Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypermethylation of CpG Islands in Primary and Metastatic Human Prostate Cancer

Aberrant DNA methylation patterns may be the earliest somatic genome changes in prostate cancer. Using real-time methylation-specific PCR, we assessed the extent of hypermethylation at 16 CpG islands in DNA from seven prostate cancer cell lines (LNCaP, PC-3, DU-145, LAPC-4, CWR22Rv1, VCaP, and C42B), normal prostate epithelial cells, normal prostate stromal cells, 73 primary prostate cancers, 91 metastatic prostate cancers, and 25 noncancerous prostate tissues. We found that CpG islands at GSTP1, APC, RASSF1a, PTGS2, and MDR1 were hypermethylated in >85% of prostate cancers and cancer cell lines but not in normal prostate cells and tissues; CpG islands at EDNRB, ESR1, CDKN2a, and hMLH1 exhibited low to moderate rates of hypermethylation in prostate cancer tissues and cancer cell lines but were entirely unmethylated in normal tissues; and CpG islands at DAPK1, TIMP3, MGMT, CDKN2b, p14/ARF, and CDH1 were not abnormally hypermethylated in prostate cancers. Receiver operator characteristic curve analyses suggested that CpG island hypermethylation changes at GSTP1, APC, RASSF1a, PTGS2, and MDR1 in various combinations can distinguish primary prostate cancer from benign prostate tissues with sensitivities of 97.3–100% and specificities of 92–100%. Hypermethylation of the CpG island at EDNRB was correlated with the grade and stage of the primary prostate cancers. PTGS2 CpG island hypermethylation portended an increased risk of recurrence. Furthermore, CpG island hypermethylation patterns in prostate cancer metastases were very similar to the primary prostate cancers and tended to show greater differences between cases than between anatomical sites of metastasis.
Advances in the understanding of priapism

Priapism, a persistent penile erection lasting longer than 4 hours and unrelated to sexual activity, is one of the most common emergencies treated by urologists. Priapism can be categorized as ischemic, recurrent ischemic (stuttering), and non-ischemic. Advances in understanding the pathophysiology of various types of priapism have led to targeted management strategies. This review aims to provide an up-to-date picture of the pathophysiology and management of priapism. A search of Medline and PubMed for relevant publications using the term “priapism” was performed. In addition to the “classical” articles, emphasis was placed on publications from January 2013 to September 2016 to evaluate the most recent literature available. Though advances in both basic and clinical research continue and effective treatment options are available, methods for the prevention of priapism continue to be elusive.
A hybrid biomechanical intensity based deformable image registration of lung 4DCT

Deformable image registration (DIR) has been extensively studied over the past two decades due to its essential role in many image-guided interventions (IGI). IGI demands a highly accurate registration that maintains its accuracy across the entire region of interest. This work evaluates the improvement in accuracy and consistency by refining the results of Morfeus, a biomechanical model-based DIR algorithm. A hybrid DIR algorithm is proposed based on, a biomechanical model–based DIR algorithm and a refinement step based on a B-spline intensity-based algorithm. Inhale and exhale reconstructions of four-dimensional computed tomography (4DCT) lung images from 31 patients were initially registered using the biomechanical DIR by modeling contact surface between the lungs and the chest cavity. The resulting deformations were then refined using the intensity-based algorithm to reduce any residual uncertainties. Important parameters in the intensity-based algorithm, including grid spacing, number of pyramids, and regularization coefficient, were optimized on 10 randomly-chosen patients (out of 31). Target registration error (TRE) was calculated by measuring the Euclidean distance of common anatomical points on both images after registration. For each patient a minimum of 30 points/lung were used. Grid spacing of 8 mm, 5 levels of grid pyramids, and regularization coefficient of 3.0 were found to provide optimal results on 10 randomly chosen patients. Overall the entire patient population (n = 31), the hybrid method resulted in mean ± SD (90th%) TRE of 1.5 ± 1.4 (2.9) mm compared to 3.1 ± 1.9 (5.6) using biomechanical DIR and 2.6 ± 2.5 (6.1) using intensity-based DIR alone. The proposed hybrid biomechanical modeling intensity based algorithm is a promising DIR technique which could be used in various IGI procedures. The current investigation shows the efficacy of this approach for the registration of 4DCT images of the lungs with average accuracy of 1.5 mm.
The Cerebellum-Specific Munc13 Isoform Munc13-3 Regulates Cerebellar Synaptic Transmission and Motor Learning in Mice

Munc13 proteins form a family of three, primarily brain-specific phorbol ester receptors (Munc13-1/2/3) in mammals. Munc13-1 is a component of presynaptic active zones in which it acts as an essential synaptic vesicle priming protein. In contrast to Munc13-1, which is present in most neurons throughout the rat and mouse CNS, Munc13-3 is almost exclusively expressed in the cerebellum. Munc13-3 mRNA is present in granule and Purkinje cells but absent from glia cells. Munc13-3 protein is localized to the synaptic neuropil of the cerebellar molecular layer but is not found in Purkinje cell dendrites, suggesting that Munc13-3, like Munc13-1, is a presynaptic protein at parallel fiber–Purkinje cell synapses. To examine the role of Munc13-3 in cerebellar physiology, we generated Munc13-3-deficient mutant mice. Munc13-3 deletion mutants exhibit increased paired-pulse facilitation at parallel fiber–Purkinje cell synapses. In addition, mutant mice display normal spontaneous motor activity but have an impaired ability to learn complex motor tasks. Our data demonstrate that Munc13-3 regulates synaptic transmission at parallel fiber–Purkinje cell synapses. We propose that Munc13-3 acts at a similar step of the synaptic vesicle cycle as does Munc13-1, albeit with less efficiency. In view of the present data and the well established vesicle priming function of Munc13-1, it is likely that Munc13-3-loss leads to a reduction in release probability at parallel fiber–Purkinje cell synapses by interfering with vesicle priming. This, in turn, would lead to increases in paired-pulse facilitation and could contribute to the observed deficit in motor learning.
Physical Conditioning Programs for Workers With Back and Neck Pain: A Cochrane Systematic Review

Objective. To determine the effect on time lost from work of physical conditioning programs for workers with back and neck pain. Data Sources. Randomized trials were located by searching MEDLINE, EMBASE, CINAHL, PsycINFO, the Cochrane Controlled Trial Register, and PEDro. Review Methods. Two reviewers independently extracted data and assessed trial quality. Where data could be pooled, meta-analysis was performed. Based on cost considerations, we nominated a mean saving of 10 sick days per year or a number needed to treat to return 1 person to work of 10 as the smallest treatment effects that would be clinically worthwhile. Results. Nineteen trials in 21 publications yielded 23 contrasts relevant to this review. These trials provide evidence that physical conditioning programs that included a cognitive-behavioral approach could produce a clinically worthwhile reduction in the number of sick days taken at 12 months (average of 45 days; 95% confidence interval 3–88) when compared to general practitioner care or advice for workers with chronic back pain. There was little evidence of an effect on time lost from work of specific exercise programs that did not include a cognitive-behavioral component. Conclusion. Physical conditioning programs that incorporate a cognitive-behavioral approach reduce the number of sick days for workers with chronic back pain when compared to usual care. Spine 2003;28:E391–E395
Indirect control invariance of Decoherence-Splitting Manifold (DSM)

Quantum coherence of open quantum systems is usually compromised because of the interaction with the ambient environment. Here, we introduce the concept of Decoherence Splitting Manifold (DSM), a submanifold of the space of density operators, wherein the system's density matrix clearly exhibits a splitting between a unitarily evolving subdensity corresponding to some given set of its eigenvalues, which we aim to preserve, and another subdensity, in which eigenvalues are not preserved. The eigenspace of the eigenvalues that are preserved provides the concept of (time-varying) Decoherence Protected Subspace (DPS), a concept that subtlety differs from the (time-varying) Decoherence Free Subspace (DFS) in the way the protected subspace is embedded in the full Hilbert space. With the DSM concept, the DPS is reformulated as a complex vector bundle over the DSM. In the absence of the traditional DFS, looking for less restrictive spaces and/or utilizing quantum control may help generate and/or retain a decoherence-free subevolution. This is achieved by searching for a DSM whose tangent bundle distribution is invariant under indirect control of an auxiliary qubit.
Eurographics/ Acm Siggraph Symposium on Computer Animation (2007) on the Beat! Timing and Tension for Dynamic Characters

Permission to make digital or hard copies of part or all of this wor k for per sonal or classr oom use is granted without fee provided that copies are not made or distributed for commer cial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this wor k owned by other s than ACM must be honored. Abstracting with cr edit is permitted. To copy other wise, to republish, to post on ser ver s, or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from Permissions Dept, ACM Abstract Dynamic simulation is a promising complement to kinematic motion synthesis, particularly in cases where simulated characters need to respond to unpredictable interactions. Moving beyond simple rag-doll effects, though, requires dynamic control. The main issue with dynamic control is that there are no standardized techniques that allow an animator to precisely specify the timing of the motion while still providing natural response to external disturbances. The few proposed techniques that address this problem are based on heuristically or manually tuning proportional-derivative (PD) control parameters and do not generalize easily. We propose an approach to dynamic character control that is able to honor timing constraints, to provide natural-looking motion and to allow for realistic response to perturbations. Our approach uses traditional PD control to interpolate between key-frames. The key innovation is that the parameters of the PD controllers are computed for each joint analytically. By continuously updating these parameters over time, the controller is able to respond naturally to both external perturbations and changes in the state of the character.
A Comprehensive Analysis of In Vitro and In Vivo Genetic Fitness of Pseudomonas aeruginosa Using High-Throughput Sequencing of Transposon Libraries

High-throughput sequencing of transposon (Tn) libraries created within entire genomes identifies and quantifies the contribution of individual genes and operons to the fitness of organisms in different environments. We used insertion-sequencing (INSeq) to analyze the contribution to fitness of all non-essential genes in the chromosome of Pseudomonas aeruginosa strain PA14 based on a library of ∼300,000 individual Tn insertions. In vitro growth in LB provided a baseline for comparison with the survival of the Tn insertion strains following 6 days of colonization of the murine gastrointestinal tract as well as a comparison with Tn-inserts subsequently able to systemically disseminate to the spleen following induction of neutropenia. Sequencing was performed following DNA extraction from the recovered bacteria, digestion with the MmeI restriction enzyme that hydrolyzes DNA 16 bp away from the end of the Tn insert, and fractionation into oligonucleotides of 1,200–1,500 bp that were prepared for high-throughput sequencing. Changes in frequency of Tn inserts into the P. aeruginosa genome were used to quantify in vivo fitness resulting from loss of a gene. 636 genes had <10 sequencing reads in LB, thus defined as unable to grow in this medium. During in vivo infection there were major losses of strains with Tn inserts in almost all known virulence factors, as well as respiration, energy utilization, ion pumps, nutritional genes and prophages. Many new candidates for virulence factors were also identified. There were consistent changes in the recovery of Tn inserts in genes within most operons and Tn insertions into some genes enhanced in vivo fitness. Strikingly, 90% of the non-essential genes were required for in vivo survival following systemic dissemination during neutropenia. These experiments resulted in the identification of the P. aeruginosa strain PA14 genes necessary for optimal survival in the mucosal and systemic environments of a mammalian host.
Challenges in automated verification and synthesis for molecular programming

Molecular programming is concerned with building synthetic nanoscale devices from molecules, which can be programmed to autonomously perform a specific task. Several artifacts have been demonstrated experimentally, including DNA circuits that can compute a logic formula and molecular robots that can transport cargo. In view of their natural interface to biological components, many potential applications are envisaged, e.g. point-of-care diagnostics and targeted delivery of drugs. However, the inherent complexity of the resulting biochemical systems makes the manual process of designing such devices error-prone, requiring automated design support methodologies, analogous to design automation tools for digital systems. This paper gives an overview of the role that probabilistic modelling and verification techniques can play in designing, analysing, debugging and synthesising programmable molecular devices, and outlines the challenges in achieving automated verification and synthesis software technologies in this setting.
The Use of Genetic Markers to Determine Risk for Prostate Cancer at Prostate Biopsy

Purpose: We examined a panel of 13 polymorphisms in 13 different genes to determine whether specific genotypes can help predict prostate cancer at the time of biopsy among men prescreened with prostate-specific antigen and digital rectal exam. Experimental Design: We examined 2,088 consecutive men who were referred for prostate biopsy from 1997 to 2003. Thirteen genes were examined, including TNF308, GSTT1, KLK2, endostatin, MCRA, MCRV, tyrosinase, MSR1, CHK2, RNasel, HOGG1-326, HOGG1-11657, and HRAS1. Odds ratio for detection of prostate cancer were adjusted for age, race, prostate-specific antigen, digital rectal exam, family history of prostate cancer, and urinary symptoms. Results: Of the 2,088 men, 996 (47.7%) had cancer detected. Four genes (TNF308, GSTT1, KLK2, and HOGG1-326) were significantly associated with prostate cancer. The adjusted odds ratios (OR) for prostate cancer for patients with the AA genotype of the TNF308 gene was 1.92 [95% confidence interval (95% CI), 1.0-1.5, P = 0.05], compared with those with the GG genotype, and for patients with the TT genotype of the KLK2 gene, the OR was 1.5 (95% confidence interval, 1.0-2.2, P = 0.04), compared with the CC genotype. The OR for patients with a homozygous deletion of the GSTT1 gene was 0.81 (95% CI, 0.6-1.0, P = 0.06) compared with those with the deletion, and the OR for patients with the GG genotype of the HOGG1-326 gene was 0.68 (95% CI, 0.5-1.0, P = 0.05) compared with the CC genotype. Patients who had all four alleles that were positively associated with prostate cancer had an OR of 9.33 (95% CI, 2.4-35.8, P = 0.0005) for prostate cancer compared with patients with alleles that were negatively associated with prostate cancer. Conclusions: Of the 13 polymorphisms, two were found to be positively associated with prostate cancer (TNF308 and KLK2) and two were negatively associated with prostate cancer (GSTT1 and HOGG1-326). Future studies are required to confirm these results.
Ocean retrievals for WindSat: radiative transfer model, algorithm, validation

We have developed an ocean retrieval algorithm for WindSat. The ocean retrievals are for sea-surface temperature (SST), wind speed (SSWS) and direction (SSWD), atmospheric water vapor, cloud water, and rain rate. The algorithm is based on our AMSR-E algorithm, which has been adapted to the WindSat channel set and incidence angles. One major change to the AMSR-E algorithm is the addition of the wind direction retrieval, which is made possible by WindSat measurements of the 3rd and 4th Stokes brightness temperatures. The 3rd Stokes parameter at 10.7 GHz is corrected for Faraday rotation. To compute wind direction, a maximum-likelihood approach is used similar to the method used for microwave scatterometers. A set of possible wind vectors solutions (i.e., ambiguities) is found that minimize the difference between the observations and the radiative transfer model. A median filter is then used to select the most likely ambiguity. The ocean algorithm uses all 22 WindSat channels. Retrievals for a 9-month period are presented and are compared to a variety of validation datasets. The physical basis for the algorithm is the radiative transfer model (RTM). This model expresses the microwave brightness temperature in terms of SST, wind vector, and atmospheric profiles of temperature and moisture. The WindSat observations in conjunction with Reynolds SST and numerical weather prediction model surface winds are used to refine the sea-surface emissivity component of the RTM. Some differences are found between the new emissivity model and earlier models that were based on aircraft and previous satellite observations.
Are rotation curves in NGC 6946 and the Milky Way magnetically supported

The inner disk rotation of NGC 6946 and the Milky Way is dominated by gravity but magnetism is not negligible at radii where the rotation curve becomes flat, and indeed could become dominant at very large radii. Values of the order of 1 μG, or even less, produce a centripetal force when the absolute value of the slope of the curve [Bφ, R ] (azimuthal field strength versus radius) is less than the slope of a Bφ-profile proportional to R–1. The ∝ R–1-profile is here called the critical profile. From the hypothesis of magnetically driven rotation curves, the following is to be expected: at large radii, a “subcritical” profile (slope flatter than R–1); at still larger radii a Bφ-profile becoming asymptotically critical as the density becomes asymptotically vanishing. Recent observations of magnetic fields in NGC 6946 and the Milky Way are in very good agreement with these predictions. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Modulation of exon skipping and inclusion by heterogeneous nuclear ribonucleoprotein A1 and pre-mRNA splicing factor SF2/ASF

The essential splicing factor SF2/ASF and the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) modulate alternative splicing in vitro of pre-mRNAs that contain 5' splice sites of comparable strengths competing for a common 3' splice site. Using natural and model pre-mRNAs, we have examined whether the ratio of SF2/ASF to hnRNP A1 also regulates other modes of alternative splicing in vitro. We found that an excess of SF2/ASF effectively prevents inappropriate exon skipping and also influences the selection of mutually exclusive tissue-specific exons in natural beta-tropomyosin pre-mRNA. In contrast, an excess of hnRNP A1 does not cause inappropriate exon skipping in natural constitutively or alternatively spliced pre-mRNAs. Although hnRNP A1 can promote alternative exon skipping, this effect is not universal and is dependent, e.g., on the size of the internal alternative exon and on the strength of the polypyrimidine tract in the preceding intron. With appropriate alternative exons, an excess of SF2/ASF promotes exon inclusion, whereas an excess of hnRNP A1 causes exon skipping. We propose that in some cases the ratio of SF2/ASF to hnRNP A1 may play a role in regulating alternative splicing by exon inclusion or skipping through the antagonistic effects of these proteins on alternative splice site selection.
Pathophysiology of exercise intolerance in chronic diseases: the role of diminished cardiac performance in mitochondrial and heart failure patients

Objective Exercise intolerance is a clinical hallmark of chronic conditions. The present study determined pathophysiological mechanisms of exercise intolerance in cardiovascular, neuromuscular, and metabolic disorders. Methods In a prospective cross-sectional observational study 152 patients (heart failure reduced ejection fraction, n=32; stroke, n=34; mitochondrial disease, n=28; type two diabetes, n=28; and healthy controls, n=30) performed cardiopulmonary exercise testing with metabolic and haemodynamic measurements. Peak exercise O2 consumption and cardiac power output were measures of exercise tolerance and cardiac performance. Results Exercise tolerance was significantly diminished in patients compared with controls (ie, by 45% stroke, 39% mitochondria disease, and 33% diabetes and heart failure, p<0.05). Cardiac performance was only significantly reduced in heart failure (due to reduced heart rate, stroke volume, and blood pressure) and mitochondrial patients (due reduced stroke volume) compared with controls (ie, by 53% and 26%, p<0.05). Ability of skeletal muscles to extract oxygen (ie, arterial-venous O2 difference) was diminished in mitochondrial, stroke, and diabetes patients (by 24%, 22%, and 18%, p<0.05), but increased by 21% in heart failure (p<0.05) compared with controls. Cardiac output explained 65% and 51% of the variance in peak O2 consumption (p<0.01) in heart failure and mitochondrial patients, whereas arterial-venous O2 difference explained 69% (p<0.01) of variance in peak O2 consumption in diabetes, and 65% and 48% in stroke and mitochondrial patients (p<0.01). Conclusions Different mechanisms explain exercise intolerance in patients with heart failure, mitochondrial dysfunction, stroke and diabetes. Their better understanding may improve management of patients, their stress tolerance and quality of life.
Affective expressions of machines

Emotions should play an important role in the design of interfaces because people interact with machines as if they were social actors [4]. We developed and tested a model for the convincingness of affective expressions, based on Fogg and Hsiang Tseng [3]. The empirical data did not support our original model. Furthermore, the experiment investigated if the type of emotion (happiness, sadness, anger, surprise, fear and disgust), knowledge about the source (human or machine), the level of abstraction (natural face, computer rendered face and matrix face) and medium of presentation (visual, audio/visual, audio) of an affective expression influences its convincingness and distinctness. Only the type of emotion and multimedia presentations had an effect on convincingness. The distinctness of an expression depends on the abstraction and the media through which it is presented.