gebhart/patrepeval huggingface dataset:
Post-translational Modifications Required for Coagulation Factor Secretion and Function (1998)

Protein translocation into and transport through the secretory pathway in eukaryotic cells is accompanied by a multitude of covalent modifications that occur on the polypeptide backbone. The sequence of post-translational modifications that occur on a polypeptide is carefully regulated both temporally and spatially, where certain modifications only occur within the endoplasmic reticulum (ER) and others only occur within the Golgi compartment (Fig. 1). In many cases these modifications are required for proper polypeptide folding and secretion. In addition, post-translational modifications can affect the half-life of the protein in the plasma and may be required for functional activity of the polypeptide. The mechanisms that direct post-translational modifications recognize specific structural determinants within the polypeptide backbone. The efficiency of these modifications is determined by the specific host cell enzymatic machinery, the availability of substrates and cofactors, as well as structural properties of the polypeptide. To evaluate the role of post-translational modification in protein function investigators have studied proteins treated with chemicals or enzymes to remove modifications, proteins synthesized in the presence of inhibitors of specific modification reactions, proteins expressed in either different cell types or in cell mutants with defects in specific enzymatic machinery required to perform modifications, or proteins engineered through recombinant DNA technology that contain mutations that prevent modifications. The interpretation of results utilizing different strategies needs to be qualified to consider secondary effects due to the approach utilized. As a consequence, it is desirable to utilize several independent approaches to confirm the importance of any specific modification...
Interfacial tension governs the formation of self-organized honeycomb-patterned polymer films (2009)

Hexagonally packed water droplets condensed on a polymer solution are potential templates for the formation of honeycomb-patterned porous polymer films. A small number of surface-active molecules is indispensable for the stabilization of water droplets during solvent evaporation. Biocompatible surfactants; e.g., phospholipids, are required for the fabrication of biodegradable honeycomb-patterned polymer films, which can be used as novel biomedical materials, mainly in vivo. Among various kinds of phospholipids, dioleoylphosphatidylethanolamine (DOPE) has been reported to be the most suitable surfactant for the formation of honeycomb-patterned PLA films. Interfacial tension between a water droplet and the polymer solution is largely dependent on the chemical structure of the phospholipids. DOPE shows high interfacial tension, resulting in the stabilization of water droplets during solvent evaporation. Dierucoylphosphatidylcholine (DEPC) and dierucoylphosphatidylethanolamine (DEPE), both of which display high interfacial tension, were also found to be suitable biocompatible surfactants.
Effect of Citric Acid and Glycine Addition on Acrylamide and Flavor in a Potato Model System (2006)

Acrylamide levels in cooked/processed food can be reduced by treatment with citric acid or glycine. In a potato model system cooked at 180 degrees C for 10-60 min, these treatments affected the volatile profiles. Strecker aldehydes and alkylpyrazines, key flavor compounds of cooked potato, were monitored. Citric acid limited the generation of volatiles, particularly the alkylpyrazines. Glycine increased the total volatile yield by promoting the formation of certain alkylpyrazines, namely, 2,3-dimethylpyrazine, trimethylpyrazine, 2-ethyl-3,5-dimethylpyrazine, tetramethylpyrazine, and 2,5-diethyl-3-methylpyrazine. However, the formation of other pyrazines and Strecker aldehydes was suppressed. It was proposed that the opposing effects of these treatments on total volatile yield may be used to best advantage by employing a combined treatment at lower concentrations, especially as both treatments were found to have an additive effect in reducing acrylamide. This would minimize the impact on flavor but still achieve the desired reduction in acrylamide levels.
Patterns of Allelic Loss of Synchronous Adenocarcinomas of the Lung (2005)

Distinction of multiple primary lung carcinomas from intrapulmonary metastases using empiric clinical and histopathologic criteria can be difficult. Recent advances have provided several molecular markers that can be used for clonal analysis of separate tumor nodules and enhance tumor staging and subsequent treatment and prognosis. To address this issue, we performed a microdissection-based allelotyping of 20 cases of histologically similar, pathologic stage T4 adenocarcinomas (ADCs). Loss of heterozygosity (LOH) analysis included a panel of 15 polymorphic microsatellite markers located on 1p, 3p, 5q, 9p, 9q, 10q, 17p, and 22q. The tumor size, visceral pleural and angiolymphatic invasion, lymph node status, outcome, and survival were assessed. Allelotypes of 60 cases of solitary primary non-small cell lung carcinomas (NSCLC) (stages I-II) were used to define the percentage of discordant LOH patterns within solitary primary lung carcinoma that would discriminate between survivors and nonsurvivors. These criteria were used in the analysis of pathologic stage T4 ADC. Two groups of stage T4 cases were created: molecularly homogenous (≤40% discordances) (14 cases, 70%), and molecularly heterogenous (>40% discordances) (6 cases, 30%). Molecularly homogenous tumors were more frequently associated with visceral pleural invasion (92% vs. 8%) (P = 0.018). Allelotype did not correlate with age, gender, tumor size, tumor differentiation, lymph node status, angiolymphatic invasion, survival, or outcome. Our study showed that discordant and concordant genotypic profiles exist in morphologically similar synchronous ADC of the lung.
High‐Temperature Electrochemistry: A Review (2004)

Abstract High‐temperature electrochemistry remains a relatively unexplored field of research, although in recent years significant developments have been made. This report details the main experimental methods and approaches to heating an electrochemical system under both isothermal and non‐isothermal conditions and gives an insight into the experimental and electroanalytical results obtainable under such conditions. It has been shown that the promotion of mass transport at high‐temperatures, through diffusion or convection, often results in increased current signals. This increase benefits electroanalytical measurements by lowering detection limits. High temperatures also usefully enhance the sensitivity of systems with sluggish kinetics.
Hath1, Down-Regulated in Colon Adenocarcinomas, Inhibits Proliferation and Tumorigenesis of Colon Cancer Cells (2004)

A striking feature of colon tumors is the significant reduction of goblet cells. Although targeted deletion of Math1 in mice leads to a loss of intestinal secretory cells, including goblet cells, the role of Hath1 in colon tumorigenesis remains unknown. Here we report that Hath1, the human ortholog of Math1, was dramatically down-regulated in colon tumor samples and colon cancer cell lines. Overexpression of Hath1 in HT29, an aggressive colon cancer cell line, resulted in a significant inhibition on cell proliferation, anchorage-independent growth in soft agar and, more importantly, growth of human colon cancer cell xenografts in athymic nude mice. Such inhibition was accompanied by altered expression of a goblet cell differentiation marker, MUC2, and cell cycle regulators cyclin D1 and p27kip1. Hath1 expression also was up-regulated on inhibition of the Wnt pathway, which has been well implicated in colon tumorigenesis. Hence, this study suggests that Hath1 may be a novel factor downstream of the Wnt pathway capable of suppressing anchorage-independent growth of colon cancer cell lines. More importantly, this study is the first to establish a link between down-regulation of Hath1 expression and colon tumorigenesis.
Mycobacterial Cell Wall-DNA Complex (MCC) for the treatment of carcinoma in situ of the bladder: Non-clinical and clinical phase I-II results (2005)

4587 Background: We report on MCC preclinical activity and the results from 2 clinical trials in patients with carcinoma in situ of the bladder (CIS). Methods: Immune stimulatory and anti-cancer activities of MCC were determined; toxicology profile following intravesical and intravenous administration was characterized. Clinical efficacy and safety were evaluated in two trials where 128 patients with CIS associated or not with papillary tumors (<T2) received MCC (4 or 8 mg). Patients received 6 weekly intravesical instillations and a maintenance treatment of up to 10 months. Safety was evaluated by adverse events (AEs); complete response (CR) was defined as negative biopsy, cystoscopy and cytology. Results: Apoptosis and inhibition of proliferation were shown in vitro in bladder cancer ATCC cell lines and in human bladder tumour cells in primary culture. Immuno-stimulation was seen in human PBMC. In toxicology studies MCC was non toxic intravenously at a human equivalent dose up to 4.32 mg/kg. In 2 clinical studies MCC was well tolerated by all patients with 20–37% drug related AEs and less than 1% drug-related SAEs. The CR rates were 63%, 49% and 41% at weeks 12, 24 and 60 for the phase I study. For the phase II study, the CR rates at weeks 12, 26, months 12 and 18 in the ITT population were 27%, 27%, 32% and 23% at a dose of 4 mg and 46%, 46%, 64% and 73% at a dose of 8 mg. Increases in urinary cytokines and apoptosis markers were observed in the majority of patients. Conclusions: Pre-clinical and clinical data demonstrated anticancer activity of MCC, clinical efficacy and an excellent safety profile. MCC is different from and has a different mechanism of action than BCG, the standard treatment for CIS. A multicenter phase 3 trial is being set up to confirm the efficacy and safety of MCC at a dose of 8 mg. No significant financial relationships to disclose.
Plant-Growth-Promoting Rhizobacteria (2009)

Several microbes promote plant growth, and many microbial products that stimulate plant growth have been marketed. In this review we restrict ourselves to bacteria that are derived from and exert this effect on the root. Such bacteria are generally designated as PGPR (plant-growth-promoting rhizobacteria). The beneficial effects of these rhizobacteria on plant growth can be direct or indirect. This review begins with describing the conditions under which bacteria live in the rhizosphere. To exert their beneficial effects, bacteria usually must colonize the root surface efficiently. Therefore, bacterial traits required for root colonization are subsequently described. Finally, several mechanisms by which microbes can act beneficially on plant growth are described. Examples of direct plant growth promotion that are discussed include (a) biofertilization, (b) stimulation of root growth, (c) rhizoremediation, and (d) plant stress control. Mechanisms of biological control by which rhizobacteria can promote plant growth indirectly, i.e., by reducing the level of disease, include antibiosis, induction of systemic resistance, and competition for nutrients and niches.
Molecular similarity based on electrostatic potential and electric field (1987)

A new definition of molecular similarity in terms of electron density is proposed and a method for calculating similarity based on molecular electrostatic potential and molecular electric field introduced. It is applied to some simple isosteres.
Conformer Profiles and Biological Activities of Peptides (2002)

Small, zwitterionic peptides (2-6 residues) are flexible molecules that occur in solution as an ensemble of conformational forms in dynamic equilibrium. They occur widely in Nature as components of the peptide pool produced by protein hydrolysis. Molecular modelling provides information on the conformations they adopt in aqueous solution. Contrary to expectations, they exist in a limited range of conformational forms that arise from particular combinations of backbone torsions. From the computed energies of the conformers, those with similar conformations can be aggregated and a profile of the conformer population displayed using a 3D pseudo- Ramachandran plot. Several different generic peptide transporters have evolved with complementary substrate specificities in response to these varied conformational forms. Molecular recognition templates (MRTs) define the stereo-electronic features of particular conformations that determine peptide recognition and binding by these transporters. The binding and transport of any peptide correlates with the proportion of its conformers that occur in a particular MRT. Specific con former binding appears generally to involve little or no ligand rearrangement, which minimises conformational entropy loss. Conformational analysis of peptide analogues, evaluation of their similarities to normal peptides and comparison of their conformer profiles with MRTs, allows estimates of their molecular recognition as putative bioactive ligands for such proteins, this is illustrated for a variety of pseudopeptides, isosteres and conformationally-constrained analogues. For peptide therapeutics, such as β-lactam antibiotics, inhibitors of angiotensin-converting enzyme, antiviral and chemotherapeutic agents, this approach can be used to evaluate in silico virtual libraries of drug analogues to estimate their potential for targeted delivery and oral availability.
Differential effects of mutations in the chromophore pocket of recombinant phytochrome on chromoprotein assembly and Pr‐to‐Pfr photoconversion (1999)

Site-directed mutagenesis was performed with the chromophore-bearing N-terminal domain of oat phytochrome A apoprotein (amino acid residues 1-595). Except for Trp366, which was replaced by Phe (W366F), all the residues exchanged are in close proximity to the chromophore-binding Cys321 (i.e. P318A, P318K, H319L, S320K, H322L and the double mutant L323R/Q324D). The mutants were characterized by their absorption maxima, and the kinetics of chromophore-binding and the Pr-->Pfr conversion. The strongest effect of mutation on the chromoprotein assembly, leading to an almost complete loss of the chromophore binding capability, was found for the exchanges of His322 by Leu (H322L) and Pro318 by Lys (P318K), whereas a corresponding alanine mutant (P318A) showed wild-type behavior. The second histidine (H319) is also involved in chromophore fixation, as indicated by a slower assembly rate upon mutation (H319L). For the other mutants, an assembly process very similar to that of the wild-type protein was found. The light-induced Pr-->Pfr conversion kinetics is altered in the mutations H319L and S320K and in the double mutant L323R/Q324D, all of which exhibited a significantly faster I700 decay and accelerated Pfr formation. P318 is also involved in the Pr-->Pfr conversion, the millisecond steps (formation of Pfr) being significantly slower for P318A. Lacking sufficient amounts of W366F, assembly kinetics could not be determined in this case, while the fully assembled mutant underwent the Pr-->Pfr conversion with kinetics similar to wild-type protein.
Dual Resistance to Adamantanes and Oseltamivir Among Seasonal Influenza A(H1N1) Viruses: 2008–2010 (2010)

Two distinct genetic clades of seasonal influenza A(H1N1) viruses have cocirculated in the recent seasons: clade 2B oseltamivir-resistant and adamantane-susceptible viruses, and clade 2C viruses that are resistant to adamantanes and susceptible to oseltamivir. We tested seasonal influenza A(H1N1) viruses collected in 2008-2010 from the United States and globally for resistance to antivirals approved by the Food and Drug Administration. We report 28 viruses with both adamantane and oseltamivir (dual) resistance from 5 countries belonging to 4 distinct genotypes. Because of limited options for antiviral treatment, emergence of dual-resistant influenza viruses poses a public health concern, and their circulation needs to be closely monitored.
Efficient Synthesis of N-[(2-Hydroxyethoxy)methyl]-2-alkyl-3-hydroxy-4-pyridinone by a Modified Hilbert-Johnson Reaction (1996)

Abstract Ethyleneglycol derivatives of 2-methyl (and ethyl)-3-hydroxy-4-pyridinone were synthesized by a modified Hilbert-Johnson reaction. The synthesis proceedes by reaction of O-protected 2-alkyl-3-hydroxy-4-pyridinone with hexamethyldisilazane in the presence of chlorotrimethylsilane followed by trimethylsilyl trifluoromethanesulfonate catalized alkylation with benzyloxy-ethoxymethylchloride in dichloroethane and deprotection by hydrogenation. The overall yield was 87%. This method provides a useful way to produce oligo- or polyethyleneglycol substituted hydroxypyridinones.
The optical properties and laser irradiation of some common glasses (1990)

The reflectance spectra of four common glasses have been measured from 300 to 2000 cm-1. The glasses examined were Vitreosil, Tempax, Sodalime, and BK7. A Kramers-Kronig analysis of the reflectance data was used to calculate the real and imaginary parts of the refractive index. These were used to predict how the glasses would react to high-power carbon dioxide laser irradiation. The results indicated that the lower optical absorption coefficient and the lower thermal expansion coefficient of the Vitreosil glass should make it less susceptible to laser induced damage.
Local Treatment of Spasmodic Torticollis with Botulinum Toxin (1987)

Fifty-six patients with spasmodic torticollis were treated with local injections of botulinum toxin. The drop out rate was 21%. The remaining 44 patients were followed for a period of 3 to 21 months. Thirty-two patients (76%) had pain relief out of 42 presenting with pain; 37 (66%) improved in the amount of sustained movements of torticollis. The efficacy was reproducible after repeated injections.
Gender-Dependent Pathways of Hypoxia-Ischemia-Induced Cell Death and Neuroprotection in the Immature P3 Rat (2007)

Previously, we demonstrated neuroprotection with 2-iminobiotin (2-IB) after cerebral hypoxia-ischemia (HI) in female, but not in male P7 rats. Given the different patterns of brain injury in more immature rats, we examined whether these gender differences could also be observed in P3 rats. HI was induced by unilateral carotid ligation and FiO2 reduction, followed by 2-IB administration. HSP70 protein expression and cytochrome c release from the mitochondria, markers of short-term outcome, were induced by HI to the same extent in male and female animals. However, reduction in HSP70 production and cytochrome c release by 2-IB was seen in female rats only. Long-term cerebral injury after HI, assessed with histology, was similar in male and female P3 rats, but long-term neuroprotection by 2-IB was observed in female rats only. In conclusion, 2-IB provides neuroprotection after cerebral HI in female, but not in male immature P3 rats.
Induction by EGF and Interferon-γ of Tyrosine Phosphorylated DNA Binding Proteins in Mouse Liver Nuclei (1993)

Intraperitoneal injection of epidermal growth factor (EGF) into mice resulted in the appearance in liver nuclei of three tyrosine phosphorylated proteins (84, 91, and 92 kilodaltons) within minutes after administration of EGF. Administration of interferon-gamma (IFN-gamma) resulted in the appearance in liver nuclei of two tyrosine phosphorylated proteins (84 and 91 kilodaltons). The 84- and 91-kilodalton proteins detected after either EGF or IFN-gamma administration were identified as the IFN-gamma activation factors (GAF). Furthermore, gel shift analysis revealed that these GAF proteins, detected after either EGF or IFN-gamma administration, specifically bound to the sis-inducible element of the c-fos promoter. Thus, GAF proteins participate in nuclear signaling in both IFN-gamma and EGF pathways.
Aminoglycosides Induce Acute Cell Signaling and Chronic Cell Death in Renal Cells that Express the Calcium-Sensing Receptor (2005)

The aminoglycoside antibiotics (AGAs) are calcium-sensing receptor (CaR) agonists that are toxic to the renal proximal tubule. Proximal tubule-derived opossum kidney (OK) cells express CaR-like proteins and respond to AGAs with intracellular Ca2+ mobilization and extracellular regulated protein kinase (ERK) phosphorylation. To examine the possible cellular basis of AGA toxicity, acute and chronic responses to AGA treatment in OK cells and in CaR stably transfected HEK-293 cells (CaR-HEK) were studied. Changes in cell-fate signaling, proliferation, and cell death were detected by semiquantitative Western blotting, Hoechst staining, cell counting, and FACS analysis. Confocal microscopy was used to study the relative internalization of fluorophore-labeled gentamicin in CaR-transfected and -nontransfected cells. Here it is reported that the AGA neomycin and gentamicin elicit acute, phosphatidylinositol-3 kinase-dependent phosphorylation of Akt, glycogen synthase kinase 3beta, and p38 mitogen-activated protein kinase. After 24 h of gentamicin treatment, OK cell proliferation was observed, whereas after 4 d, the OK cells underwent cell death, an effect that was mimicked by the CaR agonists spermine and polyarginine. Furthermore, gentamicin elicited substantially more cell death in CaR-HEK cells than in nontransfected HEK-293 cells. The pan-specific caspase inhibitor Z-VAD significantly inhibited cell death in both OK and CaR-HEK cells. Finally, the intracellular uptake of Texas Red-labeled gentamicin was equivalent in both CaR-transfected and vector-transfected HEK-293 cells, suggesting that the CaR does not enhance drug uptake. Together, these observations demonstrate that the AGAs induce both acute and chronic cell fate changes in OK cells and CaR-HEK cells and that the proximal tubular CaR is likely to contribute to signaling underlying the renal toxicity of the AGAs.
Highly Specific Auto-Antibodies against Claudin-18 Isoform 2 Induced by a Chimeric HBcAg Virus-Like Particle Vaccine Kill Tumor Cells and Inhibit the Growth of Lung Metastases (2011)

Strategies for antibody-mediated cancer immunotherapy, such as active immunization with virus-like particle (VLP)-based vaccines, are gaining increasing attention. We developed chimeric hepatitis B virus core antigen (HBcAg)-VLPs that display a surface epitope of the highly selective tumor-associated cell lineage marker claudin-18 isoform 2 (CLDN18.2) flanked by a mobility-increasing linker. Auto-antibodies elicited by immunization with these chimeric HBcAg-VLPs in 2 relevant species (mouse and rabbit) bind with high precision to native CLDN18.2 at physiologic densities on the surface of living cells but not to the corresponding epitope of the CLDN18.1 splice variant that differs by merely one amino acid. The induced auto-antibodies are capable of efficiently killing CLDN18.2 expressing cells in vitro by complement-dependent and antibody-dependent cell-mediated cytotoxicity. Moreover, they provide partial protective immunity against the challenge of mice with syngeneic tumor cells stably expressing CLDN18.2. Our study provides a first proof-of-concept that immunization combining VLPs as antigen carriers with specific conformational epitopes of a highly selective differentiation antigen may elicit auto-antibodies with high cytocidal and tumoricidal potential.