Miracle-dz/UniFAR-FTUs huggingface dataset:
The significance of caveolae in the glomeruli in glomerular disease

Aims The aim of this study was to demonstrate expression of cell membrane invagination ‘caveolae’ in glomeruli and to correlate this with functional and structural characteristics of the human glomerular diseases. Methods The expression of caveolin-1 (Cav-1), which is the main component of caveolae, was examined in the glomeruli, and the relationship between Cav-1 expression and pathological and clinical findings was determined in 99 patients with glomerular disease and in 50 renal transplantation donors as controls. Results Cav-1 was expressed very weakly in the controls, and the area of Cav-1 expression relative to the total glomerular area was 0.57±0.65%. However, the area of Cav-1 expression was significantly larger in each glomerular disease (IgA nephropathy, 1.05±1.36%, p<0.05; crescent glomerulonephritis, 1.86±1.19%, p<0.001; minimal change disease, 2.38±1.24%, p<0.001; focal segmental glomerulosclerosis, 2.88±2.05%, p<0.01; membranous nephritis, 4.27±2.95%, p<0.001; membranoproliferative glomerulonephritis, 4.49±3.15%, p<0.001; and diabetic nephropathy, 2.45±1.52%, p<0.001; compared with the controls. Cav-1 expression was significantly decreased in glomerular disease treated with steroids. Co-localisation of Cav-1 and the endothelial marker ‘pathologische anatomie leiden-endothelium’ was prominent in an immunofluorescence study, and caveolae on the glomerular endothelial cells were observed in electron microscopy. Conclusions The expression of Cav-1 was significantly increased in the glomeruli of patients with glomerular disease, and it was related to urinary albumin excretion. Cav-1 expression and caveolae were observed in glomerular endothelial cells. It is hypothesised that they play a role in the recovery phase of capillary injury or endocytosis of albumin into endothelial cells. Basic research should be performed to elucidate the role played by Cav-1 and caveolae.
Underspecifying and Predicting Voice for Surface Realisation Ranking

This paper addresses a data-driven surface realisation model based on a large-scale reversible grammar of German. We investigate the relationship between the surface realisation performance and the character of the input to generation, i.e. its degree of underspecification. We extend a syntactic surface realisation system, which can be trained to choose among word order variants, such that the candidate set includes active and passive variants. This allows us to study the interaction of voice and word order alternations in realistic German corpus data. We show that with an appropriately underspecified input, a linguistically informed realisation model trained to regenerate strings from the underlying semantic representation achieves 91.5% accuracy (over a baseline of 82.5%) in the prediction of the original voice.
Control of Response Selection by Reinforcer Value Requires Interaction of Amygdala and Orbital Prefrontal Cortex

Goal-directed actions are guided by expected outcomes of those actions. Humans with bilateral damage to ventromedial prefrontal cortex, or the amygdala, are deficient in their ability to use information about positive and negative outcomes to guide their choice behavior. Similarly, rats and monkeys with orbital prefrontal or amygdala damage have been found to be impaired in their responses to changing values of outcomes. In the present study, we tested whether direct, functional interaction between the amygdala and the orbital prefrontal cortex is necessary for guiding behavior based on expected outcomes. Unlike control monkeys, rhesus monkeys with surgical disconnection of these two structures, achieved by crossed unilateral lesions of the amygdala in one hemisphere and orbital prefrontal cortex in the other, combined with forebrain commissurotomy, were unable to adjust their choice behavior after a change in the outcome (here, a reduction in the value of a particular reinforcer). The lesions did not affect motivation to work for a food reinforcer, or food preferences, per se. Hence, the amygdala and orbital prefrontal cortex act as part of an integrated neural system guiding decision-making and adaptive response selection.
A Proposal for a Coherence Corpus in Machine Translation

Coherence in Machine Translation (MT) has received little attention to date. One of the main issues we face in work in this area is the lack of labelled data. While coherent (human authored) texts are abundant and incoherent texts could be taken from MT output, the latter also contains other errors which are not specifically related to coherence. This makes it difficult to identify and quantify issues of coherence in those texts. We introduce an initiative to create a corpus consisting of data artificially manipulated to contain errors of coherence common in MT output. Such a corpus could then be used as a benchmark for coherence models in MT, and potentially as training data for coherence models in supervised settings.
The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype.

HE PHILADELPHIA (Ph) chromosome was the first T chromosomal abnormality associated with a specific malignant disease in humans, namely chronic myeloid leukemia (CML). ’ Later it was identified as one partner in a reciprocal translocation between chromosomes 9 and 22, referred to as t(9;22)(q34;q11). 2 We know now that this translocation results in the formation of two hybrid genes, BCR-ABL on the Ph chromosome and ABL-BCR on 9q+. The BCR-ABL gene encodes a fusion protein with elevated tyrosine kinase activity3 which is regarded as central to the mechanism that underlies the chronic phase of CML.435 The role, if any, of the reciprocal fusion gene, ABL-BCR, remains u n k n ~ w n . ~ * ~ More than 95% of patients with clinically ‘acceptable’ CML have a BCR-ABL gene in their leukemia cells,8 so the t(9;22) can generally be regarded as the hallmark of CML. However, it is not exclusive to CML because it is found in 10% to 20% of adults’ and in 2% to 5% of children’0,’’ with acute lymphoblastic leukemia (ALL), as well as in occasional bona fide cases of acute myeloid leukemia (AML),’2-’6 and mye10ma.2”22 In the current issue of Blood, Pane et a123 add to this list a new disease entity, namely Ph’ chronic neutrophilic leukemia (CNL), with a novel position for the breakpoint in the BCR gene. They bring into focus the fascinating suggestion that the precise location of the breakpoint in BCR (and in ABL), and thus the composition of the fusion BCR-ABL protein, may determine the disease phenotype.
Ieee Transactions on Information Forensics and Security – This Is Pre-print 1

—This paper presents an objective evaluation of the effects of eye tracking specification and stimulus presentation on the biometric viability of complex eye movement patterns (CEM). are evaluated to identify acceptable conditions under which to collect eye movement data. The results suggest the use of eye tracking equipment capable of at least 0.5° spatial accuracy and 250 Hz temporal resolution for biometric purposes, while stimulus had little effect on the biometric viability of eye movements.
Exploring the Genome and Phenotype of Multi-Drug Resistant Klebsiella pneumoniae of Clinical Origin

Klebsiella pneumoniae is an important nosocomial pathogen with an extraordinary resistant phenotype due to a combination of acquired resistant-elements and efflux mechanisms. In this study a detailed molecular characterization of 11 K. pneumoniae isolates of clinical origin was carried out. Eleven clinical isolates were tested for their susceptibilities, by disk diffusion and broth microdilution and interpreted according to CLSI guidelines. Efflux activity was determined by measuring the extrusion of ethidium bromide and biofilm formation was assessed following static growth in Müeller-Hinton and minimal media M9 broths at two temperatures and time points. Template DNA from all 11 isolates was extracted and sequenced. The study collection was found to be resistant to several (extended-spectrum beta-lactam) ESBL-type compounds along with several (fluoro)quinolones (FQ). Resistance to tetracycline accounted for 55% of the study collection (n = 6) and three of the 11 isolates were resistance to carbapenems. Genotyping identified blaCTX-M-15 (82%), blaSHV-12 (55%), and blaTEM-1B (45%) ESBL encoding genes and FQ resistance was associated the presence of the oqxAB operon, identified in 10 of the 11 isolates and qnrB gene in one isolate. The polymorphisms detected in the quinolone resistance-determining regions (QRDRs) were associated with isolates of the clonal group CG15. Sequence types (ST) identified were representative of previously described clonal groups including CG258 (n = 7), CG15 (n = 3), and CG147 (n = 1). Plasmid replicon type databases were queried indicating the presence of IncFII and IncFIB replicon types in the majority of the isolates (91%), followed by IncFIA (45%), and IncR (45%). Two of the 11 isolates were found positive for yersiniabactin siderophore-encoding genes. No differences in the ability to efflux ethidium bromide were identified. Biofilm formation was stronger when the isolates were grown under stressed conditions at 37°C for a period up to 96 h. These data confirm the fact that well-recognized clonal groups of K. pneumoniae of importance to human health carries a diverse repertoire of antimicrobial resistance determinants, particularly related to critically important drugs in the ESBL and FQ classes. The capacity of most isolates to form strong biofilms, when stressed under laboratory-simulated conditions, supports the risk to human health associated with nosocomial infections deriving from indwelling medical devices.
Handling knowledge uncertainty in risk-based requirements engineering

Requirements engineers are faced with multiple sources of uncertainty. In particular, the extent to which the identified software requirements and environment assumptions are adequate and sufficiently complete is uncertain; the extent to which they will be satisfied in the system-to-be is uncertain; and the extent to which obstacles to their satisfaction will occur is uncertain. The resolution of such domain-level uncertainty requires estimations of the likelihood that those different types of situations may or may not occur. However, the extent to which the resulting estimates are accurate is uncertain as well. This meta-level uncertainty limits current risk-based methods for requirements engineering. The paper introduces a quantitative approach for managing it. An earlier formal framework for probabilistic goals and obstacles is extended to explicitly cope with uncertainties about estimates of likelihoods of fine-grained obstacles to goal satisfaction. Such estimates are elicited from multiple sources and combined in order to reduce their uncertainty margins. The combined estimates and their uncertainties are up-propagated through obstacle refinement trees and then through the system's goal model. Two metrics are introduced for measuring problematic uncertainties. When applied to the probability distributions obtained by up-propagation to the top-level goals, the metrics allow critical leaf obstacles with most problematic uncertainty margins to be highlighted. The proposed approach is evaluated on excerpts from a real ambulance dispatching system.
Elimination of Noisy Information from Web Pages

-A Web page typically contains many information blocks. Besides, the content blocks, it usually has such blocks as navigation panels, copyright and privacy notices, and advertisements. These blocks that are not the main content blocks of the page, we call them as noisy blocks. We show that the information contained in these noisy blocks can seriously harm Web data mining. Thus eliminating these noises is of great importance. In our work we focus on identifying and removing local noises in web pages to improve the performance of mining. A simple idea for detection and removal of noises a new DOM tree structure is proposed. The result shows the remarkable increase in F score and accuracy is obtained.
Can flow cytometry of bone marrow aspirate predict outcome of patients with diffuse large B cell lymphoma? A retrospective single centre study

Bone marrow (BM) trephine biopsy is a part of routine staging of patients with newly diagnosed diffuse large B cell lymphoma (DLBCL). The significance of lymphoid monoclonal population on flow cytometry (FC) of the BM aspirate in the presence of negative BM histology has not been clarified. In this study, we assessed the clinical role of positive FC in predicting outcome of patients with DLBCL and a negative BM histology. We retrospectively analysed 101 patients diagnosed with DLBCL at a single institution between years 1994–2003. Three groups of patients were compared: patients with histologic involvement of the BM (BM+), patients with no histologic involvement of the BM but with positive FC (BM−FC+) and patients with neither histologic or FC evidence of BM involvement (BM−FC−). The BM+ group included 13 patients (13%). The BM−FC+ group 16 patients (16%), and the BM−FC−included 72 patients (71%). Median age of the cohort was 67 years. Disease stage and International Prognostic Index score were significantly higher in the BM+ and BM−FC+ groups compared with the BM−FC− group. Median overall survival (OS) for the BM−FC−, BM−FC+ and BM + groups were 4.6, 2.2 and 0.9 years, respectively. Median progression free survival (PFS) for the BM−FC−, BM−FC+ and BM+ groups were 3.2, 1.4 and 0.6 years, respectively (p=0.01 for both analysis). In multivariable Cox regression models adjusting for age, sex, stage and International Prognostic Index, there was no significant differences in OS or PFS between the BM−FC+ and BM−FC− groups.
An Investigation of Response and Stimulus Modality Transfer Effects after Dual-Task Training in Younger and Older

It has been shown that dual-task training leads to significant improvement in dual-task performance in younger and older adults. However, the extent to which training benefits to untrained tasks requires further investigation. The present study assessed (a) whether dual-task training leads to cross-modality transfer in untrained tasks using new stimuli and/or motor responses modalities, (b) whether transfer effects are related to improved ability to prepare and maintain multiple task-set and/or enhanced response coordination, (c) whether there are age-related differences in transfer effects. Twenty-three younger and 23 older adults were randomly assigned to dual-task training or control conditions. All participants were assessed before and after training on three dual-task transfer conditions; (1) stimulus modality transfer (2) response modality transfer (3) stimulus and response modalities transfer task. Training group showed larger improvement than the control group in the three transfer dual-task conditions, which suggests that training leads to more than specific learning of stimuli/response associations. Attentional costs analyses showed that training led to improved dual-task cost, only in conditions that involved new stimuli or response modalities, but not both. Moreover, training did not lead to a reduced task-set cost in the transfer conditions, which suggests some limitations in transfer effects that can be expected. Overall, the present study supports the notion that cognitive plasticity for attentional control is preserved in late adulthood.
Rule-based SLA management for revenue maximisation in Cloud Computing Markets

This paper introduces several Business Rules for maximising the revenue of Providers in Cloud Computing Markets. These rules apply in both negotiation and execution time, and enforce the achievement of Business-Level Objectives by establishing a bidirectional data flow between market and resource layers. The experiments demonstrate that the revenue is maximized by using both resource data when negotiating, and economic information when managing the resources.
Unexpected sequences and structures of mtDNA required for efficient transcription from the first heavy-strand promoter

Human mtDNA contains three promoters, suggesting a need for differential expression of the mitochondrial genome. Studies of mitochondrial transcription have used a reductionist approach, perhaps masking differential regulation. Here we evaluate transcription from light-strand (LSP) and heavy-strand (HSP1) promoters using templates that mimic their natural context. These studies reveal sequences upstream, hypervariable in the human population (HVR3), and downstream of the HSP1 transcription start site required for maximal yield. The carboxy-terminal tail of TFAM is essential for activation of HSP1 but not LSP. Images of the template obtained by atomic force microscopy show that TFAM creates loops in a discrete region, the formation of which correlates with activation of HSP1; looping is lost in tail-deleted TFAM. Identification of HVR3 as a transcriptional regulatory element may contribute to between-individual variability in mitochondrial gene expression. The unique requirement of HSP1 for the TFAM tail may enable its regulation by post-translational modifications.
Immature cortical neurons are uniquely sensitive to glutamate toxicity by inhibition of cystine uptake

Using the N18‐RE‐105 neuroblastoma X retina cell line, we previously described Ca2+‐dependent quisqualate‐type glutamate toxicity caused by the inhibition of high‐affinity cystine uptake, leading to glutathione depletion and accumulation of cellular oxidants. We now demonstrate that primary cultures of rat cortical neurons (E17; 24‐72 h in culture), but not glia, also degenerate when exposed to culture medium with reduced cystine or containing competitive inhibitors of cystine uptake, including glutamate. At this developmental stage, neurotoxicity did not occur as a consequence of continuous exposure to glutamate receptor subtype agonists, N‐methyl‐d‐aspartate, kainate, or 2(RS)‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropioniate. However, those that inhibited neuronal cystine uptake — quisqualate, glutamate, homocysteate, β‐N‐oxalyl‐l‐α,β‐diaminopropionic acid, and ibotenate—were neurotoxic. Toxicity related to quisqualate did not correlate with the development of quisqualate‐stimulated phosphatidylinositol turnover. The toxic potencies of glutamate, quisqualate, and homocysteate were inversely proportional to the concentration of cystine in the medium, suggesting that they competitively inhibit cystine uptake. Autoradiographic analysis of the cellular localization of l‐[35S]cystine uptake indicated that embryonic neurons have a high‐affinity transport system that is sensitive to quisqualate, whereas nonneuronal cells in the same cultures have a low‐affinity system that is insensitive to quisqualate but potently blocked by d‐aspartate and glutamate. Exposure to glutamate or homocysteate resulted in a time‐dependent depletion of the cellular antioxidant glutathione. The centrally acting antioxidant idebenone and α‐tocopherol completely blocked the neurotoxicity resulting from glutamate exposure. We propose that competitive inhibition of cystine transport and reduction of extracellular cystine levels result in neuronal cell death due to accumulation of cellular oxidants. — Murphy, T. H. ; Schnaar, R. L. ; Coyle, J. T. Immature cortical neurons are uniquely sensitive to glutamate toxicity by inhibition of cystine uptake. FASEB J. 4: 1624‐1633; 1990.
Magmatism and extension rates at rifted margins

Rifted margins are commonly classified as either magma-rich or magma-poor. Magma-poor margins are often implicitly related to ultraslow–slow extension. Conversely, therefore, magma-rich margins should represent more rapid extension. Although supported by numerical modelling, these relationships are based on limited data and depend on a perhaps spurious comparison between continental margins and spreading ridges. Three case studies from the Atlantic margins are therefore presented here as a local, by no means complete, examination of this concept. Extension rates for magma-poor margins are mainly derived from offshore Iberia, while the best documented rates on magma-rich margins are probably those in the NE Atlantic. Particularly for the NE Atlantic, there is a dependence on the initial oceanic spreading rate as pre-break-up rates are very difficult to quantify. Our two southerly examples, the Central Atlantic and southern South Atlantic, are both magma-rich in parts and have been described as opening during ultraslow–slow plate separation. Both would therefore seem to contradict the positive ‘rate-magmatism’ correlation. However, on closer examination, a wide range of initial extension rates are actually possible. This is largely due to poor constraints on break-up ages. The assumption that break-up is synchronous with flood basalt extrusion is flawed, and may have caused initial extension rates to have been significantly underestimated. Additionally, averaging between widely spaced oceanic magnetic anomalies allows for a wide range of extension rates. New, well-constrained ages and event chronologies from critical areas of conjugate margins are needed to determine whether this relationship has global validity.
Representational and nonrepresentational gestures in boys with learning disabilities.

This study was designed to investigate the gestural abilities of boys with learning disabilities. Eighteen boys with learning disabilities (who had a low veTbal-high performance vVISC profile) and 24 normal boys between the ages of 9 and 13 were given a gestural test that consisted of two sets of tasks, one requiring the symbolic representation of implement usage-on command and on imitation (representational items) and the other requiring the imitation of hand positions (nonrepresentational items). The items were classified according to place of action as either on-self or away-from-self. The results indicated that the learning-disabled subjects performed at a significantly lower level than the normal control group on the gestural representation tasks. There was a significant difference between instruction (command vs. imitation) and between place of action (self vs. away). Further, the learningdisabled subjects made significantly more spatial errors than the control subjects on imitation of gestural representation and nonrepresentation tasks. Results are discussed in terms of the need to investigate the various parameters of praxis.
Abnormal Development of Dendritic Spines inFMR1 Knock-Out Mice

Fragile X syndrome is caused by a mutation in theFMR1 gene leading to absence of the fragile X mental retardation protein (FMRP). Reports that patients and adultFMR1 knock-out mice have abnormally long dendritic spines of increased density suggested that the disorder might involve abnormal spine development. Because spine length, density, and motility change dramatically in the first postnatal weeks, we analyzed these properties in mutant mice and littermate controls at 1, 2, and 4 weeks of age. To label neurons, a viral vector carrying the enhanced green fluorescent protein gene was injected into the barrel cortex. Layer V neurons were imaged on a two-photon laser scanning microscope in fixed tissue sections. Analysis of >16,000 spines showed clear developmental patterns. Between 1 and 4 weeks of age, spine density increased 2.5-fold, and mean spine length decreased by 17% in normal animals. Early during cortical synaptogenesis, pyramidal cells in mutant mice had longer spines than controls. At 1 week, spine length was 28% greater in mutants than in controls. At 2 weeks, this difference was 10%, and at 4 weeks only 3%. Similarly, spine density was 33% greater in mutants than in controls at 1 week of age. At 2 or 4 weeks of age, differences were not detectable. The spine abnormality was not detected in neocortical organotypic cultures. The transient nature of the spine abnormality in the intact animal suggests that FMRP might play a role in the normal process of dendritic spine growth in coordination with the experience-dependent development of cortical circuits.