gebhart/patrepeval huggingface dataset:
ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer (2006)

For colorectal cancer, it is recommended that carcinoembryonic antigen (CEA) be ordered preoperatively, if it would assist in staging and surgical planning. Postoperative CEA levels should be performed every 3 months for stage II and III disease for at least 3 years if the patient is a potential candidate for surgery or chemotherapy of metastatic disease. CEA is the marker of choice for monitoring the response of metastatic disease to systemic therapy. Data are insufficient to recommend the routine use of p53, ras, thymidine synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, microsatellite instability, 18q loss of heterozygosity, or deleted in colon cancer (DCC) protein in the management of patients with colorectal cancer. For pancreatic cancer, CA 19-9 can be measured every 1 to 3 months for patients with locally advanced or metastatic disease receiving active therapy. Elevations in serial CA 19-9 determinations suggest progressive disease but confirmation with other studies should be sought. New markers and new evidence to support the use of the currently reviewed markers will be evaluated in future updates of these guidelines.
Autoantibodies to nonhistone chromosomal proteins HMG‐1 and HMG‐2 in sera of patients with juvenile rheumatoid arthritis (1990)

IgG antibodies against the high mobility group (HMG) nonhistone chromosomal proteins HMG-1 and/or HMG-2 were detected in the sera of 49 (39%) of 126 antinuclear antibody (ANA)-positive patients with juvenile rheumatoid arthritis (JRA), by immunoblotting. Clinical diagnosis classified these patients in 2 major groups, 105 with pauciarticular-onset JRA and 21 with polyarticular-onset JRA. Anti-HMG-1 and/or anti-HMG-2 antibodies were found in 8 (25%) of 32 pauciarticular-onset JRA patients with uveitis and in 34 (47%) of 73 patients without uveitis, whereas anti-HMG-1 and/or anti-HMG-2 antibodies were found in 4 (24%) of 17 children with polyarticular-onset JRA without uveitis. Among 53 sera from ANA-negative JRA patients, 3 (6%) were positive for anti-HMG-1 and/or anti-HMG-2 antibodies, whereas no reactivity to HMG-1 or HMG-2 proteins was observed in 48 sera from age-matched children with nonrheumatic diseases.
Liver transplantation for hepatocellular carcinoma with portal vein tumor thrombus (2009)

Objective To evaluate the clinically applied value of liver transplantation for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVVT). Methods The clinical data of 146 HCC patients with PVTT undergoing liver transplantation from Jan. 2002 to Dec. 2006 were analyzed retrospectively. Ten cases of recurrent HCC after liver resection and 8 deaths during the operation were excluded from this study. The remaining 128 patients were followed up,and the relative risk factors influencing patients' survival were evaluated by univariate and multivariate analysis.Results The median follow-up periods of 128 patients were 13.0 months. The 6-, 12-,and 24-month cumulative survival rate was 78.1%, 51.6 % and 29. 7% respectively. The univariate analysis revealed that the grade of tumor thrombus,morphologic types and number of neoplasms were found to be significantly associated with patients' survival. The multivariate Cox regression analysis demonstrated the prognostic factors associated with patients' survival were grade of tumor thrombus,and number of neoplasms. Conclusion The long-term survival of HCC patients with PVTT treated by liver transplantation is not satisfaction.

Key words: 
Carcinoma, hepatocellular;  Portal vein;  Embolism;  Liver transplantation
Pharmacology and Pharmacokinetics of Paclitaxel (1994)

There remain several pharmacologic considerations relating to paclitaxel that are being, or need to be, explored. Some of the more important of these include the following issues: Further elaboration of the metabolic fate of paclitaxel. A multicenter study is currently being planned to determine the complete metabolic fate of paclitaxel, using radiolabeled (14C) drug. Establishing criteria for optimal dosing and scheduling, particularly in patients with organ dysfunction. Evaluation of the optimal use of paclitaxel in combination with other drugs, and the potential interactions of these drugs, which may result in different response and toxicity patterns. Several aspects of drug-drug interactions are being considered. Interactions between paclitaxel and other drugs that are highly protein bound. Interactions with the P-450 enzyme system, in which antineoplastic agents that are currently used in combination with paclitaxel, such as cisplatin and doxorubicin, have been shown to modulate these enzymes. Interactions at the level of hepatic metabolism between paclitaxel and the H2-antagonists used as a premedication to prevent hypersensitivity reactions. Different compounds of this class, including cimetidine, ranitidine, and famotidine, have variable modulatory effects on P-450 enzymes. The choice of a specific agent may therefore affect response and toxicity patterns, although to date, no clinically significant drug interactions have been observed. Interactions between paclitaxel and other drugs used as supportive therapy that may inhibit P-450 enzymes. One such drug is erythromycin, which has been shown in a rat model to block significantly the excretion of doxorubicin through the MDR mechanism (unpublished data, J.G. Kuhn).(ABSTRACT TRUNCATED AT 250 WORDS)
A signal analysis of network traffic anomalies (2002)

Identifying anomalies rapidly and accurately is critical to the efficient operation of large computer networks. Accurately characterizing important classes of anomalies greatly facilitates their identification; however, the subtleties and complexities of anomalous traffic can easily confound this process. In this paper we report results of signal analysis of four classes of network traffic anomalies: outages, flash crowds, attacks and measurement failures. Data for this study consists of IP flow and SNMP measurements collected over a six month period at the border router of a large university. Our results show that wavelet filters are quite effective at exposing the details of both ambient and anomalous traffic. Specifically, we show that a pseudo-spline filter tuned at specific aggregation levels will expose distinct characteristics of each class of anomaly. We show that an effective way of exposing anomalies is via the detection of a sharp increase in the local variance of the filtered data. We evaluate traffic anomaly signals at different points within a network based on topological distance from the anomaly source or destination. We show that anomalies can be exposed effectively even when aggregated with a large amount of additional traffic. We also compare the difference between the same traffic anomaly signals as seen in SNMP and IP flow data, and show that the more coarse-grained SNMP data can also be used to expose anomalies effectively.
Universal approximation bounds for superpositions of a sigmoidal function (1993)

Approximation properties of a class of artificial neural networks are established. It is shown that feedforward networks with one layer of sigmoidal nonlinearities achieve integrated squared error of order O(1/n), where n is the number of nodes. The approximated function is assumed to have a bound on the first moment of the magnitude distribution of the Fourier transform. The nonlinear parameters associated with the sigmoidal nodes, as well as the parameters of linear combination, are adjusted in the approximation. In contrast, it is shown that for series expansions with n terms, in which only the parameters of linear combination are adjusted, the integrated squared approximation error cannot be made smaller than order 1/n/sup 2/d/ uniformly for functions satisfying the same smoothness assumption, where d is the dimension of the input to the function. For the class of functions examined, the approximation rate and the parsimony of the parameterization of the networks are shown to be advantageous in high-dimensional settings.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
In Silico Drug Discovery Approaches on Grid Computing Infrastructures (2010)

The first step in finding a "drug" is screening chemical compound databases against a protein target. In silico approaches like virtual screening by molecular docking are well established in modern drug discovery. As molecular databases of compounds and target structures are becoming larger and more and more computational screening approaches are available, there is an increased need in compute power and more complex workflows. In this regard, computational Grids are predestined and offer seamless compute and storage capacity. In recent projects related to pharmaceutical research, the high computational and data storage demands of large-scale in silico drug discovery approaches have been addressed by using Grid computing infrastructures, in both; pharmaceutical industry as well as academic research. Grid infrastructures are part of the so-called eScience paradigm, where a digital infrastructure supports collaborative processes by providing relevant resources and tools for data- and compute-intensive applications. Substantial computing resources, large data collections and services for data analysis are shared on the Grid infrastructure and can be mobilized on demand. This review gives an overview on the use of Grid computing for in silico drug discovery and tries to provide a vision of future development of more complex and integrated workflows on Grids, spanning from target identification and target validation via protein-structure and ligand dependent screenings to advanced mining of large scale in silico experiments.
Network Rigidity and Metabolic Engineering in Metabolite Overproduction (1991)

In order to enhance the yield and productivity of metabolite production, researchers have focused almost exclusively on enzyme amplification or other modifications of the product pathway. However, overproduction of many metabolites requires significant redirection of flux distributions in the primary metabolism, which may not readily occur following product deregulation because metabolic pathways have evolved to exhibit control architectures that resist flux alterations at branch points. This problem can be addressed through the use of some general concepts of metabolic rigidity, which include a means for identifying and removing rigid branch points within an experimental framework.
A mutant of Escherichia coli conditionally defective in the synthesis of holo-[acyl carrier protein]. (1981)

Supplementation of Escherichia coli pantothenate auxotrophs with varying concentrations of pantothenate results in a concomitant variation of the intracellular level of CoA but has no effect on the level of holo-[acyl carrier protein] (holo-[ACP]) (Alberts, A., and Vagelos, P. R. (1966) J. Biol. Chem. 241, 5201-5204). The 4-phosphopantetheine moiety of CoA is transferred by the enzyme holo-[ACP] synthase to apo-[acyl carrier protein] (apo-[ACP]) to form holo-[ACP], the form active in lipid synthesis. We mutagenized an E. coli K12 pantothenate auxotroph and selected for mutants unable to grow on a low concentration of pantothenate (0.25 microM) but that grew on a much higher level (25 microM). One of these strains was completely deficient in holo-[ACP] synthase. Reversion and recombinational genetic analyses indicated that the mutant growth phenotype was due to an altered holo-[ACP] synthase activity. The changes in the intracellular levels of CoA and holo-[ACP] engendered by manipulation of the levels of pantothenate supplementation were consistent with a deficiency in holo-[ACP] synthase activity in cultures supplemented with low levels of pantothenate. The site of the genetic lesion (called acpS) was localized on the E. coli genetic map.
Altered acyl chain length specificity of Rhizopus delemar lipase through mutagenesis and molecular modeling (1997)

The acyl binding site of Rhizopus delemar prolipase and mature lipase was altered through site-directed mutagenesis to improve lipase specificity for short- or medium-chain length fatty acids. Computer-generated structural models of R. delemar lipase were used in mutant protein design and in the interpretation of the catalytic properties of the resulting recombinant enzymes. Molecular dynamics simulations of the double mutant, val209trp + phe112trp, predicted that the introduction of trp112 and trp209 in the acyl binding groove would sterically hinder the docking of fatty acids longer than butyric acid. Assayed against a mixture of triacylglycerol substrates, the val209trp + phe112trp mature lipase mutant showed an 80-fold increase in the hydrolysis of tributyrin relative to the hydrolysis of tricaprylin while no triolein hydrolysis was detected. By comparison, the val94Trp mutant, predicted to pose steric or geometric constraints for docking fatty acids longer than caprylic acid in the acyl binding groove, resulted in a modest 1.4-fold increase in tricaprylin hydrolysis relative to the hydrolysis of tributyrin. Molecular models of the double mutant phe95asp + phe214arg indicated the creation of a salt bridge between asp95 and arg214 across the distal end of the acyl binding groove. When challenged with a mixture of triacylglycerols, the phe95asp + phe214arg substitutions resulted in an enzyme with 3-fold enhanced relative activity for tricaprylin compared to triolein, suggesting that structural determinants for medium-chain length specificity may reside in the distal end of the acyl binding groove. Attempts to introduce a salt bridge within 8 A of the active site by the double mutation leu146lys + ser115asp destroyed catalytic activity entirely. Similarly, the substitution of polar Gln at the rim of the acyl binding groove for phe112 largely eliminated catalytic activity of the lipase.
[Isolation of protoplasts of Xanthomonas rubrilineans and their use in the study of localization of aminopeptidases]. (1992)

The culture of Xanthomonas rubrilineans was able to synthesize a number of intracellular aminopeptidases. To study localization of the enzymes in the cells, a protoplasting procedure was developed providing the yield of 99.7 per cent. The following subcellular fractions were isolated: periplasmic, cytoplasmic and membranous. It was shown that alanine aminopeptidase was a cytoplasmic enzyme and glutamate peptidase was a membrane-bound enzyme.
Titelbild: Angew. Chem. 16/2002 (2002)

Das Titelbild zeigt das Molecular Modeling eines sternförmigen sowie die schematische Darstellung eines linearen metallo-supramolekularen Polymers. Diese Moleküle sind wegen ihrer einzigartigen Eigenschaften für Werkstoffe von größtem Interesse. Metallo-supramolekulare Polymere entstehen durch gezielte Kombination von Polymeren, deren Materialeigenschaften die Werkstoffentwicklung der vergangenen Jahre dominierten, mit supramolekularen Liganden, deren Fähigkeit zur spontanen Selbstorganisation neuartige Strukturen auf molekularer Ebene entstehen lässt, und Übergangsmetallionen, deren physikalische Eigenschaften charakteristische Funktionalitäten einbringen. Die Eigenschaften der Einzelkomponenten ermöglichen die Charakterisierung mit etablierten Methoden wie UV/Vis-Spektroskopie, NMR-Spektroskopie und Gelpermeationschromatographie. Die Kombination erfordert jedoch auch die Anwendung neuer Methoden wie analytische Ultrazentrifugation oder MALDI-TOF-Massenspektrometrie. Mehr zu metallo-supramolekularen Polymeren auf der Basis von Bipyridin- und Terpyridinkomplexen erfahren Sie im Aufsatz von U. S. Schubert und C. Eschbaumer auf S. 3016 ff.
Effects of indomethacin on demineralized bone‐induced heterotopic ossification in the rat (1991)

Indomethacin inhibits bone formation when treatment is initiated before the implantation of demineralized bone matrix (DBM). For the inhibition of bone induction to occur, indomethacin treatment had to be initiated 6 h or more before implantation of DBM. Initiating the drug treatment at or after the time of DBM implantation had no effects on the amounts of new bone formed. The inhibition by indomethacin is dose related over a range between 0.04 and 4 mg/kg body weight. Recovered day-1 DBM implants, transplanted into indomethacin pre- and posttreated syngeneic rats, formed bone at the same rate as controls did. However, recovered day-1 DBM implants lyophilized before transplantation showed decreased bone formation but significant dystrophic calcification as judged by a lower alkaline phosphatase activity and an elevated calcium content.
Clinical value of pancreatitis-associated protein in acute pancreatitis. (1997)

Our results indicate that the clinical value of PAP in acute pancreatitis is quite limited and, in particular, that PAP is not a useful marker for determining the severity of the disease.
Absence of Vasoactive Intestinal Peptide Expression in Hematopoietic Cells Enhances Th1 Polarization and Antiviral Immunity in Mice (2011)

Vasoactive intestinal peptide (VIP) induces regulatory dendritic cells (DC) in vitro that inhibit cellular immune responses. We tested the role of physiological levels of VIP on immune responses to murine CMV (mCMV) using VIP-knockout (VIP-KO) mice and radiation chimeras engrafted with syngenic VIP-KO hematopoietic cells. VIP-KO mice had less weight loss and better survival following mCMV infection compared with wild-type (WT) littermates. mCMV-infected VIP-KO mice had lower viral loads, faster clearance of virus, with increased numbers of IFN-γ(+) NK and NKT cells, and enhanced cytolytic activity of NK cells. Adaptive antiviral cellular immunity was increased in mCMV-infected VIP-KO mice compared with WT mice, with more Th1/Tc1-polarized T cells, fewer IL-10(+) T cells, and more mCMV-M45 epitope peptide MHC class I tetramer(+) CD8(+) T cells (tetramer(+) CD8 T cells). mCMV-immune VIP-KO mice had enhanced ability to clear mCMV peptide-pulsed target cells in vivo. Enhanced antiviral immunity was also seen in WT transplant recipients engrafted with VIP-KO hematopoietic cells, indicating that VIP synthesized by neuronal cells did not suppress immune responses. Following mCMV infection there was a marked upregulation of MHC-II and CD80 costimulatory molecule expression on DC from VIP-KO mice compared with DC from WT mice, whereas programmed death-1 and programmed death ligand-1 expression were upregulated in activated CD8(+) T cells and DC, respectively, in WT mice, but not in VIP-KO mice. Because the absence of VIP in immune cells increased innate and adaptive antiviral immunity by altering costimulatory and coinhibitory pathways, selective targeting of VIP signaling represents an attractive therapeutic target to enhance antiviral immunity.
Precomputed search trees: planning for interactive goal-driven animation (2006)

We present a novel approach for interactively synthesizing motions for characters navigating in complex environments. We focus on the runtime efficiency for motion generation, thereby enabling the interactive animation of a large number of characters simultaneously. The key idea is to precompute search trees of motion clips that can be applied to arbitrary environments. Given a navigation goal relative to a current body position, the best available solution paths and motion sequences can be efficiently extracted during runtime through a series of table lookups. For distant start and goal positions, we first use a fast coarse-level planner to generate a rough path of intermediate sub-goals to guide each iteration of the runtime lookup phase.We demonstrate the efficiency of our technique across a range of examples in an interactive application with multiple autonomous characters navigating in dynamic environments. Each character responds in real-time to arbitrary user changes to the environment obstacles or navigation goals. The runtime phase is more than two orders of magnitude faster than existing planning methods or traditional motion synthesis techniques. Our technique is not only useful for autonomous motion generation in games, virtual reality, and interactive simulations, but also for animating massive crowds of characters offline for special effects in movies.
Single Layered Small Intestinal Submucosa in the Repair of Severe Chordee and Complicated Hypospadias (2003)

Although this study includes a small population of patients and has limited followup, our favorable experience with single layer SIS suggests that it is a safe and effective, commercially available material for corporal body grafting to correct severe chordee as part of a multistage surgical approach to repair complex hypospadias. A larger series of patients with longer followup is necessary to determine if the chordee correction remains durable. Our experience is insufficient to judge its efficacy in single stage repairs.
A Reconfigurable Architecture with Sequential Logic-Based Stochastic Computing (2017)

Computations based on stochastic bit streams have several advantages compared to deterministic binary radix computations, including low power consumption, low hardware cost, high fault tolerance, and skew tolerance. To take advantage of this computing technique, previous work proposed a combinational logic-based reconfigurable architecture to perform complex arithmetic operations on stochastic streams of bits. The long execution time and the cost of converting between binary and stochastic representations, however, make the stochastic architectures less energy efficient than the deterministic binary implementations. This article introduces a methodology for synthesizing a given target function stochastically using finite-state machines (FSMs), and enhances and extends the reconfigurable architecture using sequential logic. Compared to the previous approach, the proposed reconfigurable architecture can save hardware area and energy consumption by up to 30% and 40%, respectively, while achieving a higher processing speed. Both stochastic reconfigurable architectures are much more tolerant of soft errors (bit flips) than the deterministic binary radix implementations, and their fault tolerance scales gracefully to very large numbers of errors.
Nanomedicine in pulmonary delivery (2009)

The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed.
Synthesis and Pharmacological Activities of Novel 3-(Isoxazol-3-yl)-quinazolin-4(3H)-one Derivatives (1999)

Several new 3-(isoxazol-3-yl)-quinazolin-4(3H)-one derivatives were synthesized and tested for their analgesic and antiinflammatory activities, as well as for their acute toxicity and ulcerogenic effect. A few compounds were as active as phenylbutazone in the writhing and acetic acid peritonitis tests. They had a very low ulcerogenic effect.