gebhart/patrepeval huggingface dataset:
Tumor-enhancing effects of cholic acid are exerted on the early stages of colon carcinogenesis via induction of aberrant crypt foci with an enhanced growth phenotype (1998)

The objective of the study was to establish whether cholic acid (CHA) enhanced colonic tumor incidence in the early phase of carcinogenesis. Male, Sprague-Dawley rats (n = 180) were injected twice with azoxymethane (AOM) (15 mg·kg -1 body weight·week -1 , s.c., given 1 week apart). Following the first AOM injection, animals were randomly assigned to two groups, control AIN-93G diet (CON) or control diet containing 0.2% CHA by weight (CHA). Three weeks after the first injection, 20 animals (10 animals/group) were killed and aberrant crypt foci (ACF) were enumerated. The remaining animals were further subdivided and animals randomly assigned to CON or CHA diets, creating four treatments: CON-CON, CON-CHA, CHA-CHA, and CHA-CON. After 3, 12, and 20 weeks (following the first carcinogen injection), the animals were killed and the number and crypt multiplicity of ACF enumerated. Macroscopic tumors were evaluated at week 20. Total ACF were not different between groups. Average crypt multiplicity and medium (4-6 crypts/focus) and large (&gt;= 7 crypts/focus) ACF were greater in CHA-CHA and CHA-CON compared with CON-CON and CON-CHA (p &lt; 0.01). Transient exposure to CHA (CHA-CON) was sufficient to induce development of ACF with an accelerated growth phenotype and elicit a tumor-enhancing effect. CHA-CHA had the highest tumor incidence (82.8%, p &lt; 0.05) followed by CHA-CON (56.7%, p &lt; 0.05), and tumor multiplicity and number of tumors per rat in CHA-CON were similar to CHA-CHA (2.29 and 1.3 versus 2.33 and 1.9, respectively). Delayed intervention with CHA (CON-CHA) produced a tumor outcome similar to CON-CON (31 and 30%, respectively), it did not enhance colonic tumor incidence. Taken collectively these results suggest CHA was effective in enhancing colon carcinogenesis during early phases and ineffective in post-initiation phases.Key words: aberrant crypt foci, cholic acid, colon, tumors.
Pharmacokinetics of tramadol and the metaboliteO‐desmethyltramadol in dogs (2004)

Tramadol is an analgesic and antitussive agent that is metabolized to O-desmethyltramadol (M1), which is also active. Tramadol and M1 exert their mode of action through complex interactions between opiate, adrenergic, and serotonin receptors. The pharmacokinetics of tramadol and M1 were examined following intravenous and oral tramadol administration to six healthy dogs, as well as intravenous M1 to three healthy dogs. The calculated parameters for half-life, volume of distribution, and total body clearance were 0.80 +/- 0.12 h, 3.79 +/- 0.93 L/kg, and 54.63 +/- 8.19 mL/kg/min following 4.4 mg/kg tramadol HCl administered intravenously. The systemic availability was 65 +/- 38% and half-life 1.71 +/- 0.12 h following tramadol 11 mg/kg p.o. M1 had a half-life of 1.69 +/- 0.45 and 2.18 +/- 0.55 h following intravenous and oral administration of tramadol. Following intravenous M1 administration the half-life, volume of distribution, and clearance of M1 were 0.94 +/- 0.09 h, 2.80 +/- 0.15 L/kg, and 34.93 +/- 5.53 mL/kg/min respectively. Simulated oral dosing regimens at 5 mg/kg every 6 h and 2.5 mg/kg every 4 h predict tramadol and M1 plasma concentrations consistent with analgesia in humans; however, studies are needed to establish the safety and efficacy of these doses.
Clusterin Expression in Malignant Lymphomas: A Survey of 266 Cases (2002)

Clusterin expression has been reported to be characteristic of systemic anaplastic large cell lymphoma and usually negative in cutaneous anaplastic large cell lymphoma as well as other lymphoma types. We surveyed clusterin expression using immunohistochemical methods in 266 cases of non-Hodgkin's lymphoma and Hodgkin's disease to further assess the diagnostic utility of this marker. Clusterin immunostaining was observed in 40 of 49 (82%) systemic anaplastic large cell lymphomas and 12 of 29 (41%) cutaneous anaplastic large cell lymphomas. Clusterin also was expressed in 5 of 43 (12%) diffuse large B-cell lymphomas (4 of 5 CD30+), 1 of 14 (7%) peripheral T-cell lymphomas, 1 of 32 (3%) cases of nodular sclerosis Hodgkin's disease, and 1 case of mycosis fungoides in large cell transformation. Clusterin was negative in all other neoplasms assessed including follicular lymphoma of all grades (n = 24), mantle cell lymphoma (n = 13), marginal zone B-cell lymphoma (n = 12), precursor T-cell or B-cell lymphoblastic leukemia/lymphoma (n = 10), mixed cellularity Hodgkin's disease (n = 8), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 7), Burkitt lymphoma (n = 7), mycosis fungoides (n = 4), nodular lymphocyte predominant Hodgkin's disease (n = 3), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (n = 2), and plasmacytoma (n = 2). We conclude that clusterin is a marker of anaplastic large cell lymphoma and that addition of clusterin to antibody panels designed to distinguish systemic anaplastic large cell lymphoma from classical Hodgkin's disease is useful. However, clusterin is also positive in a substantial subset of cutaneous anaplastic large cell lymphomas, a smaller subset of diffuse large B-cell lymphomas, and rarely in cases of peripheral T-cell lymphoma and nodular sclerosis Hodgkin's disease.
Race to find COVID-19 treatments accelerates (2020)

WHO launches megatrial to test repurposed drugs and experimental drug candidates.
Alternate protein frameworks for molecular recognition. (1995)

In an effort to determine whether proteins with structures other than the immunoglobulin fold can be used to mimic the ligand binding properties of antibodies, we generated a library from the four-helix bundle protein cytochrome b562 in which the two loops were randomized. Panning of this library against the bovine serum albumin (BSA) conjugate of N-methyl-p-nitrobenzylamine derivative 1 by phage display methods yielded cytochromes in which residues Trp-20, Arg-21, and Ser-22 in loop A and Arg-83 and Trp-84 in loop B were conserved. The individual mutants, which fold into native-like structure, bind selectively to the BSA-1 conjugate with micromolar dissociation constants (Kd), in comparison to a monoclonal antibody that binds selectively to 1 with a Kd of 290 nM. These and other antibody-like receptors may prove useful as therapeutic agents or as reagents for both intra- and extracellular studies.
Pig cells that lack the gene for α1-3 galactosyltransferase express low levels of the gal antigen (2003)

Fetal-pig fibroblasts homozygous for the knockout of the alpha1-3 galactosyltransferase gene appear to express low but detectable levels of the gal antigen.
A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. (1986)

Homotypic adhesion by phorbol ester-stimulated lymphocytes requires LFA-1 and Mg+2 and does not involve like-like interactions between LFA-1 molecules on adjacent cells. The latter finding suggested that a second molecule, distinct from LFA-1, also participates in LFA-1-dependent adhesion. The identification of such a molecule was the object of this investigation. After immunization with LFA-1-deficient EBV-transformed lymphoblastoid cells, a MAb was obtained that inhibits phorbol ester-stimulated aggregation of LFA-1+ EBV lines. This MAb defines a novel cell surface molecule, which is designated intercellular adhesion molecule 1 (ICAM-1). ICAM-1 is distinct from LFA-1 in both cell distribution and structure. In SDS-PAGE, ICAM-1 isolated from JY cells is a single chain of Mr = 90,000. As shown by MAb inhibition, ICAM-1 participates in phorbol ester-stimulated adhesion reactions of B lymphocyte and myeloid cell lines and T lymphocyte blasts. However, aggregation of one T lymphocyte cell line (SKW-3) was inhibited by LFA-1 but not ICAM-1 MAb. It is proposed that ICAM-1 may be a ligand in many, but not all, LFA-1-dependent adhesion reactions.
Backscattering albedo contrast in OCT using plasmon-resonant gold nanorods (2007)

Gold nanorods ~14 × 44nm exhibit a surface-plasmon resonance (SPR) peaked near 800nm which is dominated by absorption, not scattering. Because biological tissues in the near-infrared wavelength regime are predominantly scattering (high albedo), the addition of trace amounts of nanorods can be detected by their lowering of the albedo. Albedo is a preferred measurement parameter because it is insensitive to inhomogeneities in the density of scatterers. For optical coherence tomography (OCT) imaging applications, a related parameter called the backscattering albedo, equal to the ratio of the backscattering coefficient to the total extinction, is introduced for detecting gold nanorods. Here we use this parameter to investigate gold nanorods as contrast agents for optical coherence tomography (OCT). Measurements in 2% intralipid tissue phantoms reveal a sensitivity to ~30ppm nanorods when the density of the intralipid is randomized by 0.4% (or a fraction of 0.2). This has application toward molecular imaging using targeted nanorods within densely scattering, inhomogeneous tissues.
Epitaxial Lateral Overgrowth of GaN (2001)

Since there is no GaN bulk single crystal available, the whole technological development of GaN based devices relies on heteroepitaxy. Numerous defects are generated in the heteroepitaxy of GaN on sapphire or 6H-SiC, mainly threading dislocations (TDs). Three types of TDs are currently observed, a type (with Burgers vector 1/3〈〉); c type (with 〈0001〉) and mixed a+c (1/3〈〉). The Epitaxial Lateral Overgrowth (ELO) technology produces high quality GaN with TD densities in the mid 106 cm—2, linewidth of the low-temperature photoluminescence (PL) near-bandgap recombination peaks <1 meV and deep electron traps reduced below 1014 cm—3 (compared to mid 1015 cm—3 in standard GaN). Numerous modifications of the ELO process have been proposed in order either to avoid technological steps (mask-less ELO) or to improve it (pendeo-epitaxy). Basically developed on either sapphire or 6H-SiC, the ELO technology is also achievable on (111)Si or (111)3C-SiC/Si provided that an appropriate buffer layer is grown to avoid cracks. More sophisticated technologies have been implemented to further increase the useable part of the ELO GaN surface (two technological steps, three-step ELO). Unfortunately, in-depth understanding of the basic ELO process is still missing, i.e. of the growth anisotropy and bending of dislocations.
Comparison of polarization handling methods in coherent optical systems (1991)

The authors compare three polarization handling methods in coherent optical systems. These methods are: endless polarization control, polarization diversity, and data-induced polarization switching. These methods are also compared with active, data-synchronous polarization switching. It is seen that endless polarization control is potentially the most powerful candidate, however, the choice of polarization control devices remain questionable. Polarization diversity is as versatile as polarization control and is potentially the fastest method; however, it yields lower receiver sensitivity. Endless control or a well-designed diversity receiver should be used for coherent trunk systems. Data-induced polarization switching is restricted to frequency-shift-keying (FSK) systems. It promises a loss span similar to that of diversity, but is far simpler, which makes it recommendable for FSK distribution systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Nicotine is Chemotactic for Neutrophils and Enhances Neutrophil Responsiveness to Chemotactic Peptides (1984)

Neutrophils contribute to chronic bronchitis and pulmonary emphysema associated with cigarette smoking. Nicotine was found to be chemotactic for human neutrophils but not monocytes, with a peak activity at approximately 31 micromolar. In lower concentrations (comparable to those in smokers' plasma), nicotine enhanced the response of neutrophils to two chemotactic peptides. In contrast to most other chemoattractants for neutrophils, however, nicotine did not affect degranulation or superoxide production. Nicotine thus may promote inflammation and consequent lung injury in smokers.
Genetic variants and abnormal processing of pre-miR-182, a circadian clock modulator, in major depression patients with late insomnia (2010)

Previous studies in mice have reported five different microRNAs (miRNAs; miR-219-1/132/183/96/182) to be modulators of the endogenous circadian clock and have presented experimental evidence for some of the genes involved in the molecular clock machinery as target sites. Moreover, disruption of circadian rhythms has long been implicated in the pathophysiology of major depression (MD). We investigated these miRNAs and some of their target sites at the sequence and functional levels as possible predisposing factors for susceptibility to MD and related chronobiological subphenotypes. Mutational screening was performed in a sample of 359 MD patients and 341 control individuals. We found a significant association between the T allele of the rs76481776 polymorphism in the pre-miR-182 and late insomnia in MD patients. Previous studies have reported an association between insomnia and CLOCK gene, a predicted miR-182 target site. A significant overexpression of miR-182 was detected by quantitative real-time polymerase chain reaction in cells transfected with the mutated form of the pre-miR-182 when compared with wild-type form. Moreover, a significant reduction in luciferase activity of plasmids with 3' UTR of ADCY6, CLOCK and DSIP genes was shown when transfecting cells with the mutated form of pre-miR-182 compared with cells that did not express miR-182. These data indicate that abnormal processing of pre-miR-182 in patients carrying the T allele of the rs76481776 polymorphism may contribute to the dysregulation of circadian rhythms in MD patients with insomnia, which could influence expression levels of the mature form of miR-182 and might increase downregulation in some of its target genes.
Norbornene-Based Copolymers Containing Platinum Complexes and Bis(carbazolyl)benzene Groups in Their Side-Chains (2009)

Two norbornene-functionalized tetradentate cyclometalated platinum(II) complexes were synthesized and copolymerized with a bis(carbazolyl)benzene-based comonomer using ring-opening metathesis polymerization (ROMP). The copolymers are soluble in common solvents and the molecular weights of these copolymers can be well controlled as a result of the living character of the ROMP. The photophysical and electrochemical properties of the copolymers were compared to their corresponding small molecules. The copolymers showed almost identical photophysical and electrochemical properties demonstrating the inertness of the polymer backbone toward the photophysical properties of the tethered platinum complexes. All complexes exhibit bright photoluminescence in the green region with lifetimes around 0.4 μs and solution phosphorescence quantum efficiencies as high as 0.56, which suggest that these materials could be interesting for OLED applications.
Functional Analysis of Adenovirus-5 Host-range Deletion Mutants Defective for Transformation of Rat Embryo Cells (1980)

Several lines of evidence indicate that the adenoviral genes that mediate cellular transformation are located within the left-hand 12% of the conventional viral genetic map. Adenovirus 2 (Ad2) left-end sequences are consistently present (Gallimore et al. 1974) and transcribed (Flint et al. 1975, 1976) in transformed cells. Other regions of the viral genome need not be present. Furthermore, rat kidney cells can be transformed by DNA fragments derived from the lefthand 12% of the addnoviral chromosome (Graham et al. 1975; van der Eb et al. 1979). The region required for transformation corresponds to one of the viral gene blocks expressed early after infection (region E1, 1.5–11.5 map units) (Philipson et al. 1975; Sharp et al. 1975; Berk and Sharp 1977; Chow et al. 1977).
Cannabis as a Substitute for Alcohol: A Harm-Reduction Approach (2004)

ABSTRACT Ninety-two Northern Californians who use cannabis as an alternative to alcohol obtained letters of approval from the author. Their records were reviewed to determine characteristics of the cohort and efficacy of the treatment, which was defined as reduced harm to the patient. All patients reported benefit, indicating that for at least a subset of alcoholics, cannabis use is associated with reduced drinking. The cost of alcoholism to individual patients and society at large warrants testing of the cannabis-substitution approach and study of the drug-of-choice phenomenon.
Nuclear Targeting of Macromolecular Polyanions by an HIV-Tat Derived Peptide (2002)

New therapies based on gene transfer and protein delivery require a better understanding of the basic mechanisms of macromolecular membrane transport. We have studied cellular uptake of macromolecular polyanions, i.e. DNA and glycosaminoglycans, and a polybasic HIV-Tat derived peptide (GRKKRRQRRRPPQC) using fluorescence assisted cell sorting and confocal fluorescence microscopy. The transactivator of HIV transcription (Tat) peptide stimulated cellular uptake of both DNA and heparan sulfate in a time-, concentration-, and temperature-dependent manner. Peptide-polyanion complexes accumulated in large, acidic, cytoplasmic vesicles formed de novo. This was followed by transfer of polyanion into the nuclear compartment and subsequent disappearance of the endolysosomal vesicles. In the absence of polyanion the Tat peptide displayed rapid accumulation in the nuclear compartment. However, in the presence of polyanion the peptide was almost exclusively retained in cytoplasmic vesicles. Cell-surface proteoglycans played a pivotal role in the uptake of complexes exhibiting a relatively high peptide to polyanion ratio, corresponding to a net positive charge of the complexes. Uptake of polyanions per se or complexes with a relatively low peptide to polyanion ratio was favored by proteoglycan deficiency in the recipient cells, indicating the existence of distinct transport mechanisms. Moreover, expression of full-length HIV-Tat as well as exogenous addition of HIV-Tat peptide resulted in cellular accumulation of endogenous proteoglycans. We conclude that an HIV-Tat derived peptide efficiently targets extraneous DNA and glycosaminoglycans to the nuclear compartment and that proteoglycans serve a regulatory role in these processes, which may have implications for directed gene and drug delivery in vivo.
Species- and length of exposure-dependent differences in the benzo(a)pyrene:DNA adducts formed in embryo cell cultures from mice, rats, and hamsters. (1985)

The activation of benzo(a)pyrene (BaP) to DNA-binding metabolites in early-passage embryo cell cultures prepared from various species of rodents was investigated by exposing cells from mice (BALB/c and Sencar), rats (Wistar and Fischer 344), and Syrian hamsters to [3H]BaP for various lengths of time. The BaP:DNA adducts containing cis-vicinal hydroxyl groups such as those formed from 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti-BaPDE) were separated from the other types of BaP:DNA adducts by immobilized boronate chromatography, and the individual adducts were analyzed by high-performance liquid chromatography. A number of BaP:DNA adducts were present in the DNA from the cultures from all three species after 5 h of BaP treatment. After a 24-h exposure to BaP, the mouse and hamster embryo cell DNA contained a large amount of the adduct formed by reaction of (+)-anti-BaPDE with the 2-amino group of deoxyguanosine (dGuo) and a small amount of a 7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene:dGuo adduct. A large number of BaP:DNA adducts derived from 7 beta, 8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene and other unidentified BaP metabolites were present in rat embryo cell cultures at all times. Neither the Fischer 344 nor the Wistar rat embryo cell cultures had a significant amount of (+)-anti-BaPDE:dGuo adduct after 5 h of BaP treatment, and in the Wistar rat cells larger amounts of other adducts were present even after a 96-h exposure to BaP. In cell cultures from all three species the proportion of (+)-anti-BaPDE:dGuo adduct increased as the length of time of exposure to BaP increased. There are major differences in the metabolic activation of BaP to DNA binding metabolites in embryo cells from various species of rodents. However, the variations between cell cultures from different strains of rats or mice are not as great as the variations between cell cultures from different species. The time-dependent alterations in the BaP:DNA adducts indicate that analysis after various lengths of time of exposure to BaP is essential to characterize accurately the pathways of metabolic activation of BaP in cells from various species and tissues.
Effects of Different Frequencies (2–3 Days/Week) of Aquatic Therapy Program in Adults with Chronic Low Back Pain. A Non-Randomized Comparison Trial (2012)

Eight weeks of aquatic therapy program decrease levels of back pain and disability, increase quality of life, and improve health-related fitness in adults with chronic low back pain without effects in body composition. A dose-response effect was observed in some parameters, with greater benefits when exercising 3 days per week compared with 2 days.
NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models (2016)

These data support further evaluation of NKTR-214 in humans for a variety of tumor types, adding to the repertoire of potent and potentially curative cancer immunotherapies.
Future directions of multicomponent seismic methods in the marine environment (2002)

Several different types of applications of multicomponent data have been demonstrated in both the offshore and onshore environment. To date, however, actual applications have not been as widespread as the potential benefits of the methods may suggest. Barriers to widespread application of the technique are not only limited by the lack of fidelity in the actual recording. Of course, the better the data the more likely the application, but good data—although necessary for successful interpretation—may not be sufficient to lead to universal usage.
Cysteine residues of SNAP-25 are required for SNARE disassembly and exocytosis, but not for membrane targeting (2001)

The release of neurotransmitter at a synapse occurs via the regulated fusion of synaptic vesicles with the plasma membrane. The fusion of the two lipid bilayers is mediated by a protein complex that includes the plasma membrane target soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein (SNAP) receptors (t-SNAREs), syntaxin 1A and synaptosome-associated protein of 25kDa (SNAP-25), and the vesicle SNARE (v-SNARE), vesicle-associated membrane protein (VAMP). Whereas syntaxin 1A and VAMP are tethered to the membrane by a C-terminal transmembrane domain, SNAP-25 has been suggested to be anchored to the membrane via four palmitoylated cysteine residues. We demonstrate that the cysteine residues of SNAP-25 are not required for membrane localization when syntaxin 1A is present. Analysis of the 7S and 20S complexes formed by mutants that lack cysteine residues demonstrates that the cysteines are required for efficient SNARE complex dissociation. Furthermore, these mutants are unable to support exocytosis, as demonstrated by a PC12 cell secretion assay. We hypothesize that syntaxin 1A serves to direct newly synthesized SNAP-25 through the Golgi transport pathway to the axons and synapses, and that palmitoylation of cysteine residues is not required for targeting, but to optimize interactions required for SNARE complex dissociation.