gebhart/patrepeval huggingface dataset:
Do organic solvents affect the catalytic properties of lipase? Intrinsic kinetic parameters of lipases in ester hydrolysis and formation in various organic solvents (1995)

When it is assumed that organic solvents do not interfere with the binding process nor with the catalytic mechanism, the contribution of substrate-solvent interactions to enzyme kinetics can be accounted for by just replacing substrate concentrations in the equations by thermodynamic activities. It appears from the transformation that only the affinity parameters (K(m), K(sp)) are affected by this. Thus, in theory, the values of these corrected, intrinsic parameters (K(m) (int), k(sp) (int)) and the maximal rate (V(1)) should be equal for all media. This was tested for hydrolysis, transesterification, and esterification reactions catalyzed by pig pancreas lipase and Pseudomonas cepacia lipase in various organic solvents. Correction was carried out via experimentally determined activity coefficients for the substrates in these solvents or, if not feasible, from values in data bases. However, although the kinetic performances of each enzyme in the solvents became much more similar after correction, differences still remained. Analysis of the enzyme suspensions revealed massive particles, which explains the low activity of enzymes in organic solvents. However, no correlation was found between estimates of the amount of catalytically available enzyme (present at the surface of suspended particles or immobilized on beads) and the maximal rates observed. Moreover, the solvents had similar effects on the intrinsic parameters of suspended and immobilized enzyme. The possible causes for the effects of the solvents on the catalytic performance of the enzymes, remaining after correction for solvent-substrate interactions and the amount of participating enzyme, are discussed with respect to the premises on which the correction method is based. (c) 1995 John Wiley & Sons, Inc.
An In-House Newsletter (2006)

Prior to satisfying its readers, the salaried employees, the aim of an in-house magazine is to meet the expectations of the top management which originated it. What are the effects of this prerequisite on the contents of these newspapers ? To answer this question, an ethnographic study was carried out inside an advertising agency in charge of the production of the in-house magazine of a state-owned company currently under reorganization. The study revealed the self-applied censorship of the reporters, of the persons interviewed and of their managers. This censorship results in distorted hard-to-credit statements and subsequent lessens the credibility of the top management which approves such proceedings. As the social climate of the company gets worse, the newspaper, which turns out to be a tool of management rather than an information medium, seems to definitely move away from the objectives set by the agency.
Interleukin-1 blockade overcomes erlotinib resistance in head and neck squamous cell carcinoma (2016)

Erlotinib has demonstrated poor clinical response rates for head and neck squamous cell carcinoma (HNSCC) to date and the majority of respondents acquire resistance to erlotinib relatively quickly. To elucidate novel pathways involved in erlotinib resistance, we compared the gene expression profiles of erlotinib-resistant (ER) vs. erlotinib-sensitive (ES) HNSCC cell lines. Enrichment analysis of microarray data revealed a deregulation of the IL-1 signaling pathway in ER versus ES-HNSCC cells. Gene expression of interleukin-1 alpha (IL1A) and interleukin-1 beta (IL1B) were significantly upregulated by > 2 fold in ER-SQ20B and ER-CAL 27 cells compared to their respective ES-cells. Secretion of the IL-1 receptor antagonist (IL-1RA) was significantly reduced in ER-cells compared to ES-cells. Blockade of IL-1 signaling using a recombinant IL-1R antagonist (anakinra) was able to inhibit the growth of ER-SQ20B and ER-CAL 27 but not ES-SQ20B and ES-CAL 27 xenografts as a single agent and in combination with erlotinib. ER-SQ20B xenografts treated with anakinra ± erlotinib were found to be less vascularized than ER-SQ20B xenografts treated with water or erlotinib. Mice bearing ER-SQ20B xenografts had significantly lesser circulating levels of G-CSF and IL-1β when treated with anakinra ± erlotinib compared to those treated with water or erlotinib alone. Furthermore, augmented mRNA levels of IL1A or interleukin-1 receptor accessory protein (IL1RAP) were associated with shortened survival in HNSCC patients. Altogether, blockade of the IL-1 pathway using anakinra overcame erlotinib resistance in HNSCC xenografts and may represent a novel strategy to overcome EGFR inhibitor resistance for treatment of HNSCC patients.
Cervical Carcinoma Antigen, Carcinoembryonic Antigen (CEA), and Nonspecific Cross-Reacting Antigen (NCA) in Appraisal of Uterine Cervix Smears (1985)

The distribution of cervical carcinoma antigens (AgCaCx), CEA, and NCA in different pathologic states of the uterine cervix was studied in cytologic smears by an immunofluorescence method (IF) using specific immune sera against perchloric acid (PCA) extract of cervical squamous cell carcinoma, anti-CEA, and anti-NCA. After excluding cross-reactivity with CEA and NCA, the presence of AgCaCx was demonstrated in the majority of cervical carcinomas, severe dysplasias, and only in one-fourth of squamous metaplasias, especially when accompanied by mild or moderate dysplasias. The intensity and percentage of IF-positive cells varied from case to case. The preparations of uterine cervix without pathologic changes usually were negative. Similar results were obtained with anti-CEA serum. NCA was present in the majority of smears independent of histologic diagnosis. The most intense fluorescence was observed in upper layers of the epithelium. NCA could be a differentiation antigen of stratified squamous cell epithelium.
Autologous Bone Graft: Properties and Techniques (2010)

Bone grafting is involved in virtually every procedure in reconstructive orthopaedic surgery. Although autologous bone grafts have excellent biologic and mechanical properties, considerable donor site morbidity and the limited volume available must be taken into consideration. Currently, there are no heterologous or synthetic bone substitutes available that have superior biologic or mechanical properties. This review article summarizes the biologic and mechanical properties of autologous bone grafts, differentiates various autologous bone graft types, and compares them with other bone substitutes.
Fast training and selection of Haar features using statistics in boosting-based face detection (2007)

Training a cascade-based face detector using boosting and Haar features is computationally expensive, often requiring weeks on single CPU machines. The bottleneck is at training and selecting Haar features for a single weak classifier, currently in minutes. Traditional techniques for training a weak classifier usually run in 0(NT log N), with N examples (approximately 10,000), and T features (approximately 40,000). We present a method to train a weak classifier in time 0(Nd <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> + T), where d is the number of pixels of the probed image sub-window (usually from 350 to 500), by using only the statistics of the weighted input data. Experimental results revealed a significantly reduced training time of a weak classifier to the order of seconds. In particular, this method suffers very minimal immerse in training time with very large increases in members of Haar features, enjoying a significant gain in accuracy, even with reduced training time.
Binding of Clostridium difficile Surface Layer Proteins to Gastrointestinal Tissues (2002)

Clostridium difficile is the etiological agent of antibiotic-associated diarrhea, a potentially serious condition frequently affecting elderly hospitalized patients. While tissue damage is primarily induced by two toxins, the mechanism of gut colonization, and particularly the role of bacterial adherence to the mucosa, remains to be clarified. Previous studies have shown binding of C. difficile whole cells to cultured cell lines and suggested the existence of multiple adhesins, only one of which has been molecularly characterized. In this paper, we have investigated tissue binding of C. difficile surface layer proteins (SLPs), which are the predominant outer surface components and are encoded by the slpA gene. The adherence of C. difficile to HEp-2 cells was studied by enzyme-linked immunosorbent assay and fluorescence-activated cell sorter analysis, which showed that antibodies to the high-molecular-weight (MW) SLP inhibited adherence. Immunohistochemical analysis of human gastrointestinal tissue sections revealed strong binding both to the surface epithelium lining the digestive cavities and to the subjacent lamina propria, while glands were negative. A similar pattern was observed in the mouse. By using purified recombinant SLPs, we show that binding is largely mediated by the high-MW SLP. By Western blotting analysis, we have identified two potential ligands of the C. difficile SLPs, one of which may be specific to the gut. By using purified extracellular matrix components immobilized on nitrocellulose, we also show SLP binding to collagen I, thrombospondin, and vitronectin, but not to collagen IV, fibronectin, or laminin. These results raise the possibility that the SLPs play a role both in the initial colonization of the gut by C. difficile and in the subsequent inflammatory reaction.
P50-M High-Throughput and Automatic Plasmid DNA Preparation with SeqPrep Technology (2007)

SeqPrep technology is developed for easy and quick DNA preparation from bacterial culture. It consists of a surface-modified microplate and a cell lysis/DNA-binding solution. The DNA binds to the surface while cells get lysed. With this technology, DNA preparation is not only highly automatable but also very easy manually. Several robotic plaforms have been validated for plasmid DNA preparation with SeqPrep. Data will be presented. Optimization for individual labs’ needs will be discussed in four aspects of the preparation process: bacterial culture, cell harvest, DNA isolation and DNA elution.
Effect of pacemaker location on cardiac function in complete A-V heart block (1963)

These experiments were designed to determine if the location of ectopic ventricular stimulation influences ventricular performance. Heart block was produced in dogs by ligating the A-V bundle. Small bipolar electrodes were implanted in the apex, high lateral wall, and posterior septal region in six dogs. Several days after recovery dye dilution cardiac outputs, femoral arterial, and right atrial pressures were measured while stimulating from each of the three sites at varying rates between 60 and 240 beats/min. Mean cardiac outputs from stimulation at each of the three sites were similar and their 95% confidence intervals overlapped. Mean systemic pressure did not change significantly with frequency or location of ventricular stimulation. The experiments suggest that the pathway of ventricular activation does not affect ventricular function in complete heart block.
Revealing bio-lines of exoplanets by Fourier spectroscopy (2014)

Earth-like extra-solar planets have luminosities which are many orders of magnitude less than those of their parent star. We propose and test a method for identifying molecular spectral bands in light from such a planet by looking at an offcenter part of an infrared Fourier transform interferogram. This results in superior sensitivity to narrow spectral bands, which are expected in the planet’s spectrum, but are absent in the parent star. We support this by astronomical observations to illustrate the method in the visible. The results suggest that this method is applicable to searches for planet biolines, and for differentiating between narrow lines and wide lines in other astronomical scenarios.
The calculus of service availability (2017)

You're only as available as the sum of your dependencies.
DETAILED THERMAL AND FLOW FIELDS IN A RECTANGULAR DUCT WITH INCLINED RIBS (2023)

In the present study, the thermal and flow fields in a rectangular duct with aspect ratio of 1/8 are investigated experimentally using Liquid Crystal Thermography (LCT) and Particle Image Velocimetry (PIV). Circular ribs were attached staggered on the wide walls and the rib height-to-hydraulic diameter ratio was kept as 0.06 with an attack angle of 60&#176;. Both laminar and turbulent cases were tested. The heat transfer distributions between adjacent inclined ribs were reconstructed by evaluation of the acquired liquid crystal images. A significant spanwise variation in heat transfer coefficient on the rib-roughened wall was observed, with high heat transfer coefficient at the upstream end of the rib and low levels at the other end. In the streamwise distribution between two consecutive ribs, the temperature distribution showed a sawtooth fashion at high Reynolds number. The PIV technique was then applied to perform the flow field measurements to catch the flow structures introduced by the ribs. The spanwise profile of the main flow velocity was found altered, and a secondary flow was detected over the cross section. The strong secondary flow resulted in a three-dimensional flow field. The flow separation zone behind each rib was observed at Re&#61;5800, where the flow redevelops after the reattachment point. This flow behavior was responsible for the detailed distribution of the heat transfer coefficient.
Phase 2 Randomized Safety and Efficacy Trial of Nebulized Denufosol Tetrasodium in Cystic Fibrosis (2007)

Denufosol administered three times daily for 28 days appeared to be safe and well tolerated in this population with mild cystic fibrosis and provided preliminary evidence of potential benefit in lung function.
ONCOLYSIS BY CLOSTRIDIA. I. ACTIVITY OF CLOSTRIDIUM BUTYRICUM (M-55) AND OTHER NONPATHOGENIC CLOSTRIDIA AGAINST THE EHRLICH CARCINOMA. (1964)

Summary Intravenous injections of suspensions of spores of Cl. butyricum (Strain M-55) produced a more or less extensive lysis of tumor tissue. A number of other strains of nonpathogenic clostridia did not show substantially improved results. In genreal, strains which were able to ferment carbohydrate performed equally well, whereas primarily proteolytic strains gave inferior results. Combination of Strain M-55 with Cl. felsineum , as well as a combination of Strain M-55 with culture filtrates of Cl. paraputrificum , did not yield improved results. All growth phases of Cl. butyricum could at least in principle produce the phenomenon of oncolysis, but the results were most unfavorable if vegetative forms were used. To some extent an enhancement of oncolysis could be obtained by a combination of spores with certain tumor extracts.
Inhibition of heregulin signaling by an aptamer that preferentially binds to the oligomeric form of human epidermal growth factor receptor-3 (2003)

Human epidermal growth factor receptor-3 (HER3) is a member of the type I receptor tyrosine kinase family. Several members of this family are overexpressed in various carcinomas. Specifically, HER2 is found to be overexpressed in 20-30% of breast cancers. In contrast to epidermal growth factor receptor or HER2, the kinasedeficient HER3 self-associates readily at low nanomolar concentrations and in the absence of its ligands, various isoforms of heregulin (hrg). Binding of hrg disrupts HER3 oligomerization and leads to the formation of signaling-competent heterodimers, preferentially with HER2. Elevated levels of HER3 contribute to increased drug resistance observed in HER2-overexpressing cells. We have used the SELEX (systematic evolution of ligands by exponential enrichment) methodology to select RNA aptamers against the oligomeric state of the extracellular domains of HER3 (HER3ECD, monomeric molecular mass 82,000 Da). One of the aptamers, A30, binds with high affinity to a limited number of binding sites in the oligomeric state of HER3ECD. Binding of A30 and hrg are not competitive. Instead, the disruption of HER3 oligomers by hrg results in an approximately 10-fold increase in total binding sites, but the newly created binding sites are of lower affinity. High-affinity binding of A30 inhibits hrg-dependent tyrosine phosphorylation of HER2 and the hrg-induced growth response of MCF7 cells. As an example of an aptamer against a large macromolecular protein complex, A30 can serve as a tool for the analysis of receptor interactions and may serve as a lead compound for the development of inhibitors against overexpressed receptor tyrosine kinases in carcinomas.
Lack of Awareness and Treatment of Hyperlipidemia in Type II Diabetes in a Community Survey (1989)

Cardiovascular disease is the leading cause of morbidity, disability, and death among patients with type II (non-insulin-dependent) diabetes mellitus. Moreover, hyperlipidemia is also common among these patients. Despite this, there are virtually no data regarding the level of awareness and treatment of hyperlipidemia among diabetic subjects at the community level. We therefore examined 374 Mexican-Americans and 86 non-Hispanic whites with type II diabetes identified in an epidemiologic survey that involved 3279 Mexican-Americans and 1847 non-Hispanic whites who resided in San Antonio, Tex. More than 40% of the diabetic subjects were hyperlipidemic according to the criteria of the National Cholesterol Education Program, and an additional 23% had hypertriglyceridemia and/or low levels of high-density lipoprotein cholesterol. By contrast, less than one fourth of the nondiabetic subjects were hyperlipidemic. Only approximately 25% of non-Hispanic whites with diabetes were aware of their hyperlipidemia, and less than 10% were receiving treatment. Awareness and treatment were even less frequent among Mexican-Americans with diabetes. Community physicians should be encouraged to give early attention to the management of lipid disorders in their diabetic patients.
Somatic Generation of Immune Diversity (Nobel Lecture) (1988)

How does an organism manage during its lifetime to respond to a huge number of different antigens , even though the number of antibody genes is, of necessity, limited? The Nobel Prize for Medicine was awarded to Susumu Tonegawa in 1987 for providing an answer to this question. Tonegawa discovered that not a single complete gene for an antibody peptide chain is inherited by an organism. Instead, the genetic information in the germ line is contained in several hundred gene segments. Somatic recombination of these gene segments during the differentiation of B lymphocytes results in the production of tens of thousands of complete genes. Somatic hypermutation of these genes leads to further diversification of antibody peptide chains in such a way that B cells that carry immunoglobulin receptors displaying good recognition of specific antigens are selected for in a later phase of B‐cell differentiation.
Nanoliter microfluidic hybrid method for simultaneous screening and optimization validated with crystallization of membrane proteins (2006)

High-throughput screening and optimization experiments are critical to a number of fields, including chemistry and structural and molecular biology. The separation of these two steps may introduce false negatives and a time delay between initial screening and subsequent optimization. Although a hybrid method combining both steps may address these problems, miniaturization is required to minimize sample consumption. This article reports a "hybrid" droplet-based microfluidic approach that combines the steps of screening and optimization into one simple experiment and uses nanoliter-sized plugs to minimize sample consumption. Many distinct reagents were sequentially introduced as approximately 140-nl plugs into a microfluidic device and combined with a substrate and a diluting buffer. Tests were conducted in approximately 10-nl plugs containing different concentrations of a reagent. Methods were developed to form plugs of controlled concentrations, index concentrations, and incubate thousands of plugs inexpensively and without evaporation. To validate the hybrid method and demonstrate its applicability to challenging problems, crystallization of model membrane proteins and handling of solutions of detergents and viscous precipitants were demonstrated. By using 10 microl of protein solution, approximately 1,300 crystallization trials were set up within 20 min by one researcher. This method was compatible with growth, manipulation, and extraction of high-quality crystals of membrane proteins, demonstrated by obtaining high-resolution diffraction images and solving a crystal structure. This robust method requires inexpensive equipment and supplies, should be especially suitable for use in individual laboratories, and could find applications in a number of areas that require chemical, biochemical, and biological screening and optimization.
Preclinical pharmacokinetics, pharmacodynamics, tissue distribution, and tumor penetration of anti-PD-L1 monoclonal antibody, an immune checkpoint inhibitor (2016)

MPDL3280A is a human monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1), and exerts anti-tumor activity mainly by blocking PD-L1 interaction with programmed cell death-1 (PD-1) and B7.1. It is being investigated as a potential therapy for locally advanced or metastatic malignancies. The purpose of the study reported here was to characterize the pharmacokinetics, pharmacodynamics, tissue distribution and tumor penetration of MPDL3280A and/or a chimeric anti-PD-L1 antibody PRO304397 to help further clinical development. The pharmacokinetics of MPDL3280A in monkeys at 0.5, 5 and 20 mg · kg(-1) and the pharmacokinetics / pharmacodynamics of PRO304397 in mice at 1, 3 10 mg · kg(-1) were determined after a single intravenous dose. Tissue distribution and tumor penetration for radiolabeled PRO304397 in tumor-bearing mouse models were determined. The pharmacokinetics of MPDL3280A and PRO304397 were nonlinear in monkeys and mice, respectively. Complete saturation of PD-L1 in blood in mice was achieved at serum concentrations of PRO304397 above ∼ 0.5 µg · mL(-1). Tissue distribution and tumor penetration studies of PRO304397 in tumor-bearing mice indicated that the minimum tumor interstitial to plasma radioactivity ratio was ∼ 0.3; saturation of target-mediated uptake in non-tumor tissues and desirable exposure in tumors were achieved at higher serum concentrations, and the distribution into tumors was dose-and time-dependent. The biodistribution data indicated that the efficacious dose is mostly likely higher than that estimated based on simple pharmacokinetics/pharmacodynamics in blood. These data also allowed for estimation of the target clinical dose for further development of MPDL3280A.