gebhart/patrepeval huggingface dataset:
Extended support with a left ventricular assist device as a bridge to heart transplantation. (1992)

The Heartmate-1000IP, an intracorporeal, pneumatically activated, pulsatile left ventricular assist device (LVAD) with textured blood-contacting surfaces, is undergoing clinical evaluation as a bridge to heart transplantation (HTx). During a 3 year period (January 1988 to April 1991), the authors evaluated 12 patients who required extended LVAD support (greater than 30 days) while awaiting HTx. Duration of support ranged from 31 to 233 days (mean, 117 days). LVAD performance was excellent, with average pump flow indices of 2.5-3.5 L/min/m2. Long-term antithrombotic therapy consisted of dipyridamole and aspirin in all except one patient who received only low-molecular-weight dextran. After the initial recovery period, prothrombin and partial thromboplastin times returned to baseline levels. Plasma-free hemoglobin levels averaged less than 10 mg/dl. One patient is currently receiving support (91+ days); the 11 other patients underwent successful HTx, with follow-up ranging from 7 to 36 months. The authors' cumulative experience with this LVAD totals more than 1,506 days of support (greater than 4 years) without evidence of any thromboembolic episodes. These results suggest that this LVAD provides an effective bridge to HTx for extended periods.
Cryogenic Nitrogen as a Hydraulic Fracturing Fluid in the Devonian Shale (1998)

Abstract With proper engineering, liquid nitrogen can be used safely as a hydraulic fracturing fluid. The fluid's extremely cold temperature (−300 to −320°F) will induce thermal tensile stresses in the fracture face. These stresses exceed the tensile strength of the Devonian shale, causing the fracture face to fragment. Because of the extreme temperatures, treated water can be used as a diverter between fracturing stages. This water freezes instantly when it contacts the first treatment zone. This paper discusses the successful application of this technology to stimulate the Devonian shale in Eastern Kentucky.
Formulation and Evaluation of Floating Oral In Situ Gelling System of Amoxicillin (2011)

Purpose. Effective Helicobacter pylori eradication requires delivery of the antibiotic locally in the stomach. High dose of amoxicillin (750 to 1000 mg) is difficult to incorporate in floating tablets but can easily be given in liquid dosage form. Keeping the above facts in mind, we made an attempt to develop a new floating in situ gelling system of amoxicillin with increased residence time using sodium alginate as gelling polymer to eradicate H. pylori. Methods. Floating in situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methyl cellulose K100, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, floating lag time, total floating time, and in vitro drug release. The formulation was optimized using a 3(2) full factorial design. Dissolution data were fitted to various models to ascertain kinetic of drug release. Regression analysis and analysis of variance were performed for dependent variables. Results. All formulations (F(1)-F(9)) showed floating within 30 s and had total floating time of more than 24 h. All the formulations showed good pourability. It was observed that concentration of sodium alginate and HPMC K100 had significant influence on floating lag time, cumulative percentage drug release in 6 h and 10 h. The batch F(8) was considered optimum since it showed more similarity in drug release (f(2) = 74.38) to the theoretical release profile. Conclusion. Floating in situ gelling system of amoxicillin can be formulated using sodium alginate as a gelling polymer to sustain the drug release for 10 to 12 h with zero-order release kinetics.
Replication of nodamura virus after transfection of viral RNA into mammalian cells in culture (1992)

Nodamura virus (NOV) was purified from the hind limbs of infected suckling mice and used as a source of the two genomic RNAs of the virus, RNA 1 and RNA 2. Upon transfection of the viral RNAs into baby hamster kidney (BHK21) cells in culture, vigorous RNA replication ensued and single-stranded RNAs 1 and 2 accumulated to reach an abundance which approximated that of the cellular rRNAs. Transient synthesis of a small subgenomic RNA (RNA 3) was also observed, and double-stranded versions of RNAs 1, 2, and 3 were detected. Three major viral proteins were synthesized in transfected cells. Protein A (about 115 kDa) and protein B (about 15 kDa) were made transiently at early times after transfection, whereas a large amount of protein alpha (43 kDa), the precursor to the two viral coat proteins, was made continuously starting later in the infectious cycle. When very low concentrations of viral RNAs were used for transfection, preferential replication of RNA 1 occurred. This result was attributed to segregation of the transfected viral RNAs to separate cells in culture and the subsequent replication and amplification of RNA 1 in cells that had received no RNA 2. Accordingly, multiple passages of the viral RNAs by transfection at the limit dilution resulted in the purification of RNA 1 free of RNA 2 and demonstrated that RNA 1 was capable of prolonged autonomous replication which was also accompanied by the continuous synthesis of RNA 3. In cells transfected with RNA 1 alone, protein alpha was not synthesized and proteins A and B were made continuously. Electron microscopic analysis of BHK21 cells 24 h after transfection with NOV RNAs 1 and 2 showed that large numbers of virus particles accumulated in the cytoplasm and formed paracrystalline arrays in some regions. Whole NOV purified from transfected BHK21 cells was infectious for suckling mice and had an electrophoretic mobility that was similar but not identical to that of NOV purified from infected mouse muscle. The high yield of NOV, its simple genetic composition, and its unusual genome strategy make this virus an attractive system for the study of viral RNA replication in animal cells.
Perspectives of biodegradable natural polysaccharides for site-specific drug delivery to the colon. (2007)

The ability to deliver drugs to the human colon in a specific manner has become feasible over the years. Targeting pharmaceutical drugs to the colon makes it possible to achieve local or systemic drug delivery to this site. To deliver the compounds in a non-degraded form to the lower part of the gastrointestinal tract, they must first of all pass through the stomach, the upper part of the intestine and must use the characteristics of the colon to specifically release the drugs in this part of the digestive tract. Among the different approaches available to achieve targeted drug release to the colon, the use of especially biodegradable polymers holds great promise. This family of natural polymers has great appeal to drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and, for the most part, low toxicity and biodegradability yet high stability. The most favorable property of these materials is their approval as pharmaceutical excipients. Polysaccharidases are bacterial enzymes that are available in sufficient quantity to be exploited in colon targeting. Bacterial sources of polysaccharidases as well as a detailed treatise of the enzymatic flora of the colonic region is reviewed, followed by a wide range of the polysaccharides which can be used solely for the purpose of colon-specific drug delivery. Present article also discusses few of the mechanisms by which members of the intestinal microbiota degrade complex polysaccharides. A final overview of the various approaches to target drugs to the colon utilizing natural polysaccharides, the limits and the future developments in this field with these natural polymers is discussed which leads to the conclusion that polysaccharides show high potential in achieving colon-specific drug delivery.
Altered Nuclear Transfer in Stem-Cell Research — A Flawed Proposal (2004)

The study of human embryonic stem cells is a matter of intense public debate, primarily because derivation of such cells requires the destruction of human blastocysts, a procedure that some find morally objectionable. William Hurlbut, M.D., of Stanford University and a member of the President's Council on Bioethics has recently proposed to the council an alternative way to derive embryonic stem cells that, he argues, circumvents this objection.1 The chair of the council, Leon Kass, M.D., Ph.D., favors Hurlbut's proposal.2 We believe that it is flawed.Hurlbut's proposal is based on the observation that mouse embryos carrying a mutation in . . .
Solution conformations and hydrolytic stability of 2′ ‐ and 3′ ‐substituted 2′,3′‐dideoxyribonucleosides, including some potential inhibitors of human immunodeficiency virus (1992)

Abstract Sugar ring conformations of a number of 2′ ‐ and 3′ ‐substituted 2′,3′‐dideoxyribonucleosides were determined in 2 H 2 O by 1 H NMR spectroscopy. First‐order rate constants for the cleavage of their N ‐glycosidic bond in aqueous acid were measured. The dependence of sugar ring conformation and hydrolytic stability on the polar nature of the 2′/3′‐substitutent is discussed.
Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI‐guided focused ultrasound (2007)

Abstract The clinical application of chemotherapy to brain tumors has been severely limited because antitumor agents are typically unable to penetrate an intact blood‐brain barrier (BBB). Although doxorubicin (DOX) has been named as a strong candidate for chemotherapy of the central nervous system (CNS), the BBB often prevents cytotoxic levels from being achieved. In this study, we demonstrate a noninvasive method for the targeted delivery of DOX through the BBB, such that drug levels shown to be therapeutic in human tumors are achieved in the normal rat brain. Using MRI‐guided focused ultrasound with preformed microbubbles (Optison) to locally disrupt the BBB and systemic administration of DOX, we achieved DOX concentrations of 886 ± 327 ng/g tissue in the brain with minimal tissue effects. Tissue DOX concentrations of up to 5,366 ± 659 ng/g tissue were achieved with higher Optison doses, but with more significant tissue damage. In contrast, DOX accumulation in nontargeted contralateral brain tissue remained significantly lower for all paired samples ( p &lt; 0.001). These results suggest that targeted delivery by focused ultrasound may render DOX chemotherapy a viable treatment option against CNS tumors, despite previous accessibility limitations. In addition, MRI signal enhancement in the sonicated region correlated strongly with tissue DOX concentration ( r = 0.87), suggesting that contrast‐enhanced MRI could perhaps indicate drug penetration during image‐guided interventions. Our technique using MRI‐guided focused ultrasound to achieve therapeutic levels of DOX in the brain offers a large step forward in the use of chemotherapy to treat patients with CNS malignancies. © 2007 Wiley‐Liss, Inc.
Clusters of PE and PPE genes of Mycobacterium tuberculosis are organized in operons: Evidence that PE Rv2431c is co‐transcribed with PPE Rv2430c and their gene products interact with each other (2006)

About 10% of the coding capacity of the Mycobacterium tuberculosis (M. tb) genome is devoted to the PE/PPE family of genes scattered throughout the genome. We have identified 28 PE/PPE operons which are organized within the M. tb genome in such a way that most PE members are upstream to PPE members. One example of such a gene arrangement is the PPE gene Rv2430c, earlier shown by us to code for a highly antigenic protein eliciting strong B-cell responses in TB patients [Choudhary, R.K., Mukhopadhyay, S., Chakhaiyar, P., Sharma, N., Murthy, K.J.R., Katoch V.M. and Hasnain, S.E. (2003) PPE antigen Rv2430c of Mycobacterium tuberculosis induces a strong B cell response. Infect. Immun. 71, 6338-6343], situated downstream to PE gene Rv2431c. Rv2431c and Rv2430c are transcribed as an operon. Expression of either rRv2431c or rRv2430c alone in E. coli limited their localization to the inclusion bodies. However, when they were co-expressed, both the proteins appeared in the soluble fraction. These two proteins interact with each other and form oligomers when alone, however, when present together they exist as heteromer.
Cholesterol-dependent Formation of GM1 Ganglioside-bound Amyloid β-Protein, an Endogenous Seed for Alzheimer Amyloid (2001)

GM1 ganglioside-bound amyloid beta-protein (GM1/Abeta), found in brains exhibiting early pathological changes of Alzheimer's disease (AD) including diffuse plaques, has been suggested to be involved in the initiation of amyloid fibril formation in vivo by acting as a seed. To elucidate the molecular mechanism underlying GM1/Abeta formation, the effects of lipid composition on the binding of Abeta to GM1-containing lipid bilayers were examined in detail using fluorescent dye-labeled human Abeta-(1-40). Increases in not only GM1 but also cholesterol contents in the lipid bilayers facilitated the binding of Abeta to the membranes by altering the binding capacity but not the binding affinity. An increase in membrane-bound Abeta concentration triggered its conformational transition from helix-rich to beta-sheet-rich structures. Excimer formation of fluorescent dye-labeled GM1 suggested that Abeta recognizes a GM1 "cluster" in membranes, the formation of which is facilitated by cholesterol. The results of the present study strongly suggested that increases in intramembrane cholesterol content, which are likely to occur during aging, appear to be a risk factor for amyloid fibril formation.
Rescue of high-specificity Cas9 variants using sgRNAs with matched 5’ nucleotides (2017)

We report that engineered Cas9 variants with improved specificity-eCas9-1.1 and Cas9-HF1-are often poorly active in human cells, when complexed with single guide RNAs (sgRNAs) with a mismatch at the 5' terminus, relative to target DNA sequences. Because the nucleotide at the 5' end of sgRNAs, expressed under the control of the commonly-used U6 promoter, is fixed to a guanine, these attenuated Cas9 variants are not useful at many target sites. By using sgRNAs with matched 5' nucleotides, produced by linking them to a self-cleaving ribozyme, the editing activity of Cas9 variants can be rescued without sacrificing high specificity.
New suppressors of signal-sequence mutations, prlG, are linked tightly to the secE gene of Escherichia coli. (1989)

Analysis of more than 100 extragenic suppressors of the lamB14D signal-sequence mutation (changes Val in the hydrophobic core region at position 14 to Asp) has revealed alterations that appear to lie at prlA (secY) and secA (prlD), two loci known to be mutable to suppressor alleles, and a new suppressor termed prlG. One allele of the new suppressor class, prlG1, has been characterized in some detail. This suppressor counteracts, to some degree, the export defect conferred by a variety of signal-sequence mutations in two different genes, lamB and malE. Genetic analysis shows that the dominant suppressor mutations are linked tightly to, and probably allelic with, the gene secE. This result, coupled with data obtained with conditional-lethal alleles of secE, argues strongly that SecE is an important component of the cellular protein export machinery in Escherichia coli.
IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor α subunit CD25 (2010)

IL-2 is crucial to T cell homeostasis, especially of CD4(+) T regulatory cells and memory CD8(+) cells, as evidenced by vigorous proliferation of these cells in vivo following injections of superagonist IL-2/anti-IL-2 antibody complexes. The mechanism of IL-2/anti-IL-2 antibody complexes is unknown owing to a lack of understanding of IL-2 homeostasis. We show that IL-2 receptor alpha (CD25) plays a crucial role in IL-2 homeostasis. Thus, prolongation of IL-2 half-life and blocking of CD25 using antibodies or CD25-deficient mice led in combination, but not alone, to vigorous IL-2-mediated T cell proliferation, similar to IL-2/anti-IL-2 antibody complexes. These data suggest an unpredicted role for CD25 in IL-2 homeostasis.
Robust readout of bosonic qubits in the dispersive coupling regime (2018)

High-fidelity qubit measurements play a crucial role in quantum computation, communication, and metrology. In recent experiments, it has been shown that readout fidelity can be improved by performing repeated quantum nondemolition (QND) readouts of a qubit's state through an ancilla. For a qubit encoded in a two-level system, the fidelity of such schemes is limited by the fact that a single error can destroy the information in the qubit. On the other hand, if a bosonic system is used, this fundamental limit can be overcome by utilizing higher levels such that a single error still leaves states distinguishable. In this work, we present a robust readout scheme which leverages both repeated QND readouts and higher-level encodings to asymptotically suppress the effects of mode relaxation and individual measurement infidelity. We calculate the measurement fidelity in terms of general experimental parameters, provide an information-theoretic description of the scheme, and describe its application to several encodings, including cat and binomial codes.
Mathematical modelling of aircraft noise based on identified directivity patterns (1996)

This paper deals with measurement and modelling of aircraft directivity patterns and their use for quantifying and assessing the A-weighted aircraft noise in the vicinity of airports. The directivity patterns of aircraft noise radiation are estimated from noise records of the flyover noise gathered from an array of microphones, synchronised in time with tracking radar geometrical records of the flown flight path. The data processing considers the effects of spherical spreading, atmospheric absorption and delay time between the source and receiver. The resulting one-third-octave noise spectra are used to identify coefficients of a polynomial which describe the directivity pattern of the aircraft in flight. These spectra are a function of the propagation distance and emission angle and take the form of series expansions of cosine terms, involving 32 coefficients. The model combines the directivity contributions of different aircraft noise sources such as jet and fan noise, combustion noise and airframe noise together with propagation phenomena. For the prediction of noise at various aircraft speeds the polynomial model is extended by a velocity dependent term adjusted for convective amplification. Using the adjusted measured directivity patterns the takeoff ground roll noise can be predicted accurately. In addition to assessing the impact of aircraft noise around airports the directivity pattern of an aircraft can be used for sophisticated studies such as calculating the sensitivity of noise level on the ground due to changes of the propagation distance and emission angle as well as Monte Carlo statistical modelling of vertical and horizontal flight path dispersion. An example of statistical prediction is presented.
Glucose-Dependent Modulation of Insulin Secretion and Intracellular Calcium Ions by GKA50, a Glucokinase Activator (2007)

Because glucokinase is a metabolic sensor involved in the regulated release of insulin, we have investigated the acute actions of novel glucokinase activator compound 50 (GKA50) on islet function. Insulin secretion was determined by enzyme-linked immunosorbent assay, and microfluorimetry with fura-2 was used to examine intracellular Ca(2+) homeostasis ([Ca(2+)](i)) in isolated mouse, rat, and human islets of Langerhans and in the MIN6 insulin-secreting mouse cell line. In rodent islets and MIN6 cells, 1 micromol/l GKA50 was found to stimulate insulin secretion and raise [Ca(2+)](i) in the presence of glucose (2-10 mmol/l). Similar effects on insulin release were also seen in isolated human islets. GKA50 (1 micromol/l) caused a leftward shift in the glucose-concentration response profiles, and the half-maximal effective concentration (EC(50)) values for glucose were shifted by 3 mmol/l in rat islets and approximately 10 mmol/l in MIN6 cells. There was no significant effect of GKA50 on the maximal rates of glucose-stimulated insulin secretion. In the absence of glucose, GKA50 failed to elevate [Ca(2+)](i) (1 micromol/l GKA50) or to stimulate insulin release (30 nmol/l-10 micromol/l GKA50). At 5 mmol/l glucose, the EC(50) for GKA50 in MIN6 cells was approximately 0.3 micromol/l. Inhibition of glucokinase with mannoheptulose or 5-thioglucose selectively inhibited the action of GKA50 on insulin release but not the effects of tolbutamide. Similarly, 3-methoxyglucose prevented GKA50-induced rises in [Ca(2+)](i) but not the actions of tolbutamide. Finally, the ATP-sensitive K(+) channel agonist diazoxide (200 micromol/l) inhibited GKA50-induced insulin release and its elevation of [Ca(2+)](i.) We show that GKA50 is a glucose-like activator of beta-cell metabolism in rodent and human islets and a Ca(2+)-dependent modulator of insulin secretion.
Electrical stimulation with Pt electrodes. VIII. Electrochemically safe charge injection limits with 0.2 ms pulses (neuronal application) (1990)

The charge injection limits of a Pt electrode using 0.2 ms charge balanced, biphasic current pulses ranged from 50 to 150 microC/cm2 geometric if the potential excursions of the electrode are kept below those at which H2 or O2 is produced. These charge densities are three to ten times smaller than the currently accepted value based on earlier experiments in which the reversible surface reactions were fully utilized and the pulse widths were longer.
Mode Estimation of Model-based Programs: Monitoring Systems with Complex Behavior. (2001)

Deductive mode-estimation has become an essential component of robotic space systems, like NASA’s deep space probes. Future robots will serve as components of large robotic networks. Monitoring these networks will require modeling languages and estimators that handle the sophisticated behaviors of robotic components. This paper introduces RMPL, a rich modeling language that combines reactive programming constructs with probabilistic, constraint-based modeling, and that offers a simple semantics in terms of hidden Markov models (HMMs). To support efficient realtime deduction, we translate RMPL models into a compact encoding of HMMs called probabilistic hierarchical constraint automata (PHCA). Finally, we use these models to track a system’s most likely states by extending traditional HMM belief update. 1