gebhart/patrepeval huggingface dataset:
Structure and expression of the human FHIT gene in normal and tumor cells. (1997)

The FHIT gene, encoded by 10 exons in a 1.1-kb transcript, encompasses approximately 1 Mb of genomic DNA, which includes the hereditary RCC t(3;8) translocation break at 3p14.2, the FRA3B common fragile region, and homozygous deletions in various cancer-derived cell lines. Because some of these genetic landmarks (e.g., the t(3;8) break between untranslated FHIT exons 3 and 4, a major fragile region that includes a viral integration site between exons 4 and 5, and cancer cell homozygous deletions in intron 5) do not necessarily affect coding exons and yet apparently affect expression of the gene product, we examined the FHIT locus and its expression in detail in more than 10 tumor-derived cell lines to clarify mechanisms underlying aberrant expression. We observed some cell lines with apparently continuous large homozygous deletions, which included one or more coding exons; cell lines with discontinuous deletions, some of which included or excluded coding exons; and cell lines that exhibited heterozygous and/or homozygous deletions, by Southern blot analysis for the presence of specific exons. Most of the cell lines that exhibited genomic alterations showed alteration of FHIT transcripts and absence or diminution of Fhit protein.
Performance Characteristics of the Vidas SARS-CoV-2 IgM and IgG Serological Assays (2021)

The COVID-19 pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread worldwide. Serological testing for SARS-CoV-2-specific antibodies plays an important role in understanding and controlling the pandemic, notably through epidemiological surveillance.
Movement Disorders in Autosomal Dominant Spinocerebellar Ataxias: A Prospective Multicenter NIH Cohort Study (S43.001) (2013)

OBJECTIVE: To prospectively characterize the type of extra-cerebellar movement disorders and their determinants in a large cohort of spinocerebellar ataxia (SCA) subjects.
mRNA stability influences the temporal order of inflammatory gene induction (136.1) (2009)

Abstract The inflammatory response is regulated by a great number of genes. It is still unknown whether and how these genes are organized to function as groups. We have performed a global analysis of about 200 genes induced in cultured cells by TNF, a proinflammatory cytokine. We found that genes can be divided roughly into three groups with different induction kinetics. Group I genes are activated quickly but then quickly repressed. Group II genes are also activated rapidly but reach maximal activity later and remain at the induced level longer. The Group III genes are activated in a delayed, slow but steady manner. The activation pattern of a gene remains largely the same in different cell types and species and is not specified by the extracellular signals. In addition, some genes within the same group have similar related functions. This suggests that these genes are temporally organized to function as groups. While transcriptional regulation is important, we found that a key parameter characterizing the grouping of genes is the stability of their mRNAs. The early mRNAs are very unstable, while the late mRNAs are highly stable. The instability of mRNAs correlates with the number of AU-rich elements in their 3’-untranslated regions (3’UTR). Changing mRNA stability either through extracellular LPS treatment or by switching the 3’UTRs but not the promoter/enhancer regions that control expression of GFP transgenes resulted in corresponding changes of the gene activation kinetics. These show that the inflammatory response is pre-set at the genome level and that the 3’UTR of a gene is a key element for organizing genes into functional groups.
Data from An Immune Response Enriched 72-Gene Prognostic Profile for Early-Stage Non–Small-Cell Lung Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Current staging methods are imprecise for predicting prognosis of early-stage non–small-cell lung cancer (NSCLC). We aimed to develop a gene expression profile for stage I and stage II NSCLC, allowing identification of patients with a high risk of disease recurrence within 2 to 3 years after initial diagnosis.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We used whole-genome gene expression microarrays to analyze frozen tumor samples from 172 NSCLC patients (pT1-2, N0-1, M0) from five European institutions, who had undergone complete surgical resection. Median follow-up was 89 months (range, 1.2-389) and 64 patients developed a recurrence. A random two thirds of the samples were assigned as the training cohort with the remaining samples set aside for independent validation. Cox proportional hazards models were used to evaluate the association between expression levels of individual genes and patient recurrence-free survival. A nearest mean analysis was used to develop a gene-expression classifier for disease recurrence.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; We have developed a 72-gene expression prognostic NSCLC classifier. Based on the classifier score, patients were classified as either high or low risk of disease recurrence. Patients classified as low risk showed a significantly better recurrence-free survival both in the training set (&lt;i&gt;P&lt;/i&gt; &lt; 0.001; &lt;i&gt;n&lt;/i&gt; = 103) and in the independent validation set (&lt;i&gt;P&lt;/i&gt; &lt; 0.01; &lt;i&gt;n&lt;/i&gt; = 69). Genes in our prognostic signature were strongly enriched for genes associated with immune response.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our 72-gene signature is closely associated with recurrence-free and overall survival in early-stage NSCLC patients and may become a tool for patient selection for adjuvant therapy.&lt;/p&gt;&lt;/div&gt;
Varying surface hydrophobicities of coatings made of recombinant spider silk proteins (2012)

The engineered spider silk protein eADF4(C16) reveals similarities to amphiphilic block copolymers. Drop cast of protein solutions on different hydrophobic as well as hydrophilic templates out of different starting solvents (hexafluoroisopropanol, formic acid and aqueous buffers) generated silk films varying in structure and surface properties. Here, the underlying secondary structure of the proteins, the mechanical integrity at increased temperatures, homogeneity and surface topography of silk films, as well as the wettability were investigated in detail. Interestingly, the used templates had impact on microphase separation of the silk molecules as seen by the content of β-sheet structures; as well as on silk film surface hydrophobicities.
Hierarchical control of the DC microgrid with improved reliability (2017)

DC Microgrid takes an important role in the use of renewable energy inside houses or rural areas since the penetration of DC sources and the increase of DC loads. However, there are reliability issues in abnormal situations because the protections used in DC components are very slow in their response which can cause the blackout of the system. Normally, DC microgrids are controlled using a three-level hierarchical control, being the secondary level the responsible of the DC bus regulation through the elements connected. To manage difference power in the DC bus, the DC microgrid generator and storage elements must respond delivering or consuming that power but when this difference is higher/lower than the limits of the system, it can not be achieved. In this work, a load control is proposed for a DC microgrid which allows increasing the number of the agents involved in the DC bus regulation and improving the reliability of the system. A simulation is implemented in MATLAB/SIMULINK which shows the dynamical responses of the elements in a real operation for a day. The simulation results show a good response when the load power consumption is greater than the generated energy, making the load disconnect and connected once the DC bus regulation reaches the reference value.
Circadian variation of metabotropic glutamate receptor 5 availability in the rat brain (2016)

The metabotrophic subtype 5 glutamate receptor (mGluR5) plays a critical role in synaptic plasticity besides its involvement in numerous neurological disorders, such as depression. As mGluR5 availability in humans is altered in sleep deprivation, we hypothesized that mGluR5 availability underlies a circadian variation. To investigate whether mGluR5 underlies potential circadian changes we measured its density in a randomized fashion at six different daytimes in 11 adult Sprague-Dawley rats. mGluR5 density was quantified by positron emission tomography (PET) using the radioactive ligand [<sup>11</sup> C]ABP688. [<sup>11</sup> C]ABP688 uptake was quantified in nine regions of interest with a reference tissue model. Significant differences in the binding potential (BP<sub>ND</sub> ) and therefore mGluR5 availability between the different circadian times were found in cortex, cingulate cortex, amygdala, caudate putamen and nucleus accumbens. Further post-hoc statistical analysis (Tukey-Kramer test) of the different time-points revealed significant changes in BP<sub>ND</sub> between 07:00 hours (start of light-on phase) and 15:00 hours (last time-point of the light-on phase) in the caudate putamen. This study shows that mGluR5 availability is increased during the light-on, or sleep phase, of rodents by approximately 10%. Given that altered mGluR5 densities play a role in psychiatric disorders, further investigation is warranted to evaluate their circadian involvement in mood changes in humans.
[Immune response to HBsAg, HBcAg and e-antigen in patients with acute hepatitis and HBsAg carriers with and without liver diseases]. (1976)

Humoral and/or cell-mediated (CMI) immune responses to HBAg components, human and rabbit liver specific proteins (HLP and RLP) and tuberculin were tested in patients with acute virus B and non-B-hepatitis, asymptomatic HBsAg carriers and HBsAg positive chronic active hepatitis (CAH). Furthermore, the presence of HBsAg, HBcAg and/or "e"-antigen has been studied in patients with sera and/or liver tissue. Asymptomatic HBsAg carriers are characterized by a status of immunological tolerance against HBsAg. HBcAg in liver nuclei could not be detected. All sera were positive for anti-HBc, some had anti "e". - Patients with uneventful acute virus-B-hepatitis developed CMI against HBsAg 4-6 weeks and anti-HBs 4-6 months after onset of the disease. Acute virus hepatitis without detectable HBsAg are defined as non-B-hepatitis by negative humoral and cell-mediated immune reaction against HBsAg 1-12 months after onset of the disease. - Patients with type B chronic active hepatitis are characterized by inadequate CMI against HBsAg without immune elimination of virus and virusantigens. Acute and chronic type-B-hepatitis showed temporary or constant CMI against HLP. These findings suggest an alteration or a carrier function of membrane antigens of virus infected hepatocytes or an induction of new membrane antigens by a virus. The results indicate that recovery from type B-hepatitis is associated with the ability to elicit a specific immune response to HBsAg. Furthermore immune responses to virus, virus antigens and virusinfected hepatocytes seemed to be the pathogenic principle of virus induced acute and chronic liver diseases.
On the Use of 5-Hole Probes in the Testing of Industrial Centrifugal Compressors (2004)

This paper addresses the use of 5-hole probes in the testing of industrial centrifugal compressors. The 5-hole probes utilized for this work are of the conical-tip type and were used in a non-nulling configuration (i.e. the probes do not need to be rotated or moved in any way during the tests). These 5-hole probes proved to be fairly robust, making them practical for a non-laboratory setting such as an industrial multistage compressor test stand. A discussion of 5-hole probes and how they function is provided, including an overview of the mathematical formulations and calibrations required to translate the pressure data gathered from the 5 holes into static and total pressures, velocities and flow angles. A method to transform these variables from a probe-based coordinate system to a machine-based coordinate system is also presented and schematics of this process are provided to aid the reader’s understanding. The testing performed on a prototype multistage centrifugal compressor using 5-hole probes is also discussed showing that the probes provided valuable insight into the flowfield exiting the impellers and at the return bend. The hub-to-shroud velocity profile exiting an impeller was found to be more skewed than expected and was contributing to poor performance in the downstream stationary components. The measured flowfield from one of the tests is also compared against 3-D CFD results and comments are offered regarding the agreement between the analytical and measured results. Advantages and disadvantages of 5-hole probes as compared to more conventional instrumentation are presented. Finally, conclusions are drawn regarding the value of 5-hole probe data in the development and/or troubleshooting of high performance turbomachinery and in the validation / calibration of design and analysis tools.
Ion voltage diagnostics in the far-field plume of a high-specific impulse Hall thruster (2003)

The effects of the magnetic field and discharge voltage on the far-field plume of the NASA 173Mv2 laboratory-model Hall thruster were investigated. A cylindrical Langmuir probe was used to measure the plasma potential and a retarding potential analyzer was employed to measure the ion voltage distribution. The plasma potential was affected by relatively small changes in the external magnetic field, which suggested a means to control the plasma surrounding the thruster. As the discharge voltage increased, the ion voltage distribution showed that the acceleration efficiency increased and the dispersion efficiency decreased. This implied that the ionization zone was growing axially and moving closer to the anode, which could have affected thruster efficiency and lifetime due to higher wall losses. However, wall losses may have been reduced by improved focusing efficiency since the total efficiency increased and the plume divergence decreased with discharge voltage.
Acaricide toxicity and resistance in larvae of different strains of Tetranychus urticae and Panonychus ulmi (Acari: Tetranychidae) (2001)

The toxicities of eight structurally different acaricidal compounds to six-legged larvae (first motile stage) of three laboratory strains of the two-spotted spider mite, Tetranychus uritcae, and the European red mite, Panonychus ulmi, were evaluated following spray application. The larvae of five field-derived strains of T urticae originating from France, Italy, Brazil, California and Florida were also tested for their susceptibilities to discriminating concentrations of several acaricides resulting in 95% mortality when applied to the organophosphate-resistant laboratory reference strain WI. The spray bioassay used was robust and gave repeatable results with a wide range of acaricidal compounds, irrespective of their mode of action (ovo-larvicides or primarily acting on motile life stages). Compounds tested were abamectin, azocyclotin, chlorpyrifos, clofentezine, deltamethrin, fenpyroximate, hexythiazox and pyridaben. Larvae of one of the laboratory strains of T urticae, AK, originally collected in Japan in 1996 and maintained without further selection pressure, exhibited 2000- and > 4000-fold resistance to the mitochondrial electron transport inhibitors pyridaben and fenpyroximate, respectively. Another strain of T urticae, AU, obtained from Australia and maintained in the laboratory under selection with hexythiazox and clofentezine since 1987 showed > 770- and > 1000-fold resistance to clofentezine and hexythiazox, respectively. The same resistance pattern was observed against larvae of a laboratory strain of P ulmi, CE, also selected with hexythiazox. Larvae of one of the field-derived strains of T urticae, BR, showed a lower susceptibility to a number of compounds, whilst the others were susceptible to all compounds except the organophosphates.
Optimization of a Series of Triazole Containing Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors and the Discovery of CC-115 (2015)

We report here the synthesis and structure-activity relationship (SAR) of a novel series of triazole containing mammalian target of rapamycin (mTOR) kinase inhibitors. SAR studies examining the potency, selectivity, and PK parameters for a series of triazole containing 4,6- or 1,7-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones resulted in the identification of triazole containing mTOR kinase inhibitors with improved PK properties. Potent compounds from this series were found to block both mTORC1(pS6) and mTORC2(pAktS473) signaling in PC-3 cancer cells, in vitro and in vivo. When assessed in efficacy models, analogs exhibited dose-dependent efficacy in tumor xenograft models. This work resulted in the selection of CC-115 for clinical development.
A Review of the Clinical Indications for the Plasma Heparin Assay (1993)

The basis for the clinical indications for the use of the plasma heparin assay for anticoagulation control are reviewed, and alternatives for currently used laboratory methods of monitoring heparin therapy in selected clinical situations are recommended. Many literature references support the role of plasma heparin assay with combined heparin and warfarin therapy, with combined heparin and recombinant tissue plasminogen activator therapy, in situations in which heparin resistance is noticed in the presence of a circulating anticoagulant, and in patients receiving heparin in an unrecognized manner, as well as with the use of the low molecular weight heparins. For now, however, in the absence of any prospective clinical trials establishing the superiority of the plasma heparin assay compared with the APTT, the recommendations outlined are presented as guidelines for the more specific monitoring of heparin therapy using currently available techniques.
Reduction in hospitalisations with dupilumab in Japanese adults with atopic dermatitis in a real‐world setting (2023)

Abstract Background In a recent post hoc analysis of multinational clinical trial data, dupilumab treatment for patients with moderate or severe atopic dermatitis (AD) reduced all‐cause and AD‐related hospitalisations. Objectives We studied the impact of dupilumab on health care resource utilisation (HCRU) and AD medication by comparing use during the 6 months either side of starting dupilumab (index) in a real‐world setting. Methods This observational, retrospective, cohort study used Japanese hospital claims data (1 April 2018 to 28 February 2019). A total of 357 patients (mean [range] age 45 [15–92] years; 65.5% male) with ≥1 AD diagnosis and ≥1 dupilumab prescription were included. Outcome variables included AD treatments and HCRU during the 6 months pre‐ and post‐index. Results The number of all‐cause hospitalisations decreased by 43.1% (from 51 in the 6 months before to 29 in the 6 months after dupilumab initiation), with a 96.0% reduction in skin/subcutaneous tissue disease‐related hospitalisations (25 to 1). Use of nonsteroidal systemic immunosuppressants, phototherapy and systemic corticosteroids decreased (by 59.8%, 59.5% and 30.6%, respectively) after dupilumab initiation. At 180 days after dupilumab initiation, 86.8% of patients were still taking dupilumab. Conclusions Overall, these results suggest that dupilumab can reduce skin/soft tissue‐related hospitalisations and use of various other AD medications in a real‐world setting.
An all-fibre-optic Fourier transform spectrometer (1996)

A novel fibre-optic Fourier transform spectrometer was constructed. The optical retardation between the arms of a Mach - Zehnder-type interferometer made of single-mode optical fibre is modulated by variation of the fibre temperature. Spectra of a multimode laser diode and a broad-band light source were recorded. Frequency shifts within the observed spectra can be explained with the frequency dispersion of the coefficient of the dependence of the refractive index on temperature, . An oversampling scheme utilizing a phase-locked loop circuit was successfully tested. This allows for the acquisition of spectra with shorter wavelength components than the wavelength of the reference laser if a fibre with sufficiently low cut-off wavelength is employed. Thus, the accessible wavelength region may be extended to the near UV using a conventional silica fibre. Coherent averaging of multiple interferograms was successfully applied to enhance the signal-to-noise ratio of interferograms.
Central Composite Experimental Design Applied to the Catalytic Carbon-Sulfur Bond Formation by Fluorapatite Catalyst (2013)

The aim of this study was to apply experimental design in the optimization of the thia-Michael addition reaction between chalcone derivatives and mercaptans catalyzed by Fluorapatite catalyst (FAP). The central composite design was used to design an experimental program to provide data to model the effects of various factors on reaction yield (Y). The variables chosen were catalyst weight (X1), reaction time (X2) and solvent volume (X3). The mathematical relationship of reaction yield on the three significant independent variables can be approximated by a nonlinear polynomial model. Predicted values were found to be in good agreement with experimental values. The optimum reaction conditions (x1= 350 mg, x2= 30 min and x3= 2 mL) for reaction model (chalcone and thiophenol) obtained by response surface were applied to other substrates. This study has shown that central composite design could efficiently be applied for the modeling of catalytic carbon-sulfur bond formation by FAP catalyst under mild reaction condition with high yield, and it is an economical way of obtaining the maximum amount of information with the fewest number of experiments.
Tear miRNAs identified in a murine model of Sjögren’s Syndrome as potential diagnostic biomarkers and indicators of disease mechanism (2021)

ABSTRACT Objective The tear miRNAome of the male NOD mouse, a model of ocular symptoms of Sjögren’s syndrome (SS), was analyzed to identify possible tear biomarkers of the disease. Methods Male NOD mice, aged 12-14 weeks, were used to identify tear miRNAs associated with development of autoimmune dacryoadenitis. Age-matched female NOD mice that do not develop the autoimmune dacryoadenitis characteristic of SS were used as negative controls while age- and sex-matched male BALB/c mice served as healthy controls. Total RNA was isolated from stimulated tears pooled from 5 mice per sample and tear miRNAs were sequenced and analyzed. Putative miRNA hits were validated using RT-qPCR in a separate mouse cohort, and the pathways influenced by the validated hits were identified using Ingenuity Pathway Analysis. Results In comparison to tears from both healthy (male BALB/c) and negative control (female NOD) mice, initial analysis identified 7 upregulated and 7 downregulated miRNAs in male NOD mouse tears. Of these, 8 were subsequently validated by RT-qPCR in tears from additional mouse cohorts. miRNAs previously implicated in SS pathology included mmu-miR-146a/b-5p, which were significantly downregulated in the male NOD mouse tears, as well as mmu-miR-150-5p and mmu-miR-181a-5p, which were upregulated in the male NOD mouse tears. All other validated hits including the upregulated miR-181b-5p and mmu-miR-203-3p, as well as the downregulated mmu-miR-322-5p and mmu-miR-503-5p, represent novel putative indicators of autoimmune dacryoadenitis in SS. Conclusions A panel of differentially expressed miRNAs were identified in tears of SS model male NOD mice, including some never previously linked to SS. These may have potential utility as diagnostic biomarkers for ocular symptoms of SS; evaluation of the pathways influenced by these dysregulated miRNAs may also provide further insights into SS pathogenesis.