gebhart/patrepeval huggingface dataset:
An Intramolecular Disulfide Bond between Conserved Extracellular Cysteines in the Gonadotropin-Releasing Hormone Receptor Is Essential for Binding and Activation<sup>1</sup> (1997)

In this study, site-directed mutagenesis and biochemical strategies have been used to establish whether disulfide bonding between extracellular Cys residues contributes to the structural integrity of the GnRH receptor (GnRH-R) and, if so, to delineate the nature of the bonding patterns involved. The majority of G protein-coupled receptors (GPCRs) contain a pair of conserved Cys residues in the first and second extracellular domains, and these residues have been shown to form a receptor stabilizing disulfide bridge structure. However, many GPCRs contain other nonconserved Cys residues, and in some GPCRs these have also been shown to contribute to receptor integrity and stability. The rat GnRH-R contains four extracellular Cys residues. Two are conserved throughout the GPCR superfamily and lie at positions Cys114 and Cys195 in the first and second extracellular loops, respectively. The other two Cys residues occupy nonconserved positions at Cys14 in the amino terminus and Cys199 in the second extracellular loop. To assess the role of extracellular Cys residues in disulfide bonding interactions, each of these residues were mutated to Ala, expressed in COS-1 cells, and ligand binding and second messenger properties ascertained. To monitor levels of wild-type (WT) and mutant receptor cell surface expression, a hemagglutinin (HA) epitope tag was incorporated into the receptor constructs (GnRH-R WT, Cys14Ala, Cys114Ala, Cys195Ala, and Cys199Ala). Cys199Ala mutant maintained levels of receptor binding and second messenger production comparable with the WT GnRH-R, whereas mutant Cys14Ala exhibited some ligand binding and functional receptor activity, albeit at a reduced level. Mutations Cys114Ala and Cys195Ala showed no functional responses despite displaying levels of cell surface expression similar to the WT receptor. Specific binding of the WT and mutant receptors Cys14Ala and Cys199Ala was inhibited in the presence of the disulfide bond reducing agent, DTT, implying that disulfide bonds are formed and can be reduced in these mutant receptors. This study demonstrates that GnRH-R residues Cys114 and Cys195 have a disulfide bonding interaction role essential for the maintenance of receptor function. In contrast, Cys14 and Cys199 are not involved in disulfide bonding that is required for ligand binding or second messenger production.
Platelet C1- inhibitor. A secreted alpha-granule protein. (1985)

In order to characterize which proteins of the contact phase of coagulation interact with platelets, human platelets were studied immunochemically and functionally to determine if they contain C1- inhibitor. By means of monospecific antibody to C1- inhibitor, a competitive enzyme-linked immunosorbent assay (CELISA) was developed to measure directly platelet C1- inhibitor. With the CELISA, from 33 to 115 ng of C1- inhibitor antigen per 10(8) platelets from 15 normal donors was quantified in lysates of washed human platelets solubilized in nonionic detergent. The mean concentration in 10(8) platelets was 62 +/- 33 ng (SD). Plasma C1- inhibitor either in the platelet suspension medium or on the surface of the platelets could account for only from 6.5 to 16% of the total antigen measured in the solubilized platelets. Upon functional studies, platelets contained 84 +/- 36 ng (SD) of C1- inhibitor activity in 10(8) platelets. As assessed by the CELISA, platelet C1- inhibitor antigen was immunochemically identical to plasma and purified C1- inhibitor. In contrast, the mean concentration of platelet C1- inhibitor antigen in platelets from four patients with classical hereditary angioedema was 8.3 ng/10(8) platelets (range, 5.3 to 11.3 ng/10(8) platelets). 25 and 31% of the total platelet C1- inhibitor was secreted without cell lysis from normal platelets after exposure to collagen (20 micrograms/ml) and thrombin (1 U/ml), respectively, and this secretion was blocked by metabolic inhibitors. Platelet subcellular fractionation showed that platelet C1- inhibitor resided mostly in alpha-granules, similar to the location of platelet fibrinogen. Thus, human platelets contained C1- inhibitor, which became available by platelet secretion. The identification of platelet C1- inhibitor suggests that platelets may modulate the activation of the proteins of early blood coagulation and the classical complement pathways.
Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. (1998)

Epidemiological and laboratory data support a role for vitamin D in the growth and differentiation of human prostatic cells. These findings prompted us to ask whether prostatic cells could convert 25-hydroxyvitamin D3 (25-OH-D3), the major circulating metabolite of vitamin D3, to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the hormonally active metabolite, in a manner similar to cultured human keratinocytes. Therefore, we investigated three well-characterized human prostate cancer cell lines, LNCaP, DU 145, and PC-3; two primary cultures of cells derived from noncancerous human prostates (one normal and one benign prostatic hyperplasia); and primary cultures of normal human keratinocytes for their ability to synthesize 1,25(OH)2D3. Assays were performed in the presence of 25-OH-D3 as the enzyme substrate and 1,2-dianilinoethane, an antioxidant and free radical scavenger, and in the presence and absence of clotrimazole, a cytochrome P450 inhibitor. DU 145 and PC-3 cells produced 0.31 +/- 0.06 and 0.07 +/- 0.01 pmol of 1,25(OH)2D3/mg protein/h, respectively. No measurable 1,25(OH)2D3 was detected in LNCaP cells. The normal and benign prostatic hyperplasia primary cultures and keratinocyte cultures produced 3.08 +/- 1.56, 1.05 +/- 0.31, and 2.1 +/- 0.1 pmol of 1,25(OH)2D3/mg protein/h, respectively, using a calf thymus receptor binding assay to measure 1,25(OH)2D3 in the presence of 1,2-dianilinoethane. The identity of the analyte as 1,25(OH)2D3 was supported by high performance liquid chromatography using [3H]25-OH-D3 as the enzyme substrate and a solvent system that is specific for 1,25(OH)2D3. The production of 1,25(OH)2D3 in the prostate cancer cell lines and in the primary cultures was completely inhibited in the presence of clotrimazole. This report demonstrates that two of three human prostate cancer cell lines, as well as primary cultures of noncancerous prostatic cells, possess 1alpha-hydroxylase activity and can synthesize 1,25(OH)2D3 from 25-OH-D3. Together with recent data indicating that 1,25(OH)2D3 inhibits the invasiveness of human prostate cancer cells (G. G. Schwartz et al., Cancer Epidemiol. Biomark. Prev., 6: 727-732, 1997), these data suggest a potential role for 25-OH-D3 in the chemoprevention of invasive prostate cancer.
Anomeric Configuration Analysis–Extension of the Ring Oxygen Helicity Rule to Aromatic Glycofuranosides (1982)

A strong Cotton effect associated with the ring oxygen was studied in aromatic glycofuranosides. Phenyl and phenyl 1-thioglycofuranosides gave a strong band at 180 nm and 200–210 nm respectively, similar to the corresponding glycopyranosides, suggesting that the ring oxygen helicity rule can be extended to these aromatic glycofuranosides or the band can be used to determine their anomeric configurations and conformations.
Severe Acquired Immune Deficiency Syndrome in Male Homosexuals: Diminished Capacity to Make Interferon-a in Vitro Associated with Severe Opportunistic Infections (1983)

Natural killer cell function, directed against either K562 tumor targets or herpes simplex virus type 1-infected fibroblasts, was often low in patients with acquired immune deficiency syndrome (AIDS) but failed to distinguish these patients from either male homosexual controls or patients with lymphadenopathy. Mononuclear cells from patients with AIDS and opportunistic infections generated diminished levels of interferon-alpha in response to herpes simplex virus type 1-infected fibroblasts. This deficiency discriminated patients with severe opportunistic infections from most individuals with either generalized lymphadenopathy or Kaposi's sarcoma only and from male homosexual control subjects. The deficiency in interferon-alpha generation may be the consequence of the opportunistic infections that these individuals have contracted or may be a direct manifestation of AIDS itself.
Generalized 3D and 4D motion compensated whole-body PET image reconstruction employing nested EM deconvolution (2014)

Whole-body dynamic and parametric PET imaging has recently gained increased interest as a clinically feasible truly quantitative imaging solution for enhanced tumor detectability and treatment response monitoring in oncology. However, in comparison to static scans, dynamic PET acquisitions are longer, especially when extended to large axial field-of-view whole-body imaging, increasing the probability of voluntary (bulk) body motion. In this study we propose a generalized and novel motion-compensated PET image reconstruction (MCIR) framework to recover resolution from realistic motion-contaminated static (3D), dynamic (4D) and parametric PET images even without the need for gated acquisitions. The proposed algorithm has been designed for both single-bed and whole-body static and dynamic PET scans. It has been implemented in fully 3D space on STIR open-source platform by utilizing the concept of optimization transfer to efficiently compensate for motion at each tomographic expectation-maximization (EM) update through a nested Richardson-Lucy EM iterative deconvolution algorithm. The performance of the method, referred as nested RL-MCIR reconstruction, was evaluated on realistic 4D simulated anthropomorphic digital XCAT phantom data acquired with a clinically feasible whole-body dynamic PET protocol and contaminated with measured non-rigid motion from MRI scans of real human volunteers at multiple dynamic frames. Furthermore, in order to assess the impact of our method in whole-body PET parametric imaging, the reconstructed motion-corrected dynamic PET images were fitted with a multi-bed Patlak graphical analysis method to produce metabolic uptake rate (K <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">i</inf> parameter in Patlak model) images of highly quantitative value. Our quantitative Contrast-to-Noise (CNR) and noise vs. bias trade-off analysis results suggest considerable resolution enhancement in both dynamic and parametric motion-degraded whole-body PET images after applying nested RL-MCIR method, without amplification of noise.
Enhancement of antitumor activity of docetaxel by celecoxib in lung tumors (2005)

Our study investigates the effect of a highly selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on the cytotoxicity of docetaxel in nude mice bearing A549 tumor xenografts and elucidates the molecular mechanisms of the antitumor effect of this combination. Female nu/nu mice, xenografted with s.c. A549 tumors were treated with either celecoxib (150 mg/kg/day), docetaxel (10 mg/kg) or a combination of both. The tumor tissues were quantified for the induction of apoptosis, intratumor levels/expressions of prostaglandin E2 (PGE2), 15 deoxy prostaglandin J2 (15-d PGJ2), microsomal prostaglandin E synthase (mPGES) and cytoplasmic phospholipase A2 (cPLA2). The combination of celecoxib with docetaxel significantly inhibited the tumor growth (p < 0.03) as compared to celecoxib or docetaxel alone, decreased the levels of PGE2 by 10-fold and increased the 15-d PGJ2 levels by 4-fold as compared to control. The combination also enhanced the peroxisome proliferator-activated receptor (PPAR)-gamma expression, decreased the expression of cPLA2, mPGES and vascular endothelial growth factor (VEGF), but had no effect on the expression of COX-1 or COX-2 in tumor tissues. TUNEL staining of the tumor tissues showed a marked increase in the apoptosis in the combination group as compared to the celecoxib- or docetaxel-treated groups and this was associated with an increase in the intratumor p53 expression. In conclusion, the combination of celecoxib with docetaxel produces a greater antitumor effect in s.c. A549 tumors as compared to celecoxib or docetaxel alone and this effect is associated with concomitant alterations in the intratumor levels of PGE2 and 15-d PGJ2.
Lysosomal Lipases of Rat Liver and Kidney (1968)

Abstract The subcellular distribution in rat liver and rat kidney of the enzymes hydrolyzing triglycerides at acid pH has been studied. The lipase was shown to be lysosomal by the purification of lysosomes and by the isolation of Triton WR 1339-filled liver lysosomes. The lipase was found to be bound to the lysosomal membranes, had a pH optimum of 4.2, and required Triton X-100 in the reaction mixture for maximum activity. The lysosomal lipase had maximum activity against glycerol tridecanoate but had considerable activity against other long chain triglycerides. The lipase was inhibited by NaCl, NaF, iodoacetate, and Hg++ ions and was not affected by Ca++, Mg++, ethylenediamine tetraacetate, protamine sulfate, and sodium taurocholate. This is the first clear demonstration of a lipase in lysosomes. It is suggested that the lipase is involved in the intralysosomal digestion of triglycerides entering lysosomes by autophagy.
Bacterial keratinase: prospects for prion degradation. (2009)

Infective prion protein is the agent responsible for prion diseases in human and animals. The health, environmental, and cost implications of its occurrence is enormous. The current methods of chemical and heat treatments for prion inactivation is limited by considerations of environmental acceptability, application compatibility and cost, making effective enzymatic inactivation option highly attractive. A Gram-positive bacterium has been isolated which show significant proteolytic activity on casein-agar plate and keratinolytic activity on keratin azure. Optimum keratinase activity (14 U/ml) was expressed by the crude extract of a 24h culture under optimized conditions (pH 10, 37°C and 0.8% (w/v) substrate concentration). Purified supernatant yielded active fraction with purification factor of 108.7 and specific activity of 2,000 U/mg. SDS-PAGE showed a homogenous band on gel and molecular weight was determined by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI MS), as 27.9 kDa. The optimum pH and temperature for this enzyme were determined as 8.5 and 50°C respectively, and showed considerable stability for up to two months when stored at 4°C as free keratinase. Recalcitrant melanized feather was degraded within 48h suggesting strong prospects for this bacterial keratinase in prion degradation since keratin and prion protein are structurally similar.
Adaptive Query Processing for Internet Applications (2000)

As the area of data management for the Internet has gained in popularity, recent work has focused on effectively dealing with unpredictable, dynamic data volumes and transfer rates using adaptive query processing techniques. Important requirements of the Internet domain include: (1) the ability to process XML data as it streams in from the network, in addition to working on locally stored data; (2) dynamic scheduling of operators to adjust to I/O delays and flow rates; (3) sharing and re-use of data across multiple queries, where possible; (4) the ability to output results and later update them. An equally important consideration is the high degree of variability in performance needs for different query processing domains: perhaps an ad-hoc query application should optimize for display of incomplete and partial incremental results, whereas a corporate data integration application may need the best time-to-completion and may have very strict data "freshness" guarantees. The goal of the Tukwila project at the University of Washington is to design a query processing system that supports a range of adaptive techniques that are configurable for different query processing contexts.
Science and Art in Preparing Tissues Embedded in Plastic for Light Microscopy, with Special Reference to Glycol Methacrylate, Glass Knives and Simple Stains (1976)

Plastic embedding preserves tissue structure much more faithfully than does paraffin. Acrylic polymerization is innocuous to dye-binding groups in sections. The water solubility of glycol methacrylate monomer and the hydrophilic properties of the polymer allow for convenience in dehydration and for versatility in staining sections. Five years of experience with glycol methacrylate (GMA) embedding for light microscopy is summarized. Methods for purifying GMA monomer are cited. Procedures for fixing, dehydrating, embedding, polymerizing, sectioning and staining, using GMA, are explained. A method is provided for making glass knives long enough to cut large blocks. Simple, reliable, quick staining methods are outlined. When compared with paraffin, GMA offers opportunities for simpler, quicker procedures and yields sections of superior quality, greater information content, and less distortion.
Dendritic Cell/Peptide Cancer Vaccines: Clinical Responsiveness and Epitope Spreading (2000)

(2000). Dendritic Cell/Peptide Cancer Vaccines: Clinical Responsiveness and Epitope Spreading. Immunological Investigations: Vol. 29, No. 2, pp. 121-125.
Joint injury causes knee osteoarthritis in young adults (2005)

Osteoarthritis in young adults is most commonly a result of a previous injury to the knee. Deconditioning of the musculoskeletal system is seen with joint injury, obesity, and aging, all known risk factors for osteoarthritis. Muscular deconditioning contributes to increased joint loads and knee osteoarthritis development and progression. So far, it is unclear whether surgery reduces the development or progression of osteoarthritis. The risk for osteoarthritis development seems to increase as the amount of meniscal tissue removed increases. Knee injury prevention, rehabilitation after knee injuries, regular exercise, maintaining body weight, and a changed locomotion pattern may prevent osteoarthritis initiation and progression in young adults.
Thin silicon wafer processing and strength characterization (2013)

Thin silicon die (100 um or less) are required for a number of applications, including stacked die packages and three-dimensional integrated circuits (3D-IC). The wafer thinning process is conceptually simple, but requires optimization of the backside finish and dicing to ensure high die strength. High die strength is required to minimize yield loss during assembly and to ensure high reliability during device operation. In this paper, we describe process optimization for thin wafers and thin die, and how these processes affect the fracture strength of silicon.
A Human Corneal Epithelial Cell Line Model for Limbal Stem Cell Biology and Limbal Immunobiology (2016)

Limbal stem cell (LSC) deficiency is a visually debilitating condition caused by abnormal maintenance of LSCs. It is treated by transplantation of donor-derived limbal epithelial cells (LECs), the success of which depends on the presence and quality of LSCs within the transplant. Understanding the immunobiological responses of these cells within the transplants could improve cell engraftment and survival. However, human corneal rings used as a source of LSCs are not always readily available for research purposes. As an alternative, we hypothesized that a human telomerase-immortalized corneal epithelial cell (HTCEC) line could be used as a model for studying LSC immunobiology. HTCEC constitutively expressed human leukocyte antigen (HLA) class I but not class II molecules. However, when stimulated by interferon-γ, HTCECs then expressed HLA class II antigens. Some HTCECs were also migratory in response to CXCL12 and expressed stem cell markers, Nanog, Oct4, and Sox2. In addition because both HTCECs and LECs contain side population (SP) cells, which are an enriched LSC population, we used these SP cells to show that some HTCEC SP cells coexpressed ABCG2 and ABCB5. HTCEC SP and non-side population (NSP) cells also expressed CXCR4, but the SP cells expressed higher levels. Both were capable of colony formation, but the NSP colonies were smaller and contained fewer cells. In addition, HTCECs expressed ΔNp63α. These results suggest the HTCEC line is a useful model for further understanding LSC biology by using an in vitro approach without reliance on a supply of human tissue. Stem Cells Translational Medicine 2017;6:761-766.
Synthesis and Structure-Activity Relationships of Fenbufen Amide Analogs (2010)

The previous discoveries of butyl fenbufen amide analogs with antitumor effects were further examined. The amide analogs with 1, 3, 4 and 8 carbons chains were prepared in 70-80% yield. Fenbufen had no cytotoxic effects at concentrations ranging from 10 to 100 μM. Methyl fenbufen amide had significant cytotoxic effects at a concentration of 100 μM. As the length of the alkyl amide side chain increased, the cytotoxic effects increased, and the octyl fenbufen amide had the greatest cytotoxic effect. After treatment with 30 μM octyl fenbufen amide, nearly seventy percent of the cells lost their viability. At the concentration of 10 μM, fenbufen amide analogs did not show cytotoxicity according to the MTT assay results. The NO scavenging activities of the fenbufen amide analogs were not significantly different from those of fenbufen.
Diagnostic Markers for Detection of Acute Myocardial Infarction and Reperfusion (1992)

Journal Article Diagnostic Markers for Detection of Acute Myocardial Infarction and Reperfusion Get access Fred S. Apple, PhD Fred S. Apple, PhD Clinical Chemistry and Toxicology Laboratories, Hennepin County Medical Center, and the Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, Minn. Search for other works by this author on: Oxford Academic PubMed Google Scholar Laboratory Medicine, Volume 23, Issue 5, 1 May 1992, Page 297, https://doi.org/10.1093/labmed/23.5.297 Published: 01 May 1992
Scrolling graphene into nanofluidic channels (2013)

Here we report on the "scrolling" of planar graphene induced by water as a result of the interplay between water capillarity and graphene elasticity. This scrolling leads to the formation of stable nanochannels that encapsulate water and nanoscale objects. We demonstrate that these graphene nanochannels can be used as nanofluidic platforms for dynamic imaging of nanoscale processes in liquids with Transmission Electron Microscopes (TEMs). These water-impermeable graphene nanochannels have practical application in the design of nanofluidic devices used in biosensors and many analytical separation devices.
Clinical usefulness of the management and delivery of radiation dose-distribution images using the Internet. (1999)

Dose distribution images in radiation therapy play important roles in the management of cancer patients. To date, hard copies of these images have been stored for referral by radiation oncologists as needed. In most cases, these images are not available to medical personnel outside the radiation oncology department. We have developed a means to access these dose distribution images from the hospital via the World-Wide Web (WWW). A screen snapshot of a dose distribution image on the CRT of a treatment planning unit is copied to the WWW server and converted to a GIF (graphic interchange format) image. Similarly, we can register dose volume histograms and digitally reconstructed radiographs (DRR) on the WWW. Medical personnel can view these images through the WWW browser from anywhere in the hospital. As a result, radiation oncologists are given detailed information on target definition in treatment planning by expert physicians. The system also helps co-medical personnel in understanding dose distribution and predicting radiation injury. At the same time, it actualizes an electronic archive of dose distribution images, which is a database for quick and reliable review, evaluation, and comparison of treatment plans. This technique also fosters closer relationships among radiation oncologists, physicians, and co-medical personnel.