gebhart/patrepeval huggingface dataset:
Sites of organic acid production and absorption in gastrointestinal tract of the pig (1975)

The relationship between diet, pH, and microbial digestion of carbohydrate was examined in 24 pigs fed either a conventional or a low-protein, high-cellulose experimental diet and sacrificed 2, 4, 8, or 12 h after a meal. In animals fed the control diet contents of the cranial half of the stomach demonstrated marked, cyclic fluctuations in pH and high concentrations of organic acids. Contents of the caudal (glandular) half were lower in both pH and organic acid concentration. Despite concentrations of volatile fatty acids (VFAs) as high as 250 meq/liter in the large intestine, the pH remained relatively neutral. The VFA levels remained relatively constant throughout the length of the colon. The VFA transport across isolated gastric and large intestinal mucosa also was examined. All four types of gastric mucosa absorbed and transported VFA at substantial rates. Mucosa of pig cecum and colon transported VFA at much greater rates than gastric mucosa and greater rates than previously determined in equine large intestinal mucosa or even bovine rumen epithelium. Comparison with results of earlier studies in the pony suggested that the higher concentration of VFA in the large intestinal contents of pigs was due to the more rapid rate of digesta passage rather than to less efficient absorption of fatty acids.
Multiple-harmonic conversion of 1064 nm radiation in rare gases (1988)

The authors report the observation of very-high-order odd harmonics of Nd:YAG laser radiation in rare gases at an intensity of about 1013 W cm-2. Harmonic light as high as the 33rd harmonic in the XUV range (32.2 nm) is generated in argon. The key point is that the harmonic intensity falls slowly beyond the fifth harmonic as the order increases. Finally, a UV continuum, beginning at 350 nm and extending down towards the short wavelength region is apparent in xenon.
Effects of the Oral, Direct Factor Xa Inhibitor Rivaroxaban on Platelet‐Induced Thrombin Generation and Prothrombinase Activity<sup>1</sup> (2007)

Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in advanced development. This study was undertaken to investigate its effects on thrombin generation. In this placebo-controlled, randomized, crossover study, 12 healthy subjects received rivaroxaban (single 5- or 30-mg dose) or placebo. Thrombin generation was investigated by measuring the endogenous thrombin potential and prothrombinase-induced clotting time. Maximal effect of rivaroxaban was observed 2 hours after drug administration: prothrombinase-induced clotting time was prolonged 1.8 and 2.3 times baseline after rivaroxaban 5 and 30 mg, respectively. Collagen-induced endogenous thrombin potential was reduced by approximately 80% and approximately 90% compared with baseline after rivaroxaban 5 and 30 mg, respectively, and tissue factor-induced endogenous thrombin potential was reduced by approximately 40% (5 mg) and approximately 65% (30 mg), respectively. Thrombin generation remained inhibited for 24 hours. There was a close correlation between plasma concentration of rivaroxaban and prolongation of prothrombinase-induced clotting time and reduction in endogenous thrombin potential. Rivaroxaban strongly inhibits platelet-induced thrombin generation, after activation of either platelets or the coagulation pathway, even in the presence of minimal factor Xa inhibition in plasma.
Preferential infection of CD4+ memory T cells by human immunodeficiency virus type 1: evidence for a role in the selective T-cell functional defects observed in infected individuals. (1990)

CD4+ T cells of patients with AIDS exhibit a qualitative defect in their ability to respond to soluble antigen while their responses to mitogens remain normal. CD4+ T cells can be broadly divided phenotypically into "naive" [CD45RA+ (2H4+)] and "memory" [CD29+ (4B4+) or CD45RO+ (UCHL1+)] cell subpopulations, which represent distinct maturation stages. To determine the human immunodeficiency virus type 1 (HIV-1) infectability of memory and naive CD4+ T-cell subsets in vitro and to determine the in vivo preference of HIV-1 in these subpopulations, we obtained highly purified CD4+ T-cell subsets from normal and HIV-1-infected individuals and studied them by viral cultivation, quantitative polymerase chain reaction, and functional assays. Polymerase chain reaction studies demonstrated that the memory cell subset of CD4+ T cells is preferentially infected (4- to 10-fold more than naive T cells) by HIV-1 in vitro, and these memory cells are the principal reservoir for HIV-1 within CD4+ T cells obtained from infected individuals. Functional abnormalities attributable to CD4+ T cells in HIV-infected individuals (failure to respond in vitro to soluble antigen or to anti-CD3 monoclonal antibodies) were shown to reside primarily within these memory cells. Thus, the present study suggests that the selective functional defects present in the memory CD4+ T-cell subset of HIV-infected individuals may be a direct result of the preferential infection and consequently greater viral burden within these cells.
Production of scFv Antibody Fragments from a Hybridoma with Functional Activity Against Human Vascular Endothelial Growth Factor (2009)

Vascular endothelial growth factor (VEGF) plays a major role in the development of aberrant neovascularization in ocular diseases such as diabetic retinopathy and age-related macular degeneration (ARMD), and is an important therapeutic target for these diseases. Monoclonal antibodies specific for VEGF are in clinical use for some patients with ARMD, delivered by intraocular injection. We have shown previously that single chain antibody fragments (scFv) penetrate into the eye when applied topically to the ocular surface. Here we describe the production of a scFv from a monoclonal antibody specific for human VEGF and demonstrate its ability to decrease proliferation of human umbilical vein endothelial cells in culture. A suitably formulated anti-VEGF scFv may have potential as a less invasive topical treatment for potentially blinding neovascular diseases of the eye.
Crystal Structure of Coproporphyrinogen Oxidase (CPO). (2004)

Abstract CPO, an essential enzyme in the heme biosynthetic pathway, catalyzes the oxidative decarboxylation of two propionate side chains of coproporphyrinogen III to form vinyl groups in the product protoporphyrinogen IX. CPO mutations are responsible for the disease hereditary coproporphyria. All eukaryotes express a highly conserved, oxygen-dependant form of CPO. Yeast and human CPO have a sequence identity of 52% at the amino acid level. To probe the biochemical basis of catalytic activity and to determine the deleterious effects of clinically identified mutations, we determined the crystal structure of CPO from S. cerevisiae. This is the first reported structure of a eukaryotic CPO. A cDNA encoding CPO (Hem13p) was expressed in E. coli as a histidine tagged protein. Hem13p was purified and concentrated to 25 mg/ml and crystals were grown in the presence of 18% PEG 8000, 0.1 M HEPES, pH 7.5, 2% isopropanol, 0.2 M Na-acetate. The crystal structure was determined by optimized sulfur anomalous scattering and refined to a resolution of 2.0 Å. The protein folds into a novel structure featuring a central flat seven-stranded antiparallel beta-sheet flanked on each side with helices. The homodimeric structure of CPO is formed by a short isolated strand that forms a beta-ladder between the two monomers. Each monomer contains an active site formed between the flat beta-sheet and adjacent helices near the dimer interface. Many of the conserved residues are located at this interface. The deep active site cleft is lined by conserved residues and has been captured in an open and a closed conformation in two different crystal forms. The substrate cavity is completely buried in the closed conformation by an approximate 8 Å movement of a helix that forms a lid over the active site. The volume of the enclosed cavity precisely accommodates a modeled molecule of coproporphyrinogen III. The model indicates binding of two propionate side chains of coproporphyrinogen with two invariant arginines. The pyrrole nitrogens of the substrate are positioned to be coordinated by an invariant asparagine in a fashion similar to that described for uroporphyrinogen decarboxylase (EMBO J, 2003, 22: 6225–33). Nineteen point mutations have been described in association with hereditary coproporphyria and we have mapped these to the crystal structure. Only two mapped to the active site. Fourteen mutations were predicted to destabilize the protein and 4 of these occur at the dimer interface. Three mutations mapped to the solvent exposed surface of CPO. The crystal structure supports a model in which the enzymatic reaction occurs in an isolated cavity formed by a conformational change induced by substrate binding. The conformational change could create a binding site for molecular oxygen, the cofactor, and provide a mechanism to protect coproporphyrinogen III from inappropriate oxidation and the subsequent peroxidation of protoporphyrinogen IX.
Image Segmentation with Detection of Highlights and Inter-Reflections Using Color (1989)

Abstract : We present an approach to the construction of a computational model for color image segmentation based on the physical properties of sensors, illumination lights and surface reflectances. Using the established model, we perform color image segmentation and detect small inter-reflections as well as highlights.
Activity of antifolates against Pneumocystis carinii dihydrofolate reductase and identification of a potent new agent. (1987)

The therapy of Pneumocystis carinii (PC) pneumonia is often unsuccessful, particularly in patients with acquired immune deficiency syndrome (AIDS). Because of difficulties in growing the organism in vitro or obtaining purified organisms, current treatment choices have been made with little information on the metabolic effects of therapeutic agents on PC. This report quantitates the effects of the commonly used antifolates as well as the classic antineoplastic antifolate methotrexate and a lipid-soluble analogue, trimetrexate, on the target enzyme, dihydrofolate reductase (DHFR), in the PC organisms. Trimethoprim and pyrimethamine were found to be weak inhibitors (ID50 = 39,600 and 2,800 nM, respectively), while methotrexate and trimetrexate were potent reductase inhibitors (ID50 = 1.4 and 26.1 nM, respectively). transport studies with radiolabeled compounds showed that compounds with the classic folate structure (methotrexate and leucovorin) were not taken up by the intact PC organisms. In contrast, trimetrexate exhibited rapid uptake. These results suggest a major therapeutic advantage may be gained by combining a potent, readily transported PC DHFR inhibitor such as trimetrexate with the reduced folate leucovorin to achieve a highly potent antiprotozoan effect while preventing toxicity to mammalian cells.
Structural Determinants of Unique Properties of Human IgG4-Fc (2013)

Human IgG4, normally the least abundant of the four subclasses of IgG in serum, displays a number of unique biological properties. It can undergo heavy-chain exchange, also known as Fab-arm exchange, leading to the formation of monovalent but bispecific antibodies, and it interacts poorly with FcγRII and FcγRIII, and complement. These properties render IgG4 relatively "non-inflammatory" and have made it a suitable format for therapeutic monoclonal antibody production. However, IgG4 is also known to undergo Fc-mediated aggregation and has been implicated in auto-immune disease pathology. We report here the high-resolution crystal structures, at 1.9 and 2.35 Å, respectively, of human recombinant and serum-derived IgG4-Fc. These structures reveal conformational variability at the CH3-CH3 interface that may promote Fab-arm exchange, and a unique conformation for the FG loop in the CH2 domain that would explain the poor FcγRII, FcγRIII and C1q binding properties of IgG4 compared with IgG1 and -3. In contrast to other IgG subclasses, this unique conformation folds the FG loop away from the CH2 domain, precluding any interaction with the lower hinge region, which may further facilitate Fab-arm exchange by destabilisation of the hinge. The crystals of IgG4-Fc also display Fc-Fc packing contacts with very extensive interaction surfaces, involving both a consensus binding site in IgG-Fc at the CH2-CH3 interface and known hydrophobic aggregation motifs. These Fc-Fc interactions are compatible with intact IgG4 molecules and may provide a model for the formation of aggregates of IgG4 that can cause disease pathology in the absence of antigen.
Purification of transcription cofactor complex CRSP (1999)

Transcription of protein coding genes in metazoans involves the concerted action of enhancer binding proteins and the RNA polymerase II apparatus. The cross talk between these two classes of transcription factors is mediated by an elaborate set of cofactor complexes. For the activation of transcription by the promoter specificity protein 1 (Sp1), TATA binding protein-associated factors in the TFIID complex originally were identified as necessary coactivators, but the identity of additional cofactors required for activated transcription was unknown. Recently, we have reported the isolation and properties of a cofactor complex, CRSP (cofactor required for Sp1), which functions in conjunction with the TATA binding protein-associated factors to promote efficient activation of transcription by Sp1. CRSP contains unique subunits as well as polypeptides that are shared with other cofactor complexes. Here, we report a detailed purification protocol for the isolation of CRSP from human HeLa cells. Our purification strategy takes advantage of the ability of CRSP to bind Ni2+-nitrilotriacetic acid-agarose resin as well as other conventional chromatographic resins. We also describe a streamlined purification protocol that allows a more rapid and efficient means to isolate active CRSP.
Determination of Lutein from Green Tea and Green Tea By‐Products Using Accelerated Solvent Extraction and UPLC (2014)

We have demonstrated that the common problem of inadequate resolution between lutein and zeaxanthin during carotenoid analyses can be overcome by optimizing the combined techniques of accelerated solvent extraction and ultra performance liquid chromatography (UPLC). UPLC was highly effective for saving time, solvent, and labor, as well as providing better resolution. The results in this study demonstrated that green tea by-products could be used as new sources for industrial lutein production owing to their massive production during the extraction of green tea beverages.
Identification of a myotropic AAV by massively parallel in vivo evaluation of barcoded capsid variants (2020)

Adeno-associated virus (AAV) forms the basis for several commercial gene therapy products and for countless gene transfer vectors derived from natural or synthetic viral isolates that are under intense preclinical evaluation. Here, we report a versatile pipeline that enables the direct side-by-side comparison of pre-selected AAV capsids in high-throughput and in the same animal, by combining DNA/RNA barcoding with multiplexed next-generation sequencing. For validation, we create three independent libraries comprising 183 different AAV variants including widely used benchmarks and screened them in all major tissues in adult mice. Thereby, we discover a peptide-displaying AAV9 mutant called AAVMYO that exhibits superior efficiency and specificity in the musculature including skeletal muscle, heart and diaphragm following peripheral delivery, and that holds great potential for muscle gene therapy. Our comprehensive methodology is compatible with any capsids, targets and species, and will thus facilitate and accelerate the stratification of optimal AAV vectors for human gene therapy.
Detection of activated K-ras in non-small cell lung cancer by membrane array: A comparison with direct sequencing (2007)

The ability to detect K-ras oncogene may provide additional information for the management of patients with non-small cell lung cancer (NSCLC). In the present study, we detected the K-ras oncogene in 76 patients with NSCLC by two methods: direct sequencing of K-ras in tumor tissues and membrane array detection of the gene overexpression specific for activated K-ras in peripheral blood. The results showed that 28 (36.8%) of the 76 Taiwanese NSCLC patients had K-ras mutations, with a frequency of 36.4% (20/55) in adenocarcinomas and 38.1% (8/21) in squamous cell carcinomas. The K-ras mutations were more frequently found in smokers than in non-smokers (51.4 vs. 24.4%, P=0.015). The incidences of K-ras mutation in the subgroups of non-smokers and squamous cell carcinomas are relatively higher in Taiwan than in other countries. On the other hand, the membrane array method could positively detect circulating activated K-ras in all of the 27 NSCLC patients with K-ras mutations at codons 12, 13 and 61, and in 4 of the 48 patients with wild-type K-ras. Our results suggest that the K-ras oncogene membrane array serves as a sensitive and convenient tool for the detection of K-ras oncogene, and therefore, has a great potential for clinical applications.
A Salicylbisimine Cage Compound with High Surface Area and Selective CO<sub>2</sub>/CH<sub>4</sub> Adsorption (2010)

Preference for polar adsorbates: The crystalline porous organic cage compound shown has an exceptional high surface area (1566 m2 g−1) and selective gas uptake. The compound preferably adsorbs CO2 (9.4 wt %) over methane (0.98 wt %). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Front Cover: Macromol. Biosci. 11/2006 (2006)

Front Cover: Monomodal cationic or anionic nanoparticles of polyelectrolyte complexes (PEC) sizing around 200 nm can be prepared by mixing PDADMAC and PSS and consecutive centrifugation. The model proteins LYZ, HSA and MYO can be bound by PEC nanoparticles under electrostatically repulsive conditions and the formed PEC/protein conjugates conserve their spherical shape and colloid stability. Further details can be found in the article by W. Ouyang and M. Müller * on page 929.
Strong and Optically Transparent Films Prepared Using Cellulosic Solid Residue Recovered from Cellulose Nanocrystals Production Waste Stream (2013)

We used a new cellulosic material, cellulosic solid residue (CSR), to produce cellulose nanofibrils (CNF) for potential high value applications. Cellulose nanofibrils (CNF) were produced from CSR recovered from the hydrolysates (waste stream) of acid hydrolysis of a bleached Eucalyptus kraft pulp (BEP) to produce nanocrystals (CNC). Acid hydrolysis greatly facilitated homogenization to fibrillate CSR to CNF with only 15 passes in a microfluidizer compared with at least 47 passes to fibrillate BEP to nanofibrils. CNF from CSR were nanowhiskers with a length between 50 and 400 nm and a diameter 3-10 nm with limited aggregation while CNF from BEP were entangled networks of nanofibrils with a length of 500-1000 nm and a diameter of 10-50 nm. CNFs from CSR had good spectral transparency from UV to infrared, i.e, transmittance of CNF-CSR suspensions at 0.1% solids consistency is greater than 90% at wavelengths greater than 340 nm, compared with less than 30% for CNF suspension produced from BEP. Specific tensile strength and modulus of CNF films from CSRs reached 75 kN·m/kg and 12 MN·m/kg, respectively, approximately 175% of the respective values for conventional paper made of refined BEP.
Clinical and Laboratory Findings of Middle East Respiratory Syndrome Coronavirus Infection (2018)

There is a paucity of data regarding the differentiating characteristics of patients with laboratory-confirmed and those negative for Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea. This hospital-based retrospective study compared MERS-CoV-positive and MERS-CoV-negative patients. A total of seven positive patients and 55 negative patients with a median age of 43 years (P = 0.845) were included. No statistical differences were observed with respect to their sex and the presence of comorbidities. At the time of admission, headache (28.6% vs. 3.6%; odds ratio [OR], 10.60; 95% confidence interval [CI], 1.22-92.27), myalgia (57.1% vs. 9.1%; OR, 13.33; 95% CI, 2.30-77.24), and diarrhea (57.1% vs. 14.5%; OR, 7.83; 95% CI, 1.47-41.79) were common among MERS-CoV-positive patients. MERS-CoV-positive patients were more likely to have a low platelet count (164 ± 76.57 vs. 240 ± 79.87) and eosinophil (0.27 ± 0.43 vs. 2.13 ± 2.01; P = 0.003). Chest radiography with diffuse bronchopneumonia was more frequent in MERS-CoV-positive patients than in negative patients (100% vs. 62.5%; P = 0.491). The symptoms of headache, myalgia, and diarrhea, as well as laboratory characteristics, including low platelet counts and eosinophil, and chest X-ray showing diffuse bronchopneumonia might enhance the ability to detect patients in South Korea infected with MERS-CoV.
Basement membrane invasion of glioma cells mediated by integrin receptors (1994)

Basement membrane invasion precedes meningeal dissemination and systemic metastasis of glioma cells. In order to investigate the invasive ability of glioblastomas and the functional role of extracellular matrix receptors, the authors performed in vitro invasion assays where the number of cells was determined from freshly resected tumors (primary cultures and fifth passages) and from cell lines (U-138 MG, U-373 MG, and GaMg) that had migrated through a filter coated with a reconstituted basement membrane (Matrigel). The involvement of integrin adhesion molecules was examined by preincubation of glioma cells with blocking antibodies to specific integrin chains. Cells from all of the glioblastomas had migrated through the Matrigel after 4 to 24 hours; the number of invasive cells was highest in the cell lines. Invasion of U-138 MG cells was reduced with antibodies to alpha 7, alpha v, beta 1, and beta 3 integrin chains and markedly increased by anti-alpha 5, while invasion of U-373 MG cells was reduced by antibodies to alpha 3, alpha v, beta 1, and beta 3 and increased by anti-alpha 6. It is concluded that: 1) glioma cells are able to penetrate Matrigel, indicating that the basement membrane is not a resistant barrier for infiltrating cells; and 2) basement membrane invasion is mediated by integrins in a complex manner. Some integrins promote while others inhibit basement membrane invasion. Furthermore, the integrins involved may differ between various glioma cells.
Clearing the Air: Four Propositions About Property Rights and Environmental Protection (1999)

The term "privatization," as used throughout the law and economics literature, encompasses a
MBE growth of extremely high-quality GaAs–AlGaAs GRIN-SCH lasers with a superlattice buffer layer (1985)

It was found that a thick AlGaAs layer grown on a GaAs–AlGaAs superlattice buffer layer does not affect the optical quality of single quantum well structure successibly grown on the AlGaAs layer; that is, background impurities such as carbon and oxygen, which would come from residual gases, do not accumulate on the AlGaAs surface during molecular beam epitaxy (MBE) growth. Extremely high-quality GaAs–AlGaAs GRIN-SCH lasers were obtained by introducing a superlattice buffer layer. The minimum threshold current density of 175 A/cm2 was achieved for a broad-area Fabry–Perot laser with a cavity length of 450 μm at room temperature. This is the lowest threshold current density of semiconductor lasers with a similar cavity length.