-1) (median, 0.70 nmol g of wet peat(sup-1)). Principal-component analysis of PLFA data revealed that the degree of depth-related variation in PLFA composition was high among peatland habitats, with general differences between wet sites, with water tables within a few centimeters of the moss surface, and dry sites, with water tables >10 cm below the moss surface. However, variation in PLFA composition over the growing season was negligible. In the principal-component analyses, most PLFAs were determined to be parts of clusters of covarying fatty acids, suggesting that they originated in the same functional groups of microorganisms. Major clusters were formed by monounsaturated (typical of gram-negative eubacteria), terminally branched (gram-positive or anaerobic gram-negative eubacteria), methyl-branched and branched unsaturated (sulfate-reducing bacteria and/or actinomycetes), (omega)8 monounsaturated (methane-oxidizing bacteria), and polyunsaturated (eucaryotes) PLFAs. Within the clusters, PLFAs had rather distinct concentration-depth distributions. For example, PLFAs from sulfate-reducing bacteria and/or actinomycetes and those from methane-oxidizing bacteria had maximum concentrations slightly below and at the average water table depth, respectively.
Retrograde Axonal Transport of Transmitter Enzymes, Fucose-Labeled Protein, and Nerve Growth Factor in Streptozotocin-Diabetic Rats

Rapid axonal transport was studied by several methods in rats with serum glucose levels above 300 mg/dl as a result of treatment with streptozotocin (45–50 mg/kg) 3 days, 1 wk, 4 wk, 8 wk, or 4 mo earlier. With untreated age-matched rats as controls, rapid anterograde axonal transport in the sciatic nerves of diabetic rats appeared entirely normal. Statistically significant differences were never observed between experimental and control nerves in the basal content of acetylcholinesterase (AChE) and dopamine-β-hydroxylase (DBH) activity or in the rate of accumulation of these enzymes proximal or distal to a ligature. Therefore, the basic capacity for rapid anterograde and retrograde axonal transport of proteins was probably unimpaired in the diabetic nerves. The accumulation of labeled glycoproteins proximal to ligatures on the contralateral nerves of the same rats after injection of the L5 dorsal root ganglion with 3H-fucose was likewise normal. However, rats with 1, 4, and 8 wk of diabetes did show reduced accumulation of fucose-labeled protein distal to nerve ligations, indicating a long-lasting abnormality of retrograde axonal transport. Furthermore, this abnormality was reversed by daily insulin treatment during the second half of an 8-wk experimental period. It is therefore unlikely that the depression of retrograde transport reflects direct toxic effects of streptozotocin. We conclude that streptozotocin-induced diabetes leads to: (1) abnormal delay in the turnaround of transported proteins in distal nerve regions, perhaps combined with (2) an abnormal metabolism of glycoproteins. A delayed onset of retrograde transport is consistent with present observations of reduced accumulation of 125I-labeled nerve growth factor (NGF) below a midthigh ligature on the sciatic nerve after injection of this protein into the hindfoot of rats with 3–5 wk of diabetes. Further work on the factors controlling rapid retrograde transport of proteins in diabetic nerve is warranted.