gebhart/patrepeval huggingface dataset:
An mRNA Vaccine Protects Mice against Multiple Tick-Transmitted Flavivirus Infections (2018)

Powassan virus (POWV) is an emerging tick-transmitted flavivirus that circulates in North America and Russia. Up to 5% of deer ticks now test positive for POWV in certain regions of the northern United States. Although POWV infections cause life-threatening encephalitis, there is no vaccine or countermeasure available for prevention or treatment. Here, we developed a lipid nanoparticle (LNP)-encapsulated modified mRNA vaccine encoding the POWV prM and E genes and demonstrated its immunogenicity and efficacy in mice following immunization with one or two doses. The POWV mRNA vaccine induced high titers of neutralizing antibody and sterilizing immunity against lethal challenge with different POWV strains. The mRNA vaccine also induced cross-neutralizing antibodies against multiple other tick-borne flaviviruses and protected mice against the distantly related Langat virus. These data demonstrate the utility of the LNP-mRNA vaccine platform for the development of vaccines with protective activity against multiple flaviviruses.
Comparison of the Effects of Stimulators and Inhibitors of Resorption on the Release of Lysosomal Enzymes and Radioactive Calcium from Fetal Bone in Organ Culture* (1978)

The release of lyosomal enzymes, collagenase, and previously incorporated 45Ca from fetal rat long bones cultured in a chemically defined medium is compared. Parathyroid hormone (PTH) and prostaglandin E2 increased the release of β-glucuronidase, acetylglucosaminidase, and cathepsin D, but showed little effect on collagenase activity in the medium at 48 h. The dose-response relations for β-glucuronidase and 45Ca release were similar. However, the increase in lysosomal enzyme release was proportionally greater and occurred earlier than the increase in 45Ca release. PTH also caused a significant increase in total β-glucuronidase activity in bone plus medium. Several agents which stimulate 45Ca release at an optimal concentration, but not. at a higher concentration, including dibutyryl cAMP, isobutylmethylxanthine, and the calcium ionophore, A23187, all increased lysosomal enzyme release at the concentration which increased 45Ca release. Three inhibitors of bone resorption (calcitonin, cortisol, and colchicine) blocked lysosomal enzyme release at the same time that 45Ca release decreased. When the bones escaped from calcitonin inhibition, both 45Ca and lysosomal enzyme release increased. While colchicine blocked both lysosomal enzymes and 45Ca release, it actually increased the release of bone collagenase, and together with PTH or prostaglandin E2 caused a large increase in free collagenase activity in the medium. These data indicate that lysosomal enzyme release is closely linked to bone resorption and suggest that lysosomal enzymes may have a primary role in initiating resorption, perhaps by acting on noncollagenous matrix or tissue components before mineral removal and collagen degradation.
Use of Infrared Multiphoton Photodissociation with SWIFT for Electrospray Ionization and Laser Desorption Applications in a Quadrupole Ion Trap Mass Spectrometer (1996)

Infrared multiphoton photodissociation (IRMPD) is combined with stored wave form inverse Fourier transforms (SWIFT) to effect dissociation and ion ejection in a quadrupole ion trap mass spectrometer. The application of IRMPD to the structural characterization of biochemical ions generated by chemical ionization and electrospray ionization and the feasibility of utilizing infrared photons for the activation of laser-desorbed metal ion-crown ether complexes was examined. The effect of helium pressure on the dissociation efficiency and relative dissociation rate constants for systems with well-known thermochemistry was evaluated. The helium pressure is not detrimental to the IRMPD experiment when nominal pressures lower than 2 x 10(-5) Torr are used. At pressures close to nominally 8 x 10(-5) Torr of helium, collisonal deactivation dominates. Results show conventional CAD is a more selective dissociation technique; however, the amount of fragment ion information generated depends highly on the qz value. IRMPD, on the other hand, is independent of the value of qz such that low rf storage values can be utilized during the irradiation period. Thus, under these conditions, informative lower mass fragment ions are trapped and detected. A larger number of structurally informative fragments is generated upon irradiation with infrared photons relative to the CAD method because of the further excitation of primary fragment ions upon photoabsorption. SWIFT wave forms are successfully utilized to determine the extent of excitation of primary fragment ions as well as prove/disprove dissociation pathways of a variety of ions such as macrolide antibiotics and hydrogen-bonded complexes.
Reactive Coatings Literature Review (2002)

Abstract : This document is a review of reactive coatings to protect military personnel from chemical and biological warfare agents. We define a reactive coating as a surface coating that neutralizes chemical or biological threats by a chemical reaction. The potential advantage of reactive coatings has led to development of systems using a wide range of approaches.
Release of vasodilator, but not vasoconstrictor, neuropeptides and of enteroglucagon by intestinal ischaemia/reperfusion in the rat. (1994)

Reperfusion of ischaemic intestine is characterised by an initial hyperaemia with ensuing mucosal repair. This study investigated possible roles for gut vasoactive neuropeptides and trophic peptides in these phenomena. Groups of rats were monitored during superior mesenteric artery occlusion for five or 20 minutes, with or without subsequent reperfusion for five minutes. Peptide concentrations (fmol/ml) in arterial blood, were measured using specific radioimmunoassays. Intestinal ischaemia alone did not cause haemodynamic disturbance or peptide release. Reperfusion, after five minutes of ischaemia, resulted in arterial hypotension and a rise in plasma vasoactive intestinal polypeptide (mean (SEM)) (37 (3), control 11 (4), p < 0.001). After 20 minutes of ischaemia, reperfusion resulted in greater hypotension (p < 0.05) and release of both vasoactive intestinal polypeptide (31 (3), p < 0.05 v control) and the more potent vasodilator beta-calcitonin gene related peptide (49 (3), control 23 (1), p < 0.001). By contrast, the vasodilators alpha-calcitonin gene related peptide and substance P and the vasoconstrictors neuropeptide Y, peptide YY, and somatostatin were not released. Bombesin, a stimulatory neuropeptide, was released after 20 minutes of ischaemia/reperfusion (13 (2), control 7 (3), p < 0.05). Plasma enteroglucagon rose from control (51 (4)) to 110 (16) (p < 0.001) and to 158 (27) (p < 0.005) after five and 20 minutes of ischaemia/reperfusion. The potent enteric vasodilators vasoactive intestinal polypeptide and beta-calcitonin gene related peptide, unopposed by vasoconstrictors, may promote post-ischaemic intestinal hyperaemia. The rise in plasma enteroglucagon may point to diffuse mucosal injury and is consistent with the putative trophic role of this peptide.
THE USE OF HYPOTHERMIA AFTER CARDIAC ARREST (1959)

BENSON, DONALD W. M.D.; WILLIAMS, G. RAINEY JR. M.D.; SPENCER, FRANK C. M.D.; YATES, ADOLPH J. M.D. Author Information
Comparing total cost of care for Medicare FFS patients with pancreatic cancer by chemotherapy regimen. (2020)

721 Background: To analyze total cost of care for patients with pancreatic cancer by FDA-Approved/NCCN Category 1 regimen. Methods: Cancer episodes were identified using a methodology similar to the Medicare Oncology Care Model (OCM) in the 2014-2016 100% Medicare Limited Data Set (LDS) claims files. Index dates were established for chemotherapy claims that did not occur within 6 months of another chemotherapy claim for all Medicare fee-for-service beneficiaries. Cancer episodes were defined as the 6-month period following an index date. Each episode was assigned a cancer type based on the plurality of cancer ICD 9/10 diagnosis codes that occurred on chemotherapy claims in the episode. Episode costs were calculated from claim paid amounts, and DME and other Part B spending was estimated using episodes created in the 5% Medicare LDS files using the same methodology. We analyzed total episode costs for three FDA-Approved/NCCN Category 1 pancreatic cancer regimens: gemcitabine plus nab-paclitaxel (gem-nab), FOLFIRINOX (FFX), and liposomal irinotecan (nal-IRI). Results: We identified 110,618 cancer episodes in 2016, of which 4,018 were for pancreatic cancer (average age at index: 71.3 years). Pancreatic cancer patients in these episodes were treated with gem-nab (45% of episodes), FFX (14%), and nal-IRI (4%). The main cost drivers across all regimens were Part B chemotherapy, other Part B drugs and inpatient services. Episode costs were $41,749, $42,086, and $45,851 for patients receiving gem-nab, FFX, and nal-IRI, respectively. Part B chemotherapy costs were $13,065 (gem-nab), $3,095 (FFX), and $18,472 (nal-IRI); other Part B drug costs were $7,343 (gem-nab), $17,013 (FFX), and $10,479 (nal-IRI); and inpatient service costs were $9,044 (gem-nab), $9,069 (FFX), and $5,108 (nal-IRI). Conclusions: Total episode costs for pancreatic cancer care were similar among three FDA-Approved/NCCN Category 1 regimens, but the components of cost varied. Episodes with Nal-IRI had the largest Part B chemotherapy costs and the lowest inpatient service costs. Episodes with FFX and gem-nab had similar inpatient service costs, which were higher than episodes with nal-IRI. Episodes with FFX had the highest other Part B drug costs.
Hardware/software organization of a high-performance ATM host interface (1993)

A successful hardware/software architecture that resolves performance bottlenecks at the workstation-to-network host interface and offers high end-to-end performance is described. The solution reported carefully splits protocol processing functions into hardware and software implementations. The interface hardware is highly parallel and performs all per-cell functions with dedicated logic to maximize performance. Software provides support for the transfer of data between the interface and application memory, as well as the state management necessary for virtual circuit setup and maintenance. In addition, all higher-level protocol processing is implemented with host software. The prototype connects a RISC System/6000 to a SONET-based asynchronous transfer model (ATM) network carrying data at the OC-3c rate of 155 Mb/s. An experimental evaluation of the interface hardware and software has been performed. Several conclusions are drawn about this host interface architecture and the workstations to which it is connected.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Intermediate-range order in glasses and liquids (1989)

Many glasses and liquids exhibit a first sharp diffraction peak that is evidence for intermediate-range order caused by regularities in the packing of structural units. These tend to cluster around particular values of the wavevector when scaled by the nearest-neighbour distance or the mean inter-atomic spacing. The first sharp diffraction peak is distinguished from the pre-peak in binary metallic glasses, which occurs at higher wavevectors when scaled in this way.
Coagulation Factors VIIa and Xa Induce Cell Signaling Leading to Up-regulation of the egr-1 Gene (1999)

Intracellular signaling induced by the coagulation factors (F) VIIa and Xa is poorly understood. We report here studies on these processes in a human keratinocyte line (HaCaT), which is a constitutive producer of tissue factor (TF) and responds to both FVIIa and FXa with elevation of cytosolic Ca(2+), phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38(MAPK), and c-Jun N-terminal kinase, and up-regulation of transcription of the early growth response gene-1 (egr-1). Using egr-1 as end point, we observed with both agonists that phosphatidylinositol-specific phospholipase C and the mitogen-activated protein kinase/Erk kinase/Erk pathway were mediators of the responses. The responses to FVIIa were TF-dependent and up-regulation of egr-1 mRNA did not require presence of the TF cytoplasmic domain. Antibodies to EPR-1 and factor V had no effect on the response to FXa. We have provided evidence that TF is not the sole component of the FVIIa receptor. The requirement for proteolytic activity of both FVIIa and FXa suggests that protease-activated receptors may be involved. We now report evidence suggesting that protease-activated receptor 2 or a close homologue may be a necessary but not sufficient component of this particular signal transduction pathway. The up-regulation of egr-1 describes one way by which the initiation of blood coagulation may influence gene transcription. The ability of these coagulation proteases to induce intracellular signals at concentrations at or below the plasma concentrations of their zymogen precursors suggests that these processes may occur also in vivo.
Mutations ofRPGR in X-linked retinitis pigmentosa (RP3) (2002)

Mutations in RPGR, retinitis pigmentosa GTPase regulator, are associated with RP3 type of X-linked retinitis pigmentosa, a severe, non-syndromic form of retinal degeneration. In the majority of subjects RPGR mutations are associated with a typical rod-cone degeneration, but in a small number, cone-rod dystrophy, deafness, and abnormalities in respiratory cilia have been noted. Alternative splicing of RPGR is complex in all species examined. In RP3 patients, mutations have been found in exons 1-14 and ORF15, thus delineating a transcript necessary for normal retinal function in humans. The great majority of mutations are predicted to result in premature termination of translation. These mutations are scattered over exons 1-14 and ORF15, while most missense mutations occur in a domain with homology to the protein RCC1, encoded by exons 1-10. Exon ORF15 is a "hot spot" for mutation, at least in the British population, in which it harbors 80% of the mutations found within a sample of 47 X-linked retinitis pigmentosa patients. Most RPGR mutations are unique to single families, which makes it difficult to demonstrate phenotype-genotype correlations.
Effect of Polypeptide Sequence on Polypeptide Self-Assembly (2011)

This study represents a unique example where the self-assembly of five amphiphilic polypeptides was monitored as a function of their hydrophilic-to-lipophilic balance (HLB). The HLB was tuned by preparing a series of polypeptides with aspartic acid (Asp) and phenylalanine (Phe) according to the sequence (Asp(x)Phe(y)) where x and y vary from 1 to 3. The self-assembly of the (Asp(x)Phe(y))(n) polypeptides with M(w) values ranging from 8 to 12 K was studied in solution by fluorescence quenching and nonradiative energy transfer (NRET) fluorescence experiments. Dynamic (DLS) and static (SLS) light scattering studies were used to complement the results obtained. The fluorescence quenching experiments conducted with the chromophore pyrene used as a free probe, physically bound to the polypeptides via hydrophobic interactions, demonstrated that the chromophore was less exposed to the solution for the sequences having a higher hydrophobic character. Protective quenching was also observed for those polypeptides randomly labeled with pyrene where the phenylalanine content was high, whereas pyrene was found to be fully exposed to the quencher for the polypeptides having more hydrophilic sequences. NRET used to probe interpolymeric association was not observed between a naphthalene and a pyrene labeled polypeptide for the polypeptide sequences which were richer in aspartic acid, whereas energy transfer took place with the more hydrophobic polypeptides. This observation led to the conclusion that those sequences with a higher content of aspartic acid essentially generate unimolecular polymeric micelles, whereas those with a higher content of phenylalanine generate polymeric aggregates which offer protection from the solvent to their hydrophobic cargo. The presence of these polymeric aggregates was also confirmed by DLS and SLS studies which suggest that species 100-200 nm in diameter are present in solution.
Antiviral therapy for human immunodeficiency virus infections (1995)

Depending on the stage of their intervention with the viral replicative cycle, human immunodeficiency virus inhibitors could be divided into the following groups: (i) adsorption inhibitors (i.e., CD4 constructs, polysulfates, polysulfonates, polycarboxylates, and polyoxometalates), (ii) fusion inhibitors (i.e., plant lectins, succinylated or aconitylated albumins, and betulinic acid derivatives), (iii) uncoating inhibitors (i.e., bicyclams), (iv) reverse transcription inhibitors acting either competitively with the substrate binding site (i.e., dideoxynucleoside analogs and acyclic nucleoside phosphonates) or allosterically with a nonsubstrate binding site (i.e., non-nucleoside reverse transcriptase inhibitors), (v) integration inhibitors, (vi) DNA replication inhibitors, (vii) transcription inhibitors (i.e., antisense oligodeoxynucleotides and Tat antagonists), (viii) translation inhibitors (i.e., antisense oligodeoxynucleotides and ribozymes), (ix) maturation inhibitors (i.e., protease inhibitors, myristoylation inhibitors, and glycosylation inhibitors), and finally, (x) budding (assembly/release) inhibitors. Current knowledge, including the therapeutic potential, of these various inhibitors is discussed. In view of their potential clinical the utility, the problem of virus-drug resistance and possible strategies to circumvent this problem are also addressed.
Proteomic Approaches for the Global Analysis of Proteins (2002)

Improvements in technology that allow miniaturization and high-throughput analyses of thousand of genes and gene products have changed the focus and scope of research and development in both academia and industry. It is now possible to study entire proteomes with the goals of elucidating protein expression, subcellular localization, biochemical activities, and their regulation. Alterations in different cell types and conditions and in normal and disease states can be revealed. This wealth of information not only has facilitated our basic understanding of many biological processes but also has enormous potential for drug discovery and development.
Neutrophil-Kupffer cell interaction: a critical component of host defenses to systemic bacterial infections (2002)

Most bacteria that enter the bloodstream are taken up and eliminated within the liver. The specific mechanisms that underlie the role of the liver in the resolution of systemic bacterial infections remain to be determined. The vast majority of studies undertaken to date have focused on the function of resident tissue macrophages (Kupffer cells) that line the liver sinusoids. Indeed, it is often reported that Kupffer cells ingest and kill the bulk of organisms taken up by the liver. Recent studies indicate, however, that phagocytosis by Kupffer cells is not the principal mechanism by which organisms are eliminated. Rather, elimination depends on the complex interaction of Kupffer cells and bactericidal neutrophils that immigrate rapidly to the liver in response to infection. We discuss the critical role of neutrophil-Kupffer cell interaction in innate host defenses and, conceivably, the development and expression of adaptive immunity in the liver.
Segregation and Rearrangement of Coamplified Genes in Different Lineages of Mutant Cells That Overproduce Adenylate Deaminase (1986)

Four genes encoding proteins designated as W, X, Y1, and Y2 were found previously to be amplified at different levels in a Chinese hamster fibroblast mutant line selected for overproduction of adenylate deaminase. To gain information on the molecular mechanisms responsible, we studied the levels of amplification and the structures of these four genes in several lineages of mutant cells with comparable activities of adenylate deaminase, the selected enzyme. Only the W gene was amplified in all the lines. In one line, the X, Y1, and Y2 genes were coamplified, while in others either the Y1 gene or the pair X and Y2 were coamplified. The results were consistent with linkage of all the genes--in a particular order--in an amplifiable sequence with variable endpoints. Novel joints with a nonrandom distribution were observed. We frequently detected rearranged copies of the W gene, but very few novel joints were present in the other three genes in the six highly amplified lines examined. Some of the novel joints in gene W were highly amplified; they were generated by reamplification of a rearrangement that appeared at an early selection step. In some lines, reamplification was accompanied by deletion or mass correction of preexisting units. We discuss mechanisms which might account for these observations.
Dopamine partial agonist actions of the glutamate receptor agonists LY 354,740 and LY 379,268 (2007)

Because glutamate compounds alter the release of dopamine and prolactin, the present study examined whether group II metabotropic receptor agonists, LY 354,740 and LY 379,268, had any direct in vitro action on dopamine D2 receptors on rat striatal tissue, cloned D2Long receptors, and prolactin release from anterior pituitary cells. In competition versus the D2-specific ligand [(3)H]domperidone, LY 354,740 had a dissociation constant of 24 nM at D2(High) (the functional high-affinity state of dopamine D2 receptors), while the value for LY 379,268 was 21 nM. LY 354,740 also stimulated by 50% the incorporation of [(35)S]-GTP-gamma-S at a concentration of 120 nM, but its maximal stimulation was only 22% of the maximum elicited by dopamine. LY 379,268 stimulated by 50% the incorporation of [(35)S]-GTP-gamma-S at 280 nM, but its maximal stimulation was also only 22% of the maximum elicited by dopamine. However, both LY 354,740 and LY 379,268 potently inhibited the dopamine-induced incorporation of [(35)S]-GTP-gamma-S with inhibitory Ki values of 43 nM and 30 nM, respectively. The release of prolactin from rat isolated anterior pituitary cells in culture was 50% inhibited by 20 nM LY 379,268 and by 100 nM LY 354,740. These Ki values are similar to those known for the mGluR II receptor, suggesting that these compounds may have both glutamate and dopamine actions in vivo. The dopamine agonist and antagonist actions of these compounds indicate that these drugs have properties of a dopamine partial agonist, and may, therefore, have antipsychotic action.
Resiquimod, a new immune response modifier from the family of imidazoquinolinamines, inhibits allergen‐induced Th2 responses, airway inflammation and airway hyper‐reactivity in mice (2004)

These data indicate that R-848 effectively inhibits allergen-induced airway inflammation and hyper-reactivity by modulation of increased Th2-immune responses.
Effectiveness of aripiprazole v. Haloperidol in acute bipolar mania (2005)

Aripiprazole showed superior levels of response and tolerability to haloperidol in the treatment of an acute manic episode for up to 12 weeks.
Stem-Loop RT-PCR Quantification of siRNAs In Vitro and In Vivo (2009)

RNA interference (RNAi) is a mechanism in which the introduction of small interfering RNAs (siRNAs) into a diverse range of organisms and cell types causes degradation of the complementary mRNA. Applications of RNAi include gene function and pathway analysis, target identification and validation, and therapeutics. There is a need to develop reliable and easy-to-use assays to evaluate siRNA delivery efficiency and distribution, study pathways, and stability of siRNAs in cells (posttransfection) and in animals (postinjection). We have leveraged the Applied Biosystems TaqMan-based stem-loop RT-PCR technology, originally developed for quantification of endogenous microRNAs in cells, to fulfill these needs. The application protocols developed enable robust quantification of siRNA, including chemically modified siRNA molecules, in vitro and in vivo.