Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimal temperature selection for mutation detection by denaturing HPLC and comparison to single-stranded conformation polymorphism and heteroduplex analysis.

BACKGROUND Denaturing HPLC (DHPLC) is a semi-automated method for detecting unknown DNA sequence variants. The sensitivity of the method is dependent on the temperature at which the analysis is undertaken, the selection of which is dependent on operator experience. To circumvent this, software has been developed for predicting the optimal temperature for DHPLC analysis. We examined the utility of this software. METHODS To maximize the relevance of our data for other investigators, we have screened 42 different amplimers from CFTR, TSC1, and TSC2. The samples consisted of 103 unique sequence heterozygotes and 126 wild-type homozygous controls. RESULTS At the temperature recommended by the software, 96% (99 of 103) of heterozygotes and all of the wild-type controls were correctly classified. This compares favorably with sensitivities of 85% for single-stranded conformation polymorphism and 82% for gel-based heteroduplex analyses of the same fragments. CONCLUSIONS Software-optimized DHPLC is a highly sensitive method for mutation detection. However, where sensitivity >96% is required, our data suggest that in addition to the recommended temperature, fragments should also be run at the recommended temperature plus 2 degrees C.
Path planning in changeable environments

This thesis addresses path planning in changeable environments. In contrast to traditional path planning that deals with static environments, in changeable environments objects are allowed to change their configurations over time. In many cases, path planning algorithms must facilitate quick answers to queries in order to be useful. For example, an opponent in a training simulation needs to respond to the actions of the user without any significant delay. To achieve such performance, path planning methods usually use a preprocessing phase in which the environment is explored. As much computation time as possible is moved to this preprocessing phase such that at query time only little time is needed to solve an actual path planning query. This approach has led to many successful methods that are applicable to a broad range of problems. Because of the nature of preprocessing, existing methods have difficulty to cope with unanticipated changes that occur in the environment in a later stage. Often existing solutions are computationally expensive and may fail if no local solution exists. This thesis presents novel results for path planning in changeable environments. It is divided in three parts. The first part deals with the class of problems in which obstacles can change their configuration between the time the roadmap was created and the query. Examples of such obstacles are doors, chairs and boxes. We provide an algorithm that is able to deal with such changes in the environment while keeping the planning process efficient. The second part deals with environments in which robots have the ability to manipulate obstacles that block their path. Imagine, for example a simulation in which a firefighter commander is trained. The commander gives his (virtual) firefighters higher level commands (e.g. "walk around the building and enter it at the back"). For a realistic training, the firefighters should be able to move away obstacles that block their paths in order to, for example, clear the door. The algorithms in this part describe a novel way to deal with this type of problems by imitating human behavior. Finally, the third part deals with the problem of a robot pushing a disk in a polygonal environment. Pushing an object by a robot is often easier or more applicable than pulling since it does not involve grasping the object. A robot arm can push an object using a single finger while pulling involves more complicated behavior. Unfortunately in addition to the usual sensor errors, pushing is also sensitive to another type of uncertainty; if the object's center of mass is not exactly known then pushing an object leads to erratic behavior leading to unstable pushes. We provide solutions that are robust against sensor errors and therefore are more suited to be used in practical problems.
Linking Decisions and Actions in Dynamic Environments: How Child and Adult Cyclists Cross Roads With Traffic

Unlike affordances involving stationary objects, affordances involving moving objects change over time. This means that actions must be tightly linked to decisions, making perceiving and acting on affordances involving moving objects challenging for children and adults alike. Here, we overview our program of research on how children and adults perceive and act on moving objects in the context of bicycling across roads in an immersive virtual environment. This work shows that although children attempt to adjust their actions to fit their risky decisions, they do not fully adjust their decisions to fit their action capabilities. This mismatch between child cyclists' decisions and actions may be a risk factor for car-bicycle collisions in late childhood and early adolescence.
The effects of lead on GABAergic interneurons in rodents

Lead is a heavy metal that affects various systems and organs in the body, especially the nervous system. In this study, the in vivo and in vitro effects of lead on neurons were analyzed. We divided mouse pups into three groups based on the concentration of lead exposure: the control group, the low-dose group, and the high-dose group. Changes in behavior (measured by an open-field test and a tail suspension test), blood lead levels (measured by atomic absorption spectrophotometry), the number of GABAergic interneurons (measured by immunohistochemistry), gene expression (measured by qRT-PCR), and DNA methylation (measured by pyrosequencing) were determined in the three groups. The lead-exposed pups showed significantly higher blood lead levels (p < 0.001). Lead exposure caused hyperactivity and reduced the body weight of the exposed mice compared with that of the controls. The lead-exposed groups showed significantly lower numbers of parvalbumin and neuropeptide Y interneurons and lower expression levels of distal-less homeobox (Dlx) 1, 2, 5, and 6 genes in the cerebral cortex. To further clarify the mechanism of Dlx gene downregulation, we selected the GE6 cell line, which can differentiate into various subtypes of GABAergic interneurons, for in vitro experiments. We found that high levels of lead also inhibited the expression of Dlx 1/2/5/6 in vitro, but DNA methylation levels were not changed in the GE6 cell line. Furthermore, lead exposure significantly decreased the expression of Olig1 and Ki67 and increased that of Tubb3 in vitro. The present study revealed that lead exposure can alter behaviors, reduce the number of GABAergic interneurons, and change the expression of some important genes in neuronal cells.
Development of an Enzyme-Linked Immunosorbent Assay Based on Fusion VP2332-452 Antigen for Detecting Antibodies against Aleutian Mink Disease Virus

ABSTRACT For detection of Aleutian mink disease virus (AMDV) antibodies, an enzyme-linked immunosorbent assay (ELISA) was developed using the recombinant VP2332-452 protein as an antigen. Counterimmunoelectrophoresis (CIEP) was used as a reference test to compare the results of the ELISA and Western blotting (WB); the specificity and sensitivity of the VP2332-452 ELISA were 97.9% and 97.3%, respectively, which were higher than those of WB. Therefore, this VP2332-452 ELISA may be a preferable method for detecting antibodies against AMDV.
Enzymically accelerated biomineralization of heavy metals: application to the removal of americium and plutonium from aqueous flows.

A biological process for the removal of heavy metals from the aqueous flows is described. Metals are precipitated on the surface of immobilized cells of a Citrobacter sp. as cell-bound metal phosphates. This uses phosphate liberated by the activity of a cell-bound phosphatase. Some radionuclides (e.g. 241americium) form metal phosphates readily; efficient removal of 241Am on a continuous basis is demonstrated. At low phosphatase activities, the efficiency of uranium removal correlates with enzyme activity. High phosphatase activities are not realised as an increase in metal removal, suggesting that chemical events become rate-limiting. Studies have suggested that maximal metal uptake occurs only after nucleation and the formation of precipitation foci. A model is presented to illustrate how nucleation and crystallization processes could enhance the removal of plutonium and neptunium from dilute solutions.
A PARTICIPAÇÃO FEMININA NA PRODUÇÃO CIENTÍFICA DAS ÁREAS DE ADMINISTRAÇÃO E CIÊNCIAS CONTÁBEIS

Este artigo analisa como se caracteriza a participação feminina na produção científica das áreas de Administração e Ciências Contábeis no triênio de 2013 a 2015. Realizou-se um estudo bibliométrico, descritivo e de abordagem qualitativa-quantitativa. A amostra compreendeu 23 periódicos de Qualis A1 a B2, nos quais foram analisados todos os 1724 artigos com, pelo menos, uma participação feminina. Após a análise dos artigos, foram observadas 2740 autoras, as quais compuseram um ranking por ordem de participação em publicações nesse período. A partir das análises, verificou-se que a participação feminina ainda é inferior à masculina nos anos estudados, não havendo evolução da participação feminina nos periódicos das áreas de Administração e Ciências Contábeis. Ainda, identificou-se que os procedimentos metodológicos qualitativos são mais utilizados pelas pesquisadoras e que as diferenças regionais são relevantes, sendo sul e sudeste as regiões que apresentaram maiores volumes de publicação com pelo menos uma participação feminina.
Functional magnetic resonance imaging in rodents: Methodology and application to spinal cord injury

Functional MRI (fMRI) on spinal cord‐injured rodents at 4 and 8 weeks post injury (PI) is described. The paradigm for fMRI, based on electrical stimulation of rat paws, was automated using an in‐house designed microprocessor‐based controller that was interfaced to a stimulator. The MR images were spatially normalized to the Paxinos and Watson atlas using publicly available digital images of the cryosections. In normal uninjured animals, the activation was confined to the contralateral somatosensory cortex. In contrast, in injured animals, extensive activation, which included structures such as ipsilateral cortex, thalamus, hippocampus, and the caudate putamen, was observed at 4 and 8 weeks PI. Quantitative cluster analysis was carried out to calculate the volumes and centers of activation in individual brain structures. Based on this analysis, significant increase in activation between 4 and 8 weeks was observed only in the ipsilateral caudate putamen and thalamus. These studies suggest extensive and ongoing brain reorganization in spinal cord‐injured animals. © 2006 Wiley‐Liss, Inc.
Rapid Endotoxin-induced Alterations in Myocardial Calcium Handling: Obligatory Role of Cardiac TNF-&agr;

Background Bacterial endotoxin (lipopolysaccharide [LPS]) induces septic shock and depressed myocardial contractility. The mechanism of LPS-mediated cardiac dysfunction remains controversial. We hypothesized that LPS exerts significant effects on myocardial excitation-contraction coupling by rapid stimulation of tumor necrosis factor &agr; (TNF-&agr;) expression in the heart. Methods Isolated rat hearts were studied with and without recirculation of cell-free perfusate. The effects of LPS, exogenous TNF-&agr;, anti-TNF-&agr; antibody, and ceramidase inhibition were examined. Measurements included myocardial uptake of LPS, left ventricular contractility, myocardial oxygen consumption, intracellular calcium [Ca2+] cycling, and TNF-&agr; concentrations in coronary perfusate and myocardium. Results Lipopolysaccharide was rapidly taken up by the perfused heart. With non-recirculating perfusion, LPS had no effect on contractility, oxygen consumption, coronary vascular resistance, or intracellular free calcium concentration ([Ca2+]i). However, with recirculating perfusion contractility was significantly impaired after 30 min of LPS, associated with lower [Ca2+]i levels and attenuated systolic rise in [Ca2+]i. Significant amounts of TNF-&agr; accumulated in recirculating perfusate and myocardial tissue from LPS-perfused hearts. Ceramidase inhibition or neutralizing anti-TNF-&agr; antibody inhibited the effects of LPS on contractility and [Ca2+]i. Recombinant rat TNF-&agr; mimicked the LPS effects with faster onset. Conclusions Lipopolysaccharide exerts rapid, negative inotropic effects on the isolated whole rat heart. The reduction in contractility is associated with depressed intracellular calcium cycling. In response to LPS, TNF-&agr; is rapidly released from the heart and mediates the effects of LPS via the sphingomyelinase pathway. The present study for the first time directly links LPS-stimulated TNF-&agr; production, abnormal calcium cycling, and decreased contractility in intact hearts.
A Review of the Fossil Record of Turtles of the Clade Thalassochelydia

Abstract The Late Jurassic (Oxfordian to Tithonian) fossil record of Europe and South America has yielded a particularly rich assemblage of aquatic pan-cryptodiran turtles that are herein tentatively hypothesized to form a monophyletic group named Thalassochelydia. Thalassochelydians were traditionally referred to three families, Eurysternidae, Plesiochelyidae, and Thalassemydidae, but the current understanding of phylogenetic relationships is insufficient to support the monophyly of either group. Given their pervasive usage in the literature, however, these three names are herein retained informally. Relationships with marine turtles from the Cretaceous have been suggested in the past, but these hypotheses still lack strong character support. Thalassochelydians are universally found in near-shore marine sediments and show adaptations to aquatic habitats, but isotopic evidence hints at a broad spectrum of specializations ranging from freshwater aquatic to fully marine. A taxonomic review of the group concludes that of 68 named taxa, 27 are nomina valida, 18 are nomina invalida, 18 are nomina dubia, and 5 nomina oblita.
An intervention mechanism for assistive living in smart homes

In order to support ageing in place for elderly people, technologies and services for home environments need to be developed. An intervention mechanism is proposed in this paper in a smart home environment to provide reminders to assist elderly inhabitants to complete activities of daily living (ADL). The situation of multiple inhabitants in a single smart environment is addressed. A probabilistic learning approach is proposed to characterise inhabitants' behavioural patterns, learned from summary activities collected during a period. Activity reasoning can then be carried out given partially observed low-level sensor information. Decision support is used to monitor inhabitants' activities and thus to assist the completion of tasks if necessary. Personalised reminders at various levels of detail can be delivered based on individual need and preference. Appropriate thresholds are learned to be used to ensure delivery of predictions for which confidence is high, to avoid confusing inhabitants with incorrect reminders. The potential of our approach to support assistive living and home-health monitoring of elder patients is demonstrated.
Color impact in visual attention deployment considering emotional images

Color is a predominant factor in the human visual attention system. Even if it cannot be sufficient to the global or complete understanding of a scene, it may impact the visual attention deployment. We propose to study the color impact as well as the emotion aspect of pictures regarding the visual attention deployment. An eye-tracking campaign has been conducted involving twenty people watching half pictures of database in full color and the other half of database in grey color. The eye fixations of color and black and white images were highly correlated leading to the question of the integration of such cues in the design of visual attention model. Indeed, the prediction of two state-of-the-art computational models shows similar results for the two color categories. Similarly, the study of saccade amplitude and fixation duration versus time viewing did not bring any significant differences between the two mentioned categories. In addition, spatial coordinates of eye fixations reveal an interesting indicator for investigating the differences of visual attention deployment over time and fixation number. The second factor related to emotion categories shows evidences of emotional inter-categories differences between color and grey eye fixations for passive and positive emotion. The particular aspect associated to this category induces a specific behavior, rather based on high frequencies, where the color components influence the visual attention deployment.
Modeling inter-failure time series using neural networks

Software inter-failure time series analysis has always been a question mark for the reliability engineers. Many models have been proposed since the problem of reliability discovers, but none of them produces adequate results. This study presents a neural network perspective of modeling inter-failure time of software. We compare different parametric models of software reliability with our proposed neural network model and found the proposed more suitable.
Substrate Stiffness Regulates Proinflammatory Mediator Production through TLR4 Activity in Macrophages

Clinical data show that disease adversely affects tissue elasticity or stiffness. While macrophage activity plays a critical role in driving disease pathology, there are limited data available on the effects of tissue stiffness on macrophage activity. In this study, the effects of substrate stiffness on inflammatory mediator production by macrophages were investigated. Bone marrow–derived macrophages were grown on polyacrylamide gels that mimicked the stiffness of a variety of soft biological tissues. Overall, macrophages grown on soft substrates produced less proinflammatory mediators than macrophages grown on stiff substrates when the endotoxin LPS was added to media. In addition, the pathways involved in stiffness–regulated proinflammation were investigated. The TLR4 signaling pathway was examined by evaluating TLR4, p–NF–κB p65, MyD88, and p–IκBα expression as well as p–NF–κB p65 translocation. Expression and translocation of the various signaling molecules were higher in macrophages grown on stiff substrates than on soft substrates. Furthermore, TLR4 knockout experiments showed that TLR4 activity enhanced proinflammation on stiff substrates. In conclusion, these results suggest that proinflammatory mediator production initiated by TLR4 is mechanically regulated in macrophages.
Pre-silicon MOSFET mismatch modeling for early circuit simulations

The continuing scaling down of CMOS technologies contributes to the important of having early circuit simulations even before any real silicon data are available. This paper presents a methodology to extract a pre-silicon MOSFET mismatch model using backward propagation of variance (BPV) technique. All the required steps such as the correlation of process and electrical parameters through BSIM3v3 SPICE model and explanation of mathematical relationships among the parameters are discussed. The experimental data for mismatch analysis are projected from 0.35 um process to 0.25 um and 0.18 um processes using the technology scaling coefficient coupled with the related statistical data analysis. The good agreement between experimental and Monte Carlo SPICE simulation data verifies the proposed extraction methodology.
Structure and Backbone Dynamics of Apo- and Holo-cellular Retinol-binding Protein in Solution*

Retinoid-binding proteins play an important role in regulating transport, storage, and metabolism of vitamin A and its derivatives. The solution structure and backbone dynamics of rat cellular retinol-binding protein type I (CRBP) in the apo- and holo-form have been determined and compared using multidimensional high resolution NMR spectroscopy. The global fold of the protein is consistent with the common motif described for members of the intracellular lipid-binding protein family. The most relevant difference between the NMR structure ensembles of apo- and holoCRBP is the higher backbone disorder, in the ligand-free form, of some segments that frame the putative entrance to the ligand-binding site. These comprise α-helix II, the subsequent linker to β-strand B, the hairpin turn between β-strands C and D, and the βE-βF turn. The internal backbone dynamics, obtained from 15N relaxation data (T 1,T 2, and heteronuclear nuclear Overhauser effect) at two different fields, indicate several regions with significantly higher backbone mobility in the apoprotein, including the βC-βD and βE-βF turns. Although apoCRBP contains a binding cavity more shielded than that of any other retinoid carrier, conformational flexibility in the portal region may assist retinol uptake. The stiffening of the backbone in the holoprotein guarantees the stability of the complex during retinol transport and suggests that targeted retinol release requires a transiently open state that is likely to be promoted by the acceptor or the local environment.
Clinical inertia in the treatment of hyperglycemia in type 2 diabetes patients in primary care

Abstract Objective: To assess clinical inertia, defined as failure to intensify antidiabetic treatment of patients who have not achieved the HbA1c therapeutic goal (≤7%). Research design and methods: Multicenter cross-sectional study. Clinical inertia was assessed in a random sample of type 2 diabetes mellitus (T2DM) patients seen in primary care centers. Results: A total of 2783 patients (51.3% males; mean age: 68 [±11.5] years; diabetes duration: 7.1 [±5.6] years; mean HbA1c: 6.8 [±1.5]) were analyzed. Of those, 997 (35.8%) had HbA1c >7%. Treatment was intensified in 66.8% and consisted of: dose increase (40.5%); addition of oral antidiabetic (45.8%); or insulin treatment initiation (3.7%). Mean HbA1c values in patients for whom treatment was intensified vs. non-intensified were 8.4% (±1.2) vs. 8.2% (±1.2), p < 0.05. Clinical inertia was detected in 33.2% of patients and diminished along with treatment complexity: lifestyle changes only (38.8%), oral monotherapy (40.3%), combined oral antidiabetics (34.5%), insulin monotherapy (26.1%) and combination of insulin and oral antidiabetics (21.4%). Clinical inertia decreased as HbA1c increased: 37.3% for HbA1c values ranging between 7.1%–8%; 29.4% for the 8.1%–9% HbA1c range and 27.1% for HbA1c ≥9%. Multivariate analysis confirmed that diabetes duration, step of treatment and HbA1c were related to inertia. For each unit of HbA1c increase clinical inertia decreased 47% (OR: 0.53). Limitations: The retrospective design of the study precluded an accurate investigation about reasons for lack of intensification that could actually be justified by some patient conditions, especially patients’ lack of adherence. Conclusions: Clinical inertia affected one third of T2DM patients with poor glycemic control and was greater in patients treated with only lifestyle changes or oral monotherapy. Treatment changes were performed when mean HbA1c values were 1.4 points above therapeutic goals.