gebhart/patrepeval huggingface dataset:
Whole-genome haplotyping by dilution, amplification, and sequencing (2013)

Standard whole-genome genotyping technologies are unable to determine haplotypes. Here we describe a method for rapid and cost-effective long-range haplotyping. Genomic DNA is diluted and distributed into multiple aliquots such that each aliquot receives a fraction of a haploid copy. The DNA template in each aliquot is amplified by multiple displacement amplification, converted into barcoded sequencing libraries using Nextera technology, and sequenced in multiplexed pools. To assess the performance of our method, we combined two male genomic DNA samples at equal ratios, resulting in a sample with diploid X chromosomes with known haplotypes. Pools of the multiplexed sequencing libraries were subjected to targeted pull-down of a 1-Mb contiguous region of the X-chromosome Duchenne muscular dystrophy gene. We were able to phase the Duchenne muscular dystrophy region into two contiguous haplotype blocks with a mean length of 494 kb. The haplotypes showed 99% agreement with the consensus base calls made by sequencing the individual DNAs. We subsequently used the strategy to haplotype two human genomes. Standard genomic sequencing to identify all heterozygous SNPs in the sample was combined with dilution-amplification-based sequencing data to resolve the phase of identified heterozygous SNPs. Using this procedure, we were able to phase >95% of the heterozygous SNPs from the diploid sequence data. The N50 for a Yoruba male DNA was 702 kb whereas the N50 for a European female DNA was 358 kb. Therefore, the strategy described here is suitable for haplotyping of a set of targeted regions as well as of the entire genome.
Fgf10is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis (2001)

The importance of mesenchymal-epithelial interactions for the proper development of the pancreas has been acknowledged since the early 1960s, even though the molecule(s) mediating this process have remained unknown. We demonstrate here that Fgf10, a member of the fibroblast growth factor family (FGFs), plays an essential role in this process. We show that Fgf10 is expressed in the mesenchyme directly adjacent to the early dorsal and ventral pancreatic epithelial buds. In Fgf10(-/-) mouse embryos, the evagination of the epithelium and the initial formation of the dorsal and ventral buds appear normal. However, the subsequent growth, differentiation and branching morphogenesis of the pancreatic epithelium are arrested; this is primarily due to a dramatic reduction in the proliferation of the epithelial progenitor cells marked by the production of the homeobox protein PDX1. Furthermore, FGF10 restores the population of PDX1-positive cells in organ cultures derived from Fgf10(-/-) embryos. These results indicate that Fgf10 signalling is required for the normal development of the pancreas and should prove useful in devising methods to expand pancreatic progenitor cells.
Large T antigens of many polyomaviruses are able to form complexes with the retinoblastoma protein (1990)

Stable protein complexes between the large T antigens of mouse, monkey, baboon, or human polyomaviruses and the retinoblastoma protein were detected by an in vitro coimmunoprecipitation assay. All of the large T antigens tested were able to bind to both human and mouse retinoblastoma polypeptides, showing that these interactions have been conserved during evolution.
Measurement of corneal thickness by laser Doppler interferometry. (1992)

The laser Doppler interferometry (LDI) technique, which was recently developed for axial eye length measurement, has been modified to measure the corneal thickness of the human eye in vivo. High accuracy is achieved. The standard deviation of the technique is about 7 microns, and improvement by a factor of 5 is possible. First comparisons with a usual slit lamp pachometer show a general agreement but a systematic difference of about 20 microns. Possible reasons for this discrepancy are discussed. Finally, the new method is compared to standard optical and ultrasound pachometry from a theoretical point of view, and advantages and drawbacks of the various techniques are discussed.
Pulling it together (2011)

Transforming acidic coiled coil 3 (TACC3) is a non-motor microtubule-associated protein (MAP) that is important for mitotic spindle stability and organization. The exact mechanism by which TACC3 acts at microtubules to stabilize the spindle has been unclear. However, several recent studies identified that the TACC3 complex at microtubules contains clathrin in addition to its previously identified binding partner, colonic and hepatic tumor overexpressed gene (ch-TOG). In this complex, phosphorylated TACC3 interacts directly with both ch-TOG and clathrin heavy chain, promoting accumulation of all complex members at the mitotic spindle. This complex stabilizes kinetochore fibers within the spindle by forming cross-bridges that link adjacent microtubules in these bundles. So, TACC3 is an adaptor that recruits ch-TOG and clathrin to mitotic microtubules, in an Aurora A kinase-regulated manner. In this mini-review we will describe the recent advances in the understanding of TACC 3 function and present a model that pulls together these new data with previous observations.
Leakage suppression in the toric code (2015)

Quantum codes excel at correcting local noise but fail to correct leakage faults that excite qubits to states outside the computational space. Aliferis and Terhal have shown that an accuracy threshold exists for leakage faults using gadgets called leakage reduction units (LRUs). However, these gadgets reduce the threshold and increase experimental complexity, and the costs have not been thoroughly understood. We explore a variety of techniques for leakage resilience in topological codes. Our contributions are threefold. First, we develop a leakage model that is physically motivated and efficient to simulate. Second, we use Monte-Carlo simulations to survey several syndrome extraction circuits. Third, given the capability to perform 3-outcome measurements, we present a dramatically improved syndrome processing algorithm. Our simulations show that simple circuits with one extra CNOT per qubit reduce the accuracy threshold by less than a factor of 4 when leakage and depolarizing noise rates are comparable compared to a scenario without leakage. This becomes a factor of 2 when the decoder uses 3-outcome measurements. Finally, we make the surprising observation that for physical error rates less than 2 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-4</sup> , placing LRUs after every gate may achieve the lowest logical error rate. We expect that the ideas may generalize to other topological codes.
Causes of clinical variability in Duchenne and Becker muscular dystrophies and implications for exon skipping therapies. (2020)

Becker muscular dystrophy is caused by mutations in the DMD gene that permit significant residual dystrophin protein expression in patient muscle. This is in contrast to DMD gene mutations in Duchenne muscular dystrophy where little or no dystrophin is produced (typically < 3% normal levels). Clinically, Becker muscular dystrophy is extremely variable, from slightly milder than DMD, to asymptomatic hyperCKemia at old age. The factors driving clinical variability in Becker muscular dystrophy have now been studied in some depth, and the findings are likely highly relevant to anticipated clinical findings in exon skipping therapy in DMD. The specific mutations in Becker dystrophy play an important role, and clinical variability is less with high frequency mutations (deletions exons 45-47, 45-48). The percentage of dystrophin content in patient muscle is not well-correlated with clinical findings. Muscle MRI findings (degree of fibrofatty replacement) are very well-correlated with the degree of patient disability, regardless of mutation or muscle dystrophin content. Taken together, data to date suggest that the main determinant driving clinical disability in Becker dystrophy patients is the degree of fibrofatty replacement in muscle. Thus, as with DMD, DMD gene mutations and resulting dystrophin protein abnormalities initiate the disease process, but downstream tissue pathophysiology plays a dominant role in disease progression. Factors influencing the age-dependent rate of fibrofatty replacement of muscles are responsible for much of the clinical variability seen in Becker dystrophy, as well as Duchenne dystrophy. These fibrosis-related factors include genetic modifiers, degree of muscle inflammation, and induction of microRNAs in muscle that bind to dystrophin mRNA and down-regulate dystrophin protein content in patient muscle. Studies to date regarding clinical variability in Becker dystrophy suggest that exon skipping therapy in DMD may show variable efficacy from patient to patient.
Exploring Practical Aspects of Neural Mask-Based Beamforming for Far-Field Speech Recognition (2018)

This work examines acoustic beamformers employing neural networks (NNs) for mask prediction as front -end for automatic speech recognition (ASR) systems for practical scenarios like voice-enabled home devices. To test the versatility of the mask predicting network, the system is evaluated with different recording hardware, different microphone array designs, and different acoustic models of the downstream ASR system. Significant gains in recognition accuracy are obtained in all configurations despite the fact that the NN had been trained on mismatched data. Unlike previous work, the NN is trained on a feature level objective, which gives some performance advantage over a mask related criterion. Furthermore, different approaches for realizing online, or adaptive, NN-based beamforming are explored, where the online algorithms still show significant gains compared to the baseline performance.
The interfacial region of the tooth/glass ionomer restoration: a confocal optical microscope study. (1991)

The dynamic interactions between the tooth tissues and a glass ionomer cement were investigated, using fluorescent markers incorporated into components of glass ionomer restorations. A confocal optical microscope was used to examine the tooth/restoration interface. Samples were examined at specific intervals after restoration to determine the effect of maturation of the glass ionomer matrix. Loss of fluorescent dye from the glass ionomer restoration into the subjacent dentin indicated fluid movement across the interface during maturation. To determine the effect of shrinkage from water loss on the integrity of the tooth/restoration interface, restored teeth were maintained fully hydrated and then allowed to dry. Substantial cracking at the enamel margins after drying of the set restoration indicated the strength of the attachment to enamel and also cautioned against excessive clinical drying.
The Genesis of Neuroscience (2000)

The Genesis of Neuroscience . Edited by e r laws and george udvarhelyi (Pp 371) Published By The American Association of Neurological Surgeons, Illinois, 1998. ISBN 1-879284-62-6.

This is an incredibly enjoyable book, which provides a fascinating insight into the history of neuroscience. It was devised by the late A Earl Walker and has been put together as a tribute to his industrious efforts to trace the history of neuroscience from ancient to modem times, and it serves as a fine tribute to him. The book builds through 11 chapters from prehistoric times through Galen and Vesalius to the founders of modem day neurology from the later part of the 19th century. The book contains endless fascinating insights into multiple aspects of neuroscience and although the illustrations are a little disappointing in parts there are some rare pictures, such as one of James Parkinson himself.

The book opens with a series …
Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME. (1996)

Stress protein GRP78/BiP is highly induced in progressively growing tumors and has recently been shown to exert a protective role against lysis by cytotoxic T cells and tumor necrosis factor in vitro. This raises the question whether the in vitro observed protective function of GRP78/BiP translates into the in vivo situation in which tumors grow progressively, killing the host. Herein we report that molecular inhibition of GRP78/BiP induction in the fibrosarcoma B/C10ME, while not affecting in vitro cell proliferation, causes a dramatic increase in apoptotic cell death upon Ca2+ depletion of the endoplasmic reticulum. When B/C10ME cells incapable of inducing GRP78/BiP are injected into mice, tumors are initially formed that, however, regress presumably due to a cytotoxic T-cell response demonstrable by a strong in vitro response to the tumor with spleen cells of regressor mice. Since sensitivity to apoptosis is key to tumor rejection, these results may point to new approaches to the therapy of cancer via regulation of stress protein GRP78/BiP.
A Novel Role of Interleukin-13 Receptor α2 in Pancreatic Cancer Invasion and Metastasis (2009)

Whereas interleukin-13 receptor alpha2 chain (IL-13Ralpha2) is overexpressed in a variety of human solid cancers including pancreatic cancer, we investigated its significance in cancer invasion and metastasis. We used two pancreatic cancer cell lines, IL-13Ralpha2-negative HPAF-II and IL-13Ralpha2-positive HS766T, and generated IL-13Ralpha2 stably transfected HPAF-II as well as IL-13Ralpha2 RNA interference knocked-down HS766T cells. Ability of invasion and signal transduction was compared between IL-13Ralpha2-negative and IL-13Ralpha2-positive cells and tumor metastasis was assessed in murine model for human pancreatic cancer with orthotopic implantation of tumors. IL-13 treatment enhanced cell invasion in IL-13Ralpha2-positive cancer cell lines but not in IL-13Ralpha2-negative cell lines. Furthermore, gene transfer of IL-13Ralpha2 in negative cell lines enhanced invasion, whereas its silencing downmodulated invasion of pancreatic cell lines in a Matrigel invasion assay. In vivo study revealed that IL-13Ralpha2-positive cancer metastasized to lymph nodes, liver, and peritoneum at a significantly higher rate compared with IL-13Ralpha2-negative tumors. The expression of IL-13Ralpha2 in metastatic lesions was found to be increased compared with primary tumors, and mice with IL-13Ralpha2-positive cancer displayed cachexia and poor prognosis. Invasion and metastasis also correlated with increased matrix metalloproteinase protease activity in these cells. Mechanistically, IL-13 activated extracellular signal-regulated kinase 1/2 and activator protein-1 nuclear factors in IL-13Ralpha2-positive pancreatic cancer cell lines but not in IL-13Ralpha2-negative cell lines. Taken together, our results show for the first time that IL-13 can signal through IL-13Ralpha2 in pancreatic cancer cells and IL-13Ralpha2 may serve as a prognostic biomarker of invasion and metastasis in pancreatic cancer.
REDUCED GANGLION CELL VOLUME ON OPTICAL COHERENCE TOMOGRAPHY IN PATIENTS WITH GEOGRAPHIC ATROPHY (2017)

The patients with geographic atrophy have a small significant loss of the GCL. Ganglion cell death may precede axonal loss, and increased macular retinal nerve fiber layer volumes are not indicative of GCL volume. Residual ganglion cell stimulation by interneurons may enable vision in patients with GA.
Knowledge Acquisition Tools, Methods, and Mediating Representations (1990)

Acquiring and modeling knowledge effectively can be the most time-consuming portion of the knowledge engineering process. Little methodology is practiced beyond unstructured interviewing. Automated methods are, for the most part, still in the research stage. Several well-known factors contribute to interviewing problems: o Plausible lines of reasoning can have little to do with actual problem-solving. o Academic (novice) knowledge is often obtained in place of compiled (expert) knowledge. o Experts may be insecure. They could be afraid of losing their jobs; they may not want computers encroaching on their &amp;quot;private domain; &amp;quot; they may not want to expose their problem-solving methods to the scrutiny of colleagues or of the general public. o Interpersonal interviewing problems can result when knowledge engineers are not trained in interviewing techniques. o There are inherent problems in introspection. o Protocol analysis (discussed below) is labor intensive, error-prone, and results in a series of random behavior samples that must be synthesized by the knowledge engineer. Clancey summarized the problem as follows (1986b): &amp;quot;Knowledge acquisition is not just a problem of accessing and translating what is already known, but the familiar
IL-4 is a differentiation factor for transforming growth factor-β secreting Th3 cells and oral administration of IL-4 enhances oral tolerance in experimental allergic encephalomyelitis (1998)

We have previously shown that following oral administration of myelin basic protein (MBP), regulatory T cells are generated from gut-associated lymphoid tissue and that these cells suppress experimental allergic encephalomyelitis (EAE). These regulatory T cells produce transforming growth factor-beta (TGF-beta) with various amounts of IL-4 and IL-10 and these TGF-beta-secreting T cells have been termed Th3 cells. T cells in lymphoid organs drained by mucosal sites secrete IL-4 as a primary T cell growth factor. In the present study, we examined the role of IL-4 on oral tolerance and in the generation of TGF-beta secreting cells. Treatment of (PLJ x SJL)F1 mice with intraperitoneal (i. p.) IL-4 and low-dose oral MBP (0.5 mg) given three times reduced the severity of EAE, whereas i.p. injection of IL-4 alone or oral MBP alone given in these suboptimal doses, showed no protection. Spleen cells from protected mice produced increased amounts of TGF-beta and reduced IFN-gamma upon stimulation with MBP in vitro. Mucosal MBP-specific IgA production was significantly increased in IL-4 plus MBP fed animals. Moreover, oral administration of IL-4 (1 microg per feeding) also enhanced the suppression of EAE by oral MBP and this protective effect was reversed by administration of anti-TGF-beta antibody in vivo. Reverse transcription-PCR showed enhanced suppression of IFN-gamma in Peyer's patch in animals fed MBP and IL-4 versus those fed MBP alone. We then investigated the role of IL-4 in the generation of TGF-beta-secreting cells using MBP Ac1-11 TCR transgenic animals. Cells were cultured with IL-2, IL-4, or IFN-gamma in the presence of MBP and limiting dilution analysis for cytokine-secreting cells performed. We found that IL-4, but not IL-2 or IFN-gamma, generated TGF-beta-secreting T cells from naive splenic T cells and that these cells provided help for IgA production. These findings demonstrate that IL-4 is a differentiation factor for TGF-beta-secreting Th3 cells and oral IL-4 has a synergistic effect on low-dose oral tolerance that is associated with increased TGF-beta secretion.
Evaluación de las características delectivas de menores infractores de la Comunidad de Madrid y su influencia en la planificación del tratamiento. (2007)

espanolEl objetivo de este estudio consiste en caracterizar a los menores que estan en centros de internamiento de la Agencia de la Comunidad de Madrid para la Reeducacion y Reinsercion del Menor Infractor en cuanto a sus caracteristicas delictivas y, al mismo, tiempo validar un instrumento conocido como IGI-J (Inventario para la Gestion e Intervencion con Jovenes) [YLS/CMI (Youth Level of Service/Case Management Inventory)] que permite evaluar factores de riesgo estaticos y dinamicos para explicar la conducta delictiva y desarrollar objetivos de intervencion educativo-terapeuticos. Para ello, se ha contado con 208 menores con una edad media de 17 anos. Los resultados muestran que la media de delitos por sujeto es de 1.86 siendo los mas frecuentes los delitos contra la propiedad. En cuanto a las medidas judiciales impuestas por los delitos cometidos, la media fue de 1.44 y el promedio de la duracion de las medidas fue de 8,47 meses. Refiriendonos al IGI-J, este instrumento ha mostrado unos importantes indicadores de fiabilidad (alfa de Cronbach 0.88) y validez predictiva. Las distintas escalas discriminaron de forma adecuada entre reincidentes y no reincidentes, violentos y no violentos. Se analizan los datos en relacion a la planificacion de los programas de intervencion a desarrollar con este tipo de poblacion. EnglishThe goal of this study is to characterize minors interned in centers of the Agency of the Community of Madrid for the Reeducation and Reinsertion of Transgressing Minors with regard to their delinquent characteristics and to validate an instrument known as the YLS/CMI (Youth Level of Service/Case Management Inventory), which allows us to assess the static and dynamic risk factors that explain delinquent behavior and to develop educational-therapeutic intervention goals. Participants were 208 minors, mean age 17 years old. The results show that the average number of criminal acts per subject is 1.86, with offenses against property being the most frequent. The mean judicial measure imposed for the offenses was 1.44, and the mean duration of the measures was 8.47 months. With regard to the IGI-J, this instrument has shown satisfactory reliability indicators (Cronbach’s alpha .88) and predictive validity. The diverse scales adequately discriminated between recidivists and nonrecidivists, violent and nonviolent minors. The data are analyzed with a view to planning intervention programs to be developed with this kind of population.
Changes in the activities of ornithine decarboxylase, putrescine N-methyltransferase and N-methylputrescine oxidase in tobacco roots in relation to nicotine biosynthesis (1973)

Abstract Changes in ornithine decarboxylase, putrescine N-methyltransferase and N-methylputrescine oxidase activities in response to some treatments were investigated using hydroponically grown tobacco plants. Decapitation of shoots brought about marked elevation of the three enzyme activities, which reached their peaks 24 hr after decapitation, then declined. An excellent correlation was observed between the accumulation of nicotine and changes in the three root enzyme activities. Administration of IAA at 2.5 to 5 μconcentration significandy increased these enzyme activities in roots of decapitated plants but higher concentrations of IAA prevented the rise in enzyme activities promoted by decapitation. Nicotine strongly inhibited the rise in enzyme activities in roots of decapitated plants in all cases. The results suggest that these enzymes are under the control of a common regulatory system, in which auxin and nicotine are important components. Ornithine decarboxylase was present in all the plants examined, but putrescine N-methyltransferase and N-mediylputrescine oxidase were detected only in the roots of tobacco, Datura and Atropa plants.
PECVD grown multiple core planar waveguides with extremely low interface reflections and losses (1998)

A novel and generic method for fabricating silica-on-silicon planar lightwave circuits with cores composed of two or more different types of glasses is described. The basic process technologies used are silane/germane/nitrous-oxide based plasma enhanced chemical vapor deposition and fluorine based reactive ion etching. Very high-quality interfaces between the different core glasses are obtained with interface losses as low as 0.022/spl plusmn/0.012 dB and reflection levels below -80 dB. This technique adds flexibility and ease to the design of complex silica planar waveguide components, allowing, e.g., independent optimization of amplifying and passive sections in lossless devices based on erbium-doped planar waveguides.