gebhart/patrepeval huggingface dataset:
Challenges in the Development of Prescription Opioid Abuse-deterrent Formulations (2007)

Opioid analgesics remain the cornerstone of effective management for moderate-to-severe pain. In the face of persistent lack of access to opioids by patients with legitimate pain problems, the rate of prescription opioid abuse in the United States has escalated over the past 15 years. Abuse-deterrent opioid products can play a central role in optimizing the risk-benefit ratio of opioid analgesics--if these products can be developed cost-effectively without compromising efficacy or creating new safety issues for the target treatment population. The development of scientific methods for assessing prescription opioid abuse potential remains a critical and challenging step in determining whether a claim of abuse deterrence for a new opioid product is indeed valid and will thus be accepted by the medical, regulatory, and reimbursement communities. To explore this and other potential impediments to the development of prescription opioid abuse-deterrent formulations, a panel of experts on opioid abuse and diversion from academia, industry, and governmental agencies participated in a Tufts Health Care Institute-supported symposium held on October 27 and 28, 2005, in Boston, MA. This manuscript captures the main consensus opinions of those experts, and also information gleaned from a review of the relevant published literature, to identify major impediments to the development of opioid abuse-deterrent formulations and offer strategies that may accelerate their commercialization.
Differential Impairments of Spatial Memory and Social Behavior in Two Models of Limbic Epilepsy (1995)

To explore memory impairments in temporal lobe epilepsy, we used two experimental models in the rats: (a) kainate-induced status epilepticus (SE) resulting in excitotoxic damage and in later spontaneous seizures; and (b) amygdala kindling, known to induce no lesions (or only minor) and neuronal reorganization. Long-term effects of these models on memory were investigated with a spatial learning task in a radial-arm maze, and a social interaction test that implies degree of short-term memory. An histological analysis was made to determine neuronal damage or loss caused by epileptic activity in brain regions that could be related to memory functions. Kainate-induced epilepsy produced large memory deficits in animals tested 5 months after the injection. The rats showed severe lesions in amygdala and hippocampus and piriform and entorhinal cortex. Spatial memory was strongly diminished. The social memory test was severely impaired, probably due to the extent of amygdala injury, which is known to disturb social behavior. On the contrary, kindled rats showed no evident lesion in any brain region and displayed performances as good as those of controls in both tests. These experiments demonstrated that memory deficits appear to be related to the severity of neuronal damage in limbic areas, and the ability to develop seizures (permanence) is not solely responsible for these memory disturbances.
Hybrid routing (1990)

A general-purpose routing algorithm for very-large-scale integrated (VLSI) circuits and printed circuit board (PCB) designs is proposed. Ideas behind the maze-running algorithm and the hierarchical routing algorithm are combined into a powerful algorithm called hybrid routing. The new algorithm demonstrates a speed compatible to a hierarchical router and produces routings with quality equivalent to that obtained by a maze router. Hybrid routing is based on the maze-running method with a third search dimension added. The extra search space is built by recursively constructing a hierarchy of coarser grid meshes. By means of a parameter-controlled expansion into the coarser meshes, the hybrid router is able to find the preferred search region very quickly and will not miss local information as a hierarchical router does. A user-given parameter can turn the algorithm into a pure maze router, a pure hierarchical router, or a wide spectrum of hybrid routers with different speed/quality characteristics between the extremes. The algorithm has been implemented and integrated into a global router that can handle large-scale routing, such as that encountered in the sea-of-gates layout.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An α/β-Peptide Helix Bundle with a Pure β3-Amino Acid Core and a Distinctive Quaternary Structure (2009)

Helix bundles are among the most widely studied tertiary and quaternary structural motifs in proteins. Here we present the crystal structure of an alpha/beta-peptide foldamer that adopts a tetrameric helix-bundle quaternary structure with a hydrophobic core composed solely of beta-amino acids. The structure displays features that are unprecedented among all known helix bundles composed of either alpha-peptides or peptidic foldamers. The tetramer is characterized by an asymmetry of interaction between neighboring helices, and the side-chain packing within the hydrophobic core differs fundamentally from the knobs-into-holes arrangement typical of most helix bundles.
2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: Initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features (2011)

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.
M-sequences for OFDM peak-to-average power ratio reduction and error correction (1997)

A block coding scheme using the maximum-length shift-register sequences (m-sequences) is suggested for orthogonal frequency division multiplexing (OFDM). The scheme, with a very simple implementation, can significantly reduce the peak-to-average power ratio of OFDM signals and provide error-correcting capability at the same time.
The influence of ionic strength and pH on the aggregation properties of zinc‐free insulin studied by static and dynamic laser light scattering (1993)

The aggregation properties of zinc-free insulin have been studied using static and dynamic light scattering. The aggregation has been investigated as a function of three parameters, the concentration of sodium chloride (in the range 10-100 mM), the pH value (in the range pH 7.5-10.5), and the insulin concentration (1.8-13.4 mg/mL). The measured homodyne autocorrelation function was used to determine the apparent mean hydrodynamic diameter as well as the apparent weight-averaged molar mass of the insulin species in solution. A method of data analysis was employed, which allows the separation of light scattering contributions from the insulin oligomers and from irrelevant macromolecules and possible impurities present in the sample solutions. Also, a simple phenomenological equilibrium model describing the association of oligomers of insulin is presented. One aspect of this model is that it makes it possible to determine weight average molar masses corrected for virial effects on the Rayleigh ratio. This was necessary because virial effects cannot be isolated and corrected for by dilution since this would change the equilibrium distribution of oligomers. The basis of the model is a positive contribution to Gibbs free energy from charge repulsion depending on the protein charge and the number of monomers in the oligomers, and an assumed constant negative contribution to Gibbs free energy arising from either an entropic gain or hydrogen bonding upon association. The equilibrium model gives a good description of both the apparent weight average molar masses and the apparent hydrodynamic diameters, when the effect of the insulin concentration is taken into account by including virial effects arising from charge-charge repulsion (Donnan effect). The result shows that the association of insulin as a function of pH and ionic strength can be described by an effective charge equal to the charge derived from proton titration reduced by the number of sodium ions binding to insulin. At the lowest pH and highest salt concentration (pH 7.5, 100 mM NaCl, 12 mg/mL insulin), the weight average molar mass is close to that of the hexamer, and at the highest pH and lowest salt concentration (pH 10.5, 10 mM NaCl, 1.9 mg/mL), the weight average molar mass is close to that of the monomer. In all cases, however, a distribution of oligomers is present with a relative Gaussian width of about 30%.(ABSTRACT TRUNCATED AT 400 WORDS)
The Telesoftware and Education Project: a progress report (1982)

ABSTRACT This is a second article about the research work being conducted at Brighton Polytechnic by the Telesoftware and Education Project. Telesoftware itself is a combination of television and microcomputer engineering, a means of broadcasting software to ‘intelligent’ televisions via teletext transmissions. This article introduces the broadcast form of telesoftware, describing the format and structure of the present network and indicating where readers may view parts of the system at work. After a brief description of the receiving equipment the author raises points about the software such a network would carry, and the influence telesoftware could have on educational broadcasting. Finally, the article indicates the project's immediate concerns in anticipation of the second year's work in schools. Additional informationNotes on contributorsL. T. Mapp Leslie Mapp is Research Fellow in the Telesoftware and Education Project, run jointly by Brighton Polytechnic, the BBC and the ITCA, with support from the DOI, Schools Council, CET, SED and SCET. He introduced the Project in a previous article in Journal of Educational Television
Somatostatin receptor subtype specificity and in vivo binding of a novel tumor tracer, 99mTc-P829. (1998)

Recent data suggest that somatostatin receptors (SSTRs) are expressed on various tumor cells. High-level expression of SSTR on the tumor cell surface provides the basis for the successful clinical use of radiolabeled ligands for the in vivo localization of tumor sites. We have characterized the in vitro binding properties of the novel SSTR ligand 99mTc-P829 using primary human tumors (carcinoids, breast cancers, intestinal adenocarcinomas, pheochromocytomas, small cell and non-small cell lung cancer, and melanomas; n = 28), various tumor cell lines, and COS7 cells transfected with the human SSTR (hSSTR) subtypes 1, 2, 3, 4, and 5. 99mTc-P829 bound to primary tumor cells and tumor cell lines with high affinity and high capacity. The dissociation constants (Kd) ranged between 1 and 20 nM. 99mTc-P829 also bound with high affinity to the transfected hSSTR2 (Kd, 2.5 nM), hSSTR5 (Kd, 2 nM), and hSSTR3 (Kd, 1.5 nM). Binding of 99mTc-P829 to hSSTR3 was found to be displaceable by unlabeled P829/([ReO]-P829), SST-14, and vasoactive intestinal peptide (VIP; IC50, 2 nM) and, less effectively, by Tyr3-octreotide (IC50, 20 nM). In contrast, the binding of 99mTc-P829 to hSSTR2 and hSSTR5 could be displaced by P829/([ReO]-P829) and Tyr3-octreotide but not by VIP. 99mTc-P829 scintigraphy revealed in vivo binding to primary or metastatic tumor sites in seven of eight patients with breast cancer and six of six patients with melanoma. In summary, our data show that 99mTc-P829 binds with high affinity to many different types of primary and cloned tumor cells. Furthermore, our data identify hSSTR2, the VIP acceptor hSSTR3, and hSSTR5 as the respective target receptors. Because these receptors are frequently expressed at high levels on primary tumor cells, 99mTc-P829 appears to be a promising novel peptide tracer for tumor imaging.
Design issues in CMOS differential LC oscillators (1999)

An analysis of phase noise in differential cross-coupled inductance-capacitance (LC) oscillators is presented. The effect of tail current and tank power dissipation on the voltage amplitude is shown. Various noise sources in the complementary cross-coupled pair are identified, and their effect on phase noise is analyzed. The predictions are in good agreement with measurements over a large range of tail currents and supply voltages. A 1.8 GHz LC oscillator with a phase noise of -121 dBc/Hz at 600 kHz is demonstrated, dissipating 6 mW of power using on-chip spiral inductors.
Translational Selection on Codon Usage in Xenopus laevis (2001)

A correspondence analysis of codon usage in Xenopus laevis revealed that the first axis is strongly correlated with the base composition at third codon positions. The second axis discriminates between putatively highly expressed genes and the other coding sequences, with expression levels being confirmed by the analysis of Expressed sequence tag frequencies. The comparison of codon usage of the sequences displaying the extreme values on the second axis indicates that several codons are statistically more frequent among the highly expressed (mainly housekeeping) genes. Translational selection appears, therefore, to influence synonymous codon usage in Xenopus.
The release and trans-synaptic transmission of Tau via exosomes (2017)

Our study demonstrates that exosomes contribute to trans-synaptic Tau transmission, and thus offer new approches to control the spreading of pathology in AD and other tauopathies.
Vibrational−Exciton Couplings for the Amide I, II, III, and A Modes of Peptides (2007)

The couplings between all amide fundamentals and their overtones and combination vibrational states are calculated. Combined with the level energies reported previously (Hayashi, T.; Zhuang, W.; Mukamel, S. J. Phys. Chem. A 2005, 109, 9747), we obtain a complete effective vibrational Hamiltonian for the entire amide system. Couplings between neighboring peptide units are obtained using the anharmonic vibrational Hamiltonian of glycine dipeptide (GLDP) at the BPW91/6-31G(d,p) level. Electrostatic couplings between non-neighboring units are calculated by the fourth rank transition multipole coupling (TMC) expansion, including 1/R3 (dipole-dipole), 1/R4 (quadrupole-dipole), and 1/R5 (quadrupole-quadrupole and octapole-dipole) interactions. Exciton delocalization length and its variation with frequency in the various amide bands are calculated. The simulated infrared amide I and II absorptions and CD spectra of 24 residue alpha-helical motifs (SPE3) are in good agreement with experiment.
Pulmonary function tests in patients with amyotrophic lateral sclerosis and the association between these tests and survival. (2014)

We found single measures of upright FVC, FEV1 to be significantly associated with survival, even after controlling for relevant non-pulmonary patient characteristics. Our study demonstrated that upright FVC, FEV1, VC, and MMEFR are useful non-invasive measures in the prediction of survival in ALS.
Nucleic Acid Related Compounds. 8. Direct Conversion of 2′-Deoxyinosine to 6-Chloropurine 2′-Deoxyriboside and Selected 6-Substituted Deoxynucleosides and Their Evaluation As Substrates of Adenosine Deaminase (1973)

Trifluoroacetylation of 2′-deoxyinosine (2), obtained by enzymatic deamination of 2′-deoxyadenosine (1), gave the 3′,5′-bis-O-trifluoroacetate (3). Reaction of the electronegatively substituted deoxynucleoside, 3, with DMF-thionyl chloride complex in refluxing methylene chloride gave a high yield of 6-chloropurine 2′-deoxyriboside (4) after deblocking.Displacement of chloride of 4 by hydrosulfide to give 6-mercaptopurine 2′-deoxyriboside (5) followed by sulfur alkylation with p-nitrobenzyl bromide gave 6-S-(p-nitrobenzyl) thiopurine 2′-deoxyriboside (6) which was alternatively prepared by displacement of chloride from 4 by p-nitrobenzyl mercaptide, generated in situ from the isothiouronium salt. Methyl mercaptide reaction with 4 gave 6-methylthiopurine 2′-deoxyriboside (7). Treatment of 4 with trimethylamine gave the corresponding quaternary ammonium chloride (8) which was allowed to react with potassium fluoride to give 6-fluoropurine 2′-deoxyriboside (9). Respective amine displacements on 4 gave 6-benzylaminopurine 2'-deoxyriboside (10), and 6-hydroxylaminopurine 2′-deoxyriboside (11). Reaction of 4 with liquid ammonia completed the first reported transformation of 2′-deoxyinosine (2) to 2′-deoxyadenosine (1).Biological rationale for the synthesis of these 2′-deoxynucleosides and their evaluation as substrates of adenosine deaminase are discussed. Major mass spectral fragmentations are tabulated.
Chemical Sensors and Microinstrumentation (1989)

A chemical sensor is a measurement system designed to exhibit an experimental response relatable to the quantity of a sample chemical species or class of chemical species. It may be designed to respond to the target species as present in a gaseous, liquid, or solid sample of indeterminate volume, or to a target contained within a defined space such as within a small volume, on the surface of the sample, or on a microscopic part of the surface of the sample. Also known as a chemical transducer, the chemical sensor can be based on any characteristic of the sample species that serves to distinguish it from its matrix, including its chemical reactivity, optical or electrical properties, or mass. The student of analytical chemistry will recognize that these statements encompass the field traditionally known as instrumental analysis. The more recent popularity of the descriptor chemical sensor subtlely reflects the quite important
Rubbish in the Red Cell (1969)

The role of the erythrocyte is simple and uncomplicated: it transports oxygen and carbon dioxide in the blood. To accomplish this gaseous transfer, the erythrocyte must traverse capillaries no greater than its own diameter and sometimes even smaller. Passage through some of these straitened gates requires that the cell fold upon itself, elongate or assume the form of a parachute.1 Obviously, the cell must remain plastic and flexible to achieve these alterations in shape without rupture. Therefore, the flow characteristics of the intracellular solution of hemoglobin and enzymes must not be disturbed by the presence of concretions. The membrane itself . . .
A Metagenomic Survey of Microbes in Honey Bee Colony Collapse Disorder (2007)

In colony collapse disorder (CCD), honey bee colonies inexplicably lose their workers. CCD has resulted in a loss of 50 to 90% of colonies in beekeeping operations across the United States. The observation that irradiated combs from affected colonies can be repopulated with naive bees suggests that infection may contribute to CCD. We used an unbiased metagenomic approach to survey microflora in CCD hives, normal hives, and imported royal jelly. Candidate pathogens were screened for significance of association with CCD by the examination of samples collected from several sites over a period of 3 years. One organism, Israeli acute paralysis virus of bees, was strongly correlated with CCD.
The prgQ gene of the Enterococcus faecalis tetracycline resistance plasmid pCF10 encodes a peptide inhibitor, iCF10 (1994)

Conjugative transfer of the Enterococcus faecalis tetracycline resistance plasmid pCF10 is stimulated by a peptide pheromone, cCF10. Once a recipient strain acquires pCF10 and thus becomes a pheromone-responsive donor, cCF10 activity is no longer detected in culture filtrates. Here we show that pCF10 encodes a peptide inhibitor, iCF10, secreted by donor cells; this inhibitor antagonizes the cCF10 activity in culture filtrates. In order to detect and quantitate iCF10, we developed a reverse-phase high-performance liquid chromatography assay in which the inhibitor peptide elutes separately from the pheromone; this type of assay enabled us to determine that lack of pheromone activity in donor culture filtrates was due to secretion of a mixture of iCF10 and cCF10, rather than abolition of cCF10 secretion. The gene encoding iCF10, prgQ, is located on the EcoRI-C fragment of pCF10. The open reading frame comprising the prgQ gene encodes a 23-amino-acid precursor that resembles a signal peptide. This precursor is cleaved to the mature heptapeptide iCF10 during the secretion process.
Recombinant soluble murine IL-4 receptor can inhibit or enhance IgE responses in vivo (1993)

This study examines the effects of soluble IL-4R (sIL-4R) administration on IgE production in vivo by using an anti-IgD injection model. Anti-IgD-treated mice were given various doses of sIL-4R or anti-IL-4 mAb over a 3-day period and serum IgE levels were determined by ELISA on day 9. The sIL-4R inhibited IgE production by up to 85%. Anti-IL-4 mAb administration resulted in comparable levels of inhibition at considerably lower doses. The disparity in efficacy between sIL-4R and anti-IL-4 mAb was likely the result of differences in the biodistribution and in vivo half-life of the two IL-4-binding proteins. The specificity of the sIL-4R inhibitory effect was assessed by mixing sIL-4R with various concentrations of IL-4 before injection. Exogenous IL-4 partially overcame the inhibitory effect of high-dose sIL-4R or anti-IL-4 mAb. Unexpectedly, coadministration of suboptimal concentrations of anti-IL-4 mAb or sIL-4R with IL-4 resulted in superinduction of the IgE response. This stimulatory effect was dose dependent for both IL-4 and the IL-4 cognates and was not seen in the absence of exogenous IL-4 over the entire concentration range tested for either sIL-4R or anti-IL mAb. The results indicate that sIL-4R can block IgE secretion by neutralizing endogenous IL-4. Furthermore, sIL-4R can enhance, in a dose-dependent manner, the biologic effects of exogenously administered IL-4, presumably by altering the biodistribution of the cytokine. These findings suggest two alternative applications for cytokine-binding proteins, i.e., 1) as antagonists of biologic activities of endogenously produced cytokines and, 2) as vehicles for cytokine delivery.
Reinfection is an Uncommon Occurrence in Patients with Symptomatic Recurrent Genital Herpes (1984)

Journal Article Reinfection is an Uncommon Occurrence in Patients with Symptomatic Recurrent Genital Herpes Get access Ortwin W. Schmidt, Ortwin W. Schmidt Departments of Laboratory Medicine, Microbiology Medicine, and Pediatrics, University of Washington and the Children's Orthopedic Hospital Medical Center, Seattle, Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth H. Fife, Kenneth H. Fife Departments of Laboratory Medicine, Microbiology Medicine, and Pediatrics, University of Washington and the Children's Orthopedic Hospital Medical Center, Seattle, Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar Lawrence Corey Lawrence Corey Departments of Laboratory Medicine, Microbiology Medicine, and Pediatrics, University of Washington and the Children's Orthopedic Hospital Medical Center, Seattle, Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 149, Issue 4, April 1984, Pages 645–646, https://doi.org/10.1093/infdis/149.4.645 Published: 01 April 1984
Comments, with reply, on "A spiral nerve cuff electrode for peripheral nerve stimulation" by G.G. Naples et al (1989)

The commenters, on the basis of the history of cuff electrodes, express the opinion that the use of the cuff electrode for peripheral nerve stimulation described by G.G. Naples et al. (ibid., vol.35, no.11, p.905-16, 1988) has little future. In a reply, the authors of the original paper vigorously dispute this assertion.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>