Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: Identification of two novel mutations and establishment of multiple DNA diagnosis methods for nine mutations

We have recently identified SLC25A13 on chromosome 7q21.3 as the gene responsible for adult‐onset type II citrullinemia (CTLN2) and found seven mutations in the SLC25A13 gene of CTLN2 patients. Most recently, the SLC25A13 mutations have been detected in neonatal/infantile patients with a type of neonatal hepatitis associated with cholestasis (NICCD). In the present study, we identified a novel mutation, E601X, in the SLC25A13 gene and established multiple DNA diagnosis methods for eight mutations by using a genetic analyzer with GeneScan and the single primer extension procedure (SNaPshot). An additional novel missense mutation (variation), E601K, was detected by SNaPshot analysis and was indistinguishable from the mutation E601X detected by the PCR/RFLP method. Multiple DNA diagnoses for the nine mutations revealed that 100 (male/female: 70/30) out of 115 CTLN2 and 38 (14/24) out of 45 NICCD patients tested were homozygotes or compound heterozygotes. The frequency of homozygotes carrying SLC25A13 mutations in both alleles is estimated to be minimally 1 in 21,000 from carrier detection (18 in 1,315 individuals tested) in the Japanese population. The differences in the gender ratio and in mutation types between CTLN2 and NICCD patients are significant. It is, however, unknown whether all homozygotes with mutated SLC25A13 in both alleles suffer from NICCD, CTLN2, both, or neither. Hum Mutat 19:122–130, 2002. © 2002 Wiley‐Liss, Inc.
Examination of genetic linkage of chromosome 15 to schizophrenia in a large Veterans Affairs Cooperative Study sample.

Previous studies have reported genetic linkage evidence for a schizophrenia gene on chromosome 15q. Here, chromosome 15 was examined by genetic linkage analysis using 166 schizophrenia families, each with two or more affected subjects. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Study Program, consisted of 392 sampled affected subjects and 216 affected sibling pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizo-affective disorder, depressed. Participating families had diverse ethnic backgrounds. The largest single group were northern European American families (n = 62, 37%), but a substantial proportion was African American kindreds (n = 60, 36%). The chromosome 15 markers tested were spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the region surrounding the alpha-7 nicotinic cholinergic receptor subunit gene (CHRNA7). These markers were genotyped and the data analyzed using semiparametric affecteds-only linkage analysis. In the European American families, there was a maximum Z-score of 1.65 between markers D15S165 and D15S1010. These markers are within 1 cM from CHRNA-7, the site previously implicated in schizophrenia. However, there was no evidence for linkage to this region in the African America kindreds.
Repairing Programs with Semantic Code Search

Automated program repair can potentially reduce debugging costs and improve software quality but recent studies have drawn attention to shortcomings in the quality of automatically generated repairs. We propose a new kind of repair that uses the large body of existing open-source code to find potential fixes. The key challenges lie in efficiently finding code semantically similar (but not identical) to defective code and then appropriately integrating that code into a buggy program. We present SearchRepair, a repair technique that addresses these challenges by (1) encoding a large database of human-written code fragments as SMT constraints on input-output behavior, (2) localizing a given defect to likely buggy program fragments and deriving the desired input-output behavior for code to replace those fragments, (3) using state-of-the-art constraint solvers to search the database for fragments that satisfy that desired behavior and replacing the likely buggy code with these potential patches, and (4) validating that the patches repair the bug against program test suites. We find that SearchRepair repairs 150 (19%) of 778 benchmark C defects written by novice students, 20 of which are not repaired by GenProg, TrpAutoRepair, and AE. We compare the quality of the patches generated by the four techniques by measuring how many independent, not-used-during-repair tests they pass, and find that SearchRepair-repaired programs pass 97.3% of the tests, on average, whereas GenProg-, TrpAutoRepair-, and AE-repaired programs pass 68.7%, 72.1%, and 64.2% of the tests, respectively. We conclude that SearchRepair produces higher-quality repairs than GenProg, TrpAutoRepair, and AE, and repairs some defects
A Review and Reappraisal of Task Guidance: Aiding Workers in Procedure Following

Procedures can greatly benefit workers at tasks such as inspection, maintenance, and assembly. Procedures may serve as a guideline for expert workers or they may provide a list of directives to be followed exactly; either way, procedures serve to structure a task, to aid worker memory, and to guarantee consistency and safety. Light, inexpensive electronics may allow for the development of task guidance systems to further help workers by presenting procedures and associated information about the task. This article reviews the current state of knowledge about the development of task guidance systems, and highlights their potential value in a variety of domains. First, the characteristics of procedural tasks are discussed, as a basis for a discussion on the benefits of procedure following that task guidance systems can support, and potential problems in procedure following that task guidance systems can mitigate. Then, current research results in task guidance systems are summarized. Finally, a discussion is.
3 D scanning particle tracking velocimetry

In this article, we present an experimental setup and data processing schemes for 3D scanning particle tracking velocimetry (SPTV), which expands on the classical 3D particle tracking velocimetry (PTV) through changes in the illumination, image acquisition and analysis. 3D PTV is a flexible flow measurement technique based on the processing of stereoscopic images of flow tracer particles. The technique allows obtaining Lagrangian flow information directly from measured 3D trajectories of individual particles. While for a classical PTV the entire region of interest is simultaneously illuminated and recorded, in SPTV the flow field is recorded by sequential tomographic high-speed imaging of the region of interest. The advantage of the presented method is a considerable increase in maximum feasible seeding density. Results are shown for an experiment in homogenous turbulence and compared with PTV. SPTV yielded an average 3,500 tracked particles per time step, which implies a significant enhancement of the spatial resolution for Lagrangian flow measurements.
Simulation Based Cause and Effect Analysis of Cycle Time and Wip in Semiconductor Wafer Fabrication

Semiconductor wafer fabrication is perhaps one of the most complex manufacturing processes found today. In this paper, we construct a simulation model of part of a wafer fab using ProModel software and analyze the effect of different input variables on selected parameters, such as cycle time, WIP level and equipment utilization rates. These input variables include arrival distribution, batch size, downtime pattern and lot release control. SEMATECH DATASET which has the original actual wafer fab data is used for our analysis.
Aspects and components in real-time system development: Towards reconfigurable and reusable software

Increasing complexity of real-time systems, and demands for enabling their configurability and reusability are strong motivations for applying new software engineering principles, such as aspect-oriented and component-based development. In this paper we introduce a novel concept of aspectual component-based real-time system development. The concept is based on a design method that assumes decomposition of real-time systems into components and aspects, and provides a real-time component model that supports the notion of time and temporal constraints, space and resource management constraints, and composability. Initial results show that the successful application of the proposed concept has a positive impact on real-time system development in enabling efficient configuration of real-time systems, improved reusability and flexibility of real-time software, and modularization of crosscutting concerns. We provide arguments for this by presenting an application of the proposed concept on the design and development of a configurable embedded real-time database, called COMET. Furthermore, using the COMET system as an example, we introduce a novel way of handling concurrency in a real-time database system, where concurrency is modeled as an aspect crosscutting the system.
Interactively controlled quad remeshing of high resolution 3D models

Parametrization based methods have recently become very popular for the generation of high quality quad meshes. In contrast to previous approaches, they allow for intuitive user control in order to accommodate all kinds of application driven constraints and design intentions. A major obstacle in practice, however, are the relatively long computations that lead to response times of several minutes already for input models of moderate complexity. In this paper we introduce a novel strategy to handle highly complex input meshes with up to several millions of triangles such that quad meshes can still be created and edited within an interactive workflow. Our method is based on representing the input model on different levels of resolution with a mechanism to propagate parametrizations from coarser to finer levels. The major challenge is to guarantee consistent parametrizations even in the presence of charts, transition functions, and singularities. Moreover, the remaining degrees of freedom on coarser levels of resolution have to be chosen carefully in order to still achieve low distortion parametrizations. We demonstrate a prototypic system where the user can interactively edit quad meshes with powerful high-level operations such as guiding constraints, singularity repositioning, and singularity connections.
The contractile response during steady lengthening of stimulated frog muscle fibres.

1. Steady lengthenings at different velocities (0.025‐1.2 microns/s per half‐sarcomere; temperature 2‐5.5 degrees C) were imposed on isolated frog muscle fibres at the isometric tetanus plateau by means of a loudspeaker motor. The lengthening at the sarcomere level was measured by means of a striation follower either in fixed‐end or in length‐clamp mode. The force response was measured by a capacitance gauge transducer (resonance frequency 50 kHz). Preparations showing gross non‐homogeneity during lengthening were excluded. 2. A steady tension was in all cases reached after about 20 nm per half‐sarcomere of lengthening. Tension during this steady phase rose with speed of elongation up to 0.25‐0.4 micron/s per half‐sarcomere, when tension was 1.9‐2 times isometric tetanic force (T0). Further increase in speed produced only very little increase in the steady tension. 3. During the transitory phase, before steady tension was reached, the tension rose monotonically if speed of lengthening was less than 0.25‐0.3 micron/s per half‐sarcomere; at higher speed the tension rose above the steady level, reaching a peak when extension was 10‐14 nm per half‐sarcomere, and then fell to the steady level. Tension at the peak continued to rise with speed of lengthening above 0.3 micron/s per half‐sarcomere. 4. During the tension rise within the transitory phase of force response the segment elongated at a speed 15‐20% lower than that imposed on the whole fibre, as a consequence of tendon compliance. 5. During the steady phase, non‐homogeneity of lengthening speed began above a speed of lengthening which varied from fibre to fibre. At speeds below this value, segments elongated at the same speed as that imposed on the fibre. 6. Tension responses to large step stretches (up to 12 nm per half‐sarcomere), applied at the plateau of isometric tetanus, showed that the instantaneous elasticity of contractile machinery is not responsible for the limit in force attained with high‐speed lengthening. 7. Instantaneous stiffness was determined during the steady state of force response by superposing small steps (less than 1.5 nm per half‐sarcomere) on steady lengthening at different velocities. Stiffness was 10‐20% larger during lengthening than at the plateau of isometric tetanus and remained practically constant, independent of lengthening velocity, in the range of velocities used. 8. The results indicate that steady lengthening of a tetanized fibre induces a cross‐bridge cycle characterized by fast detachment of the cross‐bridge extended beyond a critical level. (ABSTRACT TRUNCATED AT 400 WORDS)
Thalamic structural connectivity in medial temporal lobe epilepsy

The thalamus has been implicated in various stages of medial temporal lobe epilepsy (MTLE) seizure evolution. The relative density and functional significance (in epileptogenesis) of thalamic projections to MTL subregions, however, remains to be determined. This study used structural and diffusion magnetic resonance imaging (MRI) to evaluate thalamic connection density with distinct MTL subregions in terms of location and volume. Nineteen MTLE patients with unilateral hippocampal sclerosis (HS; 12 right; 10 female) were compared to 19 age‐matched controls. Five regions of interest (ROIs) per hemisphere were created in native space: thalamus, amygdala, entorhinal cortex, hippocampus, and parahippocampus. Separate probabilistic tractography analyses were performed between the thalamus and each ipsilateral MTL subregion (four per hemisphere). Individual connectivity profiles and regional volumes were assessed. The medial pulvinar consistently showed the highest connection density with the hippocampus in healthy controls and in MTLE patients. Decreased thalamic connected volume was observed for thalamohippocampal pathways in patients with MTLE, and indicates pathway‐specific deafferentation. Regional hippocampal and thalamic atrophy was also observed, indicating gray and white matter loss in the thalamohippocampal pathway. Consistent localization of dense medial pulvinar (PuM) connectivity with the hippocampus suggests chronic PuM stimulation could modulate the MTLE seizure network. Decreased thalamic connected volume is a promising biomarker for epileptogenesis that merits longitudinal validation.
Viral Perturbations of Host Networks Reflect Disease Etiology

Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia.
Extracting foreground in video sequence using segmentation based on motion, contrast and luminance

Foreground detection is an important step in various video content analysis systems such as object tracking, recognition and counting. Due to the limitations of each algorithm based on its merits and demerits, so far, there is no consensus on the most effective method due to varying nature of videos. Accuracy and timely computational processing are the two main constraints. Whilst other methods only detect the approximate motion part(s) of object(s) in a video, this paper presents a novel approach to detect the motion part(s) and associated object(s) to get the whole subject. Our work detects foreground by using a new automatic masking technique. The proposed technique uses a set of morphological operators to separate foreground and background. The proposed algorithm is an extension of previous works [1-3]. A complex video sequence was tested to detect comprehensive foreground regions of moving object(s).
Comparison of three mixed dentition analysis methods in orthodontic patients at AKUH.

OBJECTIVE To compare the actual sum of canine and premolars and that predicted from three mixed dentition prediction methods in orthodontic patients at the Aga Khan University Hospital (AKUH), Karachi. STUDY DESIGN Cross-sectional comparative study. PLACE AND DURATION OF STUDY Orthodontic clinic at the Aga Khan University Hospital from June 2002 to December 2007. METHODOLOGY Data were collected using pretreatment records including orthodontic files and plaster casts of 121 orthodontic patients. Digital caliper was used to measure the mesiodistal widths of permanent teeth from 1st molar to 1st molar in mandibular arch, and central incisors and 1st molars in maxillary arch. The methods of Tanaka and Johnston, Moyers, and Bernabé and Flores-Mir were used to predict the mesiodistal widths of the canine and premolars. Comparison between the actual and predicted sum of the mesiodistal widths of canine and premolars was made for each prediction method, using paired sample t-test. RESULTS There were 45 males and 76 females with average ages of 13.3+/-1.3 and 13.4+/-0.8 years respectively. For males statistically significant differences were found for Moyers at the 75th percentile and Bernabé and Flores-Mir method whereas for females only the Bernabé and Flores-Mir's method showed significant results. However, no significant difference was found in both genders for Tanaka and Johnston method. CONCLUSION In the studied orthodontic patients for males Moyers 50th percentile and Tanaka and Johnston methods could be used; while for females Moyers 75th percentile and Tanaka and Johnston methods were applicable for mixed dentition analysis.
Methylation of APC and GSTP1 in Non-Neoplastic Tissue Adjacent to Prostate Tumour and Mortality from Prostate Cancer

Background Markers that can discriminate between indolent and aggressive prostate tumours are needed. We studied gene methylation in non-neoplastic tissue adjacent to prostate tumour (NTAT) in association with prostate cancer mortality. Methods From two cohorts of consecutive prostate cancer patients diagnosed at one pathology ward in Turin, Italy, we selected 157 patients with available NTAT and followed them up for more than 14 years. We obtained DNA from NTAT in paraffin-embedded prostate tumour tissues and used probe real-time PCR to analyse methylation of the glutathione S-transferase (GSTP1) and adenomatous polyposis coli (APC) gene promoters. Results Prevalence of APC and GSTP1 methylation in the NTAT was between 40 and 45%. It was associated with methylation in prostate tumour tissue for the same two genes as well as with a high Gleason score. The hazard ratio (HR) of prostate cancer mortality was 2.38 (95% confidence interval: 1.23–4.61) for APC methylation, and 2.92 (1.49–5.74) for GSTP1 methylation in NTAT. It changed to 1.91 (1.03–3.56) and 1.60 (0.80–3.19) after adjusting for Gleason score and methylation in prostate tumour tissue. Comparison of 2 vs. 0 methylated genes in NTAT revealed a HR of 4.30 (2.00–9.22), which decreased to 2.40 (1.15–5.01) after adjustment. Results were stronger in the first 5 years of follow-up (adjusted HR: 3.29, 95% CI: 1.27–8.52). Conclusions Changes in gene methylation are an early event in prostate carcinogenesis and may play a role in cancer progression. Gene methylation in NTAT is a possible prognostic marker to be evaluated in clinical studies.
Intracellular Processing, Glycosylation, and Cell Surface Expression of Human Metapneumovirus Attachment Glycoprotein

ABSTRACT The biosynthesis and posttranslational processing of human metapneumovirus attachment G glycoprotein were investigated. After pulse-labeling, the G protein accumulated as three species with molecular weights of 45,000, 50,000, and 53,000 (45K, 50K, and 53K, respectively). N-Glycosidase digestion indicated that these forms represent the unglycosylated precursor and N-glycosylated intermediate products, respectively. After an appropriate chase, these three naive forms were further processed to a mature 97K form. The presence of O-linked sugars in mature G protein was confirmed by O-glycanase digestion and lectin-binding assay using Arachis hypogaea (peanut agglutinin), an O-glycan-specific lectin. In addition, in the O-glycosylation-deficient cell line (CHO ldlD cell), the G protein could not be processed to the mature form unless the exogenous Gal and GalNAc were supplemented, which provided added evidence supporting the O-linked glycosylation of G protein. The maturation of G was completely blocked by monensin but was partially sensitive to brefeldin A (BFA), suggesting the O-linked glycosylation of G initiated in the trans-Golgi compartment and terminated in the trans-Golgi network. Enzymatic deglycosylation analysis confirmed that the BFA-G was a partial mature form containing N-linked oligosaccharides and various amounts of O-linked carbohydrate side chains. The expression of G protein at the cell surface could be detected by indirect immunofluorescence staining assay. Furthermore, cell surface immunoprecipitation displayed an efficient intracellular transport of G protein.
Inference of Bacterial Microevolution Using Multilocus Sequence Data

We describe a model-based method for using multilocus sequence data to infer the clonal relationships of bacteria and the chromosomal position of homologous recombination events that disrupt a clonal pattern of inheritance. The key assumption of our model is that recombination events introduce a constant rate of substitutions to a contiguous region of sequence. The method is applicable both to multilocus sequence typing (MLST) data from a few loci and to alignments of multiple bacterial genomes. It can be used to decide whether a subset of isolates share common ancestry, to estimate the age of the common ancestor, and hence to address a variety of epidemiological and ecological questions that hinge on the pattern of bacterial spread. It should also be useful in associating particular genetic events with the changes in phenotype that they cause. We show that the model outperforms existing methods of subdividing recombinogenic bacteria using MLST data and provide examples from Salmonella and Bacillus. The software used in this article, ClonalFrame, is available from http://bacteria.stats. ox.ac. uk/.