gebhart/patrepeval huggingface dataset:
Morphometric analysis of white matter lesions in MR images: method and validation (1994)

The analysis of MR images is evolving from qualitative to quantitative. More and more, the question asked by clinicians is how much and where, rather than a simple statement on the presence or absence of abnormalities. The authors present a study in which the results obtained with a semiautomatic, multispectral segmentation technique are quantitatively compared to manually delineated regions. The core of the semiautomatic image analysis system is a supervised artificial neural network classifier augmented with dedicated preand postprocessing algorithms, including anisotropic noise filtering and a surface-fitting method for the correction of spatial intensity variations. The study was focused on the quantitation of white matter lesions in the human brain. A total of 36 images from six brain volumes was analyzed twice by each of two operators, under supervision of a neuroradiologist. Both the intra- and interrater variability of the methods were studied in terms of the average tissue area detected per slice, the correlation coefficients between area measurements, and a measure of similarity derived from the kappa statistic. The results indicate that, compared to a manual method, the use of the semiautomatic technique not only facilitates the analysis of the images, but also has similar or lower intra- and interrater variabilities.
H.263: video coding for low-bit-rate communication (1996)

This article provides an overview of H.263, the new ITU-T Recommendation for low-bit-rate video communication. H.263 specifies a coded representation for compressing the moving picture component of audio-visual signals at low bit rates. The basic structure of the video source coding algorithm is taken from ITU-T Recommendation H.261 and is a hybrid of interpicture prediction to reduce temporal redundancy and transform coding of the prediction residual to reduce spatial redundancy. The source coder can operate on five standardized picture formats: sub-QCIF, QCIF, CIF, 4CIF, and 16CIF. The decoder has motion compensation capability with half-pixel precision, in contrast to H.261 which uses full-pixel precision and employs a loop filter. H.263 includes four negotiable coding options which provide improved coding efficiency: unrestricted motion vectors, syntax-based arithmetic coding, advanced prediction, and PB-frames.
A quantitative trait locus influencing BMI maps to the region of the beta-3 adrenergic receptor. (1999)

The beta-3 adrenergic receptor (ADRB3) has been implicated as a regulator of energy expenditure, and a polymorphism in codon 64 of this gene (Trp64Arg) has been associated in some studies with obesity and insulin resistance. However, many studies have failed to detect an effect of this variant, and the importance of the Trp64Arg variant in human obesity remains controversial. We performed a quantitative linkage analysis of the ADRB3 and obesity, using 12 markers (including the intragenic Trp64Arg polymorphism) spanning a 57-cM region of chromosome 8. The study population consisted of 470 individuals from 10 large multigenerational families of Mexican-American ancestry residing in San Antonio, TX. In two-point analysis, logarithm of odds (LOD) scores >1.0 were observed for six markers surrounding ADRB3 in a 33-cM region spanned by markers D8S1477 and D8S1136. The multipoint LOD score was 3.21, occurring between markers D8S1121 and ADRB3, approximately 2-3 cM from ADRB3. Adjusting for the presence of the Arg64 allele or excluding from the analysis the 11 individuals homozygous for the Arg64 allele did not reduce the evidence for linkage. A genome scan was conducted at 10 cM map density to detect other loci influencing variation in BMI. Multipoint LOD scores >1.0 were observed in four other regions, including two on chromosome 17, one on chromosome 6q, and one on chromosome 2p. These data suggest that the ADRB3 should continue to be regarded as a strong candidate gene for obesity even though evidence for an effect of the Trp64Arg polymorphism could not be established. It is also possible that a gene closely linked to ADRB3 may influence susceptibility to obesity.
A multi-enzyme model for pyrosequencing (2004)

Pyrosequencing is a DNA sequencing technique based on sequencing-by-synthesis enabling rapid real-time sequence determination. This technique employs four enzymatic reactions in a single tube to monitor DNA synthesis. Nucleotides are added iteratively to the reaction and in case of incorporation, pyrophosphate (PPi) is released. PPi triggers a series of reactions resulting in production of light, which is proportional to the amount of DNA and number of incorporated nucleotides. Generated light is detected and recorded by a detector system in the form of a peak signal, which reflects the activity of all four enzymes in the reaction. We have developed simulations to model the kinetics of the enzymes. These simulations provide a full model for the Pyrosequencing four-enzyme system, based on which the peak height and shape can be predicted depending on the concentrations of enzymes and substrates. Simulation results are shown to be compatible with experimental data. Based on these simulations, the rate-limiting steps in the chain can be determined, and K(M) and kcat of all four enzymes in Pyrosequencing can be calculated.
A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours (2012)

E7080 is well tolerated at doses up to 25 mg per day. Encouraging anti-tumour efficacy was observed in patients with melanoma and renal cell carcinoma.
Microbial Production of Xylitol from Glucose (1969)

A microbiological method is described for the production of xylitol, which is used as a sugar substitute for diabetics. A sequential fermentation process yielded 9.0 g of xylitol from 77.5 g of glucose via D-arabitol and D-xylulose. Candida guilliermondii var. soya (ATCC 20216) consumed 5.1 g of D-xylulose and produced 2.8 g of xylitol per 100 ml. Pentitol production from D-xylulose by yeasts was divided into three types: I, yeast-produced xylitol; II, yeast-produced D-arabitol; and III, yeast-produced xylitol and D-arabitol. D-Xylulose, but not glucose, was dissimilated to xylitol by yeasts under aerobic conditions.
Costimulation, Coinhibition and Cancer (2007)

The immune system is an important defense mechanism against cancer and is often dysfunctional in patients with malignancies. The central regulator of the anti-cancer adaptive immune response is the T lymphocyte. T lymphocyte activation requires the completion of a carefully orchestrated series of specific steps that can be preempted or disrupted by any number of critical events. Particularly important is the provision of a costimulatory signal, the binding of accessory molecules on the antigen presenting cell to receptors on the T lymphocyte. Though costimulatory signals were traditionally envisioned as T lymphocyte-activating events, recent discoveries have highlighted their duality: they can be either stimulatory (costimulation) or inhibitory (coinhibition). In this article we review costimulation and coinhibition as potential targets for cancer therapy. We begin by presenting a general framework for thinking about the immune system in the context of cancer. Our discussion then bridges the various aspects of immune dysfunction seen in cancer with the presence of coinhibitory (ex: PD-1, PD-L1, CTLA-4, BTLA) and costimulatory (ex: CD28, ICOS, 4-1BB, CD40, OX40, CD27) signaling. Lastly, we develop a model of cancer-related immune dysfunction that parallels the concept of immunoediting. Throughout the article we emphasize clinically relevant research often applicable-but not limited-to the example of renal cell carcinoma.
One-Shot Decision-Making with and without Surrogates (2019)

One-shot decision making is required in situations in which we can evaluate a fixed number of solution candidates but do not have any possibility for further, adaptive sampling. Such settings are frequently encountered in neural network design, hyper-parameter optimization, and many simulation-based real-world optimization tasks, in which evaluations are costly and time sparse. It seems intuitive that well-distributed samples should be more meaningful in one-shot decision making settings than uniform or grid-based samples, since they show a better coverage of the decision space. In practice, quasi-random designs such as Latin Hypercube Samples and low-discrepancy point sets form indeed the state of the art, as confirmed by a number of recent studies and competitions. In this work we take a closer look into the correlation between the distribution of the quasi-random designs and their performance in one-shot decision making tasks, with the goal to investigate whether the assumed correlation between uniform distribution and performance can be confirmed. We study three different decision tasks: classic one-shot optimization (only the best sample matters), one-shot optimization with surrogates (allowing to use surrogate models for selecting a design that need not necessarily be one of the evaluated samples), and one-shot regression (i.e., function approximation, with minimization of mean squared error as objective). Our results confirm an advantage of low-discrepancy designs for all three settings. The overall correlation, however, is rather weak. We complement our study by evolving problem-specific samples that show significantly better performance for the regression task than the standard approaches based on low-discrepancy sequences, giving strong indication that significant performance gains over state-of-the-art one-shot sampling techniques are possible.
Structure, tissue-specific expression, and transforming activity of the mouse met protooncogene. (1990)

A 6.7-kilobase met complementary DNA (cDNA) was isolated from a pcD cDNA library prepared from C3H mouse fibroblast cell line polyadenylated RNA. Sequence analysis of 6.7-kilobase met cDNA insert revealed that it contained the entire open reading frame and shared an overall homology of 88.1% with the human met gene. Using the mouse met cDNA as probe, high levels of met expression were observed in the kidney, brain, lung, skin, and embryonic tissue as well as in several factor responsive mouse myeloid cell lines. Under SV40 promoter control, the mouse met protooncogene cDNA in the pCD vector was able to transform NIH 3T3 cells. These transformed cells possess multiple copies of mouse met cDNA and exhibit properties of malignant cells, including growth in soft agar and induction of tumors in nude mice. Tumor explant cell lines analyzed by Western blot also reveal the presence of high levels of Mr 170,000 and 140,000 met protein product(s).
Clinical xenotransplantation: past, present and future. (1997)

The ability to use animal organs, such as from the pig, for the purposes of transplantation in humans, would clearly overcome the major shortage of human organs that greatly restricts transplantation programmes worldwide. Recent experimental advances have raised the possibility of renewed attempts at organ xenotransplantation in humans within the near future. Previous clinical experience, dating back to 1906, is briefly reviewed. The problems that still require resolution include the immunological barrier, the risk of transferring infectious agents with the transplanted organ, and uncertainty as to whether the transplanted animal organ will function satisfactorily in the human environment. Ironically, the answers to some of these problems may only be provided when clinical xenotransplantation is undertaken.
[Assessment of the efficiency of different formulae applied to calculating the optic power of an intraocular lens in trans-scleral fixation]. (2004)

The paper is dedicated to assessing the efficiency of various formulae designed to calculate the IOL optic power, when IOL is fixed transscelerally in patients with an inconsistent ligament-capsular lens apparatus. According to an analysis of the obtained data, the closest values were ensured, as regards the practical result, with theoretical formulae, i.e. Binkhorst, Hoffer-Colenbrander and Binkhorst in situ. The postoperative refraction deviation was below 0.1 diopters, which is optimal for such calculation types. Should the use of theoretical formulae be problematic due to a lack of appropriate devices, then it is acceptable to apply the SRK-II empiric formula with a correction by -1.6 diopters to guarantee the postoperative emmetropia.
Genetic data analysis II: methods for discrete population genetic data (1996)

This revised and expanded second edition of Genetic Data Analysis details the statistical methodology needed to draw inferences from discrete genetic data. Major changes from the first edition include an expanded treatment of linkage, including methods to locate human disease genes, and a new chapter on individual identification.
A Randomized, Multicenter Study Comparing the Safety and Efficacy of Sodium Phosphate Tablets With 2L Polyethylene Glycol Solution Plus Bisacodyl Tablets for Colon Cleansing (2007)

OBJECTIVE The safety and efficacy of NaP tablets have not been compared with 2L PEG lavage solution. A multicenter, investigator-blinded study was conducted to compare the colon-cleansing efficacy of a new NaP tablet formulation with that of 2L PEG solution plus bisacodyl tablets in adults undergoing colonoscopy. METHODS A total of 481 patients were randomized to receive either 32 tablets (48 g) of NaP or 2L PEG solution plus 4 (20 mg) bisacodyl tablets. Quality of colon cleansing was assessed using a 4-point scale (1 = excellent, 2 = good, 3 = fair, and 4 = inadequate), and the primary efficacy end point was mean overall colon-cleansing score. Safety assessments included recording of adverse events and changes in biochemical tests and vital signs. RESULTS A total of 411 patients were included in the efficacy analysis. The mean overall and ascending colon-cleansing scores for NaP tablets were significantly better than PEG plus bisacodyl (overall 1.5 vs 1.8, ascending 1.4 vs 1.8, P < 0.0001 for both). Patients treated with NaP tablets experienced significantly fewer adverse events (66% vs 82%, P = 0.0003) and gastrointestinal symptoms (64% vs 79%, P = 0.0001) compared with patients receiving PEG plus bisacodyl. Patients receiving NaP tablets were significantly less likely to experience abdominal distention, abdominal pain, and vomiting than patients receiving PEG plus bisacodyl (P < 0.0012). Transient fluctuations in laboratory parameters were observed in both treatment groups; however, the fluctuations were more common and of greater magnitude in the NaP group particularly in phosphorous, sodium, and potassium. CONCLUSION The colon-cleansing efficacy of the new 32-tablet NaP dosing regimen in this study was found to be significantly better than the 2L PEG solution plus bisacodyl tablets regimen. The 32-tablet NaP dosing regimen was associated with fewer adverse events. As expected electrolyte shifts were more common and of greater magnitude in the NaP group compared with the PEG plus bisacodyl group; however, both treatment groups demonstrated significant changes in electrolytes and creatinine.
Association of interferon gamma, tumor necrosis factor alpha and interleukin 6 serum levels with systemic lupus erythematosus activity. (1998)

We investigated serum level of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) using an enzyme-linked immunosorbent assay (ELISA) in 59 patients with systemic lupus erythematosus (SLE) and 16 healthy controls. We examined a possible association between serum levels of these cytokines and SLE activity, as well as correlation between IFN-gamma concentration and the level of TNF-alpha and IL-6 and also IL-6 and TNF-alpha. TNF-alpha and IL-6 were detectable in all 59 patients and normal individuals and their level was significantly higher in SLE patients than in the control group (p < 0.001 and p < 0.02, respectively). In contrast IFN-gamma was detectable in 23 (39%) patients and in only 3 (20%) healthy individuals. We found positive correlation between serum concentration of TNF-alpha and IL-6 with SLE activity and no such correlation with IFN-gamma. We also observed positive correlation between serum levels of IFN-gamma and TNF-alpha, IFN-gamma and IL-6 as well as TNF-alpha and IL-6. In conclusion, an increase in the serum levels of TNF-alpha and IL-6 may be useful markers for SLE activity.
Heparan sulfate endoglycosidase and metastatic potential in murine fibrosarcoma and melanoma. (1986)

Several fibroblast and melanoma cell lines were studied with respect to their ability to degrade heparan sulfate (HS). The optimum pH for HS degradation by HS endoglycosidase (heparanase) for all cell lines is about 5.6, but the activity of the enzyme is still present at physiological pH. The gel permeation analysis of degradation products revealed that heparanase cuts HS in fragments about one-seventh of their original size. Since the optimum pH of HS endoglycosidase activity and the terminal molecular weight of degraded HS are the same in both cell lines, it is likely that fibrosarcoma and melanoma heparanases are identical enzymes. Cell extracts and intact cells of metastatic sublines degrade HS faster than do their nonmetastatic counterparts. The degradative activity of intact cells parallels those of cell extracts, but at a much lower level; moreover, conditioned media do not appreciably degrade HS, suggesting that heparanase is scarcely released into the medium; thus, considering the differences in degradative activity between cell extracts and intact cells or conditioned medium and the occurrence of cell lysis in a tumor in vivo, we suggest that the measure of degradative activity of intact cells in vitro is not indicative of a relationship to metastasis. The total cellular content of lytic enzymes could represent the real metastatic potential of proliferating cells, but it is also necessary to find an in vitro model better representing the behavior of neoplastic cells in vivo.
Autonomous replication in human cells of multimers of specific human and bacterial DNA sequences. (1993)

Using modules of a specific 2,712-bp human DNA sequence and a specific 2,557-bp Escherichia coli DNA sequence, we created plasmids containing between 1 and 12 modules of single or chimeric sequence composition and tested them in human cells for their autonomous replication ability. We found that replication efficiency per generation increased with successive addition of human modules, to essentially 100% by six copies. Although a single copy of the bacterial module had negligible replication ability, the replication efficiency per generation of 12 bacterial modules was 66%. Chimeras composed of human and bacterial modules displayed intermediate replication levels. We also used two-dimensional gel electrophoresis to physically map where replication initiated on a half human-half E. coli plasmid. Our results suggest that autonomous replication in human cells is stimulated by simple sequence features which occur frequently in human DNA but are more rare in bacterial DNA.
Orchestrating the Human Genome Project (1990)

The Human Genome Project is under way. The Department of Energy and the National Institutes of Health are cooperating effectively to develop organizational structures and scientific priorities that should keep the project on schedule and within its budget.
Regulation of Inhibin .BETA. Chains and Follistatin mRNA Levels During Rat Hepatocyte Growth Induced by the Peroxisome Proliferator Di-n-butyl Phthalate. (2002)

Peroxisome proliferators stimulate hepatocyte growth in rat liver in vivo. Activin A, a homodimer of inhibin betaA, inhibits DNA synthesis in hepatocytes. The inhibitory action of activin A is suppressed by follistatin, an activin-binding protein. In this paper, we investigated whether administration of di-n-butyl phthalate (DBP), a peroxisome proliferator, modifies the production of activin A and follistatin in rat liver by hourly monitoring of inhibin betaA and follistatin mRNA levels by reverse transcriptase polymerase chain reaction analysis. The mRNA levels of the other inhibin beta chains (inhibin betaB and betaC) were examined in a similar manner. The inhibin betaA mRNA level decreased to about 30% by 3 h after DBP administration (8.6 mmol/kg body weight), remained low until 12 h, and returned to its original level by 24 h. The follistatin mRNA level increased to about 2 times by 6 h, and returned to its original level by 24 h. The inhibin betaB mRNA had started to increase by 1 h, peaked at 6 h at about 4 times its initial level, and returned to its original level by 12 h. The inhibin betaC mRNA level had doubled by 6 h and it returned to its original level. These results indicate that the growth stimulatory action of peroxisome proliferators may be mediated via the decrease in activin A level and activity and suggest that the increases in follistatin as well as inhibin betaB and betaC chains may play a role in peroxisome proliferator-stimulated hepatocyte growth.
The E3 ubiquitin ligase Itch regulates sorting nexin 9 through an unconventional substrate recognition domain (2010)

The level of intracellular proteins is mainly regulated through modifications by ubiquitin ligases that target them for degradation. Members of the NEDD4 family of E3 ubiquitin ligases, such as Itch (atrophin-1 interacting protein 4), possess up to four WW domains for specific association with PY motif-containing substrates. We have identified sorting nexin 9 (SNX9), a protein involved in endocytic processes, as a new substrate of Itch. Itch ubiquitylates SNX9 and regulates intracellular SNX9 levels. Using truncated proteins, we found that the interaction with SNX9 is mediated by the proline-rich domain (PRD) of Itch, a domain distinct from the conventional WW recognition domain, and the SH3 domain of SNX9. Interaction with the PRD of Itch is essential for SNX9 ubiquitylation and degradation. Furthermore, this effect is specific for Itch, as NEDD4, a related PRD-containing E3 ligase, does not bind SNX9. SNX18, a second member of the SNX family containing an SH3 domain, was also found to bind to Itch. Our results indicate that the pool of substrates of NEDD4 family E3 ubiquitin ligases extends beyond proteins containing PY motifs.
Two Nonadjacent Regions in Enteroaggregative Escherichia coli Flagellin Are Required for Activation of Toll-like Receptor 5 (2002)

Flagellin is the major structural protein of the flagella of Gram-negative bacteria. Recent work has demonstrated that flagellin is a potent trigger of innate immune responses in a number of eukaryotic cells and organisms, including both mammals and plants. In several different human epithelial cell lines, this innate immune response involves toll-like receptor 5 (TLR5). The mechanisms by which flagellin activates TLR5 and the importance of this interaction in other model systems of flagellin-induced inflammation remain unknown. In this work, random and site-directed mutagenesis of the inflammatory flagellin from enteroaggregative Escherichia coli identified two regions in the conserved D1 domain that are required for interleukin-8 release and TLR5 activation. In contrast, large regions of the variable domain could be excised without reducing the inflammatory activity. In addition, regions of the protein analogous to epitopes that trigger innate immune responses in plants are not involved in Caco-2 flagellin responses. These results highlight the complexity of the interaction between bacterial flagellin and its eukaryotic recognition partners and provide the basis for further studies to characterize the innate immune response to flagellin.