gebhart/patrepeval huggingface dataset:
A New Pathway of Nitric Oxide/Cyclic GMP Signaling InvolvingS-Nitrosoglutathione (1998)

Nitric oxide (NO), a physiologically important activator of soluble guanylyl cyclase (sGC), is synthesized from L-arginine and O2 in a reaction catalyzed by NO synthases (NOS). Previous studies with purified NOS failed to detect formation of free NO, presumably due to a fast inactivation of NO by simultaneously produced superoxide (O-2). To characterize the products involved in NOS-induced sGC activation, we measured the formation of cyclic 3',5'-guanosine monophosphate (cGMP) by purified sGC incubated in the absence and presence of GSH (1 mM) with drugs releasing different NO-related species or with purified neuronal NOS. Basal sGC activity was 0.04 +/- 0.01 and 0.19 +/- 0.06 micromol of cGMP x mg-1 x min-1 without and with 1 mM GSH, respectively. The NO donor DEA/NO activated sGC in a GSH-independent manner. Peroxynitrite had no effect in the absence of GSH but significantly stimulated the enzyme in the presence of the thiol (3.45 +/- 0.60 micromol of cGMP x mg-1 x min-1). The NO/O-2 donor SIN-1 caused only a slight accumulation of cGMP in the absence of GSH but was almost as effective as DEA/NO in the presence of the thiol. The profile of sGC activation by Ca2+/calmodulin-activated NOS resembled that of SIN-1; at a maximally active concentration of 200 ng/0.1 ml, NOS increased sGC activity to 1.22 +/- 0.12 and 8.51 +/- 0.88 micromol of cGMP x mg-1 x min-1 in the absence and presence of GSH, respectively. The product of NOS and GSH was identified as the thionitrite GSNO, which activated sGC through Cu+-catalyzed release of free NO. In contrast to S-nitrosation by peroxynitrite, the novel NO/O-2-triggered pathway was very efficient (25-45% GSNO) and insensitive to CO2. Cu+-specific chelators inhibited bradykinin-induced cGMP release from rat isolated hearts but did not interfere with the direct activation of cardiac sGC, suggesting that thionitrites may occur as intermediates of NO/cGMP signaling in mammalian tissues.
k-DPPs: Fixed-Size Determinantal Point Processes (2011)

Determinantal point processes (DPPs) have recently been proposed as models for set selection problems where diversity is preferred. For example, they can be used to select diverse sets of sentences to form document summaries, or to find multiple nonoverlapping human poses in an image. However, DPPs conflate the modeling of two distinct characteristics: the size of the set, and its content. For many realistic tasks, the size of the desired set is known up front; e.g., in search we may want to show the user exactly ten results. In these situations the effort spent by DPPs modeling set size is not only wasteful, but actually introduces unwanted bias into the modeling of content. Instead, we propose the k-DPP, a conditional DPP that models only sets of cardinality k. In exchange for this restriction, k-DPPs offer greater expressiveness and control over content, and simplified integration into applications like search. We derive algorithms for efficiently normalizing, sampling, and marginalizing k-DPPs, and propose an experts-style algorithm for learning combinations of k-DPPs. We demonstrate the usefulness of the model on an image search task, where k-DPPs significantly outperform MMR as judged by human annotators. 1.
Tumor-Specific Activation of the C-JUN/MELK Pathway Regulates Glioma Stem Cell Growth in a p53-Dependent Manner (2013)

Accumulated evidence suggests that glioma stem cells (GSCs) may contribute to therapy resistance in high-grade glioma (HGG). Although recent studies have shown that the serine/threonine kinase maternal embryonic leucine-zipper kinase (MELK) is abundantly expressed in various cancers, the function and mechanism of MELK remain elusive. Here, we demonstrate that MELK depletion by shRNA diminishes the growth of GSC-derived mouse intracranial tumors in vivo, induces glial fibrillary acidic protein (+) glial differentiation of GSCs leading to decreased malignancy of the resulting tumors, and prolongs survival periods of tumor-bearing mice. Tissue microarray analysis with 91 HGG tumors demonstrates that the proportion of MELK (+) cells is a statistically significant indicator of postsurgical survival periods. Mechanistically, MELK is regulated by the c-Jun NH(2)-terminal kinase (JNK) signaling and forms a complex with the oncoprotein c-JUN in GSCs but not in normal progenitors. MELK silencing induces p53 expression, whereas p53 inhibition induces MELK expression, indicating that MELK and p53 expression are mutually exclusive. Additionally, MELK silencing-mediated GSC apoptosis is partially rescued by both pharmacological p53 inhibition and p53 gene silencing, indicating that MELK action in GSCs is p53 dependent. Furthermore, irradiation of GSCs markedly elevates MELK mRNA and protein expression both in vitro and in vivo. Clinically, recurrent HGG tumors following the failure of radiation and chemotherapy exhibit a statistically significant elevation of MELK protein compared with untreated newly diagnosed HGG tumors. Together, our data indicate that GSCs, but not normal cells, depend on JNK-driven MELK/c-JUN signaling to regulate their survival, maintain GSCs in an immature state, and facilitate tumor radioresistance in a p53-dependent manner.
Alloplastic Replacement of Canine Trachea with Dacron* (1985)

Two by two centimeter fenestrations were created in the cervical tracheae of 2 groups of 9 mongrels each during intubation anesthesia. In one group the defect was closed with a Dacron patch of 25 to 50 micron pore-size, while in the other group a Dacron patch of pore-size 125 to 150 micron was inserted. The implant was sealed with 1 ml of fibrin adhesive. Seven dogs of each group were evaluated. Implants made of low-porosity Dacron were not incorporated in any animal, but sloughed into the tracheal lumen. Contrarywise large-pore Dacron underwent connective tissue incorporation in all but one case. As early as 90, and even more so at 270, days granulation tissue rich in fibroblasts and histiocytes had grown into the implant. On the implant, a stroma formed which was epithelialized from the margin already after 90 days. After 200 and 270 days the implant was covered with a respiratory epithelium, however, scattered undifferentiated cells still could be found in its center. Porous prosthetic fabrics when used for partial tracheal replacement can be incorporated by connective tissue and can be epithelialized if the polymer is tissue-compatible, the pore-size of the implant ranges between 120 and 150 micron, the implant is sufficiently stable, and if infection is prevented by fibrin seal.
Clinically Accurate Chest X-Ray Report Generation. (2019)

The automatic generation of radiology reports given medical radiographs has significant potential to operationally and improve clinical patient care. A number of prior works have focused on this problem, employing advanced methods from computer vision and natural language generation to produce readable reports. However, these works often fail to account for the particular nuances of the radiology domain, and, in particular, the critical importance of clinical accuracy in the resulting generated reports. In this work, we present a domain-aware automatic chest X-ray radiology report generation system which first predicts what topics will be discussed in the report, then conditionally generates sentences corresponding to these topics. The resulting system is fine-tuned using reinforcement learning, considering both readability and clinical accuracy, as assessed by the proposed Clinically Coherent Reward. We verify this system on two datasets, Open-I and MIMIC-CXR, and demonstrate that our model offers marked improvements on both language generation metrics and CheXpert assessed accuracy over a variety of competitive baselines.
Investigation of Hole Mobility in GaInP/(In)GaAs/GaAs p-Type Modulation Doped Heterostructures (1999)

Ga0.51In0.49P/(In)GaAs/GaAs heterostructure is regarded as an excellent candidate for two dimensional hole gas system as it has a large valence band offset ratio. In this paper, we report the hole mobility in GaInP/GaAs and GaInP/In0.20Ga0.80As/GaAs p-type modulation doped heterostructures grown by gas source molecular beam epitaxy with different p-channels and doping methods. The influences of Be:GaAs cap layer, δ-doping, and strained InGaAs p-channel on hole mobility are discussed, and qualitatively explained by the ionized impurity scattering mechanism. Finally, it was shown that the improvement of hole mobility could be achieved by the δ-doping method combined with strained InGaAs channel.
Evaluation of the Developmental Toxicity Potential. of 2-Ethyl-1, 3-Hexanediol in the Rat by Cutaneous Application (1994)

2-Ethyl-1,3-hexanediol (EHD; CAS No. 94-96-2) is an insect repellent and industrial chemical with skin as a major route of exposure. Groups of 25 timed-pregnant CD rats received cutaneous applications of undiluted EHD at dosages of 1.0, 2.0 and 4.0 ml/kg/day for 6 hr/day under occlusion on gestational days 6-15 inclusive. A. similar-sized control group received 4.0 ml/kg/day of deionized water with the same exposure regimein. Maternal toxicity was present at 4.0 ml/kg/day (reduced body weight gains and mild skin irritation that were not statistically significant, and increased liver weight that was statistically significant), and also minimally at 1.0 and 2.0 ml/kg/day (mild skin irritation and slightly increased but statistically significant relative liver weight to body weight ratio). At 4.0 ml/kg/day there was one visceral malformiation (unilateral hydroureter), increased incidences of three visceral variants (atelectasis, dilated lateral cerebral ventricle, and bilateral dilated ureter), and 13 skeletal variants affecting several skeletal districts. At 2.0 ml/kg/day no malformations were observed, but the incidence of two visceral variants (dilated lateral cerebral ventricle and bilateral dilated ureter) and one skeletal variant (reduced caudal segments) was increased. Under the conditions of this study, EHD was considered to be a weak developmental toxicant at 4.0 and 2.0 ml/kg/day, and 1 ml/kg/day was a “no-observed effect level” for developmental toxicity.
Guided Mesh Normal Filtering (2015)

The joint bilateral filter is a variant of the standard bilateral filter, where the range kernel is evaluated using a guidance signal instead of the original signal. It has been successfully applied to various image processing problems, where it provides more flexibility than the standard bilateral filter to achieve high quality results. On the other hand, its success is heavily dependent on the guidance signal, which should ideally provide a robust estimation about the features of the output signal. Such a guidance signal is not always easy to construct. In this paper, we propose a novel mesh normal filtering framework based on the joint bilateral filter, with applications in mesh denoising. Our framework is designed as a two-stage process: first, we apply joint bilateral filtering to the face normals, using a properly constructed normal field as the guidance; afterwards, the vertex positions are updated according to the filtered face normals. We compute the guidance normal on a face using a neighboring patch with the most consistent normal orientations, which provides a reliable estimation of the true normal even with a high-level of noise. The effectiveness of our approach is validated by extensive experimental results.
Synthesis of Methyl Ether Analogues of Sildenafil (<i>Viagra</i><sup>®</sup>) Possessing Tyrosinase Inhibitory Potential (2005)

The microwave-assisted synthesis and characterization of the ten new sildenafil (Viagra; 1) analogues 6-15 are described. A detailed structure-activity-relationship (SAR) study revealed that compounds 10 (= 4-ethoxy-N-hydroxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide) and 12 (= S-(2-hydroxyethyl) 4-ethoxy-3-(7-methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonothioate) are extremely potent mushroom tyrosinase inhibitors, with IC50 values (3.59 and 2.15 microM, resp.) below those of the standard inhibitors L-mimosine and kojic acid (IC50 = 3.68 and 16.67 microM, resp.). Compounds 10 and 12 are, thus, the currently most-effective inhibitors of tyrosinase, and bear great potential to be used for the treatment of various skin disorders such as hyperpigmentation, which is associated with high production of melanocytes.
Multimodal representation: Kneser-ney smoothing/skip-gram based neural language model (2016)

For image retrieval and caption generation, this paper considers a multimodal representation that associates image with its text description (caption) by defining a neural language model as the conditional probability of the next word given both n past words in a caption and the image that the caption describes. To address the data sparsity problem, the use of the Kneser-Ney smoothing and skip-gram models is examined by integrating each into the multimodal neural language model. A language model (LM) known as Kneser-Ney smoothing is based on absolute-discounting interpolation while skip-gram LM is based on n-grams organized by allowing intermediate tokens to be “skipped”. The multimodal representation is evaluated on the IAPR TC-12 dataset. Using perplexity and BLEU-n measures, both Kneser-Ney smoothing and skip-gram models are demonstrated to be more effective as approaches to addressing the data sparsity problem than the generic n-gram model used in previous multimodal representations. The modality-biased log-bilinear (MLBL-B) model is set as the base model in the experiment.
Increased glycosylation capacity in regenerating rat liver is paralleled by decreased activities of CMP-<i>N</i>-acetylneuraminate hydrolase and UDP-galactose pyrophosphatase (1983)

In regenerating rat liver the activities of CMP-N-acetylneuraminate hydrolase and UDP-galactose pyrophosphatase were decreased to 40-50% of control values within 35 h after partial hepatectomy. In the same time period the activities of sialyltransferase and galactosyltransferase were increased, and the initial sharp decrease in the carbohydrate content of liver and serum glycoproteins was largely restored. The antiparallel nature of these events is suggestive of an involvement of nucleotide-sugar-hydrolysis enzymes in rat liver glycoprotein biosynthesis.
Defensin‐induced adaptive immunity in mice and its potential in preventing periodontal disease (2003)

The severity of periodontal disease is dependent on a combination of host, microbial agent and environmental factors. One strong correlate related to periodontal disease pathogenesis is the immune status of the host. Here we show that human neutrophil peptide (HNP) defensins or human beta-defensins (HBD), co-administered intranasally with the antigen ovalbumin (OVA), induce unique immune responses that if used with microbial antigens may have the potential to hinder the pathogenesis of periodontal disease. C57BL/6 mice were immunized intranasally with phosphate buffered saline (PBS) containing 1 micro g HNP-1, HNP-2, HBD1 or HBD2 with and without 50 microg OVA. At 21 days, isotypes and subclasses of OVA-specific antibodies were determined in saliva, serum, nasal wash, bronchoalveolar lavage fluid, and fecal extracts. OVA-stimulated splenic lymphoid cell cultures from immunized mice were assessed for interferon (IFN)-gamma, Interleukin (IL)-4 and IL-10. In comparison with mice immunized with only OVA, HNP-1 and HBD2 induced significantly higher (P < 0.05) OVA-specific serum IgG, lower, but not significant, serum IgM and significantly lower (P < 0.05) IFN-gamma. In contrast, HNP-2 induced low OVA-specific serum IgG and higher, but not significant, serum IgM. HBD1 induced significantly higher (P < 0.05) OVA-specific serum IgG, higher, but not significant, serum IgM, and significantly higher (P < 0.05) IL-10. The elevated serum IgG subclasses contained IgG1 and IgG2b.
Comparison of Human Papillomavirus Detections in Urine, Vulvar, and Cervical Samples from Women Attending a Colposcopy Clinic (2013)

While urine-based sampling for human papillomavirus (HPV) is being explored as a simple and noninvasive approach for cervical cancer screening, data comparing HPV genotyping in urine and those in cellular sampling of the cervix and vulva, and their correlation with rigorously confirmed cervical disease status, are sparse. We performed HPV genotyping on voided-urine and clinician-collected vulvar and cervical samples from 72 women undergoing colposcopy. Although urine-based HPV carcinogenic HPV detection was lower (58.3%) than cervical (73.6%) and vulvar (72.1%) detection (P = 0.05 and 0.07, respectively), the agreement of urine HPV with cervical and vulvar HPV was moderate (kappa = 0.55) and substantial (kappa = 0.62), respectively. Urine-based carcinogenic HPV detection had a clinical sensitivity of 80.8% (95% confidence interval [CI] = 60.7 to 93.5) and a specificity of 53.3% (95% CI = 37.9 to 68.3) for diagnosing cervical intraepithelial neoplasia grades 2/3 (CIN2/3) on histology; 90.0% of CIN3 was positive for urine HPV. The corresponding sensitivity and specificity values for vulvar sampling were 92% (95% CI = 74 to 99) and 40.5% (95% CI = 25.6 to 56.7), and those for cervical sampling were 96.2% (95% CI = 80.4 to 99.9) and 40% (95% CI = 25.7 to 55.7), respectively. HPV16 was the most common carcinogenic genotype detectable in 25% of urine, 33.8% of vulvar, and 31.9% of cervical samples overall, with prevalence increasing with cervical disease grade, regardless of the sampling method. Stronger cervical HPV PCR signal strengths were associated with increased frequency of urine HPV detection. In summary, the relatively lower detection rates but comparable clinical performance of urine-based HPV sampling underscore the need for larger studies to evaluate urine-based sampling for cervical cancer screening, epidemiologic studies, and postvaccination HPV disease surveillance.
Modelling and control of laser surface treatment (1999)

According to histological and ultrastructural criteria, nongiant CNS axons in newly hatched crayfish regenerate more rapidly and with greater frequency than do similar axons in adult crayfish. Regenerative ability is greater in one species (Procambarus clarkii) than in another species (Procambarus simulans), is greater at 20-25 degrees C than at 15-16 degrees C, and is greater in nongiant axons than in giant axons. In contrast to axonal regeneration, nerve cell bodies do not regenerate in newly hatched or adult crayfish of either species. While the ability to regenerate CNS axons differs between newly hatched and adult crayfish, the ultrastructural appearance of the CNS is very similar at any age it is examined.
Gene Expression Correlates of Unexplained Fatigue (2006)

Quantitative trait analysis (QTA) can be used to test whether the expression of a particular gene significantly correlates with some ordinal variable. To limit the number of false discoveries in the gene list, a multivariate permutation test can also be performed. The purpose of this study is to identify peripheral blood gene expression correlates of fatigue using quantitative trait analysis on gene expression data from 20,000 genes and fatigue traits measured using the multidimensional fatigue inventory (MFI). A total of 839 genes were statistically associated with fatigue measures. These mapped to biological pathways such as oxidative phosphorylation, gluconeogenesis, lipid metabolism, and several signal transduction pathways. However, more than 50% are not functionally annotated or associated with identified pathways. There is some overlap with genes implicated in other studies using differential gene expression. However, QTA allows detection of alterations that may not reach statistical significance in class comparison analyses, but which could contribute to disease pathophysiology. This study supports the use of phenotypic measures of chronic fatigue syndrome (CFS) and QTA as important for additional studies of this complex illness. Gene expression correlates of other phenotypic measures in the CFS Computational Challenge (C3) data set could be useful. Future studies of CFS should include as many precise measures of disease phenotype as is practical.
MOSAIC Model for Sensorimotor Learning and Control (2001)

Humans demonstrate a remarkable ability to generate accurate and appropriate motor behavior under many different and often uncertain environmental conditions. We previously proposed a new modular architecture, the modular selection and identification for control (MOSAIC) model, for motor learning and control based on multiple pairs of forward (predictor) and inverse (controller) models. The architecture simultaneously learns the multiple inverse models necessary for control as well as how to select the set of inverse models appropriate for a given environment. It combines both feedforward and feedback sensorimotor information so that the controllers can be selected both prior to movement and subsequently during movement. This article extends and evaluates the MOSAIC architecture in the following respects. The learning in the architecture was implemented by both the original gradient-descent method and the expectation-maximization (EM) algorithm. Unlike gradient descent, the newly derived EM algorithm is robust to the initial starting conditions and learning parameters. Second, simulations of an object manipulation task prove that the architecture can learn to manipulate multiple objects and switch between them appropriately. Moreover, after learning, the model shows generalization to novel objects whose dynamics lie within the polyhedra of already learned dynamics. Finally, when each of the dynamics is associated with a particular object shape, the model is able to select the appropriate controller before movement execution. When presented with a novel shape-dynamic pairing, inappropriate activation of modules is observed followed by on-line correction.
Evolution of the Insect Yellow Gene Family (2010)

The yellow gene family is intriguing for a number of reasons. To date, yellow-like genes have only been identified in insect species and a number of bacteria. The function of the yellows is largely unknown, although a few have been associated with melanization and behavior in Drosophila, and a unique clade of genes from Apis mellifera may be involved in caste specification. Here, we show that yellow-like sequences are present in bacteria, insects, and fungi but absent from other eukaryotes apart from isolated putative sequences in Amphioxus, the Salmon Louse, and Naegleria. The yellow-like family forms a discrete gene class characterized by the presence of a major royal jelly protein domain, but eukaryote yellow-like proteins are not monophyletic. The unusual phylogenetic distribution of yellow-like sequences suggests either multiple horizontal transfer from bacteria into eukaryotes or extensive gene loss in eukaryote lineages. Comparative analysis of yellow family synteny and gene order demonstrates that a highly conserved block of three to five genes has been maintained throughout insect diversification despite extensive genome rearrangements. We show strong purifying selection on seven yellow genes over approximately 100 My separating the silkmoth and Heliconius butterflies and an association between spatial regulation of gene expression and distribution of melanic pigment in the developing butterfly wing. A single ancestral yellow-like gene has therefore undergone multiple rounds of duplication within the insects accompanied by functional constraint on both genomic location and protein evolution.