gebhart/patrepeval huggingface dataset:
Intrauterine correction of factor VIII (FVIII) deficiency (2001)

This is the first published report documenting the successful use of intrauterine infusion of factor VIII (FVIII) in order to reduce the risk of intracranial haemorrhage in a foetus with documented haemophilia A. This approach provides another option for management of newborns with documented coagulation factor deficiency. The subsequent development of an inhibitor directed against FVIII is believed to be related to exposure to exogenous FVIII in the presence of an inversion mutation and not to the intrauterine procedure.
A Simple Access to Biologically Importanttrans-Stilbenes via Ru-Catalyzed Cross Metathesis (2006)

The cross metathesis of methoxy- or acetoxy-substituted styrenes using the Grubbs II catalyst affords unsymmetrical (mixed) E-stilbenes with astonishingly high selectivity (up to 79% yield). This approach offers a short and flexible synthesis of variously substituted stilbenes, which are derivatives or precursors of biologically important compounds such as resveratrol, piceatannol, and pinostilbene.
Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial (2018)

Few trials have examined rates of hypersensitivity reactions (HSRs) with intravenous iron formulations used to treat iron deficiency anemia (IDA). This randomized, multicenter, double-blind clinical trial compared the safety, and efficacy of ferumoxytol versus ferric carboxymaltose (FCM), focusing on rates of HSRs and hypotension as the primary end point. Patients with IDA of any etiology in whom oral iron was unsatisfactory or intolerable received ferumoxytol (n = 997) or FCM (n = 1000) intravenously over ≥15 minutes on days 1 and 8 or 9 for total respective doses of 1.02 g and 1.50 g. Composite incidences of moderate-to-severe HSRs, including anaphylaxis, or moderate-to-severe hypotension from baseline to week 5 (primary safety end point) were 0.6% and 0.7% in the ferumoxytol and FCM groups, respectively, with ferumoxytol noninferior to FCM. No anaphylaxis was reported in either group. The secondary safety end point of incidences of moderate-to-severe HSRs, including anaphylaxis, serious cardiovascular events, and death from baseline to week 5 were 1.3% and 2.0% in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Least-squares mean changes in hemoglobin at week 5 were 1.4 g/dL and 1.6 g/dL in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Incidence of hypophosphatemia was 0.4% for ferumoxytol and 38.7% for FCM.
Data allocation and spatio-temporal implications for video-on-demand systems (2002)

As the number of video streams to be supported by a digital video delivery system (DVDS) increases, we more and more start to understand that the ability to reliably and cost-efficiently support a considerable number of video streams (in the magnitude of tens of thousands) largely depends on software capabilities. Even in the presence of the best hardware configuration (not ignoring software vs hardware costs), the software exploitation of the hardware capabilities is of paramount importance. It is imperative that current software developments account for the eventual scalability of the number of video streams without commensurate increase in hardware. We present strategies for the management of video streams in order to maintain and satisfy their space and time requirements. We present a detailed analysis of the issues related to queuing I/O requests and data buffering. The designs for the arrangement and scheduling of I/O requests and data buffers are presented with the objective of guaranteeing the required data availability rates for continuous media display.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A point‐charge force field for molecular mechanics simulations of proteins based on condensed‐phase quantum mechanical calculations (2003)

Molecular mechanics models have been applied extensively to study the dynamics of proteins and nucleic acids. Here we report the development of a third-generation point-charge all-atom force field for proteins. Following the earlier approach of Cornell et al., the charge set was obtained by fitting to the electrostatic potentials of dipeptides calculated using B3LYP/cc-pVTZ//HF/6-31G** quantum mechanical methods. The main-chain torsion parameters were obtained by fitting to the energy profiles of Ace-Ala-Nme and Ace-Gly-Nme di-peptides calculated using MP2/cc-pVTZ//HF/6-31G** quantum mechanical methods. All other parameters were taken from the existing AMBER data base. The major departure from previous force fields is that all quantum mechanical calculations were done in the condensed phase with continuum solvent models and an effective dielectric constant of epsilon = 4. We anticipate that this force field parameter set will address certain critical short comings of previous force fields in condensed-phase simulations of proteins. Initial tests on peptides demonstrated a high-degree of similarity between the calculated and the statistically measured Ramanchandran maps for both Ace-Gly-Nme and Ace-Ala-Nme di-peptides. Some highlights of our results include (1) well-preserved balance between the extended and helical region distributions, and (2) favorable type-II poly-proline helical region in agreement with recent experiments. Backward compatibility between the new and Cornell et al. charge sets, as judged by overall agreement between dipole moments, allows a smooth transition to the new force field in the area of ligand-binding calculations. Test simulations on a large set of proteins are also discussed.
Comparative linkage maps of the rice and maize genomes. (1993)

Genetic linkage maps have been constructed for the rice and maize genomes on the basis of orthologous loci detected with a common set of cDNA clones. Conserved linkage groups could be identified, which together account for more than two-thirds of both genomes. In some instances, entire chromosomes or chromosome arms are nearly identical with respect to gene order and gene content. The results also reveal that most of the genes (> 72%) duplicated during ancient polyploidization are still present in the maize genome in duplicate copy. The comparative maps of rice and maize provide a basis for interpreting molecular, genetic, and breeding information between these two important species and establish a framework for ultimately connecting the genetics of all grass species.
Telesonography Adoption and Use to Improve the Standard of Patient Care Within a Dominican Community (2009)

Teleradiology has far-reaching implications for the health of remote and underserved populations. With coordination of radiographic evaluation and diagnosis from a distance, teleradiology has the potential to raise the standard of patient care throughout the world. Perhaps the safest and most cost-effective mode of teleradiology today is telesonography. The current research determined that telesonography improves the standard of care at a rural, government-run primary clinic within the Dominican Republic. The work reported herein is intended to compare the use of telesonography to the current standard of sonographic examination which is referral to government hospital 60km from the clinic. the following research questions were addressed: When compared to the standard of care, (1) To what extent does the use of asynchronous telesonography increase the percentage of received sonographic reports based on the total number of ultrasound referrals (sonographic reports / total number of referrals)? (2) To what extent does the use of asynchronous telesonography increase the rate of successful follow-up visits based on the total number of ultrasound referrals? (3) To what extent does the elapsed time between ultrasound referral and sonographic report delivery decrease with the use of asynchronous telesonography? (4) To what extent does the elapsed time between ultrasound referral and patient follow-up decrease with the use of asynchronous telesonography? Research methodology included randomly assigning 100 patients with clinical indications for sonographic examination into experimental and control groups during a 9-week implementation period. Findings from this study indicate that the implemented telesonography system, along with patient awareness of such a system, while not having an appreciable effect on the time to patient follow-up, provided a 4-fold increase in the proportion of patient follow-ups and a 6-fold increase in the proportion of returned radiological reports, and delivered those reports to the referring physician 6-times faster than in the control group. This study demonstrates the feasibility of utilizing a store-and forward telesonography system within this setting. Additional research focusing on the impact of telesonography on patient outcomes within this setting is recommended.
Effects of Neuraminidase on Airway Reactivity in the Guinea Pig (1992)

We investigated the effects of neuraminidase, a viral enzyme that cleaves alpha ketosidic cell-bound sialic acids, to see if it accounts for parainfluenza and influenza virus-induced airway hyperreactivity. Accordingly, Vibrio cholerae neuraminidase was administered intratracheally in guinea pigs, and airway reactivity was assessed 3 h later. Removal of sialic acid residues was evaluated by histologic studies. Airway responsiveness was determined in anesthetized, tracheotomized, and mechanically ventilated guinea pigs by exposing them to increasing concentrations of aerosolized bronchoconstrictor agents. Respiratory system conductance was measured by the occlusion method. Neuraminidase injected intratracheally did not change airway reactivity to 10(-4) to 10(-2) M acetylcholine or 10(-4) to 2.5 x 10(-3) M histamine; nor did it prevent aerosolized albuterol from inhibiting histamine-induced bronchoconstriction. Substance P (10(-6) to 5 x 10(-5) M) had no significant bronchoconstrictor effect on guinea pigs pretreated with saline or neuraminidase. In guinea pigs pretreated with aerosols of the neutral endopeptidase inhibitor phosphoramidon (10(-4) M) before the concentration curve to aerosolized substance P was recorded, neuraminidase significantly reduced substance P-induced bronchoconstriction. When bronchoconstriction was induced by the 4-11 fragment of substance P (10(-5) to 10(-2) M), which is devoid of positive charges, it did not differ significantly in guinea pigs pretreated with saline and those pretreated with neuraminidase. These results indicate that in the guinea pig, neuraminidase injected intratracheally does not induce non-specific airway hyperreactivity and may alter the binding of substance P to its receptors.
Modulation of ATP and drug binding by monoclonal antibodies against P‐glycoprotein (1991)

The role of P-glycoprotein in mediating the drug-resistance phenotype in multidrug resistant cells is now well documented. It is thought to function as an energy-dependent drug-efflux pump of broad specificity. Structurally, P-glycoprotein is an internally duplicated molecule containing two large multi-spanning transmembrane domains and two cytoplasmic ATP binding domains. In this report we demonstrate that monoclonal antibodies C219, C494, and C32 directed against short linear regions of the P-glycoprotein molecule inhibit ATP binding to P-glycoprotein in vitro. We also provide direct evidence that both predicted ATP-binding domains bind ATP and that there is co-operativity between the two sites. In addition, the capacity of P-glycoprotein to bind the calcium channel blocker, azidopine, is inhibited differentially by the antibodies. These observations are the first evidence linking specific perturbations of the P-glycoprotein molecule with ATP and drug binding.
Oncolytic Treatment and Cure of Neuroblastoma by a Novel Attenuated Poliovirus in a Novel Poliovirus-Susceptible Animal Model (2007)

Neuroblastoma is one of the most common solid tumors in children. Treatment is of limited utility for high-risk neuroblastoma and prognosis is poor. Resistance of neuroblastoma to conventional therapies has prompted us to search for a novel therapeutic approach based on genetically modified polioviruses. Poliovirus targets motor neurons leading to irreversible paralysis. Neurovirulence can be attenuated by point mutations or by exchange of genetic elements between different picornaviruses. We have developed a novel and stable attenuated poliovirus, replicating in neuroblastoma cells, by engineering an indigenous replication element (cre), copied from a genome-internal site, into the 5'-nontranslated genomic region (mono-crePV). An additional host range mutation (A(133)G) conferred replication in mouse neuroblastoma cells (Neuro-2a(CD155)) expressing CD155, the poliovirus receptor. Crossing immunocompetent transgenic mice susceptible to poliovirus (CD155 tg mice) with A/J mice generated CD155 tgA/J mice, which we immunized against poliovirus. Neuro-2a(CD155) cells were then transplanted into these animals, leading to lethal tumors. Despite preexisting high titers of anti-poliovirus antibodies, established lethal s.c. Neuro-2a(CD155) tumors in CD155 tgA/J mice were eliminated by intratumoral administrations of A(133)Gmono-crePV. No signs of paralysis were observed. Interestingly, no tumor growth was observed in mice cured of neuroblastoma that were reinoculated s.c. with Neuro-2a(CD155). This result indicates that the destruction of neuroblastoma cells by A(133)Gmono-crePV may lead to a robust antitumor immune response. We suggest that our novel attenuated oncolytic poliovirus is a promising candidate for effective oncolytic treatment of human neuroblastoma or other cancer even in the presence of present or induced antipolio immunity.
Primary Structure of Plasminogen. Separation of two Lysine-Binding Domains and one Neoplasminogen (M.w. = 38,000) (1977)

The complete amino acid sequence of the heavy chain of human plasmin (residues 1-560) has been established. The complete sequence of the ‘light chain (residues 561-790) is accounted for but six overlaps remain to be established. We have located 17 of the 24 disulfide bridges. The remaining 7 can be assigned with high confidence on the basis of extensive homology of the light chain with serine proteases and of kringle domains K1-K5 (residues 83-161, 165-242, 255-333, 357-434 and 461-540, resp.) with the two kringle domains (residues 66-144 and 171-249) in bovine prothrombin. Of the two oligosaccharide groups one is glucosamine-based, attachedto Asn-288, the other galactosamine-based, attached to Thr-345. The former is either present or absent, the latter is heterogeneous. This variability could account for six or more of the observed electrophoretic variants of plasminogen. Degradation of native human plasminogen by porcine pancreatic elastase gave 14 small peptides (12 from the PAP region and two (residues 338-353 and 440-441, from between kringles 3 and 4 and 4 and 5, resp.), and three major fragments. Two of these, namely Kl+2+3 (residues 79-337/353 (M.w. 29,843. plus)) and K4 (residues 354-439 (M.w. 9,687)) each contain a lysine-binding site. The third,- neoplasminogen-Val-442 (residues 442-790) is activated faster than plasminogen (residues 1-790) with either urokinase or streptokinase indicating that the structure contained in residues 1-441 (PAP+K1-K4) is not necessary for activation of plasminogen, and raising quêtions regarding a possible role for leukocyte elastase in changing the affinity of plasminogen/plasmin for other proteins by removing lysine-binding sites. A 42-resi-due fragment (residues Asp-546 - Gln-575, -S-S-bridged to Lys-660 - Tyr-671) is a substrate for urokinase, which cleaves the same Arg-Val-bond (560-561) as in native plasminogen.
A Novel Microwave Tomography System Using a Rotatable Conductive Enclosure (2011)

A novel microwave tomography (MWT) setup is proposed wherein a rotatable conductive enclosure is used to generate electromagnetic scattering data that are collected at each static position of the enclosure using a minimal antenna array having as few as only four co-resident elements. The antenna array remains fixed with respect to the target being imaged and only the boundary of the conductive enclosure is rotated. To show that non-redundant scattering data can be generated in this way several 2D transverse magnetic imaging examples are considered using single-frequency synthetic data. For each example, the reconstruction of the complex permittivity profile is compared to that obtained using a homogeneous open-region MWT setup having 16 co-resident antennas. The weighted <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -norm total variation multiplicative-regularized Gauss-Newton inversion (MR-GNI) is used for all inversions and for the new MWT setup the data collected at all positions of the conductive enclosure are inverted simultaneously. The quality of images obtained from the two systems is similar, but the advantage of the new configuration is its use of a fixed minimal antenna array which will put less of a burden on the numerical system model.
Heterologous expression in Escherichia coli of an intact multienzyme component of the erythromycin‐producing polyketide synthase (1993)

6-Deoxyerythronolide B synthase 3 (DEBS 3) is proposed to catalyse the fifth and sixth condensation cycles in the assembly of the polyketide 6-deoxyerythronolide B, the first isolatable intermediate in the biosynthesis of erythromycin A by Saccharopolyspora erythraea. The gene encoding DEBS 3 has previously been cloned and sequenced, and the deduced product is predicted to house nine fatty acid synthase-like activities on a 330-kDa polypeptide chain. The gene has been engineered into a pT-7-based expression system for over-expression in Escherichia coli. Recombinant DEBS 3 was found to constitute, after induction, 1-2% of soluble intracellular protein. DEBS 3 was purified from extracts of the recombinant E. coli to apparent homogeneity, and was found not to be modified by covalent attachment of the prosthetic group 4'-phosphopantetheine. Incubation with (R,S)-methylmalonyl-CoA, the presumed source of extension units for polyketide chain assembly, led to hydrolysis of the thioester, implying that the methylmalonyl-CoA:ACP acyltransferase domains in DEBS 3 are correctly folded and able to catalyse this side-reaction. During this reaction, DEBS 3 became transiently radiolabelled, consistent with the intermediacy of an acylenzyme. The native molecular mass of the protein by gel filtration chromatography was 668 kDa which corresponds either to a dimer or to a highly asymmetric monomer.
Differential responses of yellow Avy/A and agouti A/a (BALB/c X VY) F1 hybrid mice to the same diets: glucose tolerance, weight gain, and adipocyte cellularity. (1988)

Differences in weight gain, efficiency of food utilization, glucose tolerance, insulin levels, and adipocyte cellularity were measured when three different diets were fed to lean agouti and obese yellow mice. Sets of adult and weanling agouti (A/a) and yellow (Avy/A) (BALB/c X VY) F1 hybrid mice were fed high-sucrose (HS), 10 percent fat, or regular lab chow (control). Some mice received the diets only after 12 weeks of eating lab chow (adult-fed); others ate the diets from the time of weaning. Since responses of both age groups were similar, only the data from the adult-fed groups are presented. The HS and 10 percent fat diets increased the body weight gain in both A/a and Avy/A adult mice more than the control diet; the HS diet was utilized more efficiently in the lean agouti females causing a slightly higher weight gain, whereas the 10 percent fat and HS diets were used with the same efficiency by the yellow mice. Short-term feeding (3-5 weeks) with the HS and 10 percent fat diets decreased the glucose tolerance of adult yellow but not of agouti mice. The pancreatic insulin response to a glucose load was higher in all mice fed the HS diet, whereas this response was blunted in those on the 10 percent fat diet. In agouti mice the HS and 10 percent diets increased the mean cell diameter of the parametrial adipocytes and deteriorated the glucose oxidation rate in response to insulin compared to the control diet. In the yellow littermates, on the other hand, the test diets decreased the mean cell diameter and also impaired insulin sensitivity of the adipocytes. The decrease of the mean adipocyte size was probably due to an increased number of small cells.
Potent and nontoxic antisense oligonucleotides containing locked nucleic acids (2000)

Insufficient efficacy and/or specificity of antisense oligonucleotides limit their in vivo usefulness. We demonstrate here that a high-affinity DNA analog, locked nucleic acid (LNA), confers several desired properties to antisense agents. Unlike DNA, LNA/DNA copolymers were not degraded readily in blood serum and cell extracts. However, like DNA, the LNA/DNA copolymers were capable of activating RNase H, an important antisense mechanism of action. In contrast to phosphorothioate-containing oligonucleotides, isosequential LNA analogs did not cause detectable toxic reactions in rat brain. LNA/DNA copolymers exhibited potent antisense activity on assay systems as disparate as a G-protein-coupled receptor in living rat brain and an Escherichia coli reporter gene. LNA-containing oligonucleotides will likely be useful for many antisense applications.
f-GAN: Training Generative Neural Samplers using Variational Divergence Minimization (2016)

Generative neural samplers are probabilistic models that implement sampling using feedforward neural networks: they take a random input vector and produce a sample from a probability distribution defined by the network weights. These models are expressive and allow efficient computation of samples and derivatives, but cannot be used for computing likelihoods or for marginalization. The generative-adversarial training method allows to train such models through the use of an auxiliary discriminative neural network. We show that the generative-adversarial approach is a special case of an existing more general variational divergence estimation approach. We show that any f-divergence can be used for training generative neural samplers. We discuss the benefits of various choices of divergence functions on training complexity and the quality of the obtained generative models.