Miracle-dz/UniFAR-FTUs huggingface dataset:
Diminishing Apoptosis by Deletion of Bax or Overexpression of Bcl-2 Does Not Protect against Infectious Prion Toxicity In Vivo

B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X protein (Bax), key antiapoptotic and proapoptotic proteins, respectively, have important roles in acute and chronic models of neurologic disease. Several studies have implicated Bax and Bcl-2 in mediating neurotoxicity in prion diseases. To determine whether diminishing apoptotic cell death is protective in an infectious prion disease model we inoculated mice that either were null for proapoptotic Bax or overexpressed antiapoptotic Bcl-2. Interestingly, genetic manipulation of apoptosis did not lessen the clinical severity of disease. Moreover, some disease parameters, such as behavioral alterations and death, occurred slightly earlier in mice that are null for Bax or overexpress Bcl-2. These results suggest that Bax and Bcl-2 mediated apoptotic pathways are not the major contributing factor to the clinical or pathological features of infectious prion disease.
Functional profile of the isolated uremic nephron. Impaired water permeability and adenylate cyclase responsiveness of the cortical collecting tubule to vasopressin.

Resistance of the chronically diseased kidney to vasopressin has been proposed as a possible explanation for the urinary concentrating defect of uremia. The present studies examined the water permeability and adenylate cyclase responsiveness of isolated cortical collecting tubules (CCT) from remnant kidneys of uremic rabbits to vasopressin. In the absence of vasopressin the CCTs of both normal and uremic rabbits were impermeable to water. At the same osmotic gradient, addition of a supramaximal concentration of vasopressin to the peritubular bathing medium led to a significantly lower net water flux per unit length (and per unit luminal surface area) in uremic CCTs than in normal CCTs. Transepithelial osmotic water permeability coefficient, P(f), was 0.0232 +/-0.0043 cm/s in normal CCTs and 0.0059+/-0.001 cm/s in uremic CCTs (P < 0.001). The impaired vasopressin responsiveness of the uremic CCTs was observed whether normal or uremic serum was present in the bath. Basal adenylate cyclase activity per microgram protein was comparable in normal and uremic CCTs. Stimulation by NaF led to equivalent levels of activity in both, whereas vasopressin-stimulated activity was 50% lower in the uremic than in the normal CCTs (P < 0.025). The cyclic AMP analogue, 8-bromo cyclic AMP, produced an increase in the P(f) of normal CCTs closely comparable to that observed with vasopressin. In contrast, the P(f) of uremic CCTs was only minimally increased by this analogue and was not further stimulated by theophylline. These studies demonstrate an impaired responsiveness of the uremic CCT to vasopressin. This functional defect appears to be a result, at least in part, of a blunted responsiveness of adenylate cyclase to vasopressin. The data further suggest that an additional defect in the cellular response to vasopressin may exist, involving a step (or steps) subsequent to the formation of cyclic AMP.A unifying concept of the urinary concentrating defect of uremia is proposed which incorporates a number of hitherto unexplained observations on the concentrating and diluting functions of the diseased kidney.
Requirements Elicitation and Validation with Real World Scenes

A requirements specification defines the requirements for the future system at a conceptual level (i.e., class or type level). In contrast, a scenario represents a concrete example of current or future system usage. In early RE phases, scenarios are used to support the definition of high level requirements (goals) to be achieved by the new system. In many cases, those goals can to a large degree be elicited by observing, documenting and analyzing scenarios about current system usage. To support the elicitation and validation of the goals achieved by the existing system and to illustrate problems of the old system, we propose to capture current system usage using rich media (e.g., video, speech, pictures, etc.) and to interrelate those observations with the goal definitions. Thus, we aim at making the abstraction process which leads to the definition of the conceptual models more transparent and traceable. We relate the parts of the observations which have caused the definition of a goal or against which a goal was validated with the corresponding goal. These interrelations provide the basis for: 1) explaining and illustrating a goal model to, e.g., untrained stakeholders and/or new team members; 2) detecting, analyzing, and resolving a different interpretation of the observations; 3) comparing different observations using computed goal annotations; and 4) refining or detailing a goal model during later process phases. Using the PRIME implementation framework, we have implemented the PRIME-CREWS environment, which supports the interrelation of conceptual models and captured system usage observations. We report on our experiences with PRIME-CREWS gained in an experimental case study.
A High Proportion of DNA Variants of BRCA1 and BRCA2 Is Associated with Aberrant Splicing in Breast/Ovarian Cancer Patients

Purpose: Most BRCA1/2 mutations are of unknown clinical relevance. An increasing amount of evidence indicates that there can be deleterious effects through the disruption of the splicing process. We have investigated the effect of aberrant splicing of BRCA1/2 on hereditary breast/ovarian cancer (HBOC). Experimental Design: DNA variants were analyzed with splicing prediction programs to select putative splicing mutations. Splicing assays of 57 genetic variants were done by lymphocyte reverse transcription-PCR and/or hybrid minigenes in HeLa and nontumor breast epithelial cells. Results: Twenty-four BRCA1/2 variants of Spanish HBOC patients were bioinformatically preselected. Functional assays showed that 12 variants induced anomalous splicing patterns, 6 of which accounted for 58.5% of BRCA1 families. To further evaluate the defective splicing of BRCA1/2, we analyzed 31 Breast Cancer Information Core Database (BIC) and two artificial variants that were generated by mutagenesis. Sixteen variants induced different degrees of aberrant splicing. Altogether, anomalous splicing was caused by 28 BRCA1/2 variants of all types, indicating that any DNA change can disrupt pre-mRNA processing. We show that a wide range of regulatory elements can be involved, including the canonical and cryptic splice sites, the polypyrimidine tract, and splicing enhancers/silencers. Twenty mutations were predicted to truncate the BRCA proteins and/or to delete essential domains, thus supporting a role in HBOC. Conclusions: An important fraction of DNA variants of BRCA1/2 presents splicing aberrations that may represent a relevant disease-causing mechanism in HBOC. The identification of splicing disruptions by functional assays is a valuable tool to discriminate between benign polymorphisms and pathogenic mutations. Clin Cancer Res; 16(6); 1957–67
Lexical and phonological variability in preschool children with speech sound disorder.

PURPOSE The authors of this study examined relationships between measures of word and speech error variability and between these and other speech and language measures in preschool children with speech sound disorder (SSD). METHOD In this correlational study, 18 preschool children with SSD, age-appropriate receptive vocabulary, and normal oral motor functioning and hearing were assessed across 2 sessions. Experimental measures included word and speech error variability, receptive vocabulary, nonword repetition (NWR), and expressive language. Pearson product–moment correlation coefficients were calculated among the experimental measures. RESULTS The correlation between word and speech error variability was slight and nonsignificant. The correlation between word variability and receptive vocabulary was moderate and negative, although nonsignificant. High word variability was associated with small receptive vocabularies. The correlations between speech error variability and NWR and between speech error variability and the mean length of children's utterances were moderate and negative, although both were nonsignificant. High speech error variability was associated with poor NWR and language scores. CONCLUSION High word variability may reflect unstable lexical representations, whereas high speech error variability may reflect indistinct phonological representations. Preschool children with SSD who show abnormally high levels of different types of speech variability may require slightly different approaches to intervention.
Versatile virtual honeynet management framework

Honeypots are designed to investigate malicious behaviour. Each type of homogeneous honeypot system has its own characteristics in respect of specific security functionality, and also suffers functional drawbacks that restrict its application scenario. In practical scenarios, therefore, security researchers always need to apply heterogeneous honeypots to cope with different attacks. However, there is a lack of general tools or platforms that can support versatile honeynet deployment in order to investigate the malicious behavior. In this study, the authors propose a versatile virtual honeynet management tool to address this problem. It is a flexible tool that offers security researchers the versatility to deploy various types of honeypots. It can also generate and manage the virtual honeynet through a dynamic configuration approach adapting to the mutable network environment. The experimental results demonstrate that this tool is effective to perform automated honeynet deployment toward a variety of heterogeneous honeypots.
Studies of Mechanical Properties and Absorption of Lightweight Concrete with Brazilian Expanded Clay

Brazilian Expanded Clay. The production process in a rotary kiln (or nodule) used in Brazil, characterized by the fact that certain materials expand when subjected to high temperatures (between 1000 °C and 1350 °C), such as some clays. In this temperature range, some of the material melts generating a viscous mass, while the other part chemically decomposes releasing gases which are incorporated by this mass, expanding by up to seven times its initial volume, the pore structure being maintained after its cooling. This manufacturing process promotes the formation of a glazed layer on the outside with low particle porosity, which significantly reduces the water absorption, has varying particle size and regular rounded shape, and its specific gravity comprised within the range from 0.64 to 1.51 kg/dm3 [4, .
Volume regulation by Amphiuma red blood cells. The membrane potential and its implications regarding the nature of the ion-flux pathways

After osmotic perturbation, the red blood cells of Amphiuma exhibited a volume-regulatory response that returned cell volume back to or toward control values. After osmotic swelling, cell-volume regulation (regulatory volume decrease; RVD) resulted from net cellular loss of K, Cl, and osmotically obliged H2O. In contrast, the volume-regulatory response to osmotic shrinkage (regulatory volume increase; RVI) was characterized by net cellular uptake of Na, Cl, and H2O. The net K and Na fluxes characteristic of RVD and RVI are increased by 1-2 orders of magnitude above those observed in studies of volume-static control cells. The cell membrane potential of volume-regulating and volume-static cells was measured by impalement with glass microelectrodes. The information gained from the electrical and ion-flux studies led to the conclusion that the ion fluxes responsible for cell-volume regulation proceed via electrically silent pathways. Furthermore, it was observed that Na fluxes during RVI were profoundly sensitive to medium [HCO3] and that during RVI the medium becomes more acid, whereas alkaline shifts in the suspension medium accompany RVD. The experimental observations are explained by a model featuring obligatorily coupled alkali metal-H and Cl-HCO3 exchangers. The anion- and cation-exchange pathways are separate and distinct yet functionally coupled via the net flux of H. As a result of the operation of such pathways, net alkali metal, Cl, and H2O fluxes proceed in the same direction, whereas H and HCO3 fluxes are cyclic. Data also are presented that suggest that the ion-flux pathways responsible for cell-volume regulation are not activated by changes in cell volume per se but by some event associated with osmotic perturbation, such as changes in intracellular pH.
Analysis of injuries in taekwondo athletes

[Purpose] The present study aims to provide fundamental information on injuries in taekwondo by investigating the categories of injuries that occur in taekwondo and determining the locations of these injuries. [Subjects and Methods] The data of 512 taekwondo athletes were collected. The sampling method was convenience sampling along with non-probability sampling extraction methods. Questionnaire forms were used to obtain the data. [Results] The foot, knee, ankle, thigh, and head were most frequently injured while practicing taekwondo, and contusions, strains, and sprains were the main injuries diagnosed. [Conclusion] It is desirable to decrease the possibility of injuries to the lower extremities for extending participation in taekwondo. Other than the lower extremities, injuries of other specific body parts including the head or neck could be important factors limiting the duration of participation. Therefore, it is necessary to cope with these problems before practicing taekwondo.
Model Selection for Semi-Supervised Learning with Limited Labeled Data

An important component for making semi-supervised learning applicable to real world data is the task of model selection. For the case of very limited labeled data, for which semi-supervised learning algorithms have the greatest potential to offer improvement in estimating predictive models, model selection is a significant challenge, a key open problem, and often avoided entirely in previous work. While previous work has demonstrated the benefit of semi-supervised learning in cases of very limited labeled training data, in order for such results to be achievable in practice, some effective method of selecting the hyper-parameters for these methods is necessary. In general, existing approaches rely heavily in some way on the labeled data directly for estimating either performance (e.g., error), some key characteristics of the model, or likelihood, and so can suffer when there is not much labeled data. Instead we propose an alternative, sampling approach in order to estimate model performance. The main idea is to evaluate the models on a large number of generated similar data sets, and to prefer those models that perform well on average across the data sets. New training and unlabeled/test data are generated by sampling from the large amount of unlabeled data and estimated conditional probabilities for the labels. Since these data sets are complete with labels, models can then be evaluated using the generated labels for the much larger set of unlabeled/test data. Using a variety of data sets we demonstrate the effectiveness of our approach, and, for small amounts of labeled data, large improvement over traditional methods like cross-validation, as well as better performance on average than the state-of-the-art for semi-supervised model selection.
LacZ transgene expression in the subcutaneous Dunn/LM8 osteosarcoma mouse model allows for the identification of micrometastasis

More effective treatment of patients with metastasizing osteosarcoma (OS) with a mean 5‐year survival rate of <20% requires more detailed knowledge on the complex mechanisms of metastasis for the design of new drugs, which selectively target metastasizing cells. Moreover, novel diagnostic imaging technology for early detection of metastases is needed. Mouse models, which reproduce human metastasizing OS and allow visualization of single metastatic cells are instrumental for preclinical testing of new pharmaceuticals and diagnostic instruments. Here, the low metastatic Dunn cell line and its highly metastatic LM8 subline, both equipped with a constitutively expressed lacZ gene, were used to improve the well‐established OS models in syngeneic C3H mice to achieve ex vivo visualization of single metastatic cells in affected organs by X‐gal staining. These models, combined with a technique for in situ high quality lung tissue‐maintaining perfusion revealed, as a novel finding, single metastasizing Dunn cells in lung and liver. Importantly, constitutive lacZ gene expression did not affect in vitro and in vivo tumorigenic and metastatic properties of Dunn and LM8 cells. Thus, these improved Dunn and LM8 OS mouse models will in the future serve as a benchmark for the development of new metastasis‐targeting drugs and metastasis‐imaging technology. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:938–946
Characterization of NopP, a Type III Secreted Effector of Rhizobium sp. Strain NGR234

ABSTRACT The type three secretion system (TTSS) encoded by pNGR234a, the symbiotic plasmid of Rhizobium sp. strain NGR234, is responsible for the flavonoid- and NodD1-dependent secretion of n odulation o uter p roteins (Nops). Abolition of secretion of all or specific Nops significantly alters the nodulation ability of NGR234 on many of its hosts. In the closely related strain Rhizobium fredii USDA257, inactivation of the TTSS modifies the host range of the mutant so that it includes the improved Glycine max variety McCall. To assess the impact of individual TTSS-secreted proteins on symbioses with legumes, various attempts were made to identify nop genes. Amino-terminal sequencing of peptides purified from gels was used to characterize NopA, NopL, and NopX, but it failed to identify SR3, a TTSS-dependent product of USDA257. By using phage display and antibodies that recognize SR3, the corresponding protein of NGR234 was identified as NopP. NopP, like NopL, is an effector secreted by the TTSS of NGR234, and depending on the legume host, it may have a deleterious or beneficial effect on nodulation or it may have little effect.
Modelling of Mechanical Properties of Cement Concrete Incorporating Reclaimed Asphalt Pavement

ABSTRACT In many countries there is a trend to recycle wastes obtained during pavement maintenance or reconstruction, and to forbid the landfill of these products. Thus, in some circumstances it can be tempting to use reclaimed asphalt pavement (RAP) in new hydraulic concrete mixtures. This paper presents experimental data and modelling about the effect of RAP incorporation on cement concrete mechanical properties (compressive strength, tensile strengths and E-modulus). All these properties tend to decrease with the rate of RAP dosage, and with temperature. Then attempts are made to adapt LCPC mix-design models to these innovative concretes. Two alternative hypotheses are evaluated. In the first one, RAP aggregate is viewed as composite particles playing the role of an homogenous aggregate having lower bond, strength and E-modulus as compared to normal aggregate. In the second one, the bitumen phase is assumed to be finely dispersed within the cement paste, acting as a supplementary dosage of water (or air). According to the simulations, the second hypothesis is the best one. This finding extends the scope of application of modern mix-design methods, and will help in using RAP in cement concrete, for the technical, economical and environmental benefit of the road community.
Learning to Translate in Real-time with Neural Machine Translation

Translating in real-time, a.k. a.simultaneous translation, outputs translation words before the input sentence ends, which is a challenging problem for conventional machine translation methods. We propose a neural machine translation (NMT) framework for simultaneous translation in which an agent learns to make decisions on when to translate from the interaction with a pre-trained NMT environment. To trade off quality and delay, we extensively explore various targets for delay and design a method for beam-search applicable in the simultaneous MT setting. Experiments against state-of-the-art baselines on two language pairs demonstrate the efficacy of the proposed framework both quantitatively and qualitatively.
Zarastanie rys w zaprawach cementowych z popiołem wapiennym zbrojonych rozproszonymi włóknami

The durability of concrete structures is often considered an issue as a part of the general problem of sustainability. As durability of concrete is closely related to the permeability to liquids and gases, cracks and microcracks are recognized as important factors in determination of the transport properties across concrete elements. In real structures the cracking of concrete due to various origins is inevitable and it is diffi cult to consider concrete or reinforced concrete structure without microcracks.
Kinematic and kinetic asymmetries in hemiplegic patients' gait initiation patterns.

OBJECTIVE To assess the kinetic and kinematic characteristics of hemiplegic stroke patients' gait initiation patterns during the various gait initiation phases. DESIGN AND SUBJECTS Gait initiation was studied in 3 hemiplegic subjects with a spastic equinus varus foot and 3 control subjects. METHODS Temporal and kinetic analysis of gait initiation was performed with 2 AMTI force plates, and kinematic analysis of gait initiation with an ELITE optoelectronic system. A one-way ANOVA was performed directly on the phase durations, forces, centre of pressure displacements, stride length, and ankle motion range. RESULTS Duration of the monopodal phase was shorter in hemiplegic patients when the affected leg rather than the sound one was used as the supporting leg. Propulsion forces were exerted by the hemiplegic patients' sound leg during the postural phase. Hemiplegic patients' body weight was supported more by the sound leg than by the affected leg. Knee was lifted higher on the affected side during the swing phase to compensate for the equinus. Initial contact was performed with a flat foot on the affected side. CONCLUSION Quantitative data obtained on the gait initiation phase suggest that hemiplegic patients develop asymmetrical adaptive posturo-motor strategies to compensate for their impairments.
Meticulous Prevention of Hypoglycemia Normalizes the Glycemic Thresholds and Magnitude of Most of Neuroendocrine Responses to, Symptoms of, and Cognitive Function During Hypoglycemia in Intensively Treated Patients With Short-Term IDDM

To test the hypothesis that hypoglycemia unawareness is largely secondary to recurrent therapeutic hypoglycemia in IDDM, we assessed neuroendocrine and symptom responses and cognitive function in 8 patients with short-term IDDM (7 yr) and hypoglycemia unawareness. Patients were assessed during a stepped hypoglycemic clamp, before and after 2 wk and 3 mo of meticulous prevention of hypoglycemia, which resulted in a decreased frequency of hypoglycemia (0.49 ± 0.05 to 0.045 ± 0.03 episodes/patient-day) and an increase in HbA1c (5.8 ± 0.3 to 6.9 ± 0.2%) (P < 0.05). We also studied 12 nondiabetic volunteer subjects. At baseline, lower than normal symptom and neuroendocrine responses occurred at lower than normal plasma glucose, and cognitive function deteriorated only marginally during hypoglycemia. After 2 wk of hypoglycemia prevention, the magnitude of symptom and neuroendocrine responses (with the exception of glucagon and norepinephrine) nearly normalized, and cognitive function deteriorated at the same glycemic threshold and to the same extent as in nondiabetic volunteer subjects. At 3 mo, the glycemic thresholds of symptom and neuroendocrine responses normalized, and surprisingly, some of the responses of glucagon recovered. We concluded that hypoglycemia unawareness in IDDM is largely reversible and that intensive insulin therapy and a program of intensive education may substantially prevent hypoglycemia and at the same time maintain the glycemic targets of intensive insulin therapy, at least in patients with IDDM of short duration.