gebhart/patrepeval huggingface dataset:
Detection of testosterone esters in human plasma (1995)

Abstract The detection of testosterone misuse in sports is currently based on the urinary testosterone to epitestosterone ratio, although in some rare instances physiological or pathological conditions could compromise the application of this general criterion. The detection in the body of traces of the unchanged testosterone esters really ingested would offer unequivocal confirmation of testosterone administration. In this work, the detectability of testosterone esters in humans was studied. Liquid–liquid extraction of human blood plasma and appropriate derivatization of nine testosterone esters are described. Different acyl (trifluoroacetyl, pentafluoropropionyl and heptafluorobutyryl) and trimethylsilyl derivatives were studied. The trimethylsilyl derivatives appear to be the best for screenign purposes based on the characteristics of their mass spectra, with abundant molecular ions in the high‐mass range. They also offered good conditions for tandem mass spectrometric analysis, needed to achieve the required sensitivity after oral administration of the drugs. The method was successful in the detection and determination of intramuscularly administered testosterone propionate and testosterone enanthate and orally ingested testosterone undecanoate.
Effectiveness of Six Core Strategies Based on Trauma Informed Care in Reducing Seclusions and Restraints at a Child and Adolescent Psychiatric Hospital (2011)

This study shows downward trend in seclusions/restraints among hospitalized youth after implementation of National Association of State Mental Health Program Directors six core strategies based on trauma informed care.
FlashMeta: a framework for inductive program synthesis (2015)

Inductive synthesis, or programming-by-examples (PBE) is gaining prominence with disruptive applications for automating repetitive tasks in end-user programming. However, designing, developing, and maintaining an effective industrial-quality inductive synthesizer is an intellectual and engineering challenge, requiring 1-2 man-years of effort. Our novel observation is that many PBE algorithms are a natural fall-out of one generic meta-algorithm and the domain-specific properties of the operators in the underlying domain-specific language (DSL). The meta-algorithm propagates example-based constraints on an expression to its subexpressions by leveraging associated witness functions, which essentially capture the inverse semantics of the underlying operator. This observation enables a novel program synthesis methodology called data-driven domain-specific deduction (D4), where domain-specific insight, provided by the DSL designer, is separated from the synthesis algorithm. Our FlashMeta framework implements this methodology, allowing synthesizer developers to generate an efficient synthesizer from the mere DSL definition (if properties of the DSL operators have been modeled). In our case studies, we found that 10+ existing industrial-quality mass-market applications based on PBE can be cast as instances of D4. Our evaluation includes reimplementation of some prior works, which in FlashMeta become more efficient, maintainable, and extensible. As a result, FlashMeta-based PBE tools are deployed in several industrial products, including Microsoft PowerShell 3.0 for Windows 10, Azure Operational Management Suite, and Microsoft Cortana digital assistant.
Hypothalamic Origin of the Metabolic Syndrome X (1999)

The conspicuous similarities between Cushing's syndrome and the Metabolic Syndrome X open up the possibility that hypercortisolemia is involved also in the latter. Salivary cortisol is possible to measure during undisturbed conditions including perceived stressful events during everyday life. Such measurements clearly show that normally regulated cortisol secretion is associated with excellent health in anthropometric, metabolic, and hemodynamic variables. Upon perceived stress cortisol secretion is increased and followed by the Metabolic Syndrome X (insulin resistance, abdominal obesity, elevated lipids, and blood pressure). In a minor part of the population a defect, "burned-out" cortisol secretion, occurs with decreased sex steroid and growth hormone secretions, and strong, consistent associations with the Metabolic Syndrome X. Psychosocial and socioeconomic handicaps with tendencies to abuse and depressive-anxious mood changes are consistently associated. The feedback control of cortisol secretion by central glucocorticoid receptors (GR) is blunted, and the function of the GR is abnormal. This corresponds to a polymorphism early in the GR gene locus, which is also associated with abdominal obesity and insulin resistance and is found in 14% of the Swedish male population. We suggest that the Metabolic Syndrome X is due to a discretely elevated cortisol secretion, discoverable during reactions to perceived stress in everyday life. This is based on environmental factors and expressed with different impact depending on genetic susceptibility.
Swelling Behavior and Morphological Evolution of Mixed Gelatin/Silk Fibroin Hydrogels (2005)

Mixed protein-based hydrogels have been prepared by blending gelatin (G) with amorphous Bombyx mori silk fibroin (SF) and promoting beta-crystallization of SF via subsequent exposure to methanol or methanol/water solutions. The introduction of beta crystals in SF serves to stabilize the hydrogel network and extend the solidlike behavior of these thermally responsive materials to elevated temperatures beyond the helix-->coil (h-->c) transition of G. In this work, we investigate the swelling and protein release kinetics of G/SF hydrogels varying in composition at temperatures below and above the G h-->c transition. At 20 degrees C, G and G-rich mixed hydrogels display evidence of moderate swelling with negligible mass loss in aqueous solution, resulting in porous polymer matrixes upon solvent removal according to electron microscopy. When the solution temperature is increased beyond the G h-->c transition to body temperature (37 degrees C), these gels exhibit much higher swelling with considerable mass loss due to dissolution and release of G. The extent to which these properties respond to temperature decreases systematically with increasing SF content. The unique temperature- and composition-dependent properties of G/SF hydrogels dictate the efficacy of these novel materials as stimuli-responsive delivery vehicles.
Antioxidants for Prevention of Methionine Oxidation in Recombinant Monoclonal Antibody HER2 (1997)

Recombinant humanized monoclonal antibody HER2, rhuMAb HER2, in liquid formulations undergoes oxidation when exposed to intense light and elevated temperatures (30 & 40 degrees C). Met-255 in the heavy chain of the Fc region of the antibody is the primary site of oxidation. Met-431 of the Fc fragment can also be oxidized under extreme conditions. The amount of oxidation was determined by cleaving the Fab and Fc fragments by papain digestion, and the oxidized Fc fragment was detected by hydrophobic interaction chromatography. Oxidation of rhuMAb HER2 was also formulation dependent. The presence of NaCl in the rhuMAb HER2 formulation caused an increase in oxidation at higher temperatures after contact with stainless steel containers or stainless steel components in the filling process. The corrosion of stainless steel by chloride ions at the low pH of the formulation buffer generated iron ions that catalyzed methionine oxidation in rhuMAb HER2. Temperature-induced oxidation of rhuMAb HER2 occurred by the formation of free radicals, and light-induced oxidation of rhuMAb HER2 occurred via single oxygen pathway. Antioxidants, such as methionine, sodium thiosulfate, catalase, or platinum, prevented Met oxidation in rhuMAb HER2, presumably as free radicals or oxygen scavengers. The minimum effective levels (molar ratios of protein to antioxidant) required to inhibit temperature-induced oxidation were 1:5 and 1:25 for methionine and thiosulfate, respectively. A thiosulfate adduct of rhuMAb HER2 was observed by cation-exchange chromatography. These studies demonstrate that stoichiometric amounts of methionine and thiosulfate are sufficient to eliminate temperature-induced oxidation of rhuMAb HER2 caused by free radicals that were generated by the presence of metal ion and peroxide impurities in the formulation.
Speech and language processing for next-millennium communications services (2000)

In the future, the world of telecommunications will be vastly different than it is today. The driving force will be the seamless integration of real time communications (e.g. voice, video, music, etc.) and data into a single network, with ubiquitous access to that network anywhere, anytime, and by a wide range of devices. The only currently available ubiquitous access device to the network is the telephone, and the only ubiquitous user access technology mode is spoken voice commands and natural language dialogues with machines. In the future, new access devices and modes will augment speech in this role, but are unlikely to supplant the telephone and access by speech anytime soon. Speech technologies have progressed to the point where they are now viable for a broad range of communications services, including: compression of speech for use over wired and wireless networks; speech synthesis, recognition, and understanding for dialogue access to information, people, and messaging; and speaker verification for secure access to information and services. The paper provides brief overviews of these technologies, discusses some of the unique properties of wireless, plain old telephone service, and Internet protocol networks that make voice communication and control problematic, and describes the types of voice services available in the past and today, and those that we foresee becoming available over the next several years.
Different event-related patterns of gamma-band power in brain waves of fast- and slow-reacting subjects. (1994)

Fast- and slow-reacting subjects exhibit different patterns of gamma-band electroencephalogram (EEG) activity when responding as quickly as possible to auditory stimuli. This result appears to confirm long-standing speculations of Wundt that fast- and slow-reacting subjects produce speeded reactions in different ways and demonstrates that analysis of event-related changes in the amplitude of EEG activity recorded from the human scalp can reveal information about event-related brain processes unavailable using event-related potential measures. Time-varying spectral power in a selected (35- to 43-Hz) gamma frequency band was averaged across trials in two experimental conditions: passive listening and speeded reacting to binaural clicks, forming 40-Hz event-related spectral responses. Factor analysis of between-subject event-related spectral response differences split subjects into two near-equal groups composed of faster- and slower-reacting subjects. In faster-reacting subjects, 40-Hz power peaked near 200 ms and 400 ms poststimulus in the react condition, whereas in slower-reacting subjects, 40-Hz power just before stimulus delivery was larger in the react condition. These group differences were preserved in separate averages of relatively long and short reaction-time epochs for each group. gamma-band (20-60 Hz)-filtered event-related potential response averages did not differ between the two groups or conditions. Because of this and because gamma-band power in the auditory event-related potential is small compared with the EEG, the observed event-related spectral response features must represent gamma-band EEG activity reliably induced by, but not phase-locked to, experimental stimuli or events.
Sample Preparation for Mass Spectrometry Imaging of Plant Tissues: A Review (2016)

Mass spectrometry imaging (MSI) is a mass spectrometry based molecular ion imaging technique. It provides the means for ascertaining the spatial distribution of a large variety of analytes directly on tissue sample surfaces without any labeling or staining agents. These advantages make it an attractive molecular histology tool in medical, pharmaceutical, and biological research. Likewise, MSI has started gaining popularity in plant sciences; yet, information regarding sample preparation methods for plant tissues is still limited. Sample preparation is a crucial step that is directly associated with the quality and authenticity of the imaging results, it therefore demands in-depth studies based on the characteristics of plant samples. In this review, a sample preparation pipeline is discussed in detail and illustrated through selected practical examples. In particular, special concerns regarding sample preparation for plant imaging are critically evaluated. Finally, the applications of MSI techniques in plants are reviewed according to different classes of plant metabolites.
Tumor stroma marker endosialin (Tem1) is a binding partner of metastasis‐related protein Mac‐2 BP/90K (2008)

Tumor development involves complex bidirectional interactions between tumor cells and host stromal cells. Endosialin (Tem1) has been identified as a highly O-glycosylated transmembrane glycoprotein, which is specifically expressed by tumor vessel-associated pericytes and stromal fibroblasts of a wide range of human tumors. Recent experiments in endosialin-deficient mice have unraveled a critical role of endosialin in site-specific tumor progression and metastasis. To molecularly understand the mechanisms of endosialin function, we aimed to identify extracellular endosialin ligands and identified Mac-2 BP/90K as a specific interaction partner. Detailed biochemical analyses identified a C-terminal fragment of Mac-2 BP/90K, which was shown to contain binding sites for galectin-3, and collagens as the structures responsible for endosialin binding. Subsequent expression analysis of Mac-2 BP/90K in vivo revealed weak or no expression in most normal tissues and strong up-regulation in tumor cells of human neoplastic tissues. Intriguingly, the expression patterns of Mac-2 BP/90K and endosialin were mutually exclusive in all human tissues. Correspondingly, loss-of-function adhesion experiments of Mac-2 BP/90K-expressing tumor cells on endosialin-expressing fibroblasts revealed a repulsive outcome of the Mac-2 BP/90K interaction. Taken together, the experiments identify a novel repulsive interaction between endosialin on stromal fibroblasts and Mac-2 BP/90K on tumor cells.
Phenotypic differences between oral and skin fibroblasts in wound contraction and growth factor expression (2006)

Wounds of the oral mucosa heal in an accelerated fashion with reduced scarring compared with cutaneous wounds. The differences in healing outcome between oral mucosa and skin could be because of phenotypic differences between the respective fibroblast populations. This study compared paired mucosal and dermal fibroblasts in terms of collagen gel contraction, alpha-smooth muscle actin expression (alpha-SMA), and production of the epithelial growth factors: keratinocyte growth factor (KGF) and hepatocyte growth factor/scatter factor (HGF). The effects of transforming growth factor -beta1 and -beta3 on each parameter were also determined. Gel contraction in floating collagen lattices was determined over a 7-day period. alpha-SMA expression by fibroblasts was determined by Western blotting. KGF and HGF expression were determined by an enzyme-linked immunosorbent assay. Oral fibroblasts induced accelerated collagen gel contraction, yet surprisingly expressed lower levels of alpha-SMA. Oral cells also produced significantly greater levels of both KGF and HGF than their dermal counterparts. Transforming growth factor-beta1 and -beta3, over the concentration range of 0.1-10 ng/mL, had similar effects on cell function, stimulating both gel contraction and alpha-SMA production, but inhibiting KGF and HGF production by both cell types. These data indicate phenotypic differences between oral and dermal fibroblasts that may well contribute to the differences in healing outcome between these two tissues.
<title>Infrared analyzers for process measurements</title> (1993)

Optical analysis techniques, infrared spectroscopy in the front end, are rapidly achieving new applications in process control. This progress is accelerated by the development of more rugged instrument constructions. This paper describes two analyzer techniques especially developed for use in demanding environments. First, the integrated multichannel detector techniques is suitable for applications where the measurement can be accomplished by using 2 to 4 wavelengths. This technique has been used to construct several compact, portable and battery-operated IR analyzers, and process analyzers which measure exactly simultaneously at each wavelength resulting in very high tolerance against rapid changes and flow of the process stream. Secondly, a miniaturized Fourier transform infrared (FTIR) spectrometer is being developed for use as an OEM module in specific process and laboratory instruments. Special attention has been paid to increase the resistance of FTIR technique to ambient vibrations. The module contains an integrated digital signal processing electronics for intelligent control of the spectrometer and for fast real time spectral data treatment. Application studies include on line measurement of the concentrations of diluted and colloidal organic detrimental substances, especially pitch components, in the circulating waters in paper machine wet end.
Organotellurium Compounds as Novel Initiators for Controlled/Living Radical Polymerizations. Synthesis of Functionalized Polystyrenes and End-Group Modifications (2002)

Polymer-end mimetic organotellurium compounds initiate controlled/living radical polymerization of styrene derivatives that allows accurate molecular weight control with defined end-groups. Transformations of the end-groups via radical and ionic reactions provide a variety of end-group modified polystyrenes.
p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling (2005)

p53 is a well known tumor suppressor. We show that p53 also regulates osteoblast differentiation, bone formation, and osteoblast-dependent osteoclast differentiation. Indeed, p53(-/-) mice display a high bone mass phenotype, and p53(-/-) osteoblasts show accelerated differentiation, secondary to an increase in expression of the osteoblast differentiation factor osterix, as a result. Reporter assays indicate that p53 represses osterix transcription by the minimal promoter in a DNA-binding-independent manner. In addition, p53(-/-) osteoblasts have an enhanced ability to favor osteoclast differentiation, in association with an increase in expression of macrophage-colony stimulating factor, which is under the control of osterix. Furthermore, inactivating p53 is sufficient to rescue the osteoblast differentiation defects observed in mice lacking c-Abl, a p53-interacting protein. Thus, these results identify p53 as a novel regulator of osteoblast differentiation, osteoblast-dependent osteoclastogenesis, and bone remodeling.
Analysis of the 5′ Region ofPMS2Reveals Heterogeneous Transcripts and a Novel Overlapping Gene (1995)

The PMS2 gene encodes a protein that is involved in DNA mismatch repair and is mutated in a subset of patients with hereditary nonpolyposis colon cancer (HNPCC). The previously published PMS2 cDNA sequence lacks an upstream in-frame stop codon preceding the presumptive initiating methionine. To evaluate the 5' terminus of the PMS2 coding region further, we isolated additional cDNA clones, RT-PCR products, and the corresponding 5' genomic segment of the PMS2 locus. The PMS2 gene transcripts were found to have heterogeneous but colinear 5' termini, one of which contained an in-frame termination codon preceding the initiating methionine. In addition, a novel gene encoding a 34.5-kDa polypeptide was found to initiate transcriptionally within PMS2 from the opposite strand.
Site-directed mutagenesis as a probe of enzyme structure and catalysis: tyrosyl-tRNA synthetase cysteine-35 to glycine-35 mutation (1983)

Oligodeoxynucleotide-directed mutagenesis has been used on the gene of tyrosyl-tRNA synthetase from Bacillus stearothermophilus to produce mutant enzymes altered at the adenosine 5'-triphosphate (ATP) binding site. Deliberate attempts were made to alter rather than destroy enzymic activity so that kinetic measurements may be made to identify the subtle roles of the enzyme-substrate interactions in catalysis. Cys-35, the -SH group of which is involved in binding the 3'-OH of the ribose ring of ATP, has been mutated to a serine residue [Winter, G., Fersht, A. R., Wilkinson, A. J., Zoller, M., & Smith, M. (1982) Nature (London) 299, 756-758] or glycine residue. The mutant enzymes are less active than the wild type, and the reduction in activity can be attributed to a decrease in the value of kcat and an increase in KM. Thus, the interaction energy of the side chain of Cys-35 with the substrate is not fully realized in the enzyme-substrate complex but is used preferentially to stabilize the transition state. Relative to its absence in the Gly-35 mutant, the side chain of Cys-35 is calculated to stabilize the transition state for pyrophosphate exchange by 1.2 kcal/mol and the transition state for aminoacylation by 1.0 kcal/mol.
Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM) (2004)

Inducible costimulator (ICOS), a CD28/cytotoxic T lymphocyte antigen 4 (CTLA-4) family member, is expressed on activated T cells. ICOS ligand, a B7 family member, is constitutively expressed on B cells, macrophages, and dendritic cells and is up-regulated on antigen-presenting cells (APCs) and some nonlymphoid tissues by tumor necrosis factor alpha (TNFalpha) or lipopolysaccharide (LPS). Thus, ICOS: ICOS ligand (ICOSL) blockade could reduce alloreactive T cell-APC interactions responsible for graft-versus-host disease (GVHD) and bone marrow (BM) graft rejection. ICOS blockade, achieved with ICOS-/- mice or anti-ICOS monoclonal antibody (mAb) administration, resulted in significant inhibition of GVHD in multiple strain combinations whether mediated by CD4+ and/or CD8+ T cells, alloantigen-specific T-cell receptor (TCR) transgenic (Tg) T cells, or CD28-, T helper 1 (Th1)-, or Th2-deficient T cells. Anti-ICOS significantly delayed GVHD mortality even when mAb infusions were delayed until day 5 after transplantation. ICOS blockade reduced the number of alloantigen-specific effector cells but did not prevent their activation. Imaging of green fluorescent protein-positive (GFP+) effectors indicated that ICOS blockade inhibited expansion of GVHD-causing effector T cells in secondary lymphoid and GVHD target organs. Engraftment rates were significantly higher in ICOS-/- versus wild-type (WT) mice receiving allogeneic BM, and ICOS blockade significantly inhibited expansion of host antidonor alloantigen-specific BM graft-rejecting T cells. These data suggest that the ICOS pathway may be a beneficial therapeutic target for GVHD inhibition, GVHD therapy, and BM graft promotion.