gebhart/patrepeval huggingface dataset:
Three-dimensional genome architecture and emerging technologies: looping in disease (2017)

Genome compaction is a universal feature of cells and has emerged as a global regulator of gene expression. Compaction is maintained by a multitude of architectural proteins, long non-coding RNAs (lncRNAs), and regulatory DNA. Each component comprises interlinked regulatory circuits that organize the genome in three-dimensional (3D) space to manage gene expression. In this review, we update the current state of 3D genome catalogues and focus on how recent technological advances in 3D genomics are leading to an enhanced understanding of disease mechanisms. We highlight the use of genome-wide chromatin conformation capture (Hi-C) coupled with oligonucleotide capture technology (capture Hi-C) to map interactions between gene promoters and distal regulatory elements such as enhancers that are enriched for disease variants from genome-wide association studies (GWASs). We discuss how aberrations in architectural units are associated with various pathological outcomes, and explore how recent advances in genome and epigenome editing show great promise for a systematic understanding of complex genetic disorders. Our growing understanding of 3D genome architecture-coupled with the ability to engineer changes in it-may create novel therapeutic opportunities.
Upregulation of MCAM in primary bronchial epithelial cells from patients with COPD (2003)

An increasing body of evidence indicates that the bronchial epithelium plays a crucial role in the pathophysiology of chronic obstructive pulmonary disease (COPD). The aim of this study was to identify new genes whose bronchoepithelial expression is specifically altered in COPD patients. Primary bronchial epithelial cell (PBEC) cultures were established from exsmokers with stable airflow limitation and never smokers. Complementary deoxyribonucleic acid array technology was used to investigate the differential expression of 847 cytokine and cytokine-related genes between the two groups. Statistical analysis was performed by means of significance analysis of microarrays and Bonferroni-corrected analysis of variance on ranks. Discriminant analysis and light cycler measurements as well as flow cytometry and Western blotting were used to confirm the significance of the array results at both the messenger ribonucleic acid (mRNA) and protein expression levels. With respect to array experiments, melanoma cell adhesion molecule (MCAM) was identified as the sole gene showing highly significant upregulation in PBECs from COPD patients compared to never smokers. Light cycler measurements confirmed these results, revealing a 2.9-fold and 2.0-fold increase in MCAM mRNA expression in COPD patients compared to nonsmokers and smokers, respectively. In addition, these differences are associated with higher median protein expression levels. These results strongly suggest involvement of melanoma cell adhesion molecule in the pathophysiology of the chronic airway inflammation seen in patients with chronic obstructive pulmonary disease.
BCL8 , a novel gene involved in translocations affecting band 15q11–13 in diffuse large-cell lymphoma (1997)

Translocations affecting the chromosomal region 15q11-13 and various other partners are recurrent in diffuse large-cell lymphomas (DLCL). To identify the putative gene, here named BCL8, involved in these translocations we have cloned the breakpoint region from a DLCL patient with t(14;15)(q32;q11-13) and the corresponding germ-line region from chromosome 15. The genomic locus on chromosome 15 is clonally rearranged in about 4% of DLCL in agreement with the frequency of 15q11-13 translocations. A probe derived from the BCL8 locus on chromosome 15 detected a transcript in human testis and prostate, whereas no expression was found in spleen, thymus, and blood leukocytes. Analysis of the BCL8 cDNA clones isolated from human testis cDNA library showed that the BCL8 gene generates a major transcript of 2.6 kb and a less prominent 4.5-kb species due to differential polyadenylylation. By reverse transcription-PCR analysis of RNA extracted from frozen DLCL samples and lymphoma cell lines, BCL8 expression was detected in all patients carrying 15q11-13 abnormalities and in a fraction of randomly selected DLCL patients. These results suggest that the BCL8 gene is not normally expressed in lymphoid tissues, but its expression can be activated by chromosomal translocation or by other mechanisms in DLCL. Ectopic expression of BCL8 in a significant proportion of DLCL suggests an important role for this gene in the molecular pathogenesis of B cell lymphoma.
A self-similar model for sedimentary rocks with application to the dielectric constant of fused glass beads (1981)

Abstract We develop a theory for dielectric response of water-saturated rocks based on a realistic model of the pore space. The absence of a percolation threshold manifest in Archie’s law, porecasts, electron-micrographs, and general theories of formation of detrital sedimentary rocks indicates that the pore spaces within such rocks remain interconnected to very low values of the porosity ϕ. In the simplest geometric model for which the conducting paths remain interconnected, each grain is envisioned to be coated with water. The dielectric constant of the assembly of water-coated grains is obtained by a self-consistent effective medium theory. In the dc limit, this gives Maxwell's relation for conductivity σ of the rock σ = 2σωφ/(3 − φ), where σω is the conductivity of water. In order to include the local environmental effects around a grain, a self-similar model is generated by envisioning that each rock grain itself is coated with a skin made of other coated spheres; the coating at each level consists of other coated spheres. The self-consistent complex dielectric constant ɛ* is given in this model in terms of that of water ɛω* and of rock ɛm*, by [(ɛm*−ɛ*)/(ɛm*−ɛω*)][ɛω*/ɛ*]1/3=φ for spherical particles. This gives, in the dc limit, σ = σωφ3/2. For nonspherical particles, the exponent m in Archie's law σ = σωφm is greater than 3/2 for the plate-like grains or cylinders with axis perpendicular to the external field and smaller than 3/2 for plates or cylindrical particles with axis parallel to the external field. Artificial rocks with a wide range of porosities were made from glass beads. We present data on the glass bead rocks for dc conductivity and the dielectric constant at 1.1 GHz. The data follow the conductivity and the dielectric responses given by the self-similar model. The present theory fails to explain the salinity dependence of ɛ* at lower frequencies.
Immunogenicity of bone morphogenetic proteins (2009)

Although they occur in a subgroup of patients, the immune responses against rhBMPs have no correlation with any clinical outcome or safety parameter. Clinicians, however, must be aware of the potential complications caused by the immunogenicity of BMPs until more studies clearly elucidate their safety.
Absence of IFNA and IFNB genes from human malignant glioma cell lines and lack of correlation with cellular sensitivity to interferons. (1990)

We report that 5 of 19 human malignant glioma cell lines have neither interferon alpha (IFNA) nor interferon beta (IFNB) genes that are detectable by Southern blotting. Of 5 other of these malignant glioma lines that have a single IFNB gene copy, 3 lack the IFNA genes entirely and two have one copy. One of the lines that lacks the IFNA genes entirely but has one copy of the IFNB gene has a rearrangement near the IFNB gene that is most easily interpreted as an insertion of a large segment of DNA (at least 50 kilobases) the 3' end of which is less than 1.3 kilobases 5' to the known regulatory sequences of the IFNB gene. In spite of the rearrangement, IFNB-specific RNA is highly inducible in this line by poly(I)-poly(C). The ability of interferon alpha or interferon beta to inhibit cell growth does not depend upon the presence or absence of the respective gene. This finding adds solid tumors to those tumor cell lines (acute lymphocytic leukemia, chronic myelogeneous leukemia) previously determined to lack the IFNA and IFNB genes (Diaz et al., Proc. Natl. Acad. Sci. USA, 85:5259-5263, 1988).
Targeting Tumor Antigens to Secreted Membrane Vesicles In vivo Induces Efficient Antitumor Immune Responses (2008)

Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic cells). The modes of tumor antigen capture by dendritic cells in vivo remain unclear. Here we examine the immunogenicity of the same model antigen secreted by live tumors either in association with membrane vesicles (exosomes) or as a soluble protein. We have artificially addressed the antigen to secreted vesicles by coupling it to the factor VIII-like C1C2 domain of milk fat globule epidermal growth factor-factor VIII (MFG-E8)/lactadherin. We show that murine fibrosarcoma tumor cells that secrete vesicle-bound antigen grow slower than tumors that secrete soluble antigen in immunocompetent, but not in immunodeficient, host mice. This growth difference is due to the induction of a more potent antigen-specific antitumor immune response in vivo by the vesicle-bound than by the soluble antigen. Finally, in vivo secretion of the vesicle-bound antigen either by tumors or by vaccination with naked DNA protects against soluble antigen-secreting tumors. We conclude that the mode of secretion can determine the immunogenicity of tumor antigens and that manipulation of the mode of antigen secretion may be used to optimize antitumor vaccination protocols.
Therapeutic effect of surfactant protein D in allergic inflammation of mite‐sensitized mice (2005)

These results indicate that rfh SP-D has a therapeutic effect on allergen-induced bronchial inflammation, and that this might be because of its inhibitory effect on NO and TNF-alpha production by AMs, and it thus prevents the development of T-helper type 2 cytokine response.
The Effects of a Prolonged Running Exercise on Strength Characteristics (2000)

The aim of this study was to examine concentric, isometric, and eccentric strength reductions in the quadriceps muscle following a prolonged running exercise. Before and after a 2 h run (28.4+/-1.4 km) peak torque (PT) of the knee extensors at angular velocities of -120, -90, -60, 0, 60, 120, 180, 240 degrees x s(-1) using an isokinetic dynamometer, electromyographic (EMG) activity of the vastus lateralis (VL) and vastus medialis (VM) muscles and height of a counter movement jump were recorded in twelve well-trained triathletes. Counter movement jump performances decreased by 10% and PT values were all significantly lower (p < 0.01) at each angular velocity following the run. The torque loss was significantly (p < 0.01) greater under eccentric contractions (from 18 to 21%) than under concentric ones (from 11 to 14%). EMG activity (RMS) was lower in both VL and VM muscles after the 2 h run but no difference existed in RMS losses between concentric and eccentric contractions. The present results demonstrate that 1) a prolonged running exercise more greatly affects eccentric force production in the quadriceps muscle, and 2) this specificity seems to be due to an impairment of the muscular contractile mechanism rather than a modification to the neural input.
Tutorial: Loudspeaker Nonlinearities-Causes, Parameters, Symptoms (2006)

The relationship between nonlinear distortion measurements and nonlinearities is addressed-the physical causes for signal distortion in loudspeakers, headphones, microspeakers, and other transducers. Using simulation techniques characteristic symptoms are identified for each nonlinearity and presented systematically in a guide for loudspeaker diagnostics. This information is important for understanding the implications of nonlinear parameters and for performing measurements that describe the loudspeaker more comprehensively. Practical applications of the new technique are demonstrated on three different loudspeakers.
Synthesis of deoxyoligonucleotides on a polymer support (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of deoxyoligonucleotides on a polymer supportM. D. Matteucci and M. H. CaruthersCite this: J. Am. Chem. Soc. 1981, 103, 11, 3185–3191Publication Date (Print):June 1, 1981Publication History Published online1 May 2002Published inissue 1 June 1981https://pubs.acs.org/doi/10.1021/ja00401a041https://doi.org/10.1021/ja00401a041research-articleACS PublicationsRequest reuse permissionsArticle Views2670Altmetric-Citations718LEARN 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-Alertsclose Get e-Alerts
Grapefruit juice-felodipine interaction: reproducibility and characterization with the extended release drug formulation. (1995)

1. Felodipine 10 mg extended release was administered with 250 ml regular-strength grapefruit juice or water in a randomized crossover manner followed by a second grapefruit juice treatment in 12 healthy men. The pharmacokinetics of felodipine and primary oxidative metabolite, dehydrofelodipine, were evaluated. 2. Initial grapefruit juice treatment increased felodipine AUC (mean +/- s.d.; 56.6 +/- 21.9 vs 28.1 +/- 11.5 ng ml-1 h; P < 0.001) and Cmax (8.1 +/- 2.5 vs 3.3 +/- 1.2 ng ml-1; P < 0.001) compared with water. Felodipine tmax (median; 2.8 vs 3.0 h) and t1/2 (7.3 +/- 3.7 vs 6.9 +/- 3.6 h) were not altered. 3. Readministration of felodipine with grapefruit juice produced mean felodipine AUC (61.5 +/- 32.2 ng ml-1 h) and Cmax (8.4 +/- 4.8 ng ml-1) which were similar to the initial grapefruit juice treatment 1-3 weeks previously. Felodipine AUC (r = 0.73, P < 0.01) and Cmax (r = 0.69, P < 0.02) correlated between grapefruit juice treatments among individuals. 4. The % increase in felodipine AUC with the initial grapefruit juice treatment compared with water correlated with the % increase in felodipine Cmax among individuals (r = 0.80, P < 0.01). Dehydrofelodipine AUC (74.7 +/- 28.7 vs 48.5 +/- 16.3 ng ml-1 h; P < 0.01) and Cmax (12.1 +/- 2.9 vs 7.9 +/- 2.6 ng ml-1; P < 0.01) were augmented with grapefruit juice compared with water.(ABSTRACT TRUNCATED AT 250 WORDS)
Synthesis and Identification of Small Molecules that Potently Induce Apoptosis in Melanoma Cells through G1 Cell Cycle Arrest (2005)

Late-stage malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients with such a diagnosis is 6 months. In general, the vast majority of anticancer drugs operate through induction of cell cycle arrest and cell death in either the DNA synthesis (S) or mitosis (M) phase of the cell cycle. Unfortunately, the same mechanisms that melanocytes possess to protect cells from DNA damage often confer resistance to drugs that derive their toxicity from S or M phase arrest. Described herein is the synthesis of a combinatorial library of potential proapoptotic agents and the subsequent identification of a class of small molecules (triphenylmethylamides, TPMAs) that arrest the growth of melanoma cells in the G1 phase of the cell cycle. Several of these TPMAs are quite potent inducers of apoptotic death in melanoma cell lines (IC(50) approximately 0.5 muM), and importantly, some TPMAs are comparatively nontoxic to normal cells isolated from the bone marrow of healthy donors. Furthermore, the TPMAs were found to dramatically reduce the level of active nuclear factor kappa-B (NFkappaB) in the cell; NFkappaB is known to be constitutively active in melanoma, and this activity is critical for the proliferation of melanoma cells and their evasion of apoptosis. Compounds that reduce the level of NFkappaB and arrest cells in the G1 phase of the cell cycle can provide insights into the biology of melanoma and may be effective antimelanoma agents.
Epidermal Differential Impedance Sensor for Conformal Skin Hydration Monitoring (2012)

We present the design and use of an ultrathin, stretchable sensor system capable of conformal lamination onto the skin, for precision measurement and spatial mapping of levels of hydration. This device, which we refer to as a class of 'epidermal electronics' due to its 'skin-like' construction and mode of intimate integration with the body, contains miniaturized arrays of impedance-measurement electrodes arranged in a differential configuration to compensate for common-mode disturbances. Experimental results obtained with different frequencies and sensor geometries demonstrate excellent precision and accuracy, as benchmarked against conventional, commercial devices. The reversible, non-invasive soft contact of this device with the skin makes its operation appealing for applications ranging from skin care, to athletic monitoring to health/wellness assessment.
Influence of nucleotide binding site occupancy on the thermal stability of the F1 portion of the chloroplast ATP synthase. (1993)

The irreversible thermal denaturation of the F1 portion of the chloroplast ATP synthase (CF1) was examined by differential scanning calorimetry, ATPase activity loss, and release of bound nucleotides. In nearly all cases, the loss of ATPase activity closely paralleled the temperature dependence of the excess heat capacity. Although the irreversible nature of the denaturation precluded thermodynamic interpretation, a kinetic analysis was feasible. A two-state kinetic model was found to fit the calorimetric data very well. The activation energies of thermal denaturation calculated from calorimetric data were very close to those determined from Arrhenius plots of the apparent first-order rate constants of loss of ATPase activity versus reciprocal of the temperature. The nucleotide binding site occupancy profoundly influenced the temperature at which thermal denaturation occurred. In particular, the temperature at which the maximum in excess heat capacity occurs (Tm) was increased about 8 degrees C by occupancy of tight, noncatalytic ATP binding sites and by an additional 3-4 degrees C by the presence of nucleotides in the medium during heating. The thermal denaturation of CF1, an enzyme composed of nine polypeptide chains, is highly cooperative in that it obeys the simple two-step kinetic model. Since the removal of the epsilon and delta subunits has little effect on thermal denaturation, the major forces that stabilize CF1 must, thus, be between the alpha, beta, and gamma subunits.
A high speed superscalar PA-RISC processor (2003)

A novel processor implementing Hewlett-Packard's PA-RISC 1.1 (precision architecture-reduced instruction set computer) has been designed. A single chip implemented in a 0.8- mu m three-level metal CMOS technology includes the integer processor and a floating point coprocessor. The design operates at 100 MHz and is the first superscalar PA-RISC design. The processor cache is a large configurable memory implemented with industry standard SRAMs (static RAMs). High performance is achieved by high-frequency operation and a variety of techniques used to reduce the average number of cycles per instruction.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Fibrinolysis greater than 3% is the critical value for initiation of antifibrinolytic therapy (2013)

Prognostic study, level III.
Characteristics of submicrometer gaps in buried-channel CCD structures (1991)

A planar-gate buried-channel charge-coupled-device (CCD) structure with deep submicrometer gaps was investigated. CCD test structures with gap widths from 0.15 to 0.45 mu m were fabricated using electron-beam lithography and reactive ion etching. Typical measured gap leakage currents were on the order of 0.3 pA/mm gap lengths for all gap widths. Potential wells, not barriers, were detected in the channel under the gaps. Measured potential well depths ranged from 0.15 to 1.0 V for gap widths from 0.15 to 0.45 mu m, respectively. The wells could be eliminated by applying a 1- to 4-V potential difference on adjacent electrodes for the above gap width range. Measured well depths correlate well with two-dimensional device simulation data. These results indicate that the planar-gate CCD is a viable structure for efficient charge transfer, especially for direct imaging applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Ancient mariner Sails Again: Transposition of the Human Hsmar1 Element by a Reconstructed Transposase and Activities of the SETMAR Protein on Transposon Ends (2007)

Hsmar1, one of the two subfamilies of mariner transposons in humans, is an ancient element that entered the primate genome lineage approximately 50 million years ago. Although Hsmar1 elements are inactive due to mutational damage, one particular copy of the transposase gene has apparently been under selection. This transposase coding region is part of the SETMAR gene, in which a histone methylatransferase SET domain is fused to an Hsmar1 transposase domain. A phylogenetic approach was taken to reconstruct the ancestral Hsmar1 transposase gene, which we named Hsmar1-Ra. The Hsmar1-Ra transposase efficiently mobilizes Hsmar1 transposons by a cut-and-paste mechanism in human cells and zebra fish embryos. Hsmar1-Ra can also mobilize short inverted-repeat transposable elements (MITEs) related to Hsmar1 (MiHsmar1), thereby establishing a functional relationship between an Hsmar1 transposase source and these MITEs. MiHsmar1 excision is 2 orders of magnitude more efficient than that of long elements, thus providing an explanation for their high copy numbers. We show that the SETMAR protein binds and introduces single-strand nicks into Hsmar1 inverted-repeat sequences in vitro. Pathway choices for DNA break repair were found to be characteristically different in response to transposon cleavage mediated by Hsmar1-Ra and SETMAR in vivo. Whereas nonhomologous end joining plays a dominant role in repairing excision sites generated by the Hsmar1-Ra transposase, DNA repair following cleavage by SETMAR predominantly follows a homology-dependent pathway. The novel transposon system can be a useful tool for genome manipulations in vertebrates and for investigations into the transpositional dynamics and the contributions of these elements to primate genome evolution.