gebhart/patrepeval huggingface dataset:
Effects of the tricyclic nucleoside 6-amino-4-methyl-8-(beta-D-ribofuranosyl)- pyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine on the viability and cell cycle distribution of L1210 cells in vitro. (1985)

TCN (1 microM) totally inhibited the growth of L1210 cells in culture and caused progressive loss of cellular viability, as indicated by a decreased clonogenicity and nigrosin dye exclusion. After 24 h or more of TCN treatment, a significant fraction of the cells had shrunk in size but did not fragment into dye-impermeable vesicles as reported previously for N1S1-67 hepatoma cells (P. G. W. Plagemann, J. Natl. Cancer Inst., 57: 1283-1295, 1976). TCN-induced growth inhibition was accompanied by a block of cell cycle progression in G1 or at the G1-S boundary. At all TCN concentrations studied, progression of cells out from behind this block was evident as a depletion of the early S-phase population in comparison to controls, while increasing the concentration of TCN (0.1 to 1 microM) led to a progressive retention of cells in S phase, suggesting a slowing of progression through S phase. The fraction of S-phase cells incorporating [methyl-3H]thymidine and the amount of [methyl-3H]thymidine incorporated per labeled cell were both decreased by TCN treatment. Increasing the concentration of TCN (0.1 to 1 microM) progressively decreased DNA synthesis and increased cell lethality. Thus it appeared that inhibition of DNA synthesis might cause the retention of cells in S phase which is associated with TCN lethality.
Membrane fusion induced by mutual interaction of the two charge-reversed amphiphilic peptides at neutral pH (1991)

An anionic amphiphilic peptide and the charge-reversed cationic peptide are synthesized. They contain 20 amino acids with the same sequence except for 5 Glu residues for the anionic versus 5 Lys residues for the cationic peptides. Fusion of egg phosphatidylcholine large unilamellar vesicles is assayed with the fluorescent probes by the lipid mixing and the internal content mixing at neutral pH. The peptide mixture causes a rapid and efficient membrane fusion, in spite of no fusions with each peptide by itself. Each peptide takes nearly random coils with a small amount of helix, but the peptide mixture has an ordered helical structure. The equimolar peptide mixture forms a much more hydrophobic complex than those of different molar ratios of peptides and also that of each peptide itself. The equimolar peptide mixture causes the most efficient fusion. Preincubations of two peptides before addition to vesicles cause the slower rates of fusion. The fusion is greatly reduced at higher ionic strength and nearly zero at 800 mM NaCl and 40 mM sodium phosphate. Each peptide and the peptide mixture show the same alpha-helical structure, interact with vesicles, but do not induce fusion at higher ionic strengths. These results suggest that the two peptides interact mutually through the electrostatic Coulombic interaction between the charged groups. The electrically neutralized hydrophobic complex aggregates the separate vesicles together and interacts with the hydrocarbon region of lipid bilayers to cause fusion.
Biosynthesis of the immunosuppressant immunomycin: the enzymology of pipecolate incorporation (1991)

Immunomycin, an immunosuppressant closely related to FK 506, contains a pipecolate residue in amide linkage with an acyl group in its polyketide backbone. An enzyme activating L-pipecolic acid has been isolated from Streptomyces hygroscopicus var. ascomyceticus, which produces immunomycin. Purification results in a monomer of 170 kDa exhibiting N-terminal heterogeneity, apparently arising from proteolysis of a single species. It is a dimer under native conditions. The reaction appears to use an aminoacyl adenylate as an intermediate in the activating reaction, as do most activating enzymes involved in nonribosomal peptide synthesis. A range of pipecolate and proline analogues act as substrates in the pyrophosphate-ATP exchange resulting from the adenylation reaction. Several analogues are inhibitors of the subsequent thioesterification of the enzyme. Antibody raised to the purified enzyme was used to follow antigen during the course of fermentation. Maximal levels of antigen are found when synthesis of immunomycin is maximal. Ten of twelve immunomycin nonproducing mutants lack detectable pipecolate-activating enzyme in Western blots. From the enzymatic characteristics, substrate specificity, and immunological properties, we propose that we have isolated the enzyme responsible for activating pipecolic acid for immunomycin biosynthesis.
Practical C−H Functionalization of Quinones with Boronic Acids (2011)

A direct functionalization of a variety of quinones with several boronic acids has been developed. This scalable reaction proceeds readily at room temperature in an open flask using inexpensive reagents: catalytic silver(I) nitrate in the presence of a persulfate co-oxidant. The scope with respect to quinones is broad, with a variety of alkyl- and arylboronic acids undergoing efficient cross-coupling. The mechanism is presumed to proceed through a nucleophilic radical addition to the quinone with in situ reoxidation of the resulting dihydroquinone. This method has been applied to complex substrates, including a steroid derivative and a farnesyl natural product.
Adenosine Deaminase Inhibitors:  Synthesis and Biological Evaluation of Unsaturated, Aromatic, and Oxo Derivatives of (+)-erythro-9-(2‘S-Hydroxy-3‘R-nonyl)adenine [(+)-EHNA] (2000)

The synthesis and biological evaluation of three classes of chain-modified derivatives of (+)-EHNA are described. Among the 5', 6'-unsaturated derivatives, the Z-isomer was the most potent inhibitor of adenosine deaminase (ADA) but 3-fold less active than (+)-EHNA. Several 9-aralkyladenines (ARADs) have been prepared, and their inhibitory activity was determined. A minimum of two carbon atoms separating the aromatic ring from the adenine-bearing carbon (C-3') was found to be essential for ADA activity equal to or slightly greater than that of (+)-EHNA. Finally, replacement of the C-5' carbon with an oxygen resulted in reduced potency.
Generalized B-spline surfaces of arbitrary topology (1990)

B-spline surfaces, although widely used, are incapable of describing surfaces of arbitrary topology. It is not possible to model a general closed surface or a surface with handles as a single non-degenerate B-spline. In practice such surfaces are often needed. In this paper, we present generalizations of biquadratic and bicubic B-spline surfaces that are capable of capturing surfaces of arbitrary topology (although restrictions are placed on the connectivity of the control mesh). These results are obtained by relaxing the sufficient but not necessary smoothness constraints imposed by B-splines and through the use of an n-sided generalization of B&amp;eacute;zier surfaces called S-patches.
Particle Size Analysis: A comparative study of various methods (1995)

Abstract The particle size distribution of component materials can be important parameter governing the proper function of many industrial products. At present, accurate determination of particle size by currently available methods is difficult for both theoretical and practical reasons. In this paper, some elementary notions regarding particle sizing are reviewed as is the relative performance of commercially available particle sizing instrumentation which could be used for particle size analysis of dry powders. Our results indicate that various particle size instruments yield significantly (even vastly) different particle size distributions for the same material. Without great care on the part of the investigator, the results obtained from any given instrument may not accurately describe the powder in question and thus may cause incorrect technical recommendations. The use of Fraunhofer diffraction instruments on samples containing irregularly shaped small ( &lt; 10 μm) particles of low refractive index requires considerable caution.
A critical review of the systolic time intervals. (1977)

The theoretical basis for the use of the systolic time intervals has been largely established. The method has been validated by direct measures from within the circulatory system. Standards for equipment and technique have been defined. Numerous clinical studies have demonstrated the value of this quantitative noninvasive technique for assessing left ventricular performance. At present there is need for further studies of the clinical usefulness of the systolic time intervals to improve both diagnosis and therapy of various cardiovascular disorders.
Improved and More-Rapid History Matching With a Nonlinear Proxy and Global Optimization (2006)

Abstract The generation of reservoir simulation models that match field production data has been a long-time industry challenge. This paper presents two workflows for assisted history match. One workflow minimizes the misfit between simulated versus history data with a global optimizer, by adjusting reservoir and well unknown parameters in the simulation model. An alternative workflow is used to reduce the number of numerical simulations. The workflow trains a comprehensive nonlinear proxy model with a small set of numerical simulations from experimental design. The nonlinear proxy neural network is used to characterize parameter sensitivities to reservoir parameters and to generate solution sets of the parameters that match history. The neural network solution sets can be validated with the simulator or used as initial solutions for a full optimization. The paper demonstrates that the neural network is an excellent proxy for the numerical simulator over the trained parameter space. A field example from a water injection project illustrates the approach with excellent matches for individual well fluid rates, using a number of reservoir and well parameters. The use of the proxy yields excellent matches for well production profiles.
FTY720 Immunosuppression Impairs Effector T Cell Peripheral Homing Without Affecting Induction, Expansion, and Memory (2000)

FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride) prolongs survival of solid organ allografts in animal models. Mechanisms of FTY720 immunomodulation were studied in mice infected with lymphocytic choriomeningitis virus (LCMV) to assess T cell responses or with vesicular stomatitis virus to evaluate Ab responses. Oral FTY720 (0.3 mg/kg/day) did not affect LCMV replication and specific CTL and B cells were induced and expanded normally. Moreover, the anti-viral humoral immune responses were normal. However, FTY720 treatment showed first a shift of overall distribution of CTL from the spleen to peripheral lymph nodes and lymphocytopenia was observed. This effect was reversible within 7-21 days. Together with unimpaired T and B cell memory after FTY720 treatment, this finding rendered enhancement of lymphocyte apoptosis by FTY720 in vivo unlikely. Secondly, the delayed-type hypersensitivity reaction to a viral MHC class I-presented peptide was markedly reduced by FTY720. These results were supported by impaired circulation of LCMV specific TCR transgenic effector lymphocytes in the peripheral blood and reduced numbers of tissue infiltrating CTL in response to delayed-type hypersensitivity reaction. Thirdly, in a CD8+ T cell-mediated diabetes model in a transgenic mouse expressing the LCMV glycoprotein in the islets of the pancreas, FTY720 delayed or prevented disease by reducing islet-infiltrating CTL. Thus, FTY720 effectively reduced recirculation of CD8+ effector T cells and their recruitment to peripheral lesions without affecting the induction and expansion of immune responses in secondary lymphoid organs. These properties may offer the potential to treat ongoing organ-specific T cell-mediated immunopathologic disease.
High serum YKL-40 level in a cohort of octogenarians is associated with increased risk of all-cause mortality (2007)

YKL-40 is secreted by macrophages, neutrophils, chondrocytes, endothelial-, vascular smooth muscle- and cancer cells. Interleukin (IL)-6 stimulates YKL-40 production in human in vivo studies. High serum YKL-40 is associated with poor prognosis in patients with inflammatory diseases and cancer. We studied whether serum YKL-40 was associated with systemic low-level inflammation, an immune risk phenotype, and mortality in relatively healthy 80-year old humans. Serum YKL-40, IL-6 and tumour necrosis factor (TNF)-alpha were measured by enzyme-linked immunosorbent assays (ELISAs) in octogenarians (n = 151) and serum YKL-40 in 18-30-year-olds (n = 89). Fifty-one of the octogenarians died during the 6-year follow-up. Serum YKL-40 in octogenarians was higher compared to the level in young people (median 116 versus 31 microg/l, P < 0.0005). Serum YKL-40 correlated with serum IL-6 in elderly women (Spearman's rho = 0.30, P = 0.009) and men (rho = 0.25, P = 0.003), but only with serum TNF-alpha (rho = 0.23, P = 0.05) and C-reactive protein (CRP) (rho = 0.57, P < 0.0005) among the elderly women. In addition, high serum level of YKL-40 was associated with a low CD4 : CD8 cell ratio. Univariate analysis of serum YKL-40 (logarithmically transformed and divided by tertiles) showed significant association with all-cause mortality [tertile 3: hazard ratio (HR) = 2.38, 95% confidence interval (CI): 1.19-4.78, P = 0.02]. The effect persisted after adjusting for potential confounders (sex, smoking, body mass index, chronic disease and anti-inflammatory medicine). These results suggest that serum YKL-40 is a prognostic and sensitive biomarker of all-cause mortality in octogenarians.
Multidrug resistance: clinical relevance in acute leukemia. (1993)

The multidrug resistance (MDR) phenotype represents an important major mechanism of resistance to anthracyclines and related natural products that lends itself to clinical exploitation. Overexpression of the mdr1 gene or its glycoprotein product has been linked to a number of poor prognostic factors in acute myeloid leukemia and adversely affects treatment outcome. Clinical trials are now under way testing pharmacologic modulators of MDR in acute leukemia. Although preliminary results are encouraging, MDR modulators may alter the clearance of some antineoplastics and thereby confound interpretation of randomized trials. This review examines diagnostic methods of MDR detection, its prevalence and impact in acute leukemia, and strategies for MDR reversal.
The RIIIS/J inbred mouse strain as a model for von Willebrand disease (1990)

Mice of the RIIIS/J inbred strain have prolonged bleeding times (greater than 15 minutes) after experimental injury when compared with normal C57BL/6J mice (1.8 minutes) and other strains of mice. The prolonged bleeding time was accompanied by normal platelet counts. Platelet aggregation with collagen and agglutination with ristocetin were not significantly altered in RIIIS/J mice. Also, platelets from RIIIS/J mice had normal serotonin content and normal numbers of dense granules by electron microscopy. Thus, the bleeding abnormality is not due to platelet storage pool deficiency as has been found in several other mouse mutants. The activated partial thromboplastin time (APTT) which plasma from RIIIS/J mice was prolonged compared with normal mice, and factor VIII:C activity and von Willebrand antigen levels were one half to one third that of normal mouse plasma. Factor XI activity was also significantly deficient (levels at 42% to 64% of normal). Plasma of RIIIS/J mice contained the full complement of multimers of von Willebrand factor, although each multimer was lower in concentration compared with that in normal mice. Platelet alpha-granule von Willebrand antigen levels were similar to those of normal mice. The prolonged bleeding time of RIIIS/J mice was corrected by treatment with desmopressin. Heterozygous C57BL/6J x RIIIS/J F1 animals had low plasma von Willebrand antigen levels like the RIIIS/J parent and had variable bleeding times. Inheritance of the bleeding tendency was as an incomplete dominant, autosomal trait. These data indicate the RIIIS/J strain is a suitable animal model for type IA von Willebrand disease.
Relationships and differentially expressed genes among pancreatic cancers examined by large-scale serial analysis of gene expression. (2002)

Pancreatic adenocarcinoma is among the most fatal of cancers, in part because of late diagnosis and a lack of effective therapies. Comprehensive studies are needed to better understand and address the cellular mechanisms and pathways of tumorigenesis. Serial analysis of gene expression was used to analyze gene expression profiles of pancreatic cancer cell lines, short-term cultures of normal pancreatic ductal epithelium, and primary pancreatic cancer tissue. A total of 294,920 tags representing 77,746 genes in 10 serial analysis of gene expression libraries were analyzed. A pancreatic cancer cell line (Hs766T) that exhibited a "normoid" profile of gene expression was identified. Several genes that may be involved in the fundamental nature of malignant changes in pancreatic ductal epithelium were suggested from those differentially and highly expressed in pancreatic cancer cells as compared with normal epithelium. Some overexpressed genes, such as S100A4, prostate stem cell antigen, carcinoembryonic antigen-related cell adhesion molecule 6, and mesothelin, suggest potential use as diagnostic markers. Others suggest potential novel therapeutic targets.
Demonstration of reverse symmetry waveguide sensing in aqueous solutions (2002)

A reverse symmetry waveguide is presented for evanescent wave sensing in aqueous solutions. The waveguide consists of a thin polystyrene film, supported by a thicker substrate layer of nanoporous silica on glass. The nanoporous substrate layer has a refractive index of nS=1.193, hence, with an aqueous cover refractive index of nC=1.331, a reverse symmetry (nS&amp;lt;nC) is obtained. A surface relief grating formed in the polystyrene film is used as a coupling element. Sensitivities considerably higher than for a conventional waveguide sensor are demonstrated.
Scene text extraction and translation for handheld devices (2005)

We describe a scene text extraction system for handheld devices to provide enhanced information perception services to the user. It uses a color camera attached to a personal digital assistant as an input device to capture scene images from the real world and it employs image enhancement and segmentation methods to extract written information from the scene, convert them to text information and show them to the user so that he/she can see both the real world and information together. We implemented a prototype application: an automatic sign/text language translation for foreign travelers, where people can use the system whenever they want to see text or signs in their own language where they are originally written in a foreign language in the scene.
Actinoidins A and A2: Structure determination using 2D NMR methods. (1987)

The structural analysis of the intact glycopeptide antibiotics, actinoidins A (1a) and A2 (1b), by two-dimensional 1H NMR is described. The location of the single chlorine at the A3 position and the sites of attachment of the four carbohydrate substituents in actinoidin A are elucidated based on correlation spectroscopy (COSY), double quantum coherence experiments (DQCE), homonuclear Hartmann-Hahn experiments (HOHAHA) and nuclear Overhauser spectroscopy (NOESY). Similar 2D correlation and NOE NMR experiments are then performed on the novel analog, actinoidin A2, to determine its structure. The structural difference between actinoidins A and A2 is shown to reside in the presence of L-rhamnose in actinoidin A2 in place of L-acosamine in actinoidin A. All questions concerning the stereo-chemistry of the chiral centers in both the heptapeptide core and the carbohydrate moieties in each of these antibiotics could be successfully addressed with the exception of Gl', the alpha-carbon on the N-terminal amino acid which is known to have the R-configuration from previous studies.
Morphological Control of Rod- and Fiberlike SBA-15 Type Mesoporous Silica Using Water-Soluble Sodium Silicate (2004)

Well-defined rodlike and fiberlike SBA-15 mesoporous silicas have been selectively synthesized from an aqueous reaction mixture consisting of a commercial sodium silicate solution, P123 triblock copolymer and HCl. The morphologies and physicochemical properties of the products were found to be greatly affected by the shearing stress exerted by cylindrical silicated-surfactant micelles in a flowing solution, referred to hereafter as “shearing flow”. Monodispersed rodlike particles ca. 0.5-μm wide and ca. 1−2-μm long were formed under static reaction conditions, whereas continuous stirring of the reaction mixture led to the formation of fiberlike silicas with lengths of several hundred micrometers and a relatively uniform width of ca. 10 μm. The effects of the synthesis conditions, such as the initial ratio of the reactants, time, temperature, and the acid source, in addition to shearing flow, on particle morphologies were investigated. Fiberlike silicas of various lengths were obtained from a relatively wide range of synthesis conditions, while monodispersed rodlike silicas were prepared under very specific conditions. Each fiberlike product was found to be comprised of a bundle of fibers, with each fiber formed by the coupling of rodlike particles of almost identical size, irrespective of different synthesis conditions.
Introduction (2013)

This introductory chapter expounds on the effects of New Pleading following the Bell Atlantic Corp. v. Twombly and Ashcroft v. Iqbal cases. In civil procedure, the court employs a screening process for filing pleadings or “complaints” (in the U.S. lexicon) that require adequate legal and factual sufficiency in order for that pleading to be pursued in court. In the case of Twombly and Iqbal, the court had imposed a new “plausibility” requirement unheard of in the past fifty years. The New Pleading reform is meant to save both the court and defendant the costs of litigation. However, New Pleading is not without its disadvantages—in order to balance out the complications of New Pleading, there must be a renewed focus on more cost-efficient discovery measures and cooperative management.
Effect of high energy radiation on the stress–relaxation of ultra‐high molecular weight linear polyethylene (1987)

Abstract Stress–relaxation behavior was studied in ultra‐high and normal molecular weight linear polyethylenes (UHMWPE and NMWPE) as a function of radiation dose over the range 0–128 Mrad. Irradiation up to 16 Mrad raises the crystallinity in both types of PE, as demonstrated previously, 1 and thus increases the initial modulus. Also, the initial modulus of NMWPE is higher than that of UHMWPE because the former has a higher crystallinity. Consequently, the initial stress at a constant imposed strain of 1% varies greatly between the two materials. To eliminate the effect of this initial difference on relaxed stress, the stress–relaxation data were normalized with respect to the initial stress and plotted as the fraction, retained stress after time t /initial stress. The normalized plots show no significant difference between NMWPE and UHMWPE in their stress–relaxation behavior. For both materials stress retention improves progressively with increasing radiation dose, the percentage improvement being greatest at long times (50% at 50 h and 64 Mrad, compared with 6% at 10 −2 h). These results are interpreted to indicate that radiation crosslinking in the amorphous phase is independent of molecular weight and preferentially retards those molecular motions responsible for short relaxation times. The motions in question could involve molecular flow in the amorphous phase or “pull out” of tie molecules from the crystalline lamellae.