gebhart/patrepeval huggingface dataset:
CYTOCHROME P450 EPOXYGENASE EICOSANOID PATHWAY AS NOVEL BIOMARKER AND THERAPEUTIC TARGET OF COLORECTAL CANCER (2018)

In US, there are ~130,000 new cases and ~50,000 deaths resulted from colorectal cancer (CRC) every year, making CRC the second leading cause of cancer‐related deaths. There is an urgent need to identify novel biomarkers and/or therapeutic targets of CRC, in order to reduce the risks of CRC. Here we report that the expressions of cytochrome P450 (CYP) epoxygenases and their eicosanoid metabolites (fatty acid epoxides) are dramatically increased in cell culture model, animal model, and human cancer patients of CRC; in addition, pharmacological inhibition or genetic ablation of CYP epoxygenases suppresses development of CRC in mice, illustrating that the previously unappreciated CYP epoxygenase pathway could serve as novel biomarkers and/or therapeutic targets of CRC. In a well‐established azoxymethane (AOM)/dextran sulfate sodium (DSS)‐induced CRC model in C57BL/6 mice, LC‐MS/MS showed that CYP‐derived fatty acid epoxides were the only eicosanoid metabolites which were significantly increased in both plasma and colon tissues of tumor‐bearing mice. RT‐PCR and immunoblotting analysis demonstrated that the expressions of CYP (including CYP2C38, 2C39, 2C50, 2C65, 2C70, and 2J6) were significantly increased in colon tumors. Consistent with the animal results, LC‐MS/MS showed that the serum levels of CYP‐derived fatty acid epoxides were significantly increased in patients clinically diagnosed with CRC. To study the functional roles of CYP in CRC, we tested whether pharmacological inhibition or genetic ablation of CYP affects CRC development in mice. We found that treatment with SKF‐525A and clotrimazole, which are two different inhibitors of CYP epoxygenases, suppressed AOM/DSS‐induced CRC in mice. We further showed that compared with wild‐type (WT) control mice, the AOM/DSS‐induced CRC was reduced in Cyp2c gene cluster knockout mice. To elucidate the specific metabolites involved in the pro‐CRC effects of CYP, we treated mice with epoxyoctadecenoic acids (EpOMEs) which are metabolites of linoleic acid produced by CYP, and found that EpOMEs promoted development of colonic inflammation in mice. Together, our studies showed that the previously unappreciated CYP epoxygenase pathway plays critical roles in promoting progression of CRC, in part through formation of pro‐inflammatory EpOMEs. These results suggest that the circulating levels of CYP‐derived fatty acid epoxides could serve as novel diagnostic biomarkers of CRC, and the CYP enzymes could be promising therapeutic targets of CRC. Support or Funding Information This work was supported by USDA NIFA 2016‐67017‐24423 (to G.Z.). In addition, the research is supported in part by NIEHS R01 ES002710 and Superfund Research Program P42 ES04699. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Emerging Approaches for Fluorescence-Based Newborn Screening of Mucopolysaccharidoses (2020)

Interest in newborn screening for mucopolysaccharidoses (MPS) is growing, due in part to ongoing efforts to develop new therapies for these disorders and new screening assays to identify increased risk for the individual MPSs on the basis of deficiency in the cognate enzyme. Existing tests for MPSs utilize either fluorescence or mass spectrometry detection methods to measure biomarkers of disease (e.g., enzyme function or glycosaminoglycans) using either urine or dried blood spot (DBS) samples. There are currently two approaches to fluorescence-based enzyme function assays from DBS: (1) manual reaction mixing, incubation, and termination followed by detection on a microtiter plate reader; and (2) miniaturized automation of these same assay steps using digital microfluidics technology. This article describes the origins of laboratory assays for enzyme activity measurement, the maturation and clinical application of fluorescent enzyme assays for MPS newborn screening, and considerations for future expansion of the technology.
Gender differences and job satisfaction: a study of university teachers in the United States (2005)

Purpose The purpose of this study was to examine the effects of gender on the job satisfaction of US academics. Design/methodology/approach The population for this study consisted of full‐time college and university teachers listed in the “Brain Track University Index Directories of the United States Colleges and Universities”. A sampling technique was used to select the respondents surveyed for this study. A total of 1,100 questionnaires were administered to respondents chosen from 80 universities. A total of 560 usable questionnaires were returned, giving a response rate of 51 percent. Findings The findings of this research show that there are gender differences apparent in the job satisfaction levels of university teachers surveyed for this study. Female faculty were more satisfied with their work and co‐workers, whereas, their male colleagues were more satisfied with their pay, promotions, supervision, and overall job satisfaction. Results also indicated that ranks were significant in explaining gender differences and job satisfaction of the respondents. Research limitations/implications This research is delimited to 4 year colleges and universities. Thus, the results of this study cannot be generalized to 2 year and community colleges. Practical implications Findings of the study provides institutional leaders, university and college administrators, and human resources professionals with key information that would enable them to recruit, reward, promote, and retain women faculty. The finding would also enable the government address the issues concerning female academics. Originality/value This paper offers practical recommendations to higher education administrators and human resources professionals on how to enhance job satisfaction of female faculty. It also offers suggestions to how to maintain more balanced gender equity in higher education.
Nanoparticle-Based Bio-Barcode Assay Redefines “Undetectable” PSA and Biochemical Recurrence after Radical Prostatectomy* (2020)

Carcinoma of the prostate (CaP) is the most common noncutaneous malignancy among American men and is the second leading cause of cancer death in the United States. In addition to assay improvements, we also sought to determine whether the bio-barcode assay would provide information beyond that of current commercial prostate-specific antigen (PSA) assays in the context of clinical PSA detection. The bio-barcode PSA assay and assay calibration were developed in human female serum. All patient sample data obtained using the bio-barcode assay are provided and compared with values generated using the commercial assays. The use of human female serum in our calibration curves enabled us to optimize the bio-barcode assay in a “blank” matrix similar to that of the unknown patient samples but lacking detectable PSA, and also ensured the stability of all assay components before running patient serum samples. Biochemical CaP recurrence is common after radical prostatectomy, and is often followed by clinical recurrence, metastatic disease, morbidity, and death from CaP.
A novel time spreading method for down-link OFDM-code division multiplexing systems (2005)

Orthogonal frequency division multiplexing code division multiplexing (OFDM-CDM) using a novel time spreading scheme is proposed as an alternative to multicarrier code division multiple access (MC-CDMA) systems. A residual frequency diversity gain can he fully obtained with OFDM-CDM through the adaptation of the proposed time spreading scheme which has a known frequency-hopping pattern over the whole transmission bandwidth. If there is enough frequency space to hop and the space is larger than the coherent bandwidth of the channel, we can exploit full frequency diversity in any channel environment. Simulation results verify that the proposed method achieves a gain of about 4 dB for BER of 10/sup -3/ compared to the conventional OFDM-CDM, which achieves a similar performance as frequency-interleaved MC-CDMA.
THE PRINCE CONSORT AND THE ‘GREAT’ C MAJOR: A DUBIOUS SCENARIO EXAMINED (1993)

Journal Article THE PRINCE CONSORT AND THE ‘GREAT’ C MAJOR: A DUBIOUS SCENARIO EXAMINED Get access JOHN REED JOHN REED Search for other works by this author on: Oxford Academic Google Scholar Music and Letters, Volume 74, Issue 4, November 1993, Pages 558–561, https://doi.org/10.1093/ml/74.4.558 Published: 01 November 1993
Hydrogen Charging Methods for Simulating Hydrogen Entry from Actual Environments (2020)

Researches on appropriate hydrogen charging methods for simulating hydrogen absorption in low alloy steels, stainless steels and high Ni alloy, from actual environments were overviewed. Both absorbed hydrogen concentrations and hydrogen desorption profiles were compared between various hydrogen charging conditions using thermal desorption analysis (TDA) on hydrogen-charged samples. For low alloy steels, immersion or cathodic hydrogen charging in aqueous solutions were appropriate for simulating hydrogen absorption from atmospheric corrosion or high pressure gaseous hydrogen environments. Absorbed hydrogen concentration could be controlled by adding appropriate amount of hydrogen-promoter or adjusting cathodic current density and applied potential in aqueous solutions. Comparisons in TDA profiles showed that the ratio of strongly-trapped hydrogen and weakly-trapped hydrogen changed depending upon the total amount of absorbed hydrogen. This result means the state of hydrogen in steels can change according to the amount of absorbed hydrogen. For stainless steels or high Ni alloy, cathodic hydrogen charging in aqueous solutions was appropriate for simulating high pressure gaseous hydrogen environments or galvanic coupling conditions. TDA profiles apparently differed depending on hydrogen charging temperature or duration. However, numerical simulation indicated that these profiles were decided by initial hydrogen distribution in specimens, not by trapped hydrogen, contrary to low alloy steels.
High Quality Uniform SiC Epitaxy for Power Device Applications (2007)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Ultrasensitive Molecular Sensors Based on Real‐Time Impedance Spectroscopy in Solution‐Processed 2D Materials (Adv. Funct. Mater. 12/2022) (2022)

Ultrasensitive Molecular Sensors In article number 2106830, Nicholas R. Glavin and co-workers describe a real-time impedance spectroscopy approach, which enables ultrasensitive molecular sensors in solution processed 2D nanomaterials. Through bypassing traditionally dominant interflake interactions and selectively extracting intraflake doping effects, detection of NO2 vapor down to 1 ppb is readily achievable with an ultimate limit of detection approaching 63 ppt. Image by Dr. Jo Richers (www.jorichers.com).
Salvage of Pseudoarthrosis After Tibiotalar Arthrodesis (1997)

We retrospectively reviewed the treatment of a selected group of 23 patients with pseudoarthrosis after ankle arthrodesis who underwent revision arthrodesis at an average of 1.7 years (range, 0.3-17.0 years) after the initial, unsuccessful procedure. Fourteen patients underwent isolated revision tibiotalar arthrodesis, and 9 had an additional hindfoot arthrodesis (7 tibiotalocalcaneal, 2 pantalar) performed at the time of the procedure. Rigid internal fixation with screws was performed when possible, and, in patients with poor bone quality, an external fixator was used. Autogenous bone grafting was used in 14 patients where bone loss was present. Twenty-one of 23 patients had successful union (average, 14 weeks; range, 6-48 weeks). Two patients underwent successful arthrodesis but had persistent pain from reflex sympathetic dystrophy. Overall, 19 of 23 patients were satisfied with the surgery. We conclude that revision arthrodesis for tibiotalar pseudoarthrosis is a worthwhile procedure.
P4–254: The apolipoprotein E/Aβ interaction as a novel therapeutic target for Alzheimer's disease (2006)

The direct interaction between β–amyloid (Aβ) and apolipoprotein E (apoE) has been identified as an important factor regulating brain Aβ clearance, oligomerization and deposition. We have previously demonstrated that Aβ12–28P (a modified, non–fibrillogenic, non–toxic peptide corresponding to the apoE binding site on Aβ consisting of residues 12–28) can effectively inhibit apoE/Aβ binding (KI=11.37nM) and neutralizes the promoting effect of apoE on Aβ fibrillogenesis and toxicity in cell culture (Sadowski et al. AJP,2004;165:937). Modest BBB permeability and a serum half–life of 62.2min make Aβ12–28P suitable for in vivo studies. The effect of blocking the apoE/Aβ interaction in vivo as a potential novel therapeutic approach for AD was validated using transgenic (Tg) animal models. Aβ12–28P was administered to single APP Tg mice (from the age of 12 to 18months) and to double APP/PS1 Tg mice (from the age of 2 to 7months). Behavioral testing, quantification of parenchymal and vascular Aβ deposits, ELISA measurments of the total and the soluble Aβ levels, and the level of Aβ oligomers were used as outcome measures. Treatment of APP and APP/PS1 Tg animals with Aβ12–28P resulted in a significant reduction of Aβ parenchymal and vascular deposits. No signs of toxicity, including any autoimmune reaction or brain hemorrhages were noted. Treatment with Aβ12–28P prevented memory decline in APP Tg mice. There was a significant reduction in the absolute Aβ level measured in brain homogenate while the soluble Aβ fraction and the level of Aβ oligomers remained unchanged. This observation is important due to an existing concern that blocking the apoE/Aβ interaction could destabilize fibrillar Aβ assemblies, and/or impair apoE mediated Aβ clearance, resulting in increased brain levels of soluble Aβ and thus creating conditions favoring formation of toxic oligomers. Results of our in vivo studies validate the feasibility of blocking the apoE/Aβ interaction as a novel therapeutic approach for AD. Interference with the apoE/Aβ interaction has a net effect of favoring Aβ clearance over deposition and at the same time does not increase the level of toxic oligomers or the incidence of cerebral microhemorrhages.
Stereospecific binding of diastereomeric peptides to salmon sperm DNA (1976)

Studies of the interaction specificities of L-lysyl-L-phenylalaninamide (1) and the diastereomeric dipeptide amide, L-lysyl-D-phenylalaninamide (2), with salmon sperm DNA reveal distinct differences in the binding site of the aromatic ring of the phenylalanine residue. The results of 1H nuclear magnetic resonance (NMR), spin-lattice relaxation rates, viscometric, and flow dichroism studies indicate the aromatic ring of 1 is "partially" inserted between base pairs of DNA whereas the aromatic ring of 2 points outward toward the solution. The terminal L-lysyl residue presumably interacts stereospecifically with DNA helix thus dictating the positioning of the aromatic ring of the C-terminal phenylalanine residue. In the accompanying paper (E. J. Gabbay et al. (1976), Biochemistry, following paper in this issue), the interaction of several oligopeptide amides (containing the N-terminal L-Lys-L-Phe residue) with DNA is examined. The results are found to be consistent with stereospecific binding of the terminal L-lysyl residue, and in addition, the evidence suggests that oligopeptides may bind to DNA via a modified single-stranded beta-sheet structure which is wrapped around the nucleic acid helix in a manner similar to that described by M. H. F. Wilkins (1956), Cold Spring Harbor Symp. Quant. Biol. 21, 75).
Neuronal Damage after Ischemic Injury in the Middle Cerebral Arterial Territory: Deep Watershed versus Territorial Infarction at MR Perfusion and Spectroscopic Imaging (2003)

The different temporal patterns for stroke progression in TI and WI are associated with different evolutions of hemodynamics and neuronal injury.
Growth factor consumption and production in perfusion cultures of human bone marrow correlate with specific cell production. (1995)

Perfusion cultures of human bone marrow mononuclear cells (BMMNC) provide a unique in vitro model of hematopoiesis, supporting growth of both accessory and hematopoietic elements. In this study, bioreactors were used to analyze the consumption and production of growth factors (GFs) in relation to each other and to the cells produced. The exogenously added GFs interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), and erythropoietin (Epo) each exhibited different, but reproducible, consumption kinetics. Epo and IL-3 were consumed slowly for the first 5-7 days, and then the consumption rate of both increased. Epo consumption reached a plateau by day 10, whereas IL-3 consumption continued to increase. Consumption of SCF was similar to that of Epo, but began 2-3 days earlier. GM-CSF was consumed throughout the culture period in an accelerating manner. Consumption of SCF and Epo were related, because omission of Epo from the growth medium reduced SCF consumption by 53% and omission of SCF reduced Epo consumption by 82%. A reproducible relationship between cumulative GF consumption and total cell production was observed. Epo was most potent, with 5900 molecules consumed per cell produced, whereas 69,400 molecules of SCF were consumed per cell generated. More specifically, Epo consumption was correlated (r = 0.92 and 0.96) with the number of glycophorin A-positive (glyA+) cells produced, and the rate of Epo consumption varied with the progression of cells through the erythroid lineage. Consequently, measurement of GF consumption rates may be useful for quantifying the types of cells present in a culture. Endogenous GF production was also examined. G-CSF and MIP-1 alpha were present at high levels during the first 4 days but then declined rapidly. LIF first appeared in the second week and steadily increased thereafter. Omission of SCF from the medium allowed the detection of endogenous SCF production, and the kinetics was similar to that of LIF. IL-6 production was biphasic, with a peak and decline in week 1 and an increase during week 2. TGF-beta was below the level of detection in these cultures. The results suggest that perfusion supports accessory and hematopoietic elements which interact and therefore represent a partially functional tissue ex vivo. This system provides a useful model for studying relationships within GF networks and for elucidating the conditions that result in primitive cell expansion ex vivo.
Histoire démographique des ancêtres de la population malgache actuelle à partir des données génétiques (2021)

Bien que situé à 400 km de l’Afrique, les habitants de Mada­gascar partagent des caractéristiques linguistiques, culturelles et génétiques avec des populations d’Indonésie et de la côte Est d’Afrique. Il a été montré que la population malgache est issue d’un mélange entre des populations bantu et austronésienne pendant le dernier millenium. Néanmoins, l’histoire du peuplement de l’île par les ancêtres de la population malgache actuelle reste encore incomplet et confus. Ici, nous cherchons à e...
Ataxin-2 Regulates RGS8 Translation in a New BAC-SCA2 Transgenic Mouse Model (2015)

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder with progressive degeneration of cerebellar Purkinje cells (PCs) and other neurons caused by expansion of a glutamine (Q) tract in the ATXN2 protein. We generated BAC transgenic lines in which the full-length human ATXN2 gene was transcribed using its endogenous regulatory machinery. Mice with the ATXN2 BAC transgene with an expanded CAG repeat (BAC-Q72) developed a progressive cellular and motor phenotype, whereas BAC mice expressing wild-type human ATXN2 (BAC-Q22) were indistinguishable from control mice. Expression analysis of laser-capture microdissected (LCM) fractions and regional expression confirmed that the BAC transgene was expressed in PCs and in other neuronal groups such as granule cells (GCs) and neurons in deep cerebellar nuclei as well as in spinal cord. Transcriptome analysis by deep RNA-sequencing revealed that BAC-Q72 mice had progressive changes in steady-state levels of specific mRNAs including Rgs8, one of the earliest down-regulated transcripts in the Pcp2-ATXN2[Q127] mouse line. Consistent with LCM analysis, transcriptome changes analyzed by deep RNA-sequencing were not restricted to PCs, but were also seen in transcripts enriched in GCs such as Neurod1. BAC-Q72, but not BAC-Q22 mice had reduced Rgs8 mRNA levels and even more severely reduced steady-state protein levels. Using RNA immunoprecipitation we showed that ATXN2 interacted selectively with RGS8 mRNA. This interaction was impaired when ATXN2 harbored an expanded polyglutamine. Mutant ATXN2 also reduced RGS8 expression in an in vitro coupled translation assay when compared with equal expression of wild-type ATXN2-Q22. Reduced abundance of Rgs8 in Pcp2-ATXN2[Q127] and BAC-Q72 mice supports our observations of a hyper-excitable mGluR1-ITPR1 signaling axis in SCA2, as RGS proteins are linked to attenuating mGluR1 signaling.
The potential of circulating tumor DNA (ctDNA) to guide adjuvant chemotherapy decision making in locally advanced rectal cancer (LARC). (2017)

3521 Background: The optimal approach to adjuvant chemotherapy for rectal cancer is keenly debated. Routine practice and clinical guidelines vary widely. After pre-operative chemoradiation (CRT), a pathologic complete response (pCR) or nodal involvement (pN+) are prognostic markers that can guide clinical decision-making, but markers that better define the patients (pts) that are likely or unlikely to benefit from chemotherapy are urgently needed. We investigated the potential role of ctDNA as a biomarker to guide therapy. Methods: We conducted a prospective, multi-centre study in pts with LARC (T3/T4 and/or N+) planned for CRT and curative resection. Serial plasma samples were collected pre-CRT, post-CRT, and 4-10 weeks after surgery. Somatic mutations in individual pts’ tumor were identified via sequencing of 15 genes commonly mutated in colorectal cancers. We then designed personalized assays to quantify ctDNA in plasma samples. Pts received adjuvant therapy at clinician discretion. Results: 200 pts were enrolled between Apr-2012 and Dec-2015. Median age was 62 years (range 28-86), 67% were male and 159 pts had pre-CRT and post-op ctDNA samples available for analysis. Of these, 122 (77%) pts had detectable ctDNA prior to therapy. After surgery, 19 pts had detectable ctDNA and 11 of these 19 (58%) have recurred during a median follow up of 22 months. Recurrence occurred in only 12 of 140 (8.6%) with negative ctDNA (HR 12, p &lt; 0.001). One hundred and two (64%) pts received adjuvant chemotherapy. Post-op ctDNA detection was predictive of recurrence irrespective of adjuvant chemotherapy (chemo: HR 10, p &lt; 0.001; no chemo: HR 16, p &lt; 0.001). Thirty-four pts (21%) achieved a pCR, 43 (27%) had pN+ disease. pCR (vs non-pCR) was associated with a trend for lower recurrence risk (HR 0.31, p = 0.089) and pN+ (vs pN0) with a higher recurrence risk (HR 4.2, p &lt; 0.001). ctDNA detection remained predictive of recurrence among pts with a pCR (HR 14, p = 0.014) or with pN+ disease (HR 11, p &lt; 0.001). Conclusions: Post-op ctDNA analysis stratifies pts with LARC into very high and low risk groups. ctDNA analysis remains strongly predictive of recurrence among pts with both lower risk (pCR) and higher risk (pN+) disease.