gebhart/patrepeval huggingface dataset:
The Vitamin D Endocrine System: Steroid Metabolism, Hormone Receptors, and Biological Response (Calcium Binding Proteins)* (1982)

Vitamin D is generally accepted as being essential for life in higher animals (278). It is one of the most important biological regulators of calcium and phosphorus (406) metabolism. Along with the two peptide hormones PTH and calcitonin, vitamin D is responsible for the minute-to-minute as well as the day-to-day establishment and maintenance of calcium homeostasis. The substance vitamin D, or cholecalciferol, was first identified through the nutritional studies of Sir Edward Mellanby (243), which identified rickets as a disease state resulting from a deficiency of vitamin D, as well as through the biochemical/chemical studies of McCollum and co-workers (242), who demonstrated that there was more than one fat-soluble vitamin. Together these studies established a deficiency state, namely rickets, which was attributable to the newly discovered, nutritionally important fat-soluble component, vitamin D. In retrospect, however, the most important discovery related to the appreciation by Huldschinsky (167, 168) and Hess and Gutman (148) of the importance of ultraviolet light or radiant energy to the cure and etiology of rickets; they showed that the UV rays from a mercury vapor lamp were quite effective in increasing the degree of calcification of the epiphyses of rachitic infants.
Genetic Locus for Streptolysin S Production by Group A Streptococcus (2000)

Group A streptococcus (GAS) is an important human pathogen that causes pharyngitis and invasive infections, including necrotizing fasciitis. Streptolysin S (SLS) is the cytolytic factor that creates the zone of beta-hemolysis surrounding GAS colonies grown on blood agar. We recently reported the discovery of a potential genetic determinant involved in SLS production, sagA, encoding a small peptide of 53 amino acids (S. D. Betschel, S. M. Borgia, N. L. Barg, D. E. Low, and J. C. De Azavedo, Infect. Immun. 66:1671-1679, 1998). Using transposon mutagenesis, chromosomal walking steps, and data from the GAS genome sequencing project (www.genome.ou.edu/strep. html), we have now identified a contiguous nine-gene locus (sagA to sagI) involved in SLS production. The sag locus is conserved among GAS strains regardless of M protein type. Targeted plasmid integrational mutagenesis of each gene in the sag operon resulted in an SLS-negative phenotype. Targeted integrations (i) upstream of the sagA promoter and (ii) downstream of a terminator sequence after sagI did not affect SLS production, establishing the functional boundaries of the operon. A rho-independent terminator sequence between sagA and sagB appears to regulate the amount of sagA transcript produced versus transcript for the entire operon. Reintroduction of the nine-gene sag locus on a plasmid vector restored SLS activity to the nonhemolytic sagA knockout mutant. Finally, heterologous expression of the intact sag operon conferred the SLS beta-hemolytic phenotype to the nonhemolytic Lactococcus lactis. We conclude that gene products of the GAS sag operon are both necessary and sufficient for SLS production. Sequence homologies of sag operon gene products suggest that SLS is related to the bacteriocin family of microbial toxins.
LONG TERM ORAL ETOPOSIDE AS SECOND-LINE THERAPY IN RECURRENT EPITHELIAL CARCINOMA OF THE OVARY (2006)

Abstract- There is a continuing need to identify new agents that are active in ovarian cancer. Etoposide is a derivative of the plant alkaloid epipodophyllotoxin. The availability of etoposide in oral preparation allows prolonged administration by the oral route. In this study, activity and toxicity of etoposide in women with recurrent ovarian cancer are described from a case series of women with recurrent ovarian cancer who had measurable disease. All patients had prior platinum-based chemotherapy and developed progressive disease. Oral etoposide was given as 50 mg/day for 21 days every 4 weeks until progression of disease or prohibitive toxicity. From December 1999 to January 2004, 32 patients were enrolled in this study. Thirty patients received a total of 133 cycles of etoposide. Median age of patients was 49 years (range, 19 to 75). The median number of etoposide cycles was 4 (range, 1 to 12). There were 5 partial responses (16.6%). The mean response duration was 4.8 months (range, 3.5 to 6); median progression-free interval was 7 months (range, 3 to 13) and median survival time was 12.5 months (range, 1.3 to 36). The major toxicity was leukopenia. One patient required red blood cell transfusions and the main non-hematologic toxicity was nausea and vomiting. There were no treatment-related mortalities. Although etoposide appears to exhibit modest activity in recurrent ovarian cancer after platinum-based therapy, response and survival durations are short.
Nonlinear decrease of background fluorescence in polymer thin-films – a survey of materials and how they can complicate fluorescence detection in μTAS (2003)

Polymers and plastics are receiving increased attention as materials for microfluidics and microTAS applications. Given the ubiquity of fluorescence detection techniques in micro-analytical systems, the fluorescence properties of polymers and plastics should not be overlooked. We survey some commonly available polymer thin-films for their fluorescence behaviour under standardized conditions to determine which materials are most suitable for high-sensitivity fluorescence detection lab chips. The initial fluorescence intensities of some of the materials surveyed were significantly higher than glass and fused silica controls, and decreased over the three hour period with complex kinetics. We then discuss how this has confounded fluorescence detection in our analytical context, and possible mechanisms for the decrease.
Lymphatic transport of orally administered drugs. (2002)

Several therapeutic molecules such as lipophilic drugs and peptides suffer from the problems of low oral bioavailability. Improvement of their bioavailability and simultaneous prevention of the oral degradation of the prone molecules appears to be a challenge. Lymphatic system, which is responsible for the maintenance of fluid balance, immunity and metastatic spread of cancers, is also found to play a major role in the oral absorption of lipids and lipophilic drugs from intestine. The specialized structure of gut associated lymphoid tissue can be utilized as a gateway for the delivery of particulate systems containing drugs. Even though a large gap has existed in the field of lymphatic drug delivery, the introduction of a large number of lipophilic drugs and peptides has brought a renewed interest of research in this area. In this review, the mechanisms of intestinal lymphatic drug transport, approaches taken for the delivery of macromolecules, lipophilic and peptide drugs, biochemical barriers involved in intestinal drug absorption, and animal models used in the studies of intestinal lymphatic drug transport has been discussed.
Bone Marrow-Derived Cells from Male Donors Do Not Contribute to the Endometrial Side Population of the Recipient (2012)

Accumulated evidence demonstrates the existence of bone marrow-derived cells origin in the endometria of women undergoing bone marrow transplantation (BMT). In these reports, cells of a bone marrow (BM) origin are able to differentiate into endometrial cells, although their contribution to endometrial regeneration is not yet clear. We have previously demonstrated the functional relevance of side population (SP) cells as the endogenous source of somatic stem cells (SSC) in the human endometrium. The present work aims to understand the presence and contribution of bone marrow-derived cells to the endometrium and the endometrial SP population of women who received BMT from male donors. Five female recipients with spontaneous or induced menstruations were selected and their endometrium was examined for the contribution of XY donor-derived cells using fluorescent in situ hybridization (FISH), telomapping and SP method investigation. We confirm the presence of XY donor-derived cells in the recipient endometrium ranging from 1.7% to 2.62%. We also identify 0.45-0.85% of the donor-derived cells in the epithelial compartment displaying CD9 marker, and 1.0-1.83% of the Vimentin-positive XY donor-derived cells in the stromal compartment. Although the percentage of endometrial SP cells decreased, possibly being due to chemotherapy applied to these patients, they were not formed by XY donor-derived cells, donor BM cells were not associated with the stem cell (SC) niches assessed by telomapping technique, and engraftment percentages were very low with no correlation between time from transplant and engraftment efficiency, suggesting random terminal differentiation. In conclusion, XY donor-derived cells of a BM origin may be considered a limited exogenous source of transdifferentiated endometrial cells rather than a cyclic source of BM donor-derived stem cells.
Atherosclerosis. Chronic effects of fish oil and a therapeutic diet in nonhuman primates. (1991)

Prolonged testing of marine fish oil (FO) as a dietary supplement is necessary because of widespread claims that it is antiatherogenic. The basis for such claims is inadequate because atherogenesis is chronic and may not respond to short-term changes induced by dietary treatments. A proven (vervet) model of atherosclerosis promoted by an atherogenic diet (AD) was used to test dietary supplementation with Atlantic pilchard FO for 20 months in 47 omnivorous nonhuman primates. Responses were controlled against known favorable effects of changing from the AD to a therapeutic diet (TD). Compliance was achieved, and tissue responses to the FO dose were confirmed. Compromise of reflex vasoconstriction by atherosclerosis was demonstrated for the first time in the model. Aortic, peripheral, coronary, and cerebral atherosclerosis were assessed by light microscopy and computerized image analysis. No component of atherosclerosis regressed after dietary FO, and several deteriorated. After a change to the TD, stainable lipid was cleared from aortas and there were few lipophages, but advanced atherosclerosis was not reduced. Male vervets developed more severe atherosclerosis than did females, and the association among aortic, peripheral, and coronary atherosclerosis was positive in males. Females were resistant to coronary atherosclerosis. Only mild cerebral atherosclerosis was detected. In conclusion, the FO used was not antiatherogenic in the model, and there is a need for caution. The TD regresses some components of atherosclerosis, but it was not effective against fibrosis, mineralization, and cholesterol crystals within 20 months.
A dynamic motion vector referencing scheme for video coding (2016)

Video codecs exploit temporal redundancy in video signals, through the use of motion compensated prediction, to achieve superior compression performance. The coding of motion vectors takes a large portion of the total rate cost. Prior research utilizes the spatial and temporal correlation of the motion field to improve the coding efficiency of the motion information. It typically constructs a candidate pool composed of a fixed number of reference motion vectors and allows the codec to select and reuse the one that best approximates the motion of the current block. This largely disconnects the entropy coding process from the block's motion information, and throws out any information related to motion consistency, leading to sub-optimal coding performance. An alternative motion vector referencing scheme is proposed in this work to fully accommodate the dynamic nature of the motion field. It adaptively extends or shortens the candidate list according to the actual number of available reference motion vectors. The associated probability model accounts for the likelihood that an individual motion vector candidate is used. A complementary motion vector candidate ranking system is also presented here. It is experimentally shown that the proposed scheme achieves about 1.6% compression performance gains on a wide range of test clips.
Epidermal growth factor receptor as a target for therapy with antireceptor monoclonal antibodies. (1992)

The epidermal growth factor (EGF) receptor is a potential target for antitumor therapy. Recent studies from many laboratories have found that this receptor is expressed in high levels on a variety of human tumor cells. Furthermore, the EGF receptor has been implicated in autocrine stimulation of cell growth in a number of experimental studies. We have produced anti-EGF receptor monoclonal antibodies (MAbs), which block the binding of EGF and transforming growth factor alpha (TGF-alpha), and can prevent ligand-stimulated activation of EGF receptor tyrosine kinase. These MAbs have been useful in studies of EGF receptor function. Experiments utilizing the MAbs to block ligand binding have demonstrated that autocrine stimulation of EGF receptor phosphorylation can occur via an extracellular pathway, involving TGF-alpha-mediated activation of EGF receptor on the surface of the cell. The capacity of anti-EGF receptor MAbs to inhibit cell proliferation has provided evidence of an autocrine stimulatory pathway in cultures of malignant human skin, breast, colon, and lung cells. Growth of a variety of human tumor xenografts can be inhibited in situations where autocrine dependency is demonstrable in cell culture. Imaging studies with anti-EGF receptor MAb labeled with indium 111 (111In) demonstrated selective uptake in xenografts expressing high receptor levels. Based on these observations, a phase I trial was carried out with 111In-labeled anti-EGF receptor MAb 225 IgG1 in patients with advanced squamous cell lung carcinoma, a tumor that invariably expresses large numbers of EGF receptors. In the case of squamous lung carcinoma, there is evidence that overexpression of EGF receptors correlates with worse clinical stage and worse prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Mode of Action of Cholera Toxin: Stabilization of Catecholamine-Sensitive Adenylate Cyclase in Turkey Erythrocytes (1974)

Preincubating turkey erythrocytes with cholera toxin alters their adenylate cyclase (EC 4.6.1.1) system: basal activity, maximal epinephrine-stimulatable activity, and affinity of the enzyme reaction for epinephrine are all increased. Pretreatment of erythrocytes with choleragenoid prevents these changes. Cholera toxin does not alter [(3)H]epinephrine uptake by intact erythrocytes. The increase in epinephrine-stimulatable cyclase activity appears to occur at the expense of fluoride-stimulatable activity, which is decreased by the toxin. In lysates from both toxin-treated and control cells, maximally stimulating amounts of epinephrine and fluoride, when added in combination, have a nearly additive effect on cyclase activity. These observations suggest that the adenylate cyclase system of the turkey erythrocyte may exist in two interconvertible forms, one that is catecholamine-responsive but fluoride-insensitive, and another that is fluoride-sensitive but not coupled to catecholamine receptors. Cholera toxin appears to stabilize the enzyme in its hormone receptor-coupled form.
PP.21.18 (2015)

Objective: Fixed drug combinations are increasingly used in antihypertensive therapy, so it is necessary to find the best combinations to achieve the best therapeutic effects not only in the control of arterial blood pressure (BP), but in other relevant aspects such as arterial stiffness (AS) of these patients (P). To evaluate the efficacy in reducing left ventricular hypertrophy (LVH) and arterial stiffness between two fixed combinations of antihypertensive drugs: olmesartan plus amlodipine (olm + aml) and valsartan plus amlodipine (val + aml) in patients with mild to moderate hypertension. Design and method: We studied 126 P (53 ± 9 years) with mild-moderate hypertension with LVH who received two fixed combinations of antihypertensive drugs to maintain BP below 140/90 Hgmm in the office: olm + aml group: 66 P and val + aml group: 60 P to whom an echocardiographic study to detect LVH was performed by measuring the walls of the left ventricle and central systolic and diastolic pressures (CSBP, CDBP) were measured, the augmentation index (AI) and pulse wave velocity (PWV) at baseline and 32 weeks of treatment. Results: Data from both groups were compared and are shown in the following table:Conclusions: Our data suggest that the combination of OLM + AML is significantly higher than VAL + AML in reducing LVH and in reducing arterial stiffness indices indicating that not only provide a benefit in the control of blood pressure but also in the significant reduction in cardiovascular risk and mortality, being the HVI an independent marker of mortality in hypertensive patients, which should influence the selection of a fixed combination antihypertensive comprehensive control of our patients.
Heterocyclic and Phenyl Double-Bond-Locked Combretastatin Analogues Possessing Potent Apoptosis-Inducing Activity in HL60 and in MDR Cell Lines (2005)

Two new series of combretastatin (CA-4) analogues have been prepared. The alkenyl motif of CA-4 was replaced either by a five-membered heterocyclic (isoxazoline or isoxazole) or by a six-membered ring (pyridine or benzene). The new compounds have been evaluated for their effects on tubulin assembly and for cytotoxic and apoptotic activities. Five compounds (18b, 20a, 21a, 34b, and 35b) demonstrated an attractive profile of cytotoxicity (IC50 < 1 microM) and apoptosis-inducing activity but poor antitubulin activity. The isoxazoline derivatives 18b, 20a, and 21a, demonstrated potent apoptotic activity different from that of natural CA-4. Their ability to block most cells in the G2 phase suggests that these compounds could act on targets different from the mitotic spindle. This would indicate activation of both the intrinsic and the extrinsic apoptotic pathways. The data suggest unambiguously that structural alteration of the stilbene motif of CA-4 can be extremely effective in producing potent apoptosis-inducing agents.
Fullerene–Oligonucleotide Conjugates: Photoinduced Sequence‐Specific DNA Cleavage (1995)

The guanine-specific cleavage of oligonucleotides is achieved with the conjugate 1, which contains a fullerene tethered to a tetradecadeoxyribonucleotide Nu(pNu)n. This conjugate was able to form a duplex with a complementary oligonucleotide, and triplexes with appropriate double-stranded oligonucleotides. Irradiation of the complexes leads to site-specfic cleavage of the target sequences—probably through the action of singlet oxygen.
Comprehensive profiling of the complex dendrimeric contrast agent Gadomer using a combined approach of CE, MS, and CE‐MS (2007)

The complex dendrimeric contrast agent Gadomer has been comprehensively characterized using various mass spectrometric techniques in combination with capillary electrophoresis. The analytical challenges arising from the structure of this analyte, e.g., the presence of a complex isotopic pattern originating from multiple gadolinium chelates could be overcome using this combined approach. Results obtained from initial MALDI-TOF-MS measurements could subsequently be complemented and confirmed by CE-ESI-TOF-MS measurements. Furthermore, high resolution Fourier transform-ion cyclotron resonance-MS (FT-ICR-MS) as a stand alone technique and in combination with CE was performed to obtain mass spectra of high mass accuracy and resolution of various impurities and related dendrimers present in low concentrations in several Gadomer batches. The profile of related dendrimers and impurities of lower molecular weight present in Gadomer could be elucidated and variances in the pattern of related dendrimers present in batches obtained via different synthetic routes could be detected. The qualitative analysis of Gadomer using MS techniques in combination with CE provides the fundamental basis for a framework of analytical methodologies for the characterization of Gadomer. By designing such a framework of methodologies the challenges associated with the introduction of dendrimers into the clinical stage may be overcome and the reproducible quality and safety of these innovative products can be ensured.
Gangliosides inhibit T-lymphocyte proliferation by preventing the interaction of interleukin-2 with its cell surface receptors. (1993)

Gangliosides are known to be actively shed from tumour cell membranes, and increased levels of circulating gangliosides may cause tumour-induced T-lymphocyte immunosuppression in vivo by interfering with the actions of interleukin-2 (IL-2). We have investigated the effect of gangliosides on the interaction of IL-2 with its cell surface receptors (IL-2R). Gangliosides inhibited IL-2-stimulated proliferation in synchronized populations of the IL-2-dependent cell lines CTLL-2 and HT-2. The immunosuppressive effect was most effective when gangliosides were added during the first 4 hr after IL-2-stimulation, indicating that they acted early in the IL-2 signalling pathway. Inhibition could be completely overcome by exogenous IL-2, suggesting that gangliosides inhibited growth solely by competing with IL-2R for available IL-2. In support of this proposal, gangliosides induced a concomitant dose-dependent decrease in binding of [125I]IL-2 to high-, medium- and low-affinity IL-2R. Ganglioside-treated cells recovered their high-affinity [125I]IL-2 binding after washing. The glycolipids also prevented chemical cross-linking of [125I]IL-2 to the p55/p75 complex, as well as to both IL-2R alpha (p55) and IL-2R beta (p75) independently. A thin-layer chromatography overlay technique was used to demonstrate that IL-2 binds directly to gangliosides, but not to simple neutral glycolipids or acidic lipids. Taken together, these findings indicate that gangliosides directly block the interaction of IL-2 with IL-2R, and may explain, in part, the immunosuppressive activities of gangliosides in vivo.
Hydrolysis of fatty acid esters in subcritical water (2006)

Abstract Hydrolysis of esters of higher fatty acids by subcritical water, performed in a flow‐through tubular reactor, was investigated at temperatures from 280 up to 340 °C and pressures exceeding 12 MPa, using an ester/water ratio of 1 : 2 or 1 : 4 (vol/vol). The kinetics of the hydrolysis of both the triacylglycerols and the methyl esters obeyed the rate equation valid for first‐order reactions. Conversion of the esters to free fatty acids exceeding 95% was reached at the temperature of 340 °C during 12 min. IR spectroscopy revealed structural changes in the chains of the unsaturated fatty acids and their partial polymerization during the hydrolysis.