gebhart/patrepeval huggingface dataset:
Pharmacogenomic Effects of Apolipoprotein E on Intracerebral Hemorrhage (2008)

Our data indicate that APOE genotype influences neurological outcome after intracerebral hemorrhage in a murine model. In particular APOE4 is associated with poor functional outcome and increased cerebral edema. Additionally, this outcome can be modified by the addition of an apolipoprotein E mimetic-peptide, COG1410.
Calcium cyanamide synthesis. Part 1.—Thermodynamic studies (1961)

A. J. Owen, Trans. Faraday Soc., 1961, 57, 670 DOI: 10.1039/TF9615700670
Effect of Carrier Ionic Strength in Microscale Cyclical Electrical Field-Flow Fractionation (2006)

Recent work with cyclical electrical field-flow fractionation systems has shown promise for the technique as a separation and analysis tool, but little is understood about how the carrier composition in the system affects its capabilities. The electrical properties of microscale CyElFFF systems change when the carrier ionic conditions are altered, and it is well known that the effects of increasing ionic strength carriers on retention in normal ElFFF systems are severe. Specifically, retention levels fall significantly. Accordingly, this work seeks to understand the effect that increasing carrier ionic strength in CyElFFF has on nanoparticle retention in the channels. The retention of polystyrene particles in the CyElFFF microsystem is reported at various ionic strengths of ammonium carbonate and at a variety of pH levels. The experiments are compared to the theory of CyElFFF available in the literature. The results indicate that the ionic strength of the carrier has a significant impact on retention and that high ionic strength carrier solutions lead to poor performance of the CyElFFF system. These results have significant impact on the possible uses of the technique and its applications, especially in the biomedical arena.
Conformationally defined adrenergic agents. 5. Resolution, absolute configuration, and pharmacological characterization of the enantiomers of 2-(5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthyl)imidazoline: a potent agonist at .alpha.-adrenoceptors (1987)

(+/-)-2-(5,6-Dimethoxy-1,2,3,4-tetrahydro-1-naphthyl)imidazoline has been resolved into its (+) and (-) enantiomers, and the absolute configuration was established by single-crystal X-ray diffraction studies. The more active isomer has been assigned the R absolute configuration. Cleavage of the respective (+)- and (-)-dimethyl ethers with boron tribromide provided the corresponding (+)- and (-)-2-(5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthl)imidazoline hydrobromides and these were pharmacologically characterized. In various preparations, the R enantiomer has been shown to be an extremely potent alpha agonist with preferential activity at the alpha 2-adrenergic receptor.
Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. (1992)

Alpha interferon stimulates transcription by converting the positive transcriptional regulator ISGF3 from a latent to an active form. This receptor-mediated event occurs in the cytoplasm, with subsequent translocation of the activated factor to the nucleus. ISGF3 has two components, termed ISGF3 alpha and ISGF3 gamma. ISGF3 gamma serves as the DNA recognition subunit, while ISGF3 alpha, which appears to consist of three polypeptides, is a target for alpha interferon signaling and serves as a regulatory component whose activation is required to form ISGF3. ISGF3 gamma DNA-binding activity was identified as a 48-kDa polypeptide, and partial amino acid sequence has allowed isolation of cDNA clones. ISGF3 gamma translated in vitro from recombinant clones bound DNA with a specificity indistinguishable from that of ISGF3 gamma purified from HeLa cells. Sequencing of ISGF3 gamma cDNA clones revealed significant similarity to the interferon regulatory factor (IRF) family of DNA binding proteins in the amino-terminal 117 residues of ISGF3 gamma. The other IRF family proteins bind DNA with a specificity related to but distinct from that of ISGF3 gamma. We note sequence similarities between the related regions of IRF family proteins and the imperfect tryptophan repeats which constitute the DNA-binding domain of the c-myb oncoprotein. These sequence similarities suggest that ISGF3 gamma and IRF proteins and the c-myb oncoprotein use a common structural motif for DNA recognition. Recombinant ISGF3 gamma, like the natural protein, interacted with HeLa cell ISGF3 alpha to form the mature ISGF3 DNA-binding complex. We suggest that other IRF family members may participate in signaling pathways by interacting with as yet unidentified regulatory subunits analogous to ISGF3 alpha.
The molecular characteristics of a human pancreatic acidic phosphoprotein that inhibits calcium carbonate crystal growth (1984)

A CaCO3-crystal-growth inhibitor was isolated from human pancreatic stones by using EDTA demineralization, followed by DEAE-Trisacryl chromatography. The isolated inhibitor was found to be a phosphoglycoprotein with Mr 14017 and having an unusual chemical composition. It is characterized by a high (42%) acidic amino acid content, but lacks methionine and gamma-carboxyglutamic acid. The protein contains 2.65 mol of P/mol of protein, as phosphoserine (2 mol) and phosphothreonine (0.5 mol). Isoelectric focusing of the protein yields one major band corresponding to an isoelectric point of 4.2. Immunochemical quantification of the crystal-growth inhibitor in pure pancreatic juice reveals that it constitutes 14% of the normal exocrine secretion. Our findings demonstrate that this is a novel secretory protein, which has no enzymic activity and which maintains pancreatic juice in a supersaturated state with respect to CaCO3.
Which are the antibodies to watch in 2013? (2013)

The start of the new year signals that it is time for mAbs' annual review of the therapeutic monoclonal antibodies (mAbs) in active Phase 2/3 or Phase 3 clinical studies. The entire clinical pipeline currently includes ~350 mAbs, but most of these are in early development. As of the beginning of 2013, our "Antibodies to watch" list includes 28 single mAbs and one mAb mixture that are undergoing evaluation in Phase 3 studies for inflammatory or immunological disorders, cancers, high cholesterol, osteoporosis, Alzheimer disease and infectious disease. In alphabetical order, the 28 mabs are alirocumab, AMG 145, elotuzumab, epratuzumab, farletuzumab, gantenerumab, gevokizumab, inotuzumab ozogamicin, itolizumab, ixekizumab, lebrikizumab, mepolizumab, naptumomab estafenatox, necitumumab, nivolumab, obinutuzumab, ocrelizumab, onartuzumab, racotumomab, ramucirumab, reslizumab, romosozumab, sarilumab, secukinumab, sirukumab, solanezumab, tabalumab, and vedolizumab. The mixture of actoxumab and bezlotoxumab is being evaluated in two Phase 3 studies as a treatment for Clostridium difficile infection.
Isolation and sequence characterization of a cDNA clone of human antithrombin III. (1983)

A human liver cDNA library was constructed by using poly(A)-containing RNA isolated from a human liver biopsy specimen. This library is comprised of 40,000 independent transformants with an average inserted DNA length of 1,200 base pairs. By using the previously cloned baboon antithrombin III cDNA as a specific hybridization probe, greater than 30 human antithrombin III cDNA clones were identified from this library. The clone with the longest DNA insert was selected for sequence analysis. This antithrombin III cDNA clone contains 1,479 base pairs of inserted human DNA and was designated phATIII 113. It contains DNA sequences that code for a signal peptide and the entire mature antithrombin III protein which is comprised of 432 amino acid residues.
A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. (1983)

The human lymphocyte function-associated antigen-1 (LFA-1), the complement receptor-associated OKM1 molecule, and a previously undescribed molecule termed p150,95, have been found to be structurally and antigenically related. Each antigen contains an alpha- and beta-subunit noncovalently associated in an alpha 1 beta 1-structure as shown by cross-linking experiments. LFA-1, OKM1, and p150,95 alpha-subunit designations and their molecular weights are alpha L = 177,000 Mr, alpha M = 165,000 Mr, and alpha X = 150,000 Mr, respectively. The beta-subunits are all = 95,000 Mr. Some MAb precipitated only LFA-1, others only OKM1, and another precipitates all three antigens. The specificity of these MAb for particular subunits was examined after subunit dissociation by high pH. MAb specific for LFA-1 or OKM1 bind to the alpha L- or alpha M-subunits, respectively, while the cross-reactive MAb binds to the beta-subunits. Coprecipitation experiments with intact alpha 1 beta 1-complexes showed anti-alpha and anti-beta MAb can precipitate the same molecules. In two-dimensional (2D) isoelectric focusing-SDS-PAGE, the alpha subunits of the three antigens are distinct, while the beta-subunits are identical. Biosynthesis experiments showed alpha L, alpha M, and alpha X are synthesized from distinct precursors, as is beta. The three antigens differ in expression on lymphocytes, granulocytes, and monocytes. During maturation of the monoblast-like U937 line, alpha M and alpha X are upregulated and alpha L is downregulated. Some MAb to the alpha subunit of OKM1 inhibited the complement receptor type three. LFA-1, OKM1, and p150,95 constitute a novel family of functionally important human leukocyte antigens that share a common beta-subunit.
Comparison of Computed Density and Macroscopic Morphometry in Pulmonary Emphysema (1995)

High-resolution computed tomography (HRCT) scans were obtained at 1 cm intervals in 63 subjects referred for surgical resection of a cancer or for transplantation to find out whether the relative area of lung occupied by attenuation values lower than a threshold would be a measurement of macroscopic emphysema. Using a semiautomatic procedure, the relative areas occupied by attenuation values lower than eight thresholds ranging from -900 to -970 HU were calculated on the set of scans obtained through the lobe or the lung to be resected. The extent of emphysema was quantified by a computer-assisted method on horizontal paper-mounted lung sections obtained every 1 to 2 cm. The only level for which no statistically significant difference was found between the HRCT and the morphometric data was -950 HU. To determine the number of scans sufficient for an accurate quantification, we recalculated the relative area occupied by attenuation values lower than -950 HU on progressively fewer numbers of scans and investigated the departure from the results obtained with 1 cm intervals. Because of wide variations in this departure from patient to patient, a standard cannot be recommended as the optimal distance between scans.
Existence of Retinoic Acid-Receptor-Independent Retinoid X-Receptor-Dependent Pathway in Myeloid Cell Function (2001)

We previously reported that ER-27191 (4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-pyridylmethyl)anthra[1,2-b]pyrrol-3-yl]benzoic acid) is a potent antagonist of retinoic acid receptor (RAR), and ER-35795 ((2E,4E,6E)-7-[1-(1-methylethyl)-8-chloro-1,2,3,4-tetrahydroquinolin-6-yl]-6-fluoro-3-methyl-2,4,6-nonatrienoic acid) is a novel retinoid X receptor (RXR)-specific agonist. By using these compounds, we investigated whether distinct RAR-dependent and RXR-dependent pathways operate to mediate the diverse activities of retinoids, particularly, the effects of the RXR pathway on cellular function. ER-27191 completely antagonized HL60 cell differentiation induced by all-trans-retinoic acid (atRA). However, the differentiation induced by the ER-35795 was not antagonized at all by the RAR antagonist, but was inhibited by an RXR homodimer antagonist (LGD100754, (2E,4E,6Z)-7-(3-n-propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)-3-methylocta-2,4,6-trienoic acid). Its agonistic action on RXR/RAR heterodimer, on the other hand, was neutralized by the RAR antagonist. During HL60 cell differentiation, atRA induced RARbeta mRNA, while the RXR had no effect. Interestingly, a functional RXR-pathway was also seen in lipopolysaccharide-induced inhibition of mouse splenocyte proliferation. These results strongly suggest the existence of a pharmacological RXR-dependent pathway that is activated by a ligand that can bind to RXR.
Immobilization of kluyvera sp: effect of support material upon fermentation (1983)

Kluyvera can, when a special medium is employed, produce organic acids in conventional batch reactors. Both inorganic and organic polymeric support materials were evaluated to determine the potential of immobilized cells to improve fermentation rates. Sized Sephadex beads (DEAE-Sephadex A-50) proved far superior to activated alumina in time needed to achieve immobilization and in normalized alpha-ketoglutarate fermentation rate (per gram support per day).
The Entry Mechanism of Membrane-Containing Phage Bam35 Infecting Bacillus thuringiensis (2006)

The temperate double-stranded DNA bacteriophage Bam35 infects gram-positive Bacillus thuringiensis cells. Bam35 has an icosahedral protein coat surrounding the viral membrane that encloses the linear 15-kbp DNA genome. The protein coat of Bam35 uses the same assembly principle as that of PRD1, a lytic bacteriophage infecting gram-negative hosts. In this study, we dissected the process of Bam35 entry into discrete steps: receptor binding, peptidoglycan penetration, and interaction with the plasma membrane (PM). Bam35 very rapidly adsorbs to the cell surface, and N-acetyl-muramic acid is essential for Bam35 binding. Zymogram analysis demonstrated that peptidoglycan-hydrolyzing activity is associated with the Bam35 virion. We showed that the penetration of Bam35 through the PM is a divalent-cation-dependent process, whereas adsorption and peptidoglycan digestion are not.
Prognostic and Predictive Value of DAMPs and DAMP-Associated Processes in Cancer (2015)

It is now clear that human neoplasms form, progress, and respond to therapy in the context of an intimate crosstalk with the host immune system. In particular, accumulating evidence demonstrates that the efficacy of most, if not all, chemo- and radiotherapeutic agents commonly employed in the clinic critically depends on the (re)activation of tumor-targeting immune responses. One of the mechanisms whereby conventional chemotherapeutics, targeted anticancer agents, and radiotherapy can provoke a therapeutically relevant, adaptive immune response against malignant cells is commonly known as "immunogenic cell death." Importantly, dying cancer cells are perceived as immunogenic only when they emit a set of immunostimulatory signals upon the activation of intracellular stress response pathways. The emission of these signals, which are generally referred to as "damage-associated molecular patterns" (DAMPs), may therefore predict whether patients will respond to chemotherapy or not, at least in some settings. Here, we review clinical data indicating that DAMPs and DAMP-associated stress responses might have prognostic or predictive value for cancer patients.
The effect of recipient oocyte volume on nuclear transfer in cattle (1998)

This study compared the developmental potential of bovine nuclear transfer embryos with varying amounts of cytoplasm. Embryos formed from single cytoplasts fused to blastomeres by a single electrical pulse or from double cytoplasts using a double electrical pulse resulted in reconstituted embryos containing 75% and 150% of the original oocyte volume. No differences in fusion, cleavage, or development rates to blastocysts were observed between the groups. Mean cell numbers 2 days after fusion were significantly lower in single-cytoplast clones. Cell numbers of resulting blastocysts were likewise significantly lower in single-cytoplast clones. Embryos formed by fusion of blastomeres with single cytoplasts using a single electrical pulse or from double cytoplasts using either a single or a double pulse resulted in reconstituted embryos containing 50%, 100% and 100% of the original oocyte volume. Again, no differences in fusion or cleavage rates were observed between groups, but the development to blastocysts at day 7 was significantly higher in double cytoplasts constructed with one fusion pulse than in single cytoplasts (P < 0.05). Mean cell numbers 2 days after fusion were significantly lower in single-cytoplast clones (P < 0.05), but at the blastocyst stage, no statistically significant differences in cell numbers were observed. The results of this study show that cytoplasmic volume plays a role in the development of nuclear transfer embryos. When using crude enucleation methods such as oocyte bisection, normal cytoplasmic volumes can be achieved by fusing double cytoplasts with embryonic blastomeres.
Amyloid and Alzheimer's Disease: Inside and Out (2012)

Alzheimer's disease (AD) is poised to become the most serious healthcare issue of our generation. The leading theory of AD pathophysiology is the Amyloid Cascade Hypothesis, and clinical trials are now proceeding based on this hypothesis. Here, we review the original evidence for the Amyloid Hypothesis, which was originally focused on the extracellular deposition of beta amyloid peptides (Aβ) in large fibrillar aggregates, as well as how this theory has been extended in recent years to focus on highly toxic small soluble amyloid oligomers. We will also examine emerging evidence that Aβ may actually begin to accumulate intracellularly in lysosomes, and the role for intracellular Aβ and lysosomal dysfunction may play in AD pathophysiology. Finally, we will review the clinical implications of these findings.
The Role of Carbohydrate in Erythropoietin Action* (1985)

The carbohydrate composition of human erythropoietin (epo) was determined by micro-GLC. Enzymic removal of most of the sugars results in aggregation of glycosidase-treated epo, loss of biological activity when assayed in mice, and retention of activity when assayed in marrow cell cultures or by RIA. Endoglycosidase F causes the removal of most of the carbohydrates indicating that the oligosaccharides are asparagine linked. The lack of O-linked sugar is confirmed by the absence of N-acetylgalactosamine. These findings indicate that the oligosaccharide portion of epo, although required for action in vivo, is not required for interaction with the target cells of the blood-forming system.
BiopSym: A Simulator for Enhanced Learning of Ultrasound-Guided Prostate Biopsy (2009)

This paper describes a simulator of ultrasound-guided prostate biopsies for cancer diagnosis. When performing biopsy series, the clinician has to move the ultrasound probe and to mentally integrate the real-time bi-dimensional images into a three-dimensional (3D) representation of the anatomical environment. Such a 3D representation is necessary to sample regularly the prostate in order to maximize the probability of detecting a cancer if any. To make the training of young physicians easier and faster we developed a simulator that combines images computed from three-dimensional ultrasound recorded data to haptic feedback. The paper presents the first version of this simulator.
Persuasion in clinical practice: helping people make changes Lewis Walker Persuasion in clinical practice: helping people make changes Radcliffe Publishing £23.99 174pp 9781846193835 1846193834 (2010)

Written by a GP and honorary senior clinical tutor at Aberdeen University, this book looks at how to help people make changes.
Distributed methods for solving the security-constrained optimal power flow problem (2012)

The optimal power flow is the problem of determining the most efficient, low-cost and reliable operation of a power system by dispatching the available electricity generation resources to the load on the system. Unlike the classical optimal power flow problem, the security-constrained optimal power flow (SCOPF) problem takes into account both the pre-contingency (base-case) constraints and post-contingency constraints. In the literature, the problem is formulated as a large-scale nonconvex nonlinear programming. We propose two decomposition algorithms based on the Benders cut and the alternating direction method of multipliers for solving this problem. Our algorithms often generate a solution, whose objective function value is smaller than conventional approaches.
Berenil binding to higher ordered nucleic acid structures: complexation with a DNA and RNA triple helix (1995)

Berenil is an antitrypanosomal agent that binds to nucleic acid duplexes. Recently, we reported that this drug can bind to both DNA and RNA duplexes, while exhibiting properties characteristic of both intercalation and groove binding [Pilch, D. S., Kirolos, M. A., Liu, X., Plum, G. E., & Breslauer, K. J. (1995) Biochemistry 34, 9962-9976]. In this work, we use spectroscopic, calorimetric, and hydrodynamic techniques to demonstrate that berenil also can bind to DNA and RNA triplexes. Our results reveal the following significant features: (i) Berenil binds to the poly(dA).2poly(dT) DNA triplex and to the poly(rA).2poly(rU) RNA triplex without displacing the major groove-bound third strands. (ii) Both berenil-bound triplexes melt via two distinct transitions: initial conversion of the triplex to the duplex state, with the berenil remaining bound, followed by denaturation of the duplex to its component single strands. (iii) The magnitude and even the direction of the impact of berenil binding on the thermal stability of the DNA triplex depends on both the Na+ concentration and the drug binding density (the [base triplet]/[total berenil] ratio). Specifically, at Na+ concentrations < or = 0.08 M, the DNA triplex to duplex transition is thermally stabilized, while at Na+ concentrations > or = 0.125 M it is thermally destabilized. Between these two salt concentrations, berenil binding either enhances or diminishes the thermal stability of the DNA triplex in a manner that depends on the [base triplet]/[total berenil] ratio. (iv) The effect of berenil binding on the thermal stability of the RNA triplex to duplex equilibrium also depends on the [base triplet]/[total berenil] ratio, having a weakly destabilizing effect on this equilibrium at [base triplet]/[total berenil] ratios > 5, while thermally stabilizing this equilibrium at [base triplet]/[total berenil] ratios < 5. (v) The apparent "site sizes" associated with berenil binding to the triplexes range from approximately 1 to 12 base triplets per bound berenil and depend, in part, on the host triplex. One of the site sizes common to both triplexes is consistent with berenil binding to the minor groove. (vi) Berenil exhibits a higher apparent binding affinity for the DNA triplex relative to the RNA triplex. (vii) Viscometric data reveal nonintercalative binding properties when berenil complexes with both triplexes, consistent with a minor groove binding mode. (viii) Berenil binding to either the DNA or the RNA triplex is enthalpically more favorable than berenil binding to the corresponding duplex. (ix) Berenil binding to both triplexes decreases the cooperativity of the triplex to duplex melting event.(ABSTRACT TRUNCATED AT 400 WORDS)