gebhart/patrepeval huggingface dataset:
Structure, multiple site binding, and segmental accommodation in thymidylate synthase on binding dUMP and an anti-folate (1990)

The structure of Escherichia coli thymidylate synthase (TS) complexed with the substrate dUMP and an analogue of the cofactor methylenetetrahydrofolate was solved by multiple isomorphous replacement and refined at 1.97-A resolution to a residual of 18% for all data (16% for data greater than 2 sigma) for a highly constrained structure. All residues in the structure are clearly resolved and give a very high confidence in total correctness of the structure. The ternary complex directly suggests how methylation of dUMP takes place. C-6 of dUMP is covalently bound to gamma S of Cys-198(146) during catalysis, and the reactants are surrounded by specific hydrogen bonds and hydrophobic interactions from conserved residues. Comparison with the independently solved structure of unliganded TS reveals a large conformation change in the enzyme, which closes down to sequester the reactants and several highly ordered water molecules within a cavernous active center, away from bulk solvent. A second binding site for the quinazoline ring of the cofactor analogue was discovered by withholding addition of reducing agent during crystal storage. The chemical change in the protein is slight, and from difference density maps modification of sulfhydryls is not directly responsible for blockade of the primary site. The site, only partially overlapping with the primary site, is also surrounded by conserved residues and thus may play a functional role. The ligand-induced conformational change is not a domain shift but involves the segmental accommodation of several helices, beta-strands, and loops that move as units against the beta-sheet interface between monomers.
Kinetic characterization of phenol and aniline derivates as substrates of peroxidase (2004)

The kinetic characterization of horseradish peroxidase (HRPC) substrates is difficult because the reaction products are free radicals. The application of a spectrophotometrical method, which is based on determining the time necessary for a given quantity of L-ascorbic acid to be consumed (lag period) during its reaction with the free radicals generated by the enzyme acting on the reducing substrate, makes it possible to obtain the initial steady-state rates (v0). From the kinetic study of a series of derivates of phenol and aniline, the following parameters were determined for the first time: the global catalytic constant (kcat), the Michaelis constant of HRPC for H2O2 in the presence of each reducing substrate (K(M)H2O2), the Michaelis constant of HRPC for the reducing substrate (KMS), the binding constant of the reducing substrate with HRPC compound II (k5) and the rate constant of substrate oxidation by HRPC compound II (k6). The values obtained are disccussed.
Functional Analysis of Transcription Factors in Arabidopsis (2009)

Transcription factors (TFs) regulate the expression of genes at the transcriptional level. Modification of TF activity dynamically alters the transcriptome, which leads to metabolic and phenotypic changes. Thus, functional analysis of TFs using 'omics-based' methodologies is one of the most important areas of the post-genome era. In this mini-review, we present an overview of Arabidopsis TFs and introduce strategies for the functional analysis of plant TFs, which include both traditional and recently developed technologies. These strategies can be assigned to five categories: bioinformatic analysis; analysis of molecular function; expression analysis; phenotype analysis; and network analysis for the description of entire transcriptional regulatory networks.
UTILIZATION OF EDI BY MOTOR CARRIER FIRMS : A STATUS REPORT (1992)

Presents the results of a survey of on the utilization of electronic data interchange (EDI) by motor carrier firms. The survey inquired as to what has been involved in implementing EDI services and how this service offering is expected to evolve in the next several years.
Autopipelining for Data Stream Processing (2013)

Stream processing applications use online analytics to ingest high-rate data sources, process them on-the-fly, and generate live results in a timely manner. The data flow graph representation of these applications facilitates the specification of stream computing tasks with ease, and also lends itself to possible runtime exploitation of parallelization on multicore processors. While the data flow graphs naturally contain a rich set of parallelization opportunities, exploiting them is challenging due to the combinatorial number of possible configurations. Furthermore, the best configuration is dynamic in nature; it can differ across multiple runs of the application, and even during different phases of the same run. In this paper, we propose an autopipelining solution that can take advantage of multicore processors to improve throughput of streaming applications, in an effective and transparent way. The solution is effective in the sense that it provides good utilization of resources by dynamically finding and exploiting sources of pipeline parallelism in streaming applications. It is transparent in the sense that it does not require any hints from the application developers. As a part of our solution, we describe a light-weight runtime profiling scheme to learn resource usage of operators comprising the application, an optimization algorithm to locate best places in the data flow graph to explore additional parallelism, and an adaptive control scheme to find the right level of parallelism. We have implemented our solution in an industrial-strength stream processing system. Our experimental evaluation based on microbenchmarks, synthetic workloads, as well as real-world applications confirms that our design is effective in optimizing the throughput of stream processing applications without requiring any changes to the application code.
Forms of lipoprotein lipase in rat tissues: in adipose tissue the proportion of inactive lipase increases on fasting (1996)

Previous studies have shown that the ratio of lipoprotein lipase (LPL) catalytic activity to LPL mass in tissues differs in different conditions, but it is not clear whether this occurs by a change in the catalytic efficiency of the LPL molecules, or because of a shift in the relation between active and inactive forms of the enzyme. To explore this, we have measured LPL activity and mass in detergent extracts of rat tissues. LPL specific activity was high and similar in heart, skeletal muscle, lung and brain. The liver had significantly lower specific activity, which is in accord with previous findings that the liver takes up and catabolizes LPL. The specific activity was also low in adipose tissue from fasted rats. When tissue extracts were applied to columns of heparin-agarose and eluted by a gradient of NaCl, a peak of active LPL was eluted at 1.0 M NaCl, but there was also a peak of inactive LPL protein, which was eluted at 0.6 M NaCl. In adipose tissue, LPL activity decreased by 70-80% during an overnight fast, whereas LPL mass decreased by only 20-40%. The mass ratio between inactive and active LPL, as separated by heparin-agarose chromatography, increased from 0.5 to over 2 during the fast. In hearts there was no significant difference between fed and fasted rats in total LPL activity, LPL mass or in the distribution between inactive and active forms. The results indicate that the relation between inactive (probably monomeric) and active (dimeric) forms of LPL is a target for post-translational regulation in adipose tissue.
Rheology of Synovial Fluid From Patients With Osteoarthritis and the Effects of Viscosupplements on the Rheology of Synovial Fluid (2010)

Osteoarthritis (OA) is the most common joint disorder associated with aging. It is a degenerative joint disease that is characterized by the breakdown of articular cartilage resulting in joint pain and stiffness. Articular cartilage and synovial fluid are closely linked in providing lubrication, and protective barrier between the ends of the bones. Therefore, damage to articular cartilage may result in modification in rheological properties of the synovial fluid and eventually will have an effect on the performance of the joint. In a diseased joint, the composition of the synovial fluid is changed resulting in deterioration of rheological properties. Synovial fluid becomes less viscous and therefore less effective in lubrication [6].
Temperature compensation of silicon MEMS Resonators by Heavy Doping (2011)

Passive temperature compensation of silicon MEMS resonators based on heavy n- and p-type doping is studied. Resonators are fabricated utilizing silicon with phosphorus doping level of 5·10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">19</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> and boron doping levels of 5·10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">19</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> and 2 · 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">20</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> , the latter being stress compensated with germanium. The temperature behavior of the resonance frequencies of Lamé and square extensional (SE) modes is measured. Depending on the vibration mode and crystal orientation, significant temperature compensation effects are observed: as a result of heavy n-type doping the temperature coefficient of frequency (TCF) of the SE mode is reduced from -32 ppm/K to ca. -1 ppm/K, while a Lamé mode resonator exhibits an overcompensated TCF of +18 ppm/K. In p-type resonators a TCF of ca. -2 ppm/K is observed in a Lamé-mode. Keyes' [1] theory of free carrier contribution to the elastic constants of many-valley semiconductors is used to predict the temperature behavior of the n-type resonators. Good agreement is obtained between predicted and observed temperature behavior. The n-type doping can be applied to the TCF reduction of a large class of resonators and shows great potential in improving Si resonator performance.
Chimaera and Its Modern Virus-Like Descendants (1996)

Chimaera was a monster in ancient Greek mythology combining elements from different animal species in its body. Modern molecular biology enabled the generation of harmless but useful chimaeras consisting of elements from different nonrelated viruses. The objective is that the resulting chimaeras form highly immunogenic virus-like particles (VLPs). Such chimaeric VLPs can be used as highly efficient carriers for sequential and conformational B cell epitopes and T cell epitopes. Most VLPs are readily produced in heterologous hosts and are easy to purify. This article deals with various systems of VLPs described in this topical issue of Intervirology and makes comparisons with chimaeric replication-competent viruses, recombinant virus vectors expressing foreign proteins, and DNA vaccines.
Comparison of techniques for diagnosis of proliferative enteritis of swine (1993)

In an abattoir-based case-control study, histologic, and macroscopic examination of porcine intestines at slaughter and 2 molecular assays were compared for use as diagnostic tests of proliferative enteritis (PE). Fecal samples and intestinal specimens were collected from pigs with grossly thick ileum and from clinically normal pigs at slaughter. Tissue specimens were fixed in neutral buffered 10% formalin, and sectioned. Sections stained with H&E were examined for proliferative lesions by a pathologist unaware of the group to which the pig had been assigned on the basis of results of gross examination. Adjacent tissue sections, stained with Warthin-Starry (silver) stain, were examined for presence of the intracellular bacterium of PE, ileal symbiont (IS)-intracellularis, in the enterocytes of the intestinal crypts by the senior author, who was unaware either of the group to which the pig had been assigned or diagnosis by the pathologist. Bacterial DNA was extracted from the fecal samples and assayed by dot-blot hybridization and polymerase chain reaction (PCR) for presence of IS-intracellularis DNA, without knowledge of results of the other examinations. The PCR assay for IS-intracellularis was a specific and sensitive diagnostic test for PE, and dot-blot hybridization was sensitive, but was less specific. Macroscopic examination of intestines at slaughter was a sensitive, but not specific, test. Association between IS-intracellularis and proliferative lesions was statistically examined in the same study. There was a highly significant (P = 0.0078) association between presence of naturally acquired proliferative lesions and intracellular infection induced by IS-intracellularis.(ABSTRACT TRUNCATED AT 250 WORDS)
The Role of Group Research Designs to Evaluate Social Work Practice (2012)

From the beginnings of professional social work, the discipline defined itself as being a science-based field. Indeed this reliance upon the findings of social and behavioral science was a feature distinguishing professional social work from its charitable, philanthropic, and faith-based predecessors. Beginning in the 1930s, social workers began using simple group research designs to examine the status of clients after they received social work services and participated in programs. Over time, these group research designs became more sophisticated, and permitted summary appraisals of the overall effects of social work. By the middle 1980s, meta-analyses of social work began appearing. Quasi-experiments are capable of answering some very important questions about the outcomes of social work and are the most widely used research methodology being used for this purpose.
Phosphoinositide signaling in nuclei of Friend cells: phospholipase C beta down-regulation is related to cell differentiation. (1994)

Previous investigations have demonstrated the existence of an autonomous intranuclear inositide cycle endowed with conventional lipid kinases and phospholipase C (PLC) which is the isoform beta in Swiss 3T3 cells, PC12 pheochromocytoma cells, human osteosarcoma SaOS-2 cells, and rat liver. The presence of PLC has been investigated in nuclei of Friend erythroleukemia cells. Both beta and gamma isoforms are present in these nuclei. When Friend cells undergo terminal erythroid differentiation in the presence of dimethyl sulfoxide the PLC beta isoform is down-regulated as shown by immunochemical and immunocytochemical analysis, by determination of enzymatic activity directly and in the presence of neutralizing monoclonal antibodies and also by Northern blot for PLC beta message. By contrast, the amount of PLC gamma and its activity are unaffected by erythroid differentiation. Thus, the presence of a nuclear PLC beta, the activity and expression of which are modulated during differentiation of erythroleukemia cells, implicates a role for nuclear phosphoinositide signaling in the processes of cell determination and indicates the nuclear PLC beta as a key enzyme of the cycle in relation to the erythroid differentiative commitment of murine erythroleukemia cells.
Expression of interleukin‐1β and tumour necrosis factor‐α in plasma cells from patients with multiple myeloma (1999)

Interleukin-1beta(IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) are potent bone resorbing cytokines that may contribute to the development of the osteolytic bone disease observed in patients with multiple myeloma (MM). Although these factors have been identified in cultures of bone marrow mononuclear cells isolated from patients, the identity of the cells responsible for producing IL-1beta and TNFalpha remains unclear. Using a sensitive dual-colour fluorescence in situ hybridization (FISH) technique and a two-colour immunofluorescence method we have investigated the expression of the mRNA and protein, for IL-1beta and TNFalpha, by individual bone marrow plasma cells from patients with MM and monoclonal gammopathy of undetermined significance (MGUS). The mRNA for IL-1beta and TNFalpha was identified in all cells expressing the immunoglobulin light chain from all patients with MM and MGUS. However, the IL-1beta protein could not be detected in cytoplasmic light chain positive cells in any of the patients examined. In contrast, the TNFalpha protein was detected in clonal plasma cells from patients with both MM and MGUS. Interestingly, the IL-1beta and TNFalpha mRNA and proteins were readily detected within a small proportion of the non-plasma cells from patients with both MM and MGUS. These data suggest that myeloma cells in vivo are able to produce TNFalpha but not IL-1beta. In addition, a small proportion of accessory cells are likely to be able to contribute to the production of both ILbeta and TNFalpha.
Past, Present, and Future of Measles, Mumps, and Rubella Virus Vaccines (1992)

It is a real pleasure for me to speak on this memorable occasion. Dr Saul Krugman is now entering his ninth decade while enjoying the world status of senior statesman! Saul and I have collaborated often during the last three of these decades. In the studies of new vaccines in our laboratories, our first clinical probes were made in cooperative studies with the late Dr Joseph Stokes and his colleagues and successors at the Children's Hospital of Philadelphia. Following such initial phase, Dr Krugman received the vaccines for expanded clinical studies. Hence, he has been an indispensible clinical partner in most of the new viral vaccine developments in our laboratories during the past 30 years. In discussions with Dr Wade Parks, I was advised that I might speak on any subject I choose. I chose to talk about the measles-mumps-rubella vaccine (M-M-R), a topic that has occupied Dr Krugman for nearly three decades and that is receiving renewed attention in the worlds of pediatrics and public health at the present time. This being a festive occasion, I feel I should keep it light. Therefore, I want to emphasize the science, but also to recount some of the less well-known "behind-the-scenes" activities that led to the creation and birth of M-M-R. There were lessons learned that might provide historic insight into problems that can be avoided in the future. MEASLES Measles vaccine began when the late Dr John Enders and Dr Samuel Katz and their coworkers developed and tested their Edmonston strain of attenuated live measles virus.1
Toward bridging the annotation-retrieval gap in image search by a generative modeling approach (2006)

While automatic image annotation remains an actively pursued research topic, enhancement of image search through its use has not been extensively explored. We propose an annotation-driven image retrieval approach and argue that under a number of different scenarios, this is very effective for semantically meaningful image search. In particular, our system is demonstrated to effectively handle cases of partially tagged and completely untagged image databases, multiple keyword queries, and example based queries with or without tags, all in near-realtime. Because our approach utilizes extra knowledge from a training dataset, it outperforms state-of-the-art visual similarity based retrieval techniques. For this purpose, a novel structure-composition model constructed from Beta distributions is developed to capture the spatial relationship among segmented regions of images. This model combined with the Gaussian mixture model produces scalable categorization of generic images. The categorization results are found to surpass previously reported results in speed and accuracy. Our novel annotation framework utilizes the categorization results to select tags based on term frequency, term saliency, and a WordNet-based measure of congruity, to boost salient tags while penalizing potentially unrelated ones. A bag of words distance measure based on WordNet is used to compute semantic similarity. The effectiveness of our approach is shown through extensive experiments.
A Hybrid Modular Multilevel Converter with Partial Embedded Energy Storage (2016)

Modular and cascaded multilevel converters provide a functional solution for the integration of energy storage systems (ESSs). This paper develops a hybrid multilevel converter based on the modular multilevel converter (MMC) that can be functionally extended with partial embedded ESS as a fraction of the overall converter power rating. The configuration, which can operate as a typical DC-AC converter, enables multi-directional power flow between the DC- and AC-side of the converter, as well as the embedded energy storage elements. The use of a three-phase flying-capacitor submodule eliminates the second-order harmonic oscillations present in modular cascaded multilevel converters. Current, voltage and power control are discussed in the paper while simulation results illustrate the operation of the hybrid MMC as a DC-AC converter in a typical inverter application and the additional functions and control of the embedded ESS.
Long-Wavelength Analogue of PRODAN:  Synthesis and Properties of Anthradan, a Fluorophore with a 2,6-Donor−Acceptor Anthracene Structure (2006)

We have synthesized the environment-sensitive fluorophores 2-cyano-6-dihexylaminoanthracene and 2-propionyl-6-dihexylaminoanthracene (Anthradan) starting from 2,6-diaminoanthraquinone. Anthradan is the benzologue of the well-known family of naphthalene 2-propionyl-6-dimethylaminonaphthalene (PRODAN) fluorophores. The additional spectral red shift of the anthracene avoids the autofluorescence of many biological systems and provides for more favorable excitation wavelengths for fluorescence applications. Furthermore, Anthradan exhibits polarity-sensitive emission comparable to that of PRODAN and displays high quantum yields in a range of solvents. Single molecules of these anthracene-containing fluorophores have been imaged in polymer hosts as a proof-of-principle.
High steady-state levels of p53 are not a prerequisite for tumor eradication by wild-type p53-specific cytotoxic T lymphocytes. (2000)

CTLs specific to p53 were previously shown to efficiently eradicate p53-overexpressing tumor cells in vitro as well as in vivo. In this report, we demonstrate that these CTLs can also eliminate tumors that display moderate or even low levels of p53. Neither high steady-state levels of p53 nor elevated p53 synthesis is a prerequisite for recognition of tumors by p53-specific CTLs. Instead, our data show that a high p53 turnover rate is an important factor in determining the sensitivity of tumor cells to p53-specific CTLs. Our data suggest that p53 turnover is related to the MHC class I-restricted presentation of p53-derived epitopes at the tumor cell surface and indicate that CTL-mediated immunotherapy that targets p53 can be applied to a wider range of tumors than has thus far been anticipated.
Planar microelectrode-cavity array for high-resolution and parallel electrical recording of membrane ionic currents (2008)

Increasing the throughput and resolution of electrical recording of currents through ion conducting channels and pores is an important technical challenge both for the functional analysis of ion channel proteins and for the application of nanoscale pores in single molecule analytical tasks. We present a novel design based on sub-picoliter-cavities arrayed in a polymer substrate and endowed with individual planar microelectrodes that allows low-noise and parallel electrical recording from ion channels and pores. Resolution of voltage-dependent current transitions of alamethicin channels as well as polyethylene-glycol-induced blocking events of alpha-hemolysin nanopores on the submillisecond time scale is demonstrated using this device.