Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination

A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with [3H]thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease.
Long-term Ultrasonographic Follow-up Study of Gastric Motility in Patients with Functional Dyspepsia

Although patients with functional dyspepsia complain of epigastric symptoms, the relation between these symptoms and gastric motility remains controversial. There are few reports on the clinical course of functional dyspepsia, including changes in gastric motility, observed over a considerably long period. We conducted a study to examine association between changes in symptoms and changes in ultrasonographically evaluated gastric motility over a long-term follow-up period in patients with functional dyspepsia. Forty patients (18 men, 22 women; mean age, 53.7 years) with functional dyspepsia were followed up by medical interview, physical examination, endoscopy, and ultrasonography for gastric motility. Follow-up ranged from 1.0 to 7.8 years (mean, 3.0 years). Ultrasonographic evaluation of gastric motility included gastric emptying rate and antral contractions. During the follow-up period, patients were treated with proton pump inhibitors, H2-blockers, or prokinetics. Symptoms improved in 21 patients (group A), but symptoms persisted or worsened in 19 patients (group B). There were no significant differences in clinical characteristics between the two groups. Gastric motility improved in group A but not in group B. In conclusion, improved gastric motility appears to correspond to and may explain improved symptoms in some patients with functional dyspepsia.
Escherichia coli colonization patterns among human household members and pets, with attention to acute urinary tract infection.

BACKGROUND Within-household transmission of Escherichia coli may promote urinary tract infection (UTI) but is poorly understood. METHODS Fecal samples from 228 individuals (152 humans [5 with acute UTI] and 76 pets) in 63 households were extensively processed for unique E. coli clones, as defined by random-amplified polymorphic DNA analysis and pulsed-field gel electrophoresis. Patterns of strain sharing (presence of a clone in multiple individuals) were assessed. RESULTS Of 335 E. coli clones, 90 (27%) were recovered from multiple hosts (up to 11 per clone). Within-household strain sharing (1) involved 68% of households, including 3 of 5 households in which a member had a UTI; (2) was more frequent than across-household strain sharing (27% vs. 0.8% of potential sharing pairs; P< .001); (3) increased with household size (r2=0.93; P< .001); and (4) varied by host-pair type (pet-pet, 58%; human-human, 31%; human-pet, 17%). Sex partners shared strains more commonly than did other adults (31% vs. 7% of pairs; P= .08) but accounted for only 12% of within-household strain sharing. CONCLUSIONS Within-household sharing of E. coli, including in households in which a member has a UTI, is common and can involve any combination of humans and pets. Identification of the underlying mechanism(s) could lead to novel preventive measures against UTI.
Using Decision Forest to Classify Prostate Cancer Samples on the Basis of SELDI-TOF MS Data: Assessing Chance Correlation and Prediction Confidence

Class prediction using “omics” data is playing an increasing role in toxicogenomics, diagnosis/prognosis, and risk assessment. These data are usually noisy and represented by relatively few samples and a very large number of predictor variables (e.g., genes of DNA microarray data or m/z peaks of mass spectrometry data). These characteristics manifest the importance of assessing potential random correlation and overfitting of noise for a classification model based on omics data. We present a novel classification method, decision forest (DF), for class prediction using omics data. DF combines the results of multiple heterogeneous but comparable decision tree (DT) models to produce a consensus prediction. The method is less prone to overfitting of noise and chance correlation. A DF model was developed to predict presence of prostate cancer using a proteomic data set generated from surface-enhanced laser deposition/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The degree of chance correlation and prediction confidence of the model was rigorously assessed by extensive cross-validation and randomization testing. Comparison of model prediction with imposed random correlation demonstrated biologic relevance of the model and the reduction of overfitting in DF. Furthermore, two confidence levels (high and low confidences) were assigned to each prediction, where most misclassifications were associated with the low-confidence region. For the high-confidence prediction, the model achieved 99.2% sensitivity and 98.2% specificity. The model also identified a list of significant peaks that could be useful for biomarker identification. DF should be equally applicable to other omics data such as gene expression data or metabolomic data. The DF algorithm is available upon request.
Generation of Locomotor-Like Activity in the Isolated Rat Spinal Cord Using Intraspinal Electrical Microstimulation Driven by a Digital Neuromorphic CPG

Neural prostheses based on electrical microstimulation offer promising perspectives to restore functions following lesions of the central nervous system (CNS). They require the identification of appropriate stimulation sites and the coordination of their activation to achieve the restoration of functional activity. On the long term, a challenging perspective is to control microstimulation by artificial neural networks hybridized to the living tissue. Regarding the use of this strategy to restore locomotor activity in the spinal cord, to date, there has been no proof of principle of such hybrid approach driving intraspinal microstimulation (ISMS). Here, we address a first step toward this goal in the neonatal rat spinal cord isolated ex vivo, which can display locomotor-like activity while offering an easy access to intraspinal circuitry. Microelectrode arrays were inserted in the lumbar region to determine appropriate stimulation sites to elicit elementary bursting patterns on bilateral L2/L5 ventral roots. Two intraspinal sites were identified at L1 level, one on each side of the spinal cord laterally from the midline and approximately at a median position dorso-ventrally. An artificial CPG implemented on digital integrated circuit (FPGA) was built to generate alternating activity and was hybridized to the living spinal cord to drive electrical microstimulation on these two identified sites. Using this strategy, sustained left-right and flexor-extensor alternating activity on bilateral L2/L5 ventral roots could be generated in either whole or thoracically transected spinal cords. These results are a first step toward hybrid artificial/biological solutions based on electrical microstimulation for the restoration of lost function in the injured CNS.
Mechanisms of Vascular Smooth Muscle NADPH Oxidase 1 (Nox1) Contribution to Injury-Induced Neointimal Formation

Objective—Vascular NADPH oxidases (Noxes) have been implicated in cardiovascular diseases; however, the importance of individual Nox homologues remains unclear. Here, the role of the vascular smooth muscle cell (VSMC) Nox1 in neointima formation was studied using genetically modified animal models. Methods and Results—Wire injury–induced neointima formation in the femoral artery, along with proliferation and apoptosis, was reduced in Nox1y/− mice, but there was little difference in TgSMCnox1 mice compared with wild-type (WT) mice. Proliferation and migration were reduced in cultured Nox1y/− VSMCs and increased in TgSMCnox1 cells. TgSMCnox1 cells exhibited increased fibronectin secretion, but neither collagen I production nor cell adhesion was affected by alteration of Nox1. Using antibody microarray and Western blotting analysis, increased cofilin phosphorylation and mDia1 expression and decreased PAK1 expression were detected in Nox1y/− cells. Overexpression of S3A, a constitutively active cofilin mutant, partially recovered reduced migration of Nox1y/− cells, suggesting that reduction in cofilin activity contributes to impaired migration of Nox1y/− VSMCs. Conclusions—These results indicate that Nox1 plays a critical role in neointima formation by mediating VSMC migration, proliferation, and extracellular matrix production, and that cofilin is a major effector of Nox1-mediated migration. Inhibition of Nox1 may be an efficient strategy to suppress neointimal formation.
Target Inhibition Networks: Predicting Selective Combinations of Druggable Targets to Block Cancer Survival Pathways

A recent trend in drug development is to identify drug combinations or multi-target agents that effectively modify multiple nodes of disease-associated networks. Such polypharmacological effects may reduce the risk of emerging drug resistance by means of attacking the disease networks through synergistic and synthetic lethal interactions. However, due to the exponentially increasing number of potential drug and target combinations, systematic approaches are needed for prioritizing the most potent multi-target alternatives on a global network level. We took a functional systems pharmacology approach toward the identification of selective target combinations for specific cancer cells by combining large-scale screening data on drug treatment efficacies and drug-target binding affinities. Our model-based prediction approach, named TIMMA, takes advantage of the polypharmacological effects of drugs and infers combinatorial drug efficacies through system-level target inhibition networks. Case studies in MCF-7 and MDA-MB-231 breast cancer and BxPC-3 pancreatic cancer cells demonstrated how the target inhibition modeling allows systematic exploration of functional interactions between drugs and their targets to maximally inhibit multiple survival pathways in a given cancer type. The TIMMA prediction results were experimentally validated by means of systematic siRNA-mediated silencing of the selected targets and their pairwise combinations, showing increased ability to identify not only such druggable kinase targets that are essential for cancer survival either individually or in combination, but also synergistic interactions indicative of non-additive drug efficacies. These system-level analyses were enabled by a novel model construction method utilizing maximization and minimization rules, as well as a model selection algorithm based on sequential forward floating search. Compared with an existing computational solution, TIMMA showed both enhanced prediction accuracies in cross validation as well as significant reduction in computation times. Such cost-effective computational-experimental design strategies have the potential to greatly speed-up the drug testing efforts by prioritizing those interventions and interactions warranting further study in individual cancer cases.
A practical self-shadowing algorithm for interactive hair animation

This paper presents a new fast and accurate self-shadowing algorithm for animated hair. Our method is based on a 3D light-oriented density map, a novel structure that combines an optimized volumetric representation of hair with a light-oriented partition of space. Using this 3D map, accurate hair self-shadowing can be interactively processed (several frames per second for a full hairstyle) on a standard CPU. Beyond the fact that our application is independent of any graphics hardware (and thus portable), it can easily be parallelized for better performance. Our method is especially adapted to render animated hair since there is no geometry-based precomputation and since the density map can be used to optimize hair self-collisions. The approach has been validated on a dance motion sequence, for various hairstyles.
The d-Alanine Residues ofStaphylococcus aureus Teichoic Acids Alter the Susceptibility to Vancomycin and the Activity of Autolytic Enzymes

ABSTRACT Recently, Staphylococcus aureus strains with intermediate resistance to vancomycin, the antibiotic of last resort, have been described. Multiple changes in peptidoglycan turnover and structure contribute to the resistance phenotype. Here, we describe that structural changes of teichoic acids in the cell envelope have a considerable influence on the susceptibility to vancomycin and other glycopeptides. S. aureus cells lackingd-alanine esters in teichoic acids exhibited an at least threefold-increased sensitivity to glycopeptide antibiotics. Furthermore, the autolytic activity of the d-alanine mutant was reduced compared to the wild-type, and the mutant was more susceptible to the staphylolytic enzyme lysostaphin. Vancomycin inhibited autolysis at very high concentrations but neither in the wild-type nor in the mutant was the autolytic activity influenced in the range of the MIC. Mutant cells had a considerably higher capacity to bind vancomycin.
Cross-Site and Intra-Site ASR System Combination: Comparisons on Lattice and 1-Best Methods

We evaluate system combination techniques for automatic speech recognition using systems from multiple sites who participated in the TC-STAR 2006 evaluation. Both lattice and 1-best combination techniques are tested for cross-site and intra-site tasks. For pairwise combinations the lattice based approaches can outperform 1-best ROVER with confidence scores, but 1-best ROVER results are equal (or even better) when combining three or four systems.
Interact CardioVasc Thorac Surg

The purpose of this study was to compare the outcomes of lateral tunnel (LT) and extracardiac conduit (ECC) Fontan procedures at a single institution. From April 1995 to December 2006, 165 Fontan procedures were performed (67 LT, 98 ECC). Pre-, intraand postoperative variable values were compared between two different techniques. Operative mortality was 5 (3 LT, 2 ECC). Immediate postoperative transpulmonary gradient (LT 8.5"ECC 2.5 vs. 6.6"2.4 mmHg) and central venous pressure (LT 18.3"3.8 vs. ECC 15.6"2.4 mmHg) showed significant difference (P-0.001). The LT patients had a higher incidence of sinus node dysfunction in the postoperative period (22.4% vs. ECC 11.2%; Ps0.05). Mean follow-up was 74.1"31.5 months in LT, and 31.7"28.1 months in ECC patients. There was one late death. Actuarial survival at 10 years is 92% for LT, and 89% for ECC patients (Ps0.796). The LT and ECC, both, showed comparable early and midterm outcomes in operative morbidity and mortality, postoperative hemodynamics, survival. Use of ECC for modified Fontan operation reduces the risk of sinus node dysfunction and shows better outcome of immediate postoperative hemodynamics. 2007 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.
RNA-seq differential expression studies: more sequence or more replication?

MOTIVATION RNA-seq is replacing microarrays as the primary tool for gene expression studies. Many RNA-seq studies have used insufficient biological replicates, resulting in low statistical power and inefficient use of sequencing resources. RESULTS We show the explicit trade-off between more biological replicates and deeper sequencing in increasing power to detect differentially expressed (DE) genes. In the human cell line MCF7, adding more sequencing depth after 10 M reads gives diminishing returns on power to detect DE genes, whereas adding biological replicates improves power significantly regardless of sequencing depth. We also propose a cost-effectiveness metric for guiding the design of large-scale RNA-seq DE studies. Our analysis showed that sequencing less reads and performing more biological replication is an effective strategy to increase power and accuracy in large-scale differential expression RNA-seq studies, and provided new insights into efficient experiment design of RNA-seq studies. AVAILABILITY AND IMPLEMENTATION The code used in this paper is provided on: http://home.uchicago. edu/∼jiezhou/replication/. The expression data is deposited in the Gene Expression Omnibus under the accession ID GSE51403.
Specifying Graceful Degradation

A description is given of the relaxation lattice method, a new approach to specifying graceful degradation for a large class of programs. A relaxation lattice is a lattice of specifications parameterized by a set of constraints, where the stronger the set of constraints, the more restrictive the specification. While a program is able to satisfy its strongest set of constraints, it satisfies its preferred specification, but if changes to the environment force it to satisfy a weaker set, then it will permit additional weakly consistent computations which are undesired but tolerated. The use of relaxation lattices is illustrated by specifications for programs that tolerate (1) faults, such as site crashes and network partitions, (2) timing anomalies, such as attempting to read a value too soon after it was written, (3) synchronization conflicts, such as choosing the oldest unlocked item from a queue, and (4) security breaches, such as acquiring unauthorized capabilities. >
Dismantling the Mantel tests

The simple and partial Mantel tests are routinely used in many areas of evolutionary biology to assess the significance of the association between two or more matrices of distances relative to the same pairs of individuals or demes. Partial Mantel tests rather than simple Mantel tests are widely used to assess the relationship between two variables displaying some form of structure. We show that contrary to a widely shared belief, partial Mantel tests are not valid in this case, and their bias remains close to that of the simple Mantel test. We confirm that strong biases are expected under a sampling design and spatial correlation parameter drawn from an actual study. The Mantel tests should not be used in case autocorrelation is suspected in both variables compared under the null hypothesis. We outline alternative strategies. The R code used for our computer simulations is distributed as supporting material.
How Far Can Nim in Disguise Be Stretched?

We give a complete answer to the question which moves can be adjoined to the game of nim without changing its winning strategy. The results apply to other combinatorial games with unbounded Sprague-Grundy function values. We formulate two refinements of the notion of nim-sum 0 for proving the results.
Quasi-periodic route to chaos in load resonant DC-DC converters

This paper reports first time, both numerically and experimentally, the quasi-periodic, subharmonic and chaotic behavior in a phase shift modulated load resonant converter. The study presented in this paper is restricted to third order seriesparallel load resonant converter. From hybrid system point of view, the system consists of four switching surfaces and nine possible modes. After undergoing a Hopf bifurcation of a period-one orbit, quasi-periodic behavior is obtained. Two kinds of route lead to the chaotic operation: a quasi-periodic one and a period doubling scenario.
Phenotypic characterisation of RAB6A knockout mouse embryonic fibroblasts

Rab6 is one of the most conserved Rab GTPaes throughout evolution and the most abundant Rab protein associated with the Golgi complex. The two ubiquitous Rab isoforms, Rab6A and Rab6A′, that are generated by alternative splicing of the RAB6A gene, regulate several transport steps at the Golgi level, including retrograde transport between endosomes and Golgi, anterograde transport between Golgi and the plasma membrane, and intra‐Golgi and Golgi to endoplasmic reticulum transport.
Reactive synchronization algorithms for multiprocessors

Synchronization algorithms that are efficient across a wide range of applications and operating conditions are hard to design because their performance depends on unpredictable run-time factors. The designer of a synchronization algorithm has a choice of protocols to use for implementing the synchronization operation. For example, candidate protocols for locks include test-and-set protocols and queueing protocols. Frequently, the best choice of protocols depends on the level of contention: previous research has shown that test-and-set protocols for locks outperform queueing protocols at low contention, while the opposite is true at high contention. This paper investigates reactive synchronization algorithms that dynamically choose protocols in response to the level of contention. We describe reactive algorithms for spin locks and fetch-and-op that choose among several shared-memory and message-passing protocols. Dynamically choosing protocols presents a challenge: a reactive algorithm needs to select and change protocols efficiently, and has to allow for the possibility that multiple processes may be executing different protocols at the same time. We describe the notion of consensus objects that the reactive algorithms use to preserve correctness in the face of dynamic protocol changes. Experimental measurements demonstrate that reactive algorithms perform close to the best static choice of protocols at all levels of contention. Furthermore, with mixed levels of contention, reactive algorithms outperform passive algorithms with fixed protocols, provided that contention levels do not change too frequently. Measurements of several parallel applications show that reactive algorithms result in modest performance gains for spin locks and significant gains for fetch-and-op.