gebhart/patrepeval huggingface dataset:
Abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered crushed oxycodone HCl abuse‐deterrent controlled‐release tablets in recreational opioid users (2013)

The objective of this study was to evaluate abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered, crushed reformulated OxyContin® (oxycodone HCl controlled-release) tablets (ORF), relative to crushed original OxyContin® (OC), oxycodone powder (Oxy API), and OC placebo. This randomized, double-blind, positive- and placebo-controlled crossover study enrolled healthy, adult, nonphysically dependent recreational opioid users with recent history of intranasal drug abuse (N = 27). Active treatments contained oxycodone (30 mg). Pharmacokinetics, pharmacodynamics (e.g., Overall Drug Liking [ODL], Take Drug Again [TDA], and High Visual Analog Scales [VAS]; Subjective Drug Value [SDV]; pupillometry; intranasal irritation), and safety (e.g., adverse events, vital signs, laboratory tests) were assessed to 24 hours postdose. Crushed ORF administration yielded reduced oxycodone Cmax and increased Tmax versus crushed OC and Oxy API. Peak effects for pharmacodynamic measures were delayed with ORF (1-2 hours) versus OC and Oxy API (0.5-1 hour). ODL, TDA, High VAS, and SDV Emax values were significantly lower (P ≤ .05) and some intranasal irritation ratings were greater for ORF versus OC and Oxy API. No significant or unexpected safety findings were observed. Compared with OC and Oxy API, intranasally administered ORF was associated with lower and delayed peak plasma concentrations, decreased drug-liking, and decreased intranasal tolerability. This suggests that ORF has a decreased potential for intranasal oxycodone abuse. There were no significant or unexpected safety findings. As is true for all abuse potential studies, epidemiological or other appropriate post-marketing studies are required to assess the impact of the reduction in intranasal oxycodone abuse potential observed in the present study on real-world patterns of ORF misuse, abuse, and diversion.
Dietary influence of tyrosine and phenylalanine on the response of B16 melanoma to carbidopa-levodopa methyl ester chemotherapy. (1982)

Abstract The effect of dietary tyrosine and phenylalanine on survival of adult female C57BL/6 × DBA/2 F, mice bearing i.p. slow-growing, moderately pigmented and fast-growing, highly pigmented B16 melanoma tumors was studied alone and in combination with carbidopa-levodopa methyl ester chemotherapy. These studies tested three different diets: a natural product diet containing 1.09% phenylalanine and 0.64% tyrosine (commercial diet); a chemically defined crystalline amino acid diet containing 0.6% phenylalanine and 0.3% tyrosine (purified diet); and a nutritionally deficient chemically defined diet conaining 0.08% phenylalanine and 0.04% tyrosine (deficient diet). Mice received carbidopa (100 mg/kg) and levodopa methyl ester (1000 mg/kg) i.p. daily for 12 days. The median survival of mice bearing the slow-growing tumor averaged 8 days longer than that of mice bearing the fast-growing tumor. Median survival increased by 42% (slow-growing tumor) and by 30% (fast-growing tumor) in mice maintained on the deficient diet. Drug treatment significantly increased survival in mice maintained on the purified and deficient diets but was relatively ineffective in mice maintained on the commercial diet regardless of the tumor growth characteristics. The largest increases in median survival of 61% (slow-growing tumor) and of 78% (fast-growing tumor) occurred in the treated mice maintained on the deficient diet. Plasma tyrosine and phenylalanine levels decreased by 33 and 21%, respectively, in mice maintained on the deficient diet and were unaffected by drug treatment. Tumors were 60% smaller in mice maintained on the deficient diet compared to mice maintained on the purified diet. Drug treatment resulted in decreased food intake and weight loss in all tumor-bearing dietary groups. Restricting food intake in untreated tumor-bearing mice to the amounts consumed by the drug treatment groups resulted in a parallel loss in body weight but no significant alteration in median survival. These data show that concomitant dietary tyrosine-phenylalanine restriction enhances the antitumor activity of carbidopa-levodopa methyl ester against B16 melanoma.
The identification of the Escherichia coli fts Y gene product: an unusual protein (1990)

The ftsYEX operon in Escherichia coli encodes three proteins, two of which (FtsE and FtsX) are known to be required for cell division. Although FtsE and FtsX have been identified using SDS-PAGE, the FtsY protein has not. We have used in vitro insertion mutagenesis to identify FtsY as a 92 kD polypeptide in maxicell experiments, although predictions from the DNA sequence estimated FtsY to be 54 kD. Results suggest that this disparity could be due to the unusually high percentage of acidic residues within the protein. Complementation tests indicated the presence of a promoter within ftsY required for expression of ftsE and ftsX. The FtsY protein exhibits sequence homology with the SR alpha protein of eukaryotes which is involved in protein secretion. The essential nature of the ftsY gene was also demonstrated.
Learning Structured Sparsity in Deep Neural Networks (2016)

High demand for computation resources severely hinders deployment of large-scale Deep Neural Networks (DNN) in resource constrained devices. In this work, we propose a Structured Sparsity Learning (SSL) method to regularize the structures (i.e., filters, channels, filter shapes, and layer depth) of DNNs. SSL can: (1) learn a compact structure from a bigger DNN to reduce computation cost; (2) obtain a hardware-friendly structured sparsity of DNN to efficiently accelerate the DNNs evaluation. Experimental results show that SSL achieves on average 5.1x and 3.1x speedups of convolutional layer computation of AlexNet against CPU and GPU, respectively, with off-the-shelf libraries. These speedups are about twice speedups of non-structured sparsity; (3) regularize the DNN structure to improve classification accuracy. The results show that for CIFAR-10, regularization on layer depth can reduce 20 layers of a Deep Residual Network (ResNet) to 18 layers while improve the accuracy from 91.25% to 92.60%, which is still slightly higher than that of original ResNet with 32 layers. For AlexNet, structure regularization by SSL also reduces the error by around ~1%. Open source code is in https://github.com/wenwei202/caffe/tree/scnn
Multiple transcription (actors interact with the adenovirus-2 EII-late promoter: evidence for a novel CCAAT recognition factor (1987)

Multiple cellular transcription factors have been shown to interact with the upstream region of the adenovirus-2 EIIa-late promoter. One of these factors recognises each of the three CCAAT motifs present in the EIIL promoter at positions -72, -135 and -229, as well as the CCAAT elements in the rat albumin and herpes virus thymidine kinase promoters. A mutation known to reduce thymidine kinase promoter activity in vivo and in vitro abolishes binding of the factor, termed CCAAT recognition factor (CRF), which appears to be distinct from previously identified CCAAT factors. In addition, another protein, termed upstream factor II (USFII), shares binding sites at position -110 in the EIIL promoter and in the c-fos enhancer adjacent to the serum regulatable element. The recognition site for USFII is also found in the c-fos promoter and in the adenovirus early region EIV and EIIa-early promoters. An Sp1 recognition site has also been identified at position -41, and the binding sites for Sp1, USFII and CRF are all required for efficient EIIa-late promoter function. Finally, an additional factor recognising the consensus GGGGGGNT has been detected.
Transition Scenarios for 3GPP Networks (2003)

This document describes different scenarios in Third Generation Partnership Project (3GPP) defined packet network, i.e., General Packet Radio Service (GPRS) that would need IP version 6 and IP version 4 transition. The focus of this document is on the scenarios where the User Equipment (UE) connects to nodes in other networks, e.g., in the Internet. GPRS network internal transition scenarios, i.e., between different GPRS elements in the network, are out of scope. The purpose of the document is to list the scenarios for further discussion and study.
Ocular disease pattern induced by herpes simplex virus is genetically determined by a specific region of viral DNA. (1982)

The pattern of ocular disease produced in the rabbit eye by HSV-1 (F) and HSV-1(MP) strains and recombinants F(MP)A, F(MP)B, F(MP)C, F(MP)D, F(MP)E, and F(MP)F was studied. The characteristics of ocular herpetic disease such as morphology of dendritic ulcers, severity of epithelial disease and incidence and duration of stromal disease produced in the rabbit eye are genetically determined by the virus strain. Our studies show that transfer of a defined part of the genome of the stromal disease-producing virus, HSV-1(MP), to the genome of an epithelial disease-producing virus, HSV-1(F), yielded recombinants with one or more of the disease characteristics of the donor strain. Specifically, recombinant F(MP)D produced lesions characteristic of the donor HSV-1(MP) strain; recombinants F(MP)C and F(MP)E produced stromal disease approaching the severity of the disease produced by the donor HSV-1(MP) strain, and only recombinants F(MP)A and F(MP)B retained the typically elongate lesions of the recipient HSV-1(F), whereas the recombinant strain F(MP)F produced no disease. The viral functions pertaining to the ocular disease pattern map between 0.70 and 0.83 map units in HSV-1 DNA within the BglII F DNA fragment. The pattern of stromal disease is independent of the production of glycoprotein C and fusion of HEp-2-infected cells. The functions relating to these aspects of ocular disease segregate but are closely linked.
Ramesh Chander Dogra: Jammu and Kashmir: a select and annotated bibliography of manuscripts, books and articles together with a survey of its history, languages and literature from Rajatarangini to modern times. viii, 417 p. Delhi: Ajanta Publications, 1986. Rs. 300, $6. (1988)

Ramesh Chander Dogra: Jammu and Kashmir: a select and annotated bibliography of manuscripts, books and articles together with a survey of its history, languages and literature from Rajatarangini to modern times. viii, 417 p. Delhi: Ajanta Publications, 1986. Rs. 300, $6. - Volume 51 Issue 1
Polarized fluorescent emission from aligned electrospun nanofiber sheets containing semiconductor nanorods (2015)

We fabricated sheets consisting of aligned electrospun polymer nanofibers embedded with semiconductor nanorods (NRs) and confirmed the production of polarized fluorescence emission. Electrospun nanofibers with embedded semiconductor NRs were rolled around a drum to form a sheet in which each nanofiber was aligned parallel to the rotation direction. The thickness and polarization ratio of the sheet were 1.5 μm and 0.6, respectively. We also examined how electrospinning parameters affected the polarization ratio of the sheet.
A Therapeutic Panorama of the Spongiform Encephalopathies (1990)

The spongiform encephalopathies are a group of uniformly fatal, transmissible amyloidoses of humans and animals, for which the causative agents have not yet been precisely defined; in some respects they resemble viruses, but in other respects appear to be replicating host polypeptides. A vast array of anti-infective and other drugs has been studied in animal models, among which a few membrane-active compounds (heteropolyanions and amphotericin B) consistently prolong the course of infection, and occasionally even prevent the illness. However, because no form of therapy has any effect when given after the disease becomes clinically manifest, and because there is no laboratory test to detect preclinical infection, therapeutic efforts in humans have been predictably unsuccessful. If infection and disease turn out to depend upon the pathological accumulation of an amyloidogenic host protein, the prospects for future therapy may include genetic engineering and perhaps even the ‘poisoning’ of protein crystal growth.
Transactivation of Epidermal Growth Factor Receptor Mediates Catecholamine-Induced Growth of Vascular Smooth Muscle (2004)

Stimulation of alpha1-adrenoceptors induces proliferation of vascular smooth muscle cells (SMCs) and contributes to arterial remodeling. Although activation of NAD(P)H oxidase and generation of reactive oxygen species (ROS) are required, little is known about this pathway. In this study, we examined the hypothesis that epidermal growth factor receptor (EGFR) transactivation and extracellular regulated kinases (ERK) are involved in alpha1-adrenoceptor-mediated SMC growth. Phenylephrine increased protein synthesis in association with a rapid (< or =5 minutes) and sustained (> or =60 minutes) doubling of phosphorylation of EGFR and ERK1/2, but not p38 or JNK in the media of rat aorta maintained in organ culture. Antagonists of EGFR phosphotyrosine activity (AG-1478) and ERK phosphorylation (PD-98059, U-0126) abolished phenylephrine-induced protein synthesis, whereas antagonists of p38 or JNK phosphorylation had no specific effect. A competitive antagonist (P22) for heparin binding EGF-like growth factor (HB-EGF) blocked phenylephrine-induced protein synthesis, as did downregulation of pro-HB-EGF (CRM197). Phenylephrine-induced protein synthesis was inhibited by neutralizing antibody to HB-EGF and absent in HB-EGF-/- SMCs. Inhibitors of metalloproteinases (BiPS, KB-R7785) also blocked adrenergic growth. The neutralizing antibody against HB-EGF had no effect on the two-fold increase in ROS generation induced by phenylephrine (DCF fluorescence), suggesting that stimulation of NAD(P)H oxidase by alpha1-adrenoceptor occupation precedes HB-EGF release. Cell culture studies confirmed and extended these findings. These data suggest that alpha1-adrenoceptor-mediated SMC growth requires ROS-dependent shedding of HB-EGF, transactivation of EGFR, and activation of the MEK1/2-dependent MAP kinase pathway. This trophic pathway may link sympathetic activity to arterial wall growth in adaptive remodeling and hypertrophic disease.
Contribution of delayed rectifier potassium currents to the electrical activity of murine colonic smooth muscle (1999)

1. We used intracellular microelectrodes to record the membrane potential (Vm) of intact murine colonic smooth muscle. Electrical activity consisted of spike complexes separated by quiescent periods (Vm approximately -60 mV). The spike complexes consisted of about a dozen action potentials of approximately 30 mV amplitude. Tetraethylammonium (TEA, 1-10 mM) had little effect on the quiescent periods but increased the amplitude of the action potential spikes. 4-Aminopyridine (4-AP, >= 5 mM) caused continuous spiking. 2. Voltage clamp of isolated myocytes identified delayed rectifier K+ currents that activated rapidly (time to half-maximum current, 11.5 ms at 0 mV) and inactivated in two phases (tauf = 96 ms, taus = 1.5 s at 0 mV). The half-activation voltage of the permeability was -27 mV, with significant activation at -50 mV. 3. TEA (10 mM) reduced the outward current at potentials positive to 0 mV. 4-AP (5 mM) reduced the early current but increased outward current at later times (100-500 ms) consistent with block of resting channels relieved by depolarization. 4-AP inhibited outward current at potentials negative to -20 mV, potentials where TEA had no effect. 4. Qualitative PCR amplification of mRNA identified transcripts encoding delayed rectifier K+ channel subunits Kv1.6, Kv4.1, Kv4.2, Kv4.3 and the Kvbeta1.1 subunit in murine colon myocytes. mRNA encoding Kv 1.4 was not detected. 5. We find that TEA-sensitive delayed rectifier currents are important determinants of action potential amplitude but not rhythmicity. Delayed rectifier currents sensitive to 4-AP are important determinants of rhythmicity but not action potential amplitude.
Relationships between serum IGF1 levels, blood pressure, and glucose tolerance: an observational, exploratory study in 404 subjects (2008)

IGF1 levels in the low normal range are associated with hypertension and diabetes in subjects without pituitary and cardiovascular diseases.
Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant. (1979)

A nonspecific opsonin function has been ascribed to human alpha 2 HS glycoprotein. Its serum level has been shown to be decreased in trauma patients. Recent studies from this laboratory revealed a heterogeneity among the products obtained in the course of the preparation of the protein. To date, no definitive agreement existed with regard to a molecular homogeneous entity of alpha 2 HS glycoprotein (Ba-alpha 2 glycoproteins). The purpose of the current work was to study the variations in serum level of alpha 2 HS in patients suffering from an acute inflammatory process of bacterial etiology and to determine whether a decrease in alpha 2 HS was accompanied by the appearance of fragments of this protein in the serum. A method of preparing alpha 2 HS was thus developed, using an immune absorbent as a final purification step. In an intermediary step of the preparation, alpha 2 HS was found to bind zinc when metal chelate affinity chromatography was employed. Immunologically and physico-chemically pure alpha 2 HS was obtained. The protein consists of a unique polypeptide chain of about 50,000 daltons and has a unique amino-terminal residue, alanine. However, the protein maintained its molecular integrity with difficulty, and spontaneous fragments ranging from 30,000 to less than 10,000 daltons were produced in some of the preparations. No major modification in the molecular structure of the protein was noted in the sera of subjects suffering from an acute inflammatory process. Serum level of alpha 2 HS and alpha 1 antitrypsin (AT)was determined in 23 patients. When the acute-phase (AP-)reactant alpha 1 AT was increased (difference with normal mean greater than +2 or +3 SD), the sera showed a large decrease in alpha 2 HS (difference with normal mean less than -2 or -3 SD). The serum level of alpha 2 HS, albumin, alpha 2 macroglobulin, and of positive AP-reactants, orosomucoidinal study of seven patients. The results were submitted to a principal components analysis. Alpha 2 HS showed a negative correlation with the AP-reactants alpha 1 AT, orosomucoid, and haptoglobin (P less than 0.05) and a positive correlation with albumin (P less than 0.05); these findings indicate that alpha 2 HS is a negative AP-reactant. In addition, analysis of the principal components confirms thestrong analogy between alpha 2 HS and albumin and indicates that serum level behavior of the AP-reactants during the course of the disease closely depends on the protein studied.
Photonic crystal slabs for optical micro electro mechanical systems (OMEMS) (2010)

Photonic crystals are materials with a periodic variation of composition in one, two or three directions. For some optical frequency intervals, they behave as homogeneous transparent materials where optical waves are allowed to travel without scattering, but these frequency intervals are intervened by photonic band gaps in which the propagation of light is forbidden. Photonic crystals are the photonic analogue to traditional crystals, where the periodic arrangement of atoms allows electrons and light to travel without scattering.\nWe present some fundamental properties of two-dimensional photonic crystals in form of photonic crystal slabs, with emphasis on their design, fabrication and incorporation into micro-electro-mechanical systems (MEMS). Photonic crystal slabs have become a very popular research topic because of their compactness, which makes them easily integrated with MEMS, and also because their fabrication is relatively easy compared to that of their three-dimensional relatives. The photonic crystal slabs support oscillating resonator modes [Fan and Joannopoulos, 2002], and the modes of the photonic crystal slabs can be designed to couple weakly or strongly to the outside, and give rise to interferences in the reflection or transmission spectra of the photonic crystal slabs. These interferences manifest themselves as areas of high reflectivity or transmissivity that, depending on the design, can be both very sharp (&lt; 1 nm) and very broad (&gt; 150 nm). In other words, photonic crystal slabs can be used to make both broad-band mirrors and narrow optical filters [Lousse et al., 2004, Kim et al., 2007].&lt;br&gt;\nWe have taken the fabrication technology for photonic crystal slabs one step further by developing the GOPHER-generation of photonic elements by reactive ion etching (RIE) process [Hadzialic et al., 2007b]. This is a simple method for making photonic crystals in monolithic materials. The process consists of only one lithographic step in which the photonic crystal pattern is defined. The pattern is then transferred to the underlying material by RIE. In order to achieve guided resonance modes in the photonic crystal slabs we need to have a refractive index contrast to the substrate. This is achieved by undercutting the structure in an isotropic RIE. The advantages are low internal stress, no temperature expansion coefficient mismatch, and compatibility with MEMS and CMOS processing.&lt;br&gt;\nBy integrating photonic crystal slabs with MEMS, we can make the photonic crystal slab move with respect to its mechanical support, and make devices such as tunable optical filters, scanners, displacement sensors, and more. We demonstrate one such device based on a mechanically tunable photonic crystal designed for highly position-sensitive reflection [Hadzialic et al., 2007a].
Foodborne Campylobacter: Infections, Metabolism, Pathogenesis and Reservoirs (2013)

Campylobacter species are a leading cause of bacterial-derived foodborne illnesses worldwide. The emergence of this bacterial group as a significant causative agent of human disease and their propensity to carry antibiotic resistance elements that allows them to resist antibacterial therapy make them a serious public health threat. Campylobacter jejuni and Campylobacter coli are considered to be the most important enteropathogens of this genus and their ability to colonize and survive in a wide variety of animal species and habitats make them extremely difficult to control. This article reviews the historical and emerging importance of this bacterial group and addresses aspects of the human infections they cause, their metabolism and pathogenesis, and their natural reservoirs in order to address the need for appropriate food safety regulations and interventions.