gebhart/patrepeval huggingface dataset:
Leukotriene modifiers for asthma treatment (2010)

Leukotrienes (LTs), including cysteinyl LTs (CysLTs) and LTB(4) , are potent lipid mediators that have a role in the pathophysiology of asthma. At least two receptor subtypes for CysLTs, CysLT(1) and CysLT(2) , have been identified. The activation of the CysLT(1) receptor is responsible for most of the pathophysiological effects of CysLTs in asthma, including increased airway smooth muscle activity, microvascular permeability, and airway mucus secretion. LTB(4) might have a role in severe asthma, asthma exacerbations, and the development of airway hyperresponsiveness. CysLT(1) receptor antagonists can be given orally as monotherapy in patients with mild persistent asthma, but these drugs are generally less effective than inhaled glucocorticoids. Combination of CysLT(1) receptor antagonists and inhaled glucocorticoids in patients with more severe asthma may improve asthma control and enable the dose of inhaled glucocorticoids to be reduced while maintaining similar efficacy. The identification of subgroups of asthmatic patients who respond to CysLT(1) receptor antagonists is relevant for asthma management as the response to these drugs is variable. CysLT(1) receptor antagonists have a potential anti-remodelling effect that might be important for preventing or reversing airway structural changes in patients with asthma. This review discusses the role of LTs in asthma and the role of LT modifiers in asthma treatment.
Data mining within digital images (2007)

Previous papers have studied the relationship between a bit map digital image and a given object, called the search object. In particular, to signal that it is likely, or not likely, that the search object appears, at least partially, in the image. Edges in the search object and in the digital image are then represented as objects, in the object oriented programming sense. Each edge or segment of an edge is represented as a normalized Bezier cubic parameterized curve. The normalization process is intended to remove the effect of size in the edge or edge segment. If the edges match and their orientation is the same, then the system signals that the object is likely to appear in the image and the coordinates in the image of the object are returned. The functioning of the algorithm is not dependent on scaling, rotation, translation, or shading of the image. To begin the data mining process, a collection of search objects is generated. A database is constructed using a number of images and storing information concerning the combination of search objects that appear in each image, time and space relationships between the various search objects, along with identifying information about the image. This database would then be subjected to traditional data mining techniques in order to generate useful relationships within the data. These relationships could then be used to advantage in supplying information for defense, corporate, or law enforcement intelligence.
Contributions of Viral Splice Sites and <i>cis</i> -Regulatory Elements to Lentivirus Vector Function (1999)

The mobile transgene constructs of most human immunodeficiency virus (HIV)-based lentivirus vectors currently in use contain viral long terminal repeats, a 5' untranslated region, gag sequences, and env sequences that include the Rev-responsive element (RRE). In this study, we examined the possibility of deleting HIV splice sites and gag and env sequences from an HIV type 1 recombinant vector established in our laboratory as part of our ongoing efforts to improve this vector system. Mutations in the major splice donor site (SD) markedly reduced viral RNA expression but had little effect on vector titer. Deletion of gag or env sequences, excluding RRE, led to a moderate reduction in vector titer. Interestingly, deletion of RRE slightly reduced viral RNA expression but markedly impaired vector function. Combined deletions of RRE, gag (except for the first 40 nucleotides), env, and the SD mutation resulted in a twofold increase in cytoplasmic viral RNA expression and a recovery of vector efficiency to approximately 50% of the wild-type level. This increase in cytoplasmic RNA levels is likely to be due, at least in part, to effects of the TE671 host cells, a human rhabdomyosarcoma cell line used for vector production in our system, on the cytoplasmic distribution of spliced and unspliced viral RNA. These results show that optimal lentivirus vector function can be maintained in the absence of multiple essential viral elements.
Urokinase Plasminogen Activator and Plasmin Efficiently Convert Hemofiltrate CC Chemokine 1 into Its Active [9–74] Processed Variant (2001)

We have previously isolated from human hemofiltrate an N-terminally truncated form of the hemofiltrate CC chemokine 1 (HCC-1), and characterized HCC-1[9-74] as a strong agonist of CCR1, CCR5, and to a lower extent CCR3. In this study, we show that conditioned media from human tumor cell lines PC-3 and 143B contain proteolytic activities that convert HCC-1 into the [9-74] form. This activity was fully inhibited by inhibitors of urokinase-type plasminogen activator (uPA), including PA inhibitor-1, an anti-uPA mAb, and amiloride. Pure preparations of uPA processed HCC-1 with high efficiency, without further degrading HCC-1[9-74]. Plasmin could also generate HCC-1[9-74], but degraded the active product as well. The kinetics of HCC-1 cleavage by uPA and plasmin (Michaelis constant, K(m), of 0.76 +/- 0.4 microM for uPA, and 0.096 +/- 0.05 microM for plasmin; catalytic rate constant, k(cat): 3.36 +/- 0.96 s(-1) for uPA and 6 +/- 3.6 s(-1) for plasmin) are fully compatible with a role in vivo. The activation of an abundant inactive precursor into a broad-spectrum chemokine by uPA and plasmin directly links the production of uPA by numerous tumors and their ability to recruit mononuclear leukocytes, without the need for the transcriptional activation of chemokine genes.
Primary Plasma Cell Leukemia: Clinical, Immunophenotypic, DNA Ploidy, and Cytogenetic Characteristics (1999)

We report on a series of 26 patients diagnosed with primary (de novo) plasma cell (PC) leukemia (PCL) in whom we analyzed the clinicobiologic characteristics of the disease together with the immunophenotype, DNA cell content, proliferative index, and numeric chromosomal aberrations of the neoplastic PC, and compared them with 664 multiple myeloma (MM) patients at diagnosis. The median age, sex ratio, and bone lesion extension were similar, but PCL cases displayed a higher prevalence of clinical stage III, extramedullary involvement, and Bence Jones cases, with fewer IgA cases than for MM patients. In addition, according to several prognostic indicators (β2-microglobulin serum level, proportion of S-phase PCs, proteinuria, calcium serum level, lactate dehydrogenase [LDH] and renal function), the incidence of adverse prognostic factors was significantly higher in PCL versus MM. Immunophenotypic expression was similar for CD38, CD138, CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression of CD56, CD9 HLA-DR, CD117, and CD20 antigens. Twenty-two PCL cases were diploid and one was hypodiploid, while most MM cases (57%) showed DNA hyperdiploidy. With the fluorescent in situ hydridization (FISH) technique, 12 of 13 PCL cases displayed the numeric aberrations, −13 (86%), ±1 (57%), +18 (43%), and −X in women (25%), but they lacked several numeric aberrations usually found in MM such as +3, +6, +9, +11, and +15. PCL cases had a lower overall response to therapy than MM cases (38% v 63%, P = .01332). Among PCL patients, a trend for a worse response was observed in cases treated with melphalan and prednisone (MP) versus polychemotherapy. Overall survival was significantly worse in PCL versus MM patients (8 v 36 months,P < .0001), but it was significantly better in PCL patients treated with polychemotherapy versus MP (18 v 3 months,P = .0137). By contrast, MM patients did not show significant differences in overall survival according to the treatment used, MP or polychemotherapy. Ten variables seemed to predict survival in PCL patients, but only the β2-microglobulin level and S-phase PCs retained an independent value in multivariate analysis. In summary, our study illustrates that PCs from PCL display singular phenotypic, DNA cell content, and cytogenetic characteristics that lead to a different disease evolution versus MM.
DNA, the Genetic Code (2002)

This chapter contains section titled: Stability and Variability of DNA The Amount of DNA in Nuclei, and the C-Value Paradox Repetitive DNA — Sequences with a Function, or Just Junk? DNA Replication 5-Methylcytosine — Epigenetic Modification of DNA DNA Damage and Repair DNA is Dynamic Websites
American Pain Society Recommendations for Improving the Quality of Acute and Cancer Pain Management (2005)

Efforts to improve the quality of pain management must move beyond assessment and communication of pain to implementation and evaluation of improvements in pain treatment that are timely, safe, evidence based, and multimodal.
Meta-Learning with Latent Embedding Optimization (2018)

Gradient-based meta-learning techniques are both widely applicable and proficient at solving challenging few-shot learning and fast adaptation problems. However, they have practical difficulties when operating on high-dimensional parameter spaces in extreme low-data regimes. We show that it is possible to bypass these limitations by learning a data-dependent latent generative representation of model parameters, and performing gradient-based meta-learning in this low-dimensional latent space. The resulting approach, latent embedding optimization (LEO), decouples the gradient-based adaptation procedure from the underlying high-dimensional space of model parameters. Our evaluation shows that LEO can achieve state-of-the-art performance on the competitive miniImageNet and tieredImageNet few-shot classification tasks. Further analysis indicates LEO is able to capture uncertainty in the data, and can perform adaptation more effectively by optimizing in latent space.
SCNM1, a Putative RNA Splicing Factor That Modifies Disease Severity in Mice (2003)

The severity of many inherited disorders is influenced by genetic background. We describe a modifier interaction in C57BL/6Jmice that converts a chronic movement disorder into a lethal neurological disease. The primary mutation (medJ) changes a splice donor site of the sodium channel gene Scn8a (Nav1.6). The modifier mutation is characteristic of strain C57BL/6Jand introduces a nonsense codon into sodium channel modifier 1 (SCNM1), a zinc finger protein and a putative splice factor. An internally deleted SCNM1 protein is also predicted as a result of exon skipping associated with disruption of a consensus exonic splicing enhancer. The effect of the modifier mutation is to reduce the abundance of correctly spliced sodium channel transcripts below the threshold for survival. Our finding that genetic variation in a putative RNA splicing factor influences disease susceptibility in mice raises the possibility that a similar mechanism modifies the severity of human inherited disorders.
D-Galactosamine Intoxication in Experimental Animals: Is it Only an Experimental Model of Acute Liver Failure? (2015)

Acute renal failure that developed in the course of galactosamine-induced ALF was of a functional nature, with the kidneys retaining the ability to concentrate urine and retain sodium, and there were no renal changes in the histopathological examination. It seems that the experimental model of ALF induced by galactosamine can be viewed as a model of hepatorenal syndrome that occurs in the course of acute damage and liver failure.
Isomerization‐Induced Asymmetric Coordination Chemistry: From Auxiliary Control to Asymmetric Catalysis (2010)

Asymmetric generator: Chiral (S)-2-(isopropylsulfinyl)phenol and a more electron-rich methoxy derivative (R=OCH3) are capable of inducing and even catalyzing a chirality-generating trans–cis isomerization of two 2,2′-bipyridine ligands in an octahedral coordination sphere of a ruthenium complex. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Direction-optimizing Breadth-First Search (2012)

Breadth-First Search is an important kernel used by many graph-processing applications. In many of these emerging applications of BFS, such as analyzing social networks, the input graphs are low-diameter and scale-free. We propose a hybrid approach that is advantageous for low-diameter graphs, which combines a conventional top-down algorithm along with a novel bottom-up algorithm. The bottom-up algorithm can dramatically reduce the number of edges examined, which in turn accelerates the search as a whole. On a multi-socket server, our hybrid approach demonstrates speedups of 3.3 -- 7.8 on a range of standard synthetic graphs and speedups of 2.4 -- 4.6 on graphs from real social networks when compared to a strong baseline. We also typically double the performance of prior leading shared memory (multicore and GPU) implementations.
CONTAINED CHEMISTRY (2008)

RETURN TO ISSUEPREVNewsNEXTCONTAINED CHEMISTRYSynthesizing HIGHLY POTENT COMPOUNDS is a lucrative and growing niche for custom chemical manufacturersANN M. THAYERView Author Information C&EN HOUSTONCite this: Chem. Eng. News 2008, 86, 24, 17–27Publication Date (Print):June 16, 2008Publication History Published online14 November 2010Published inissue 16 June 2008https://doi.org/10.1021/cen-v086n024.p017Copyright © 2008 AMERICAN CHEMICAL SOCIETYArticle Views22Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) SUBJECTS:Pharmaceuticals Get e-Alerts
The Impact of Crystallinity on Brequinar Sodium Hygroscopicity (1996)

The hygroscopicity of Brequinar sodium, an organ transplant immunosuppressant, at 75% relative humidity highly depends on the crystal form or crystallinity of the drug substance. Hygroscopicity and ease of water uptake of three lots of Brequinar sodium were investigated. Those lots contained different impurities at levels ranging from 0.26% to 0.5%. DSC thermograms of the hydrated samples suggest that unbound/loosely bound water was released around 90 degrees C and water of hydration was released at 175 degrees C. At equilibrium, 2% of the water was tightly bound. Stoichiometry suggests that this is a hemihydrate. Unbound/loosely bound water has no impact on the hemihydrate crystal structure as indicated by x-ray powder diffraction patterns. The results suggest that the less perfect crystals exhibited a faster water uptake and converted to a stable hemihydrate when stored at 75% relative humidity. Both the anhydrous and the hemihydrate forms of Brequinar sodium exhibited rapid dissolution rate and comparable water solubility.
REVIEW: The Southern Railway: Further Recollections (2007)

Reviews the non-fiction book "The Southern Railway: Further Recollections," by C. Pat Cates, Dick Hillman, and Sallie Loy.
Microbial Decomposition of Species of Freshwater Planktonic Algae (1974)

Abstract Suspensions of axenically grown algae underwent aerobic decomposition in a solution free of nitrogen, phosphorus, and organic carbon. The rate and extent of mineralization of algal cell carbon and nitrogen and the solubilization of algal cell phosphorus varied appreciably among the test organisms. Chlamydomonas oblonga underwent rapid decomposition; Chlorella sp. lost carbon, nitrogen, and phosphorus slowly; and Ankistrodesmus falcatus and Astemcoccus superbus lost their carbon, nitrogen, and phosphorus at intermediate rates. Microorganisms from sewage markedly influenced the rate of liberation of some of the elements contained in A. falcatus and A. superbus but had little or no effect on the mineralization of carbon and nitrogen or on the release of phosphorus from cells of C. oblonga and Chlorella sp. Cells from 14‐day cultures of C. oblonga and A. falcatus were more quickly decomposed than cells from 28‐day cultures.
Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the <i>Fgfr3</i>-deficient mouse phenotype (2004)

We generated transgenic mice that express a constitutively active mutant of MEK1 in chondrocytes. These mice showed a dwarf phenotype similar to achondroplasia, the most common human dwarfism, caused by activating mutations in FGFR3. These mice displayed incomplete hypertrophy of chondrocytes in the growth plates and a general delay in endochondral ossification, whereas chondrocyte proliferation was unaffected. Immunohistochemical analysis of the cranial base in transgenic embryos showed reduced staining for collagen type X and persistent expression of Sox9 in chondrocytes. These observations indicate that the MAPK pathway inhibits hypertrophic differentiation of chondrocytes and negatively regulates bone growth without inhibiting chondrocyte proliferation. Expression of a constitutively active mutant of MEK1 in chondrocytes of Fgfr3-deficient mice inhibited skeletal overgrowth, strongly suggesting that regulation of bone growth by FGFR3 is mediated at least in part by the MAPK pathway. Although loss of Stat1 restored the reduced chondrocyte proliferation in mice expressing an achondroplasia mutant of Fgfr3, it did not rescue the reduced hypertrophic zone, the delay in formation of secondary ossification centers, and the achondroplasia-like phenotype. These observations suggest a model in which Fgfr3 signaling inhibits bone growth by inhibiting chondrocyte differentiation through the MAPK pathway and by inhibiting chondrocyte proliferation through Stat1.
Early Start: Grand designs for learning (2012)

Paper presented at the London International Conference on Education, 19-22 November 2012, London, UK\nWell-designed environments that stimulate intellectual curiosity, encourage social interaction and promote a sense of community, support effective learning across the education spectrum. This paper presents a case study of a multi-functional facility situated at the University of Wollongong in New South Wales, Australia that meets this design brief. 'Early Start' will transform teaching, research and community engagement in the higher education sector whilst offering unique learning opportunities to children, young people and their families. Importantly, it also has the potential for addressing social, educational and economic disadvantage across many communities. The Early Start Facility incorporates state-of-the-art technologies in a purpose-built structure that includes a Children's Discovery Centre and connections to early childhood services, schools and community agencies in regional, rural and remote communities. This facility will enrich the student experience at the University of Wollongong and it will extend collaborative educational enterprises to children, their families and the broader community.
Role of Spinal NO in Antiallodynic Effect of Intrathecal Clonidine in Neuropathic Rats  (1998)

These results demonstrate that spinal NO neither contributes significantly to maintenance of allodynia nor produces detectable antiallodynic effect in this neuropathic pain model. Furthermore, this study provides functional evidence that spinal NO plays an important role in the antiallodynic effect of intrathecal clonidine in neuropathic pain.
Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma (2004)

The study shows changes in progesterone metabolizing enzyme gene expression in human breast carcinoma. Expression of SRD5A1 (5alphaR1) and SRD5A2 (5alphaR2) is elevated, and expression of AKR1C1 (20alpha-HSO), AKR1C2 (3alpha-HSO3) and AKR1C3 (3alpha-HSO2) is reduced in tumorous as compared to normal breast tissue. The changes in progesterone metabolizing enzyme expression levels help to explain the increases in mitogen/metastasis inducing 5alphaP and decreases in mitogen/metastasis inhibiting 3alphaHP progesterone metabolites found in breast tumor tissues. Understanding what causes these changes in expression could help in designing protocols to prevent or reverse the changes in progesterone metabolism associated with breast cancer.
Synthesis and Antitumor Activity of 1,5-Disubstituted 1,2,4-Triazoles as Cis-Restricted Combretastatin Analogues (2010)

A series of 1-aryl-5-(3',4',5'-trimethoxyphenyl) derivatives and their related 1-(3',4',5'-trimethoxyphenyl)-5-aryl-1,2,4-triazoles, designed as cis-restricted combretastatin analogues, were synthesized and evaluated for antiproliferative activity, inhibitory effects on tubulin polymerization, cell cycle effects, and apoptosis induction. Their activity was greater than, or comparable with, that of the reference compound CA-4. Flow cytometry studies showed that HeLa and Jurkat cells treated with the most active compounds 4l and 4o were arrested in the G2/M phase of the cell cycle in a concentration dependent manner. This effect was accompanied by apoptosis of the cells, mitochondrial depolarization, generation of reactive oxygen species, activation of caspase-3, and PARP cleavage. Compound 4l was also shown to have potential antivascular activity, since it induced endothelial cell shape change in vitro and disrupted the sprouting of endothelial cells in the chick aortic ring assay.