gebhart/patrepeval huggingface dataset:
Molecular cloning, sequencing, and expression of human myocardial fatty acid ethyl ester synthase-III cDNA. (1991)

Fatty acid ethyl ester synthase-III (FAEES-III), previously purified to homogeneity from human heart, metabolizes ethanol nonoxidatively. Using a derived partial amino acid sequence and corresponding oligonucleotide probes, the cDNA for this enzyme has been cloned from a human heart lambda gtll library. Of the five positive clones obtained, one contained a complete coding region (630 base pairs) and the entire 3'-noncoding region (41 base pairs). From this nucleotide sequence the complete 210 amino acid sequence of FAEES-III (Mr 23,307) is reported. Comparison of its amino acid sequence with that of glutathione S-transferase pi-1 suggests that they belong to the same gene family since they differ in only six nucleotides and four amino acids. The sequence of FAEES-III was also compared with those of placental glutathione S-transferase and the basic glutathione S-transferase. FAEES-III was 84% homologous with placental glutathione S-transferase but only less than 10% homologous with the basic glutathione S-transferase. Northern blots demonstrate expression of FAEES-III mRNA in normal human liver, placenta, and heart. In all cases, the mRNA for the enzyme is 0.7 kilobase in size. MCF-7 cells transfected with FAEES-III cDNA have a 14-fold increase in synthase activity and a 12-fold increase in glutathione S-transferase (GST) activity compared with control cells. MCF-7 cells transfected with GST pi-1 cDNA have a 13-fold increase in GST activity compared with control cells but no increase in synthase activity. When the supernatant of COS-7 cells transfected with FAEES-III cDNA were immunoblotted with rabbit FAEES-III antibody, a band at 24 kilodaltons was demonstrated. Thus, we have obtained the first cDNA and amino acid sequence for a human FAEES-III which also has significant GST activity, and we have identified 4 residues potentially responsible for conferring ethanol recognition to GSTs.
Lysine methylation is an endogenous post-translational modification of tau protein in human brain and a modulator of aggregation propensity (2014)

In Alzheimer's disease, the microtubule-associated protein tau dissociates from the neuronal cytoskeleton and aggregates to form cytoplasmic inclusions. Although hyperphosphorylation of tau serine and threonine residues is an established trigger of tau misfunction and aggregation, tau modifications extend to lysine residues as well, raising the possibility that different modification signatures depress or promote aggregation propensity depending on site occupancy. To identify lysine residue modifications associated with normal tau function, soluble tau proteins isolated from four cognitively normal human brains were characterized by MS methods. The major detectable lysine modification was found to be methylation, which appeared in the form of mono- and di-methyl lysine residues distributed among at least 11 sites. Unlike tau phosphorylation sites, the frequency of lysine methylation was highest in the microtubule-binding repeat region that mediates both microtubule binding and homotypic interactions. When purified recombinant human tau was modified in vitro through reductive methylation, its ability to promote tubulin polymerization was retained, whereas its aggregation propensity was greatly attenuated at both nucleation and extension steps. These data establish lysine methylation as part of the normal tau post-translational modification signature in human brain, and suggest that it can function in part to protect against pathological tau aggregation.
In Vitro and Ex Vivo Inhibition of Human Telomerase by Anti-HIV Nucleoside Reverse Transcriptase Inhibitors (NRTIs) but Not by Non-NRTIs (2012)

Telomerase is a specialized reverse transcriptase responsible for the de novo synthesis of telomeric DNA repeats. In addition to its established reverse transcriptase and terminal transferase activities, recent reports have revealed unexpected cellular activities of telomerase, including RNA-dependent RNA polymerization. This telomerase characteristic, distinct from other reverse transcriptases, indicates that clinically relevant reverse transcriptase inhibitors might have unexpected telomerase inhibition profiles. This is particularly important for the newer generation of RT inhibitors designed for anti-HIV therapy, which have reported higher safety margins than older agents. Using an in vitro primer extension assay, we tested the effects of clinically relevant HIV reverse transcriptase inhibitors on cellular telomerase activity. We observed that all commonly used nucleoside reverse transcriptase inhibitors (NRTIs), including zidovudine, stavudine, tenofovir, didanosine and abacavir, inhibit telomerase effectively in vitro. Truncated telomere synthesis was consistent with the expected mode of inhibition by all tested NRTIs. Through dose-response experiments, we established relative inhibitory potencies of NRTIs on in vitro telomerase activity as compared to the inhibitory potencies of the corresponding dideoxynucleotide triphosphates. In contrast to NRTIs, the non-nucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine and efavirenz did not inhibit the primer extension activity of telomerase, even at millimolar concentrations. Long-term, continuous treatment of human HT29 cells with select NRTIs resulted in an accelerated loss of telomere repeats. All tested NRTIs exhibited the same rank order of inhibitory potencies on telomerase and HIV RT, which, according to published data, were orders-of-magnitude more sensitive than other DNA polymerases, including the susceptible mitochondria-specific DNA polymerase gamma. We concluded that telomerase activity could be inhibited by common NRTIs, including currently recommended RTI agents tenofovir and abacavir, which warrants large-scale clinical and epidemiological investigation of the off-target effects of long-term highly active antiretroviral therapy (HAART) with these agents.
Estimating Soil Water Content from Permittivity for Different Mineralogies and Bulk Densities (2012)

Time domain reflectometry (TDR) exploits the difference in dielectric permittivity between the soil solid, gas, and liquid phases and has become increasingly popular for the determination of soil water content. The electromagnetic determination of water content in soils with high clay contents requires a good understanding of the main factors that affect the relationship between the dielectric permittivity of clay minerals and soil water content. The objectives of this study were to: (i) investigate the relationships among soil bulk density, clay content, clay mineralogy, and the soil dielectric permittivity, and (ii) evaluate the performance of the approach to correct the dissipation effects due to high clay contents. Samples were taken from five areas with different textures and bulk densities, both topsoils and subsoils. Soil physical properties, i.e., organic matter, clay, silt, and sand contents, and clay mineralogy were determined. High clay contents caused an underestimation of soil water content in the low moisture range and its overestimation in the high moisture range. Results also demonstrated that soils with similar clay contents but different mineralogies showed different permittivity values. For soil samples with equal water contents, soils with higher bulk density, or lower porosity, had a larger permittivity than soils with low bulk density and high porosity. This behavior was the result of the increase in the ratio of solid particle volume to air because the solid particles have a larger dielectric permittivity than air. Soil bulk density and clay content impact the accuracy and calibration of TDR. Smectites also cause signal attenuation and dispersion, resulting in smaller signal amplitude and longer rise time. In addition, smectites cause dispersion of the reflected signal, resulting in a longer rise time.
The small RING finger protein Z drives arenavirus budding: Implications for antiviral strategies (2003)

By using a reverse genetics system that is based on the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), we have identified the arenavirus small RING finger Z protein as the main driving force of virus budding. Both LCMV and Lassa fever virus (LFV) Z proteins exhibited self-budding activity, and both substituted efficiently for the late domain that is present in the Gag protein of Rous sarcoma virus. LCMV and LFV Z proteins contain proline-rich motifs that are characteristic of late domains. Mutations in the PPPY motif of LCMV Z severely impaired the formation of virus-like particles. LFV Z contains two different proline-rich motifs, PPPY and PTAP, which are separated by eight amino acids. Mutational analysis revealed that both motifs are required for efficient LFV Z-mediated budding. Both LCMV and LFV Z proteins recruited to the plasma membrane Tsg101, which is a component of the class E vacuolar protein sorting machinery that has been implicated in budding of HIV and Ebola virus. Targeting of Tsg101 by RNA interference caused a strong reduction in Z-mediated budding. These results indicate that Z is the arenavirus functional counterpart of the matrix proteins found in other negative strand enveloped RNA viruses. Moreover, members of the vacuolar protein sorting pathway appear to play an important role in arena-virus budding. These findings open possibilities for antiviral strategies to combat LFV and other hemorrhagic fever arenaviruses.
Code of practice for brachytherapy physics: Report of the AAPM Radiation Therapy Committee Task Group No. 56 (1997)

Recommendations of the American Association of Physicists in Medicine (AAPM) for the practice of brachytherapy physics are presented. These guidelines were prepared by a task group of the AAPM Radiation Therapy Committee and have been reviewed and approved by the AAPM Science Council.
Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKBβ (2003)

The serine/threonine kinase Akt/PKB plays key roles in the regulation of cell growth, survival, and metabolism. It remains unclear, however, whether the functions of individual Akt/PKB isoforms are distinct. To investigate the function of Akt2/PKBbeta, mice lacking this isoform were generated. Both male and female Akt2/PKBbeta-null mice exhibit mild growth deficiency and an age-dependent loss of adipose tissue or lipoatrophy, with all observed adipose depots dramatically reduced by 22 weeks of age. Akt2/PKBbeta-deficient mice are insulin resistant with elevated plasma triglycerides. In addition, Akt2/PKBbeta-deficient mice exhibit fed and fasting hyperglycemia, hyperinsulinemia, glucose intolerance, and impaired muscle glucose uptake. In males, insulin resistance progresses to a severe form of diabetes accompanied by pancreatic beta cell failure. In contrast, female Akt2/PKBbeta-deficient mice remain mildly hyperglycemic and hyperinsulinemic until at least one year of age. Thus, Akt2/PKBbeta-deficient mice exhibit growth deficiency similar to that reported previously for mice lacking Akt1/PKBalpha, indicating that both Akt2/PKBbeta and Akt1/PKBalpha participate in the regulation of growth. The marked hyperglycemia and loss of pancreatic beta cells and adipose tissue in Akt2/PKBbeta-deficient mice suggest that Akt2/PKBbeta plays critical roles in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass for which other Akt/PKB isoforms are unable to fully compensate.
Flavivirus Infection Enhancement in Macrophages: an Electron Microscopic Study of Viral Cellular Entry (1985)

The mode of entry of West Nile virus (WNV) into the macrophage-like cell line P388D1 was investigated at the electron microscopical level using synchronized infections. The presence of the antiviral monoclonal antibody F6/16A at a concentration that enhanced viral attachment to P388D1 cells ninefold made no difference to the entry pathway of WNV. In both the absence and presence of F6/16A the initial uptake of single viral particles was mediated by coated pits, and started within 30 s of warming the cells to 37 degrees C. Viral particles later appeared in fully or partially coated vesicles and later in uncoated prelysosomal endocytic vacuoles before degradation in lysosomes. However, aggregates of viral particles (five or more virus particles in cross-section), appeared to be phagocytosed whole by cells in a process which involved aggregates being engulfed by extensions of the plasma membrane. This process exhibited a slower time course than the uptake of single viral particles, becoming prominent 15 to 30 min after warming the cells to 37 degrees C. The involvement of a prelysosomal vacuolar compartment in the entry process was shown by a failure to stain for acid phosphatase. This compartment could be specifically loaded with viral particles when viral internalization occurred at 20 degrees C in the presence of 50 mM-ammonium chloride.
DNA methylation assay for colorectal carcinoma (2017)

Colorectal carcinoma (CRC) is a common cause of morbidity and mortality worldwide. Two pathogenic pathways are involved in the development of adenoma to CRC. The first pathway involves<i>APC/β-catenin</i> characterized by chromosomal instability resulting in the accumulation of mutations. The second pathway is characterized by lesions in<i>DNA mismatch repair genes</i>. Aberrant DNA methylation in selected gene promoters has emerged as a new epigenetic pathway in CRC development. CRC screening is the most efficient strategy to reduce death. Specific DNA methylation events occur in multistep carcinogenesis. Epigenetic gene silencing is a causative factor of CRC development. DNA methylations have been extensively examined in stool from CRC and precursor lesions. Many methylated genes have been described in CRC and adenoma, although no definite DNA methylation biomarkers panel has been established. Multiple DNA methylation biomarkers, including secreted frizzled-related protein 2, secreted frizzled-related protein 1, tissue factor pathway inhibitor 2, vimentin, and methylguanine DNA methyltransferase, have been further investigated, and observations have revealed that DNA methylation biomarkers exhibit with high sensitivity and specificity. These markers may also be used to diagnose CRC and adenoma in early stages. Real time polymerase chain reaction (qPCR) is sensitive, scalable, specific, reliable, time saving, and cost effective. Stool exfoliated markers provide advantages, including sensitivity and specificity. A stool qPCR methylation test may also be an enhanced tool for CRC and adenoma screening.
Strategies to Reduce Oxygen Inhibition in Photoinduced Polymerization (2013)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTStrategies to Reduce Oxygen Inhibition in Photoinduced PolymerizationSamuel Clark Ligon†, Branislav Husár†‡, Harald Wutzel†, Richard Holman§, and Robert Liska*†View Author Information† Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163/MC, A-1060 Vienna, Austria‡ Polymer Institute, Slovak Academy of Sciences, Dúbravská cesta 9, 845 41 Bratislava 45, Slovakia§ The Paint Research Association, 14 Castle Mews, High Street, TW12 2NP Hampton, United Kingdom*E-mail: [email protected]Cite this: Chem. Rev. 2014, 114, 1, 557–589Publication Date (Web):October 1, 2013Publication History Received9 January 2013Published online1 October 2013Published inissue 8 January 2014https://pubs.acs.org/doi/10.1021/cr3005197https://doi.org/10.1021/cr3005197review-articleACS PublicationsCopyright © 2013 American Chemical SocietyRequest reuse permissionsArticle Views15316Altmetric-Citations523LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Inhibition,Monomers,Organic compounds,Oxygen,Polymerization Get e-Alerts
The Effect of Medicaments on the Motility of the Oral Flora with Special Reference to the Treatment of Vincent's Infection. II (1943)

From the Department of Bacteriology and Pathology, School of Dentistry, University of Pennsylvania, Philadelphia, Pa. A previous report (1) described an in vitro test of the antibacterial properties of medicaments intended for topical application to the oral mucosa. This method employs loss of motility of the motile oral flora and growth of the nonmotile flora as a basis of comparison. The method has been adequately described and the apparatus illustrated in previous publications (1, 7). The motility test has certain advantages over the Rideal-Walker and similar tests, for it more nearly approximates clinical conditions. 1. It employs the actual bacteria which the drug is to combat, although some of these organisms cannot be grown in artificial media. 2. Since fresh saliva is used, the pH of the oral cavity, the organic and inorganic content, enzymes, putrefaction and fermentation products, detritus and end products of bacterial activity are preserved. 3. The ratio of medicament to saliva is closer to actual working conditions. 4. Chemical reactions on surfaces have been found to differ from reactions in bulk (2). While the motility test does not duplicate oral surfaces, it does have an enormously greater proportionate surface than the test tube. 5. Speed of action, power of penetration of debris, any specificity or coagulation (which would reduce penetration) are easily observed. 6. Results have closely corresponded to clinical results. 7. Loss of motility has proved to be loss of pathogenicity (3, 4). This is a report on 27 additional medicaments which have been advocated, or may be useful, for the treatment of Vincent's infection.
Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma (2004)

7507 Background: BAY 43-9006 (BAY) is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-β. BAY inhibits CRAF and BRAF (wild type/V599E mutant) and inhibits growth of melanoma xenografts. This phase I/II study was initiated to define safety, pharmacokinetics (PK), and efficacy of oral BAY administered in combination with C and P. Methods: BAY was given from day 2 to 19 of a 21 day cycle at 3 dose levels (DL): DL 1, 100 mg bid; DL 2, 200 mg bid; and DL 3, 400 mg bid. C (AUC 6) and P (225 mg/m2) were each administered on day 1. PK data were collected on days 1, 2, 22, and 23. Tumor samples were obtained pretreatment for BRAF mutation analysis. Based on responses during the dose escalation phase, melanoma pts were accrued in the expansion phase. Results: 35 melanoma patients (pts) (median age 47, PS 0–1) have been treated for at least 6 weeks and 32 are evaluable for response. Twenty-one (60%) pts received ≥ 1 prior therapy, and 68% had AJCC M1c disease. Early data shows this combination is well tolerated with no unexpected adverse events. Responses using RECIST criteria demonstrated 11 partial responses; 10 are ongoing at 3–16 months (response rate 31%). Median time to response is 3 months. Nineteen pts have stable disease as best response, and 12 remain on study for ≥3 months since entry. Median time to progression has not been reached at a median follow-up of 5 months. Preliminary PK shows lack of interaction between BAY, P, and C. There was no change in the preliminary PK values of P, the 6-OH metabolite, total platinum, or free platinum from Cycle 1 to Cycle 2. Conclusions: The combination of BAY with C and P has demonstrated activity in melanoma with a favorable safety profile and no apparent PK interaction. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Health Care; Bayer Pharmaceuticals Bayer AG; Bayer Pharmaceuticals
Evaluation of Serratia Peptidase in Acute or Chronic Inflammation of Otorhinolaryngology Pathology: A Multicentre, Double-Blind, Randomized Trial versus Placebo (1990)

The efficacy and tolerability of Serratia peptidase were evaluated in a multicentre, double-blind, placebo-controlled study of 193 subjects suffering from acute or chronic ear, nose or throat disorders. Treatment lasted 7-8 days, with the drug or placebo being administered at a rate of two tablets three times a day. After 3-4 days' treatment, significant symptom regression was observed in peptidase-treated patients. There was also a significant reduction in symptoms after 7-8 days for patients in both treatment groups but the response was more marked in those patients receiving the active drug. Statistical comparison between the two groups confirmed the greater efficacy and rapid action of the peptidase against all the symptoms examined at both stages. Tolerance was found to be very good and similar for both groups. It is concluded that Serratia peptidase has anti-inflammatory, anti-oedemic and fibrinolytic activity and acts rapidly on localized inflammation.
Band-gap change of carbon nanotubes: Effect of small uniaxial and torsional strain (1999)

We use a simple picture based on the $\ensuremath{\pi}$ electron approximation to study the band-gap variation of carbon nanotubes with uniaxial and torsional strain. We find (i) that the magnitude of slope of band gap versus strain has an almost universal behavior that depends on the chiral angle, (ii) that the sign of slope depends on the value of $(n\ensuremath{-}m)\mathrm{mod}3,$ and (iii) a novel change in sign of the slope of band gap versus uniaxial strain arising from a change in the value of the quantum number corresponding to the minimum band gap. Four orbital calculations are also presented to show that the $\ensuremath{\pi}$ orbital results are valid.
Spray-dried microparticles: a potential vehicle for oral delivery of vaccines (2012)

This study aims to formulate a microparticle-based system that protects the protein from the harsh gastric conditions and also provides appropriate uptake via M cells for desired immune response upon oral administration. The formulation was derived using a valid statistical model, analysed by JMP® (SAS). The average size and charge of the resulting microparticles were 1.51 ± 0.125 µm and + 15.7 ± 2.5 mV, respectively. Moreover, the particles provided a prolonged release over a period of 8 hrs which ensures M-cell uptake of intact particle with antigen (Kunisawa et al., 2011). This was further supported with in vivo studies where particle uptake was found in Peyer's patches of small intestine when observed for 8 h. Thus, these microparticles can be used as an efficient vaccine delivery vehicle upon oral administration.