gebhart/patrepeval huggingface dataset:
PrP genotype contributes to determining survival times of sheep with natural scrapie (1996)

Several allelic variants of the sheep PrP gene are associated with scrapie susceptibility. However, it is not known whether, and to what extent, the PrP genotype contributes to determining survival times of scrapie sheep. We therefore determined the PrP genotype and life spans of over 50 Flemish and Swifter sheep within a single scrapie-affected flock. Eighty-three per cent of the scrapie sheep were homozygous for the PrP(VQ) allele (polymorphic amino acids at codons 136 and 171 are indicated) and these sheep died from scrapie at a mean age of 25 months. In sheep heterozygous for PrP(VQ), development of scrapie was delayed or did not occur. Sheep with at least one PrP(AR) allele, including PrP(VQ)/PrP(AR) sheep, did not develop scrapie. No scrapie sheep were found without a PrP(VQ) allele. We conclude that the PrP genotype contributes to determining survival times of sheep with natural scrapie. Additionally, we describe two novel sheep PrP allelic variants.
[Thoracoscopic repair of diaphragmatic eventration sustained at knife injury: a case report]. (1998)

A 46-year-old male taxi driver was stabbed onto the left chest while on duty. On arrival soon after, he was hemodynamically stable. Computed tomography showed omental prolapse into the left thorax through the diaphragm. On the 11th day, he underwent thoracoscopy revealing omental prolapse via a 3-cm rent in the left diaphragm, which was reduced manually. The diaphragmatic orifice was lifted and debrided with suturing using a stapling cutter. The post-operative course was uneventful. Finger palpation through the orifice enabled safe suturing of the left diaphragm facing the omentum, the colon, and the stomach, all of which may suffer iatrogenic injury.
AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells (1996)

All-trans retinoic acid (ATRA) is successfully used in the cyto-differentiating treatment of acute promyelocytic leukemia (APL). Paradoxically, APL cells express PML-RAR, an aberrant form of the retinoic acid receptor type alpha (RAR alpha) derived from the leukemia-specific t(15;17) chromosomal translocation. We show here that AM580, a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist, is a powerful inducer of granulocytic maturation in NB4, an APL-derived cell line, and in freshly isolated APL blasts. After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor (G-CSF), the compound induces granulocytic maturation, as assessed by determination of the levels of leukocyte alkaline phosphatase, CD11b, CD33, and G-CSF receptor mRNA, at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects. By contrast, AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease. In NB4 cells, two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580, whereas RAR beta- or RAR gamma-specific ligands are totally ineffective. These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present. Binding experiments, using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha, show that AM580 has a lower affinity than ATRA for both receptors. However, in the presence of PML-RAR, the synthetic retinoid is a much better transactivator of retinoic acid-responsive element-containing promoters than the natural retinoid, whereas, in the presence of RAR alpha, AM580 and ATRA have similar activity. This may explain the strong cyto-differentiating potential of AM580 in PML-RAR-containing leukemic cells.
Vitamin K Epoxide Reductase Complex Subunit 1 (VKORC1): The Key Protein of the Vitamin K Cycle (2006)

Vitamin K epoxide, a by-product of the carboxylation of blood coagulation factors, is reduced to vitamin K by an enzymatic system possessing vitamin K epoxide reductase (VKOR) activity. This system is the target of coumarin-derived drugs widely used in thrombosis therapy and prophylaxis. Recently, the key protein of the VKOR system has been identified. The human VKORC1 gene maps to chromosome 16 and consists of 3 exons encoding a 163-amino acid integral ER membrane protein with three or four predicted transmembrane alpha- helices. Expression of human VKORC1 in Spodoptera frugiperda (Sf9) cells and in Pichia pastoris results in enhanced VKOR activity over low endogenous constitutive levels. Sequence based search methods reveal that human VKORC1 belongs to a large family of homologous genes found in vertebrates, insects, plants, protists, archea, and bacteria. All orthologs share five completely conserved amino acids, including two cysteines found in a tetrapeptide motif presumably required for redox function. The recent discovery of the VKORC1 gene has initiated renewed interest in understanding VKOR activity. Analysis of VKORC1 protein structure and function will be crucial in understanding the VKOR catalytic mechanism, how anticoagulant drugs modulate VKOR activity, and the role of VKORC1 in downstream physiological and pathological pathways.
Computing Redox Potentials in Solution:  Density Functional Theory as A Tool for Rational Design of Redox Agents (2002)

High-level density functional theory in combination with a continuum solvation model was employed to compute standard redox potentials in solution phase for three different classes of electrochemically active molecules: small organic molecules, metallocenes, and M(bpy)3x (M = Fe, Ru, Os; x = +3, +2, +1, 0, −1). Excellent agreement with experimentally determined redox potentials is found with an average deviation of approximately 150 mV when four different solvents commonly in use for electrochemical measurements were included. To obtain quantitative agreement between theory and experiment, the use of a large basis set is crucial especially when the redox couple includes anionic species. Whereas the addition of diffuse functions improved the results notably, vibrational zero-point-energy corrections and addition of entropy effects are less important. The computational protocol for computing redox potentials in solution, which has been benchmarked, is a powerful and novel tool that will allow a molecular-level understanding of the features dictating the properties of redox-active species.
Mobile Device Integration and Interaction with V2X Communication (2012)

In a V2X environment, message processing and data visualization are key technologies influencing both real and perceived performance and usability of a system. V2X safety applications require frequent exchange of position information by means of so called Cooperative Awareness Messages (CAMs) or Basic Safety Messages (BSMs). These messages are generated, encoded and sent by all vehicles and corresponding actions have to be executed on receiving vehicles. The in-vehicle V2X system can be divided into several components. Our approach is based on a “two-component” system, consisting of a vehicle-integrated V2X communication unit (onboard unit, OBU) and a personal portable device (PPD), such as a smart phone or tablet PC. Subject of this work is the investigation how to distribute the workload and functionality between the two components. Our goal is to find a flexible solution that maximizes the overall performance and reliability of the system. We investigate and compare several message processing approaches and try to combine the strengths of both components. As a result, we present our final setup that can handle an up to 40 timeshigher message rate compared to other investigated solutions.
Identification of amino acids involved in recognition by dengue virus NS3-specific, HLA-DR15-restricted cytotoxic CD4+ T-cell clones (1996)

The majority of T-cell clones derived from a donor who experienced dengue illness following receipt of a live experimental dengue virus type 3 (DEN3) vaccine cross-reacted with all four serotypes of dengue virus, but some were serotype specific or only partially cross-reactive. The nonstructural protein, NS3, was immuno-dominant in the CD4+ T-cell response of this donor. The epitopes of four NS3-specific T-cell clones were analyzed. JK15 and JK13 recognized only DEN3 NS3, while JK44 recognized DEN1, DEN2, and DEN3 NS3 and JK5 recognized DEN1, DEN3, and West Nile virus NS3. The epitopes recognized by these clones on the DEN3 NS3 protein were localized with recombinant vaccinia viruses expressing truncated regions of the NS3 gene, and then the minimal recognition sequence was mapped with synthetic peptides. Amino acids critical for T-cell recognition were assessed by using peptides with amino acid substitutions. One of the serotype-specific clones (JK13) and the subcomplex- and flavivirus-cross-reactive clone (JK5) recognized the same core epitope, WITDFVGKTVW. The amino acid at the sixth position of this epitope is critical for recognition by both clones. Sequence analysis of the T-cell receptors of these two clones showed that they utilize different VP chains. The core epitopes for the four HLA-DR15-restricted CD4+ CTL clones studied do not contain motifs similar to those proposed by previous studies on endogenous peptides eluted from HLA-DR15 molecules. However, the majority of these dengue virus NS3 core epitopes have a positive amino acid (K or R) at position 8 or 9. Our results indicate that a single epitope can induce T cells with different virus specificities despite the restriction of these T cells by the same HLA-DR15 allele. This finding suggests a previously unappreciated level of complexity for interactions between human T-cell receptors and viral epitopes with very similar sequences on infected cells.
Monoclonal Antibody (F5) to Human Prostate Antigen (1983)

Hybridoma culture F5 has been developed which secretes monoclonal antibody (McAb) directed to an epitope of a prostatic glycoprotein of Mr 34 kD (Prostate Antigen, PA). Tissue levels of PA have been evaluated using a competitive-binding enzyme-immunoassay based upon the inhibition of McAb binding activity to purified antigen. Results indicated the specific occurrence of high antigen concentrations in extracts prepared from prostatic tissues. The antigenicity of epitope F5 is resistant to tissue fixation and embedding protocols, and has been demonstrated upon immunoperoxidase staining procedures. Immunoperoxidase data strongly indicate that McAb F5 possesses a singular specificity towards prostatic epithelial cells. Other tissues, whether normal or cancerous, fail to express this determinant. Specimens examined included epithelial and nonepithelial tissues along with a panel of carcinomas and sarcomas. The antibody was able to detect tumor cells at extra-prostatic sites and represents a powerful probe for the detection and differential diagnosis of metastatic cancer of the prostate.
Transforming Growth Factor-β: Biological Function and Chemical Structure (1986)

Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that controls proliferation, differentiation, and other functions in many cell types. Many cells synthesize TGF-beta and essentially all of them have specific receptors for this peptide. TGF-beta regulates the actions of many other peptide growth factors and determines a positive or negative direction of their effects. Its marked ability to enhance formation of connective tissue in vivo suggests several therapeutic applications.
Women's Beliefs and Decisions About Hormone Replacement Therapy (1997)

To examine preventive health practices in older women, we conducted computer-assisted telephone interviews with 1082 women aged 50-80 who were enrollees of Group Health Cooperative of Puget Sound (June-November 1995; 80.3% response rate). We sought to describe the women's reasons for initiating, discontinuing, or not initiating hormone replacement therapy (HRT). HRT use was categorized as current (42.5%), past (20.9%), or never (36.6%) based on the interviews. The reasons most frequently cited by current users for initiating HRT were menopausal symptoms (47.3%), osteoporosis prevention (32.4%), and physician advice (30.3%). The most frequently cited reasons for quitting HRT were side effects (26.6%), physician's advice (22.9%), fear of cancer (15.4%), and not wanting menstrual periods or bleeding (15.2%). Of past users, 53.8% reported stopping HRT on their own, and 46.2% did so at their physician's advice. The reasons most commonly cited by never users for not initiating HRT were that hormones were not needed (49.9%) and that menopause is a natural event (17.9%). Among never users, 33.1% reported considering HRT, only 46.6% discussing it with their provider, and 5.0% being given an HRT prescription they did not fill. Many women made decisions about HRT independent of interactions with health care providers. Better understanding of the beliefs and decisions that influence women's choice to use or not use HRT is needed to develop more effective counseling strategies.
Evaluation of tissue adhesives in closure of scleral tunnel incisions (1995)

Using a biomechanical wound strength model, we compared the efficacy of cyanoacrylate and fibrin glues used to close scleral tunnel incisions. Scleral tunnel incisions were made in four groups of rabbits: (1) traditional self-sealing incision, (2) modified non-self-sealing incision, (3) method 2, closed with cyanoacrylate glue, or (4) method 2, closed with fibrin glue. Overall, Groups 1 and 4 showed the least clinical reaction, the slightest decrease in intraocular pressure (which recovered to baseline by day 7), and the most significant recovery of postoperative astigmatism. Initially, the bursting pressure in Groups 1 and 3 was statistically the highest (P < .005). By day 3, wound strengths in Groups 1 and 4 were comparable. Bursting pressure decreased in Groups 2 and 3 by day 7. Our results indicate that clinical responses, intraocular pressure, induced astigmatism, and ultimately wound strength were comparable in fibrin-glue-closed scleral pocket and sutureless self-sealing cataract incisions. Although cyanoacrylate glue cures immediately and initially demonstrates a strong adhesive quality, it causes a severe inflammatory response that inhibits subsequent collagen remodeling. Fibrin tissue adhesives may have an application as adjunctive means of closing scleral tunnel incisions.
Early Virologic Nonresponse to Tenofovir, Abacavir, and Lamivudine in HIV‐Infected Antiretroviral‐Naive Subjects (2005)

The tenofovir disoproxil fumarate/abacavir/lamivudine regimen resulted in an unexpected and unacceptably high rate of nonresponse and incidence of K65R and M184V/I. This 3-drug regimen should not be used.
Dendroaspis natriuretic peptide relaxes isolated human arteries and veins (2002)

The current study demonstrates that DNP is an endogenous human natriuretic peptide that relaxes human arteries more than veins. Furthermore, DNP mediated vasorelaxation involves the inward rectifying potassium channels, prostaglandins, and cGMP. This newest member of the natriuretic peptide family may have an important physiologic role in the human vasculature.
Growth and process conditions of aligned and patternable films of iron(III) oxide nanowires by thermal oxidation of iron (2008)

A simple, catalyst-free growth method for vertically aligned, highly crystalline iron oxide (α-Fe(2)O(3)) wires and needles is reported. Wires are grown by the thermal oxidation of iron foils. Growth properties are studied as a function of temperature, growth time and oxygen partial pressure. The size, morphology and density of the nanostructures can be controlled by varying growth temperature and time. Oxygen partial pressure shows no effect on the morphology of resulting nanostructures, although the oxide thickness increases with oxygen partial pressure. Additionally, by using sputtered iron films, the possibility of growth and patterning on a range of different substrates is demonstrated. Growth conditions can be adapted to less tolerant substrates by using lower temperatures and longer growth time. The results provide some insight into the mechanism of growth.
Field emission from silicon spikes with diamond coatings (1995)

Diamond-coated silicon field emitters were fabricated and investigated. Emission currents of few μA per tip at voltages of several hundred volts were obtained from very blunt tips with curvature radii up to 3 μm. The values of the effective work function calculated from Fowler–Nordheim plot were in the range from 0.3 to 1.2 eV. Two models for an explanation of the experimental data are proposed.
The Demise of Community-Owned Long Day Care Centres and the Rise of the Mythical Consumer (1999)

This paper discusses the demise of the Australian community-owned long day care sector. In so doing it also examines the way in which the language of government policy has established a framework for children's services that works against the survival of these nonprofit services. The paper asks the reader to consider the need to focus the debate back on policy outcomes for children.
Improved pronunciation features for construct-driven assessment of non-native spontaneous speech (2009)

This paper describes research on automatic assessment of the pronunciation quality of spontaneous non-native adult speech. Since the speaking content is not known prior to the assessment, a two-stage method is developed to first recognize the speaking content based on non-native speech acoustic properties and then forced-align the recognition results with a reference acoustic model reflecting native and near-native speech properties. Features related to Hidden Markov Model likelihoods and vowel durations are extracted. Words with low recognition confidence can be excluded in the extraction of likelihood-related features to minimize erroneous alignments due to speech recognition errors. Our experiments on the TOEFL® Practice Online test, an English language assessment, suggest that the recognition/forced-alignment method can provide useful pronunciation features. Our new pronunciation features are more meaningful than an utterance-based normalized acoustic model score used in previous research from a construct point of view.
The Novel Silatecan 7-tert-Butyldimethylsilyl-10-hydroxycamptothecin Displays High Lipophilicity, Improved Human Blood Stability, and Potent Anticancer Activity (2000)

We describe the rational design and synthesis of B- and A, B-ring-modified camptothecins. The key alpha-hydroxy-delta-lactone pharmacophore in 7-tert-butyldimethylsilyl-10-hydroxycamptothecin (DB-67, 14) displays superior stability in human blood when compared with clinically relevant camptothecin analogues. In human blood 14 displayed a t(1/2) of 130 min and a percent lactone at equilibrium value of 30%. The tert-butyldimethylsilyl group renders the new agent 25-times more lipophilic than camptothecin, and 14 is readily incorporated, as its active lactone form, into cellular and liposomal bilayers. In addition, the dual 7-alkylsilyl and 10-hydroxy substitution in 14 enhances drug stability in the presence of human serum albumin. Thus, the net lipophilicity and the altered human serum albumin interactions together function to promote the enhanced blood stability. In vitro cytotoxicity assays using multiple different cell lines derived from eight distinct tumor types indicate that 14 is of comparable potency to camptothecin and 10-hydroxycamptothecin, as well as the FDA-approved camptothecin analogues topotecan and CPT-11. In addition, cell-free cleavage assays reveal that 14 is highly active and forms more stable top1 cleavage complexes than camptothecin or SN-38. The impressive blood stability and cytotoxicity profiles for 14 strongly suggest that it is an excellent candidate for additional in vivo pharmacological and efficacy studies.
Distinct Muscarinic Receptor Subtypes Suppress Excitatory and Inhibitory Synaptic Responses in Cortical Neurons (1997)

Simultaneous whole cell recordings from monosynaptically connected cortical cells were performed with the use of two patch pipettes to determine the effect of acetylcholine (ACh) on both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively) in cultured neurons from rat visual cortex. For 96% of EPSPs and 73% of IPSPs, ACh potently suppressed postsynaptic potentials in a dose-dependent manner. The estimated effective concentrations to produce half maximal response (EC50S) were 30 and 210 nM for EPSPs and IPSPs, respectively. To identify what subtypes of ACh receptors are involved in the suppression of postsynaptic potentials, three different, partially selective muscarinic receptor antagonists were used. According to the comparison of estimated Schild coefficients for each of the three antagonists against the suppression by ACh, EPSPs are most likely mediated by m4 receptors, and IPSPs by m1 receptors. When cells were treated with pertussis toxin, which inactivates m2 and m4 receptors while leaving m1, m3, and m5 receptors intact, 7 of 8 EPSPs were resistant to ACh whereas 8 of 12 IPSPs were still suppressed by ACh. This result supports the interpretation that the suppression of EPSPs was mediated by m4 receptors and that of IPSPs by m1 receptors. To obtain an indication as to whether ACh works presynaptically or postsynaptically, 1/CV2 analysis was carried out. The resultant diagonal alignment of the ratio of 1/CV2 plotted against the ratio of the amplitude of postsynaptic potentials suggests a presynaptic mechanism for the suppression of both EPSPs and IPSPs. In addition, in many cases a large synaptic suppression was observed without an obvious change in the input resistance. Furthermore, in one case where a single inhibitory driver cell was recorded with three different follower cells sequentially, none of the three IPSPs was suppressed by ACh, providing additional support for the presynaptic localization of ACh action. These results suggest that in cerebral cortex ACh has, in addition to its direct facilitatory effect via m3 pharmacology, a suppressive effect on EPSPs and IPSPs via m1 and m4 muscarinic receptors, respectively, probably with a presynaptic site of action. Separation of the actions of ACh into different receptor-second messenger pathways with potential for independent interactions with other neuromodulatory systems may be an important aspect of the mechanism of cholinergic regulation of functional state in cortex. Separation of cholinergic effects at different receptors might also offer a means for selective pharmacological intervention in disorders of sleep or memory.
Disulfide bond assignment in human J chain and its covalent pairing with immunoglobulin M (1992)

The assignment of disulfide bonds in human J chain and its covalent pairing with immunoglobulin M was determined under conditions which minimize disulfide bond interchange. We show that in J chain the three intradisulfide bridges are formed between Cys 12 and 100, Cys 71 and 91, and Cys 108 and 133. Previous reports [reviewed by Koshland, M. E. (1985) Annu. Rev. Immunol. 3, 425-453] have proposed that cysteines 12, 14, or 68 were linked to the penultimate cysteine 575 of two mu chain tails. In this work, we demonstrate that cysteines 14 and 68 are disulfide-bridged to mu chains. A revised, albeit putative, model of J chain folding is presented which takes into account the correct disulfide pairing and the predictive secondary structure assignment.