gebhart/patrepeval huggingface dataset:
Interaction of the N-Terminal Domain of Apolipoprotein E4 with Heparin (2001)

Apolipoprotein E (apoE) is an important lipid-transport protein in human plasma and brain. It has three common isoforms (apoE2, apoE3, and apoE4). ApoE is a major genetic risk factor in heart disease and in neurodegenerative disease, including Alzheimer's disease. The interaction of apoE with heparan sulfate proteoglycans plays an important role in lipoprotein remnant uptake and likely in atherogenesis and Alzheimer's disease. Here we report our studies of the interaction of the N-terminal domain of apoE4 (residues 1-191), which contains the major heparin-binding site, with an enzymatically prepared heparin oligosaccharide. Identified by its high affinity for the N-terminal domain of apoE4, this oligosaccharide was determined to be an octasaccharide of the structure DeltaUAp2S(1-->[4)-alpha-D-GlcNpS6S(1-->4)-alpha-L-IdoAp2S(1-->](3)4)-alpha-D-GlcNpS6S by nuclear magnetic resonance spectroscopy, capillary electrophoresis, and polyacrylamide gel electrophoresis. Kinetic analysis of the interaction between the N-terminal apoE4 fragment and immobilized heparin by surface plasmon resonance yielded a K(d) of 150 nM. A similar binding constant (K(d) = 140 nM) was observed for the interaction between immobilized N-terminal apoE4 and the octasaccharide. Isothermal titration calorimetry revealed a K(d) of 75 nM for the interaction of the N-terminal apoE fragment and the octasaccharide with a binding stoichiometry of approximately 1:1. Using previous studies and molecular modeling, we propose a binding site for this octasaccharide in a basic residue-rich region of helix 4 of the N-terminal fragment. From the X-ray crystal structure of the N-terminal apoE4, we predicted that binding of the octasaccharide at this site would result in a change in intrinsic fluorescence. This prediction was confirmed experimentally by an observed increase in fluorescence intensity with octasaccharide binding corresponding to a K(d) of approximately 1 microM.
Structural studies of the capsular polysaccharide from Haemophilus pleuropneumoniae serotype l (1986)

The capsular polysaccharide of Haemophilus pleuropneumoniae serotype 1 (ATCC 27088) was found to be a teichoic acid type polysaccharide of a repeating disaccharide unit composed of 2-acetamido-2-deoxy-D-glucose and D-galactose units. By composition analysis, methylation, partial hydrolysis, dephosphorylation, and one- and two-dimensional 500-MHz proton nuclear magnetic resonance experiments, together with 13C nuclear magnetic resonance studies, it was concluded that the capsular polysaccharide is a high molecular weight linear polymer having the structure: (Formula: see text)
Genomic loss of 18p predicts an adverse clinical outcome in patients with high-risk breast cancer. (2002)

The impact of the genomic imbalances on the clinical outcome of 34 patients with lymph-node positive high-risk breast cancer (HRBC) was investigated using comparative genomic hybridization. All of the patients were uniformly treated with high-dose chemotherapy and autologous stem cell transplantation. The average number of chromosomal imbalances per tumor was 11 (range, 2-24), including DNA overrepresentation on chromosomes 1q (59%), 17q (38%), 8q and 16p (35% each), 20q (32%), and 19p (26%), and genomic losses involving 9p and 18q (41%), 8p, 11q, and 18p (38%), 17p (32%), 4p and Xq (29%), and 16q (26%). The most significant association among genomic changes and clinical-pathological features was the correlation of the loss of 8p with progesterone receptor positivity (P < 0.005). With a median follow-up time of 74 months, 15 patients (44%) have relapsed. In the univariate analysis, patients with gain/amplification of 17q including the HER-2/neu gene locus had a longer disease-free survival (P = 0.02), whereas those with genomic loss of 18p had a higher probability of relapse (P = 0.003). In multivariate analysis, the loss of 18p was the only parameter correlated with shorter disease-free survival (relative risk, 4.8; 95% confidence interval, 1.57-14.8; P = 0.006). In summary, our data indicate that the tumoral genomic profile may represent a valuable marker for predicting the clinical outcome in HRBC. Furthermore, the genomic loss of 18p may identify a poor prognostic subgroup of patients with HRBC.
A Specific Antibody Response to Hcv E2 Elicited in Mice by Intramuscular Inoculation of Plasmid Dna Containing Coding Sequences for E2 (1997)

As the chimpanzee, the only reliable animal model for hepatitis C virus (HCV) infection, is impractical for early stage testing of HCV vaccine candidates, we have evaluated the immune response in mice to an experimental plasmid based HCV vaccine. We used this system because DNA vaccines can be rapidly constructed without the necessity of large scale protein production and purification. In this preliminary study we tested the immune response in mice to HCV envelope glycoprotein, E2, induced by a eukaryotic expression plasmid. Protein expression was monitored by immunofluorescence in transfected tissue culture cells. Each mouse was inoculated intramuscular with 100 microg plasmid DNA and some mice were boosted after 5 weeks. Among 12 BALB/C mice inoculated, 10 developed antibody to E2 by the second week. The antibody levels increased steadily before reaching a plateau in mice receiving the booster, but in the nonboosted mice the antibody declined over time. The serum from one mouse was tested against a series of overlapping peptides covering most of E2. This serum contained antibodies recognizing two distinct epitopes beginning at amino acid 57 and amino acid 113 but no antibody was directed against peptides representing the hypervariable region of E2, antibody to which is thought to be important in HCV neutralization. We have shown that the use of plasmid based vaccines can induce a specific immune response in mice against HCV antigens. This system should be useful as the first step in vaccine development.
Potential Difference Measurements of Ocular Surface Na+Absorption Analyzed Using an Electrokinetic Model (2005)

PD measurements coupled with model computations defined quantitatively the roles of Na+ and Cl- transport processes in ocular surface ion and fluid secretion, and indicated that CFTR-dependent changes in apparent epithelial Na+ channel (ENaC) activity could be accounted for by electrochemical coupling, without requiring ENaC-CFTR interactions. The data and modeling also predicted significant enhancement of ocular surface fluid secretion by ENaC inhibitors and CFTR activators as possible therapies for dry eye syndromes.
Antihypertensive Agents and Risk of Parkinson’s Disease, Essential Tremor and Dementia: A Population-Based Prospective Study (NEDICES) (2009)

We did not find evidence of a protective effect of antihypertensive medications in these three neurodegenerative disorders.
Binding of Testosterone and Oestradiol to Sex Hormone Binding Globulin, Human Serum Albumin and other Plasma Proteins: Evidence for Non-Specific Binding of Oestradiol to Sex Hormone Binding Globulin (1983)

1. The percentage binding of testosterone (T) and oestradiol (E2) to sex hormone binding globulin (SHBG) and human serum albumin (HSA) was determined over a range of SHBG concentrations of 16-250 nmol of dihydrotestosterone (DHT) bound/l. It was found that the binding of both T and E2 to HSA was a function of their binding to SHBG and bore an inverse relationship to it. After removal of both SHBG and HSA from plasma by affinity chromatography a 'residual' binding of about 11% for T and 12% for E2 was still apparent. In addition to the specific high-affinity, low capacity binding of E2 to SHBG, non-specific low-affinity binding of 7-12% was demonstrated after selective denaturation of the specific binding site of the latter. 2. Competition studies indicated that although at the relatively higher levels of SHBG found in the normal female the physiological concentrations of E2, T and DHT need not be taken into account in estimating the unbound fractions of steroids, at the relatively lower levels of SHBG found in normal men and hirsute women, the physiological concentrations of T and DHT are effective in causing statistically significant displacement of E2 from the common, specific binding site on SHBG. 3. A simple computerized technique is described for the determination of fractions of E2 and T respectively, that are unbound to SHBG, unbound to SHBG and HSA, and unbound to all plasma proteins, when the total plasma levels of E2, T, DHT and SHBG are known.
Site-directed modification of DNA duplexes by chemical ligation (1988)

The efficiency of chemical ligation method have been demonstrated by assembling a number of DNA duplexes with modified sugar phosphate backbone. Condensation on a tetradecanucleotide template of hexa(penta)- and undecanucleotides differing only in the terminal nucleoside residue have been performed using water-soluble carbodiimide as a condensing agent. As was shown by comparing the efficiency of chemical ligation of single-strand breaks in those duplexes, the reaction rate rises 70 or 45 times if the 3'-OH group is substituted with an amino or phosphate group (the yield of products with a phosphoramidate or pyrophosphate bond is 96-100% in 6 d). Changes in the conformation of reacting groups caused by mismatched base pairs (A.A, A.C) as well as the hybrid rU.dA pair or an unpaired base make the template-directed condensation less effective. The thermal stability of DNA duplexes was assayed before and after the chemical ligation. Among all of the modified duplexes, only the duplex containing 3'-rU in the nick was found to be a substrate of T4 DNA ligase.
lipodissolve for subcutaneous fat reduction and skin retraction (2005)

According to the authors, Lipodissolve injections reduce the size of localized fat deposits and cause skin retraction in body regions containing small deposits of localized fat, cellulite, or postlipoplasty deformities. It will not replace traditional lipoplasty techniques, but is an excellent adjunct or alternative for those patients seeking minimally invasive treatment. Successful outcomes are highly dependent on the correct formula and injection technique, as well as proper patient selection.
Terahertz transmission properties of thin, subwavelength metallic hole arrays (2004)

We present experimental results of the transmission magnitude and phase change of terahertz pulses through thin metallic films patterned with subwavelength hole arrays on silicon wafers. Terahertz time-domain spectroscopy measurements reveal a sharp phase peak centered on the surface plasmon resonance. Correspondingly, and consistent with the Kramers-Kronig relations, the measured transmission magnitude has the shape of the derivative of this peak. In addition, we determine that the aperture shape has a notable effect on the transmission properties of two-dimensional hole arrays.
Synthesis of Some New Chiral Sulfonamide Ligands (2000)

Abstract Synthesis of new chiral sulfonamide ligands derived from isatoic anhydride by reaction with trans-(R,R)-1,2-diaminocyclohexane and chiral aminoacid esters.
The linearity of the end-systolic pressure-volume relationship in man and its sensitivity for assessment of left ventricular function. (1981)

The linearity and sensitivity of the end-systolic pressure-volume (P-Ves) relation to the inotropic state of the left ventricle were investigated in 11 patients with coronary heart disease and one patient with congestive cardiomyopathy. To minimize autonomic reflex responses, propranolol, 0.15 mg/kg, and atropine, 1 mg, were administered i.v. at the beginning of the study. Three ventriculograms were performed: at rest, after oral isosorbide dinitrate, 10 mg (systolic pressure decrease greater than or equal to 15 mm Hg), and during infusion of methoxamine, 2 mg/min (systolic pressure increase greater than or equal to 10 mm Hg). The three points of the Pv-Ves relation showed linearity (r greater than or equal to 0.96). The relation between the slope k of the P-Ves relation and the left ventricular ejection fraction at rest was best described by an exponential function (r = 0.94). The use of peak systolic pressure instead of end-systolic pressure showed equally good results. The intercept of the P-Ves line on the abscissa, which represents the theoretical end-systolic volume at zero pressure, was not related to the ejection fraction under control conditions. The P-Ves relation in postextrasystolic beats was displaced toward the left (smaller end-systolic volumes) and became steeper.
RNA Silencing in Plants--Defense and Counterdefense (2001)

RNA silencing is a remarkable type of gene regulation based on sequence-specific targeting and degradation of RNA. The term encompasses related pathways found in a broad range of eukaryotic organisms, including fungi, plants, and animals. In plants, it serves as an antiviral defense, and many plant viruses encode suppressors of silencing. The emerging view is that RNA silencing is part of a sophisticated network of interconnected pathways for cellular defense, RNA surveillance, and development and that it may become a powerful tool to manipulate gene expression experimentally.
Danazol. (1989)

Danazol is a synthetic attenuated androgen that can interfere with normal interactions between the pituitary-hypothalamic axis and the gonads. These effects are mediated by complex mechanisms, including those in which danazol can compete with natural steroids in binding to androgen receptors or to sex hormone-binding globulin, possibly displacing natural steroids from this protein, and in binding to reactive sites of enzymes required for synthesis of natural steroids, thereby depressing synthesis. Because of danazol's impairment of the pituitary-hypothalamic interactions with gonads, it is an effective therapeutic agent for treatment of endometriosis and cystic disease of the breast. It is effective in the treatment of hereditary angioneurotic edema, but the mechanism of this therapeutic success is unclear. Danazol has been used, without universal success, in the treatment of other gynecologic and certain hematologic disorders.
Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice (1999)

INCENP is a chromosomal passenger protein which relocates from the centromere to thel spindle midzone during the metaphase-anaphase transition, ultimately being discarded in the cell midbody at the completion of cytokinesis. Using homologous recombination, we have generated Incenp gene-targeted heterozygous mice that are phenotypically indistinguishable from their wild-type littermates. Intercrossing the hetero-zygotes results in no live-born homozygous Incenp -disrupted progeny, indicating an early lethality. Day 3.5 affected pre-implantation embryos contain large, morphologically abnormal cells that fail to fully develop a blastocoel cavity or thrive in utero and in culture. Chromatin and tubulin immunocytochemical stainings of these and day 2.5 affected embryos reveal a high mitotic index, no discernible metaphase or anaphase stages, complete absence of midbodies, micronuclei formation, morphologically irregular macronuclei with large chromosome complements, multipolar mitotic configurations, binucleated cells, internuclear bridges and abnormal spindle bundling. The phenotype is consistent with a defect in the modulation of microtubule dynamics, severely affecting chromosome segregation and resulting in poorly resolved chromatin masses, aberrant karyokinesis and internuclear bridge formation. These latter occurrences could pose a physical barrier blocking cytokinesis.
Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis (2006)

Tyrosine kinases play a central role in the activation of signal transduction pathways and cellular responses that mediate the pathogenesis of rheumatoid arthritis. Imatinib mesylate (imatinib) is a tyrosine kinase inhibitor developed to treat Bcr/Abl-expressing leukemias and subsequently found to treat c-Kit-expressing gastrointestinal stromal tumors. We demonstrate that imatinib potently prevents and treats murine collagen-induced arthritis (CIA). We further show that micromolar concentrations of imatinib abrogate multiple signal transduction pathways implicated in RA pathogenesis, including mast cell c-Kit signaling and TNF-alpha release, macrophage c-Fms activation and cytokine production, and fibroblast PDGFR signaling and proliferation. In our studies, imatinib attenuated PDGFR signaling in fibroblast-like synoviocytes (FLSs) and TNF-alpha production in synovial fluid mononuclear cells (SFMCs) derived from human RA patients. Imatinib-mediated inhibition of a spectrum of signal transduction pathways and the downstream pathogenic cellular responses may provide a powerful approach to treat RA and other inflammatory diseases.
Angiotensin-(1–7) Augments Bradykinin-Induced Vasodilation by Competing With ACE and Releasing Nitric Oxide (1997)

Recent studies have shown that angiotensin-(1-7) [Ang-(1-7)] interacts with kinins and augments bradykinin (BK)-induced vasodilator responses by an unknown mechanism. In this study, we evaluated whether the potentiation of the BK-induced vasodilation by Ang-(1-7) may be attributable to inhibition of BK metabolism, release of nitric oxide, or both. Isometric tension was measured in intact canine coronary artery rings suspended in organ chambers. 125I-[Tyr0]-BK metabolism was determined in vascular rings by assessing the degradation of the peptide by high-performance liquid chromatography. Ang-(1-7) augmented the vasodilation induced by BK in a concentration-dependent manner in rings preconstricted with the thromboxane analog U46619. The EC50 of BK (2.45 +/- 0.51 nmol/L versus 0.37 +/- 0.08 nmol/L) was shifted leftward by 6.6-fold in the presence of 2 mumol/L concentration of Ang-(1-7). The response was specific for BK. since Ang-(1-7) did not augment the vasodilation induced by either acetylcholine (0.05 mumol/L) or sodium nitroprusside (0.1 mumol/L). Moreover, neither angiotensin I nor angiotensin II (Ang II) duplicated the augmented BK response of Ang-(1-7). Pretreatment of vascular rings with the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NA; 100 mumol/L) completely abolished the effects of Ang-(1-7) on BK-induced vasodilation whereas pretreatment with indomethacin (10 mumol/L) was without effect. The potent specific BK B2 receptor antagonist, Hoe 140. nearly abolished the BK and the Ang-(1-7) potentiated responses at 2 mumol/L, whereas at a lower concentration (20 nmol/L) Hoe 140 shifted the response curve to the right for both Ang-(1-7) and vehicle; however, the augmented response to Ang-(1-7) persisted. Preincubation of vascular rings with 20 mumol/L of the AT1 (CV11974), AT2 (PD123319), or nonselective (Sar1 Thr8-Ang II) receptor antagonists had no significant effect on the Ang-(1-7)-enhanced vasodilator response to BK. Lisinopril (2 mumol/L) significantly enhanced the BK-induced vasodilator response while at the same time it abolished the synergistic action of Ang-(1-7) on BK. In addition, pretreatment with 2 mumol/L Ang-(1-7) significantly inhibited the degradation of 125I-[Tyr0]-BK and the appearance of the BK-(1-7) and BK-(1-5) metabolites in coronary vascular rings. Ang-(1-7) inhibited purified canine angiotensin converting enzyme activity with an IC50 of 0.65 mumol/L. In conclusion. Ang-(1-7) acts as a local synergistic modulator of kinin-induced vasodilation by inhibiting angiotensin converting enzyme and releasing nitric oxide.
Pulse-number distribution for the neural spike train in the cat’s auditory nerve (1985)

Pulse-number distributions (PNDs) were recorded from primary afferent fibers in the auditory nerve of the cat, using standard extracellular microelectrode recording techniques. Pure-tone and broadband-noise stimuli were used. The number of neural spikes (pulses) n was measured in a set of contiguous intervals, each of duration T seconds. The quantity n varies from one interval to another. These data were then used to determine the PND, which is the probability p(n,T) of occurrence of n spikes in the time T, versus the number n. The estimated mean and variance of p(n,T) were obtained. Two different values of T were used. An unexpected observation was that the count mean-to-variance ratio R is relatively constant and independent of the stimulus intensity. Use of the PND as a statistical measure of the underlying neural point process has a number of virtues. For example, the PND readily exhibits the existence of spike clusters (e.g., pairs) for some units. The PND is essentially unaffected by time jitter and time quantization and provides a statistically significant measure for units firing at low rates. A study of the scaled and unscaled pulse-interval distributions (PIDs), under conditions of spontaneous firing, demonstrates that the occurrences of neural events are generally not describable by a renewal process. Our investigation shows that none of the point processes customarily used to model the auditory neural spike train is consistent with all of the data. It appears that the encoding of acoustic information into nerve spikes in the peripheral auditory system takes the form of a cluster point process similar to the Neyman-Scott type. For pure-tone excitation, the PND will be well represented as a multinomial distribution in this case.
A combined micromagnetic-microfluidic device for rapid capture and culture of rare circulating tumor cells (2012)

Here we describe a combined microfluidic-micromagnetic cell separation device that has been developed to isolate, detect and culture circulating tumor cells (CTCs) from whole blood, and demonstrate its utility using blood from mammary cancer-bearing mice. The device was fabricated from polydimethylsiloxane and contains a microfluidic architecture with a main channel and redundant 'double collection' channel lined by two rows of dead-end side chambers for tumor cell collection. The microdevice design was optimized using computational simulation to determine dimensions, magnetic forces and flow rates for cell isolation using epithelial cell adhesion molecule (EpCAM) antibody-coated magnetic microbeads (2.8 μm diameter). Using this device, isolation efficiencies increased in a linear manner and reached efficiencies close to 90% when only 2 to 80 breast cancer cells were spiked into a small volume (1.0 mL) of blood taken from wild type mice. The high sensitivity visualization capabilities of the device also allowed detection of a single cell within one of its dead-end side chambers. When blood was removed from FVB C3(1)-SV40 T-antigen mammary tumor-bearing transgenic mice at different stages of tumor progression, cells isolated in the device using anti-EpCAM-beads and magnetically collected within the dead-end side chambers, also stained positive for pan-cytokeratin-FITC and DAPI, negative for CD45-PerCP, and expressed SV40 large T antigen, thus confirming their identity as CTCs. Using this isolation approach, we detected a time-dependent rise in the number of CTCs in blood of female transgenic mice, with a dramatic increase in the numbers of metastatic tumor cells appearing in the blood after 20 weeks when tumors transition to invasive carcinoma and exhibit increased growth of metastases in this model. Importantly, in contrast to previously described CTC isolation methods, breast tumor cells collected from a small volume of blood removed from a breast tumor-bearing animal remain viable and they can be easily removed from these devices and expanded in culture for additional analytical studies or potential drug sensitivity testing.
Omega-3 fatty acids and non-communicable diseases. (2003)

Results from epidemiological and dietary intervention studies have shown that omega-3 PUFA represent powerfully a class of bioactive compounds and that dietary intake of omega-3 PUFA plays a critical role in human health in relation to non-communicable diseases.