gebhart/patrepeval huggingface dataset:
Dissecting the transcriptional networks underlying breast cancer: NR4A1 reduces the migration of normal and breast cancer cell lines (2010)

Abstract Introduction Breast cancer currently accounts for more than one-quarter of all female cancers and, despite the great progress in treatment observed in the past few years, the need for identification of new gene targets that can be used for diagnosis, prognosis and therapy is evident. A previous study identified the transcription factor NR4A1 as a gene upregulated in primary breast cancer compared with normal tissue by microarray analysis and sequencing technologies. The purpose of the study was to identify the role of NR4A1 in normal mammary epithelial and breast cancer cell biology. Methods NR4A1 expression in breast tumours was assessed by semiquantitative and real-time PCR using RNA from normal and tumour samples or breast cancer cell lines. Immunohistochemistry on tissue microarrays was performed to check NR4A1 protein expression in breast tumours. MCF-10A and 226L normal mammary epithelial cells as well as the tumour lines PMC42, ZR-75-1 and MDA-MB-231 were transduced with full-length NR4A1, and the ability of NR4A1-overexpressing cells to migrate was tested using scratch wound or transwell migration assays. Proliferation was measured using the MTT and BrdU assays, while apoptosis was determined by the Annexin V assay. The ability of the cells to adhere to extracellular matrix was tested by adhesion assays and integrin cell surface expression was measured by flow cytometry. Activation of the FAK as well as ERK1/2 and PI3K pathways was checked by western blotting. Results Breast tissue microarray analysis showed NR4A1 expression in primary tumours, which was reduced in higher grade and metastatic tumours. Ectopic expression of NR4A1 in MCF-10A, 226L, PMC42 and ZR-75-1 cells led to reduced ability of the cells to migrate, while no differences were observed in their proliferation and apoptotic index. NR4A1 expression altered the ability of the MCF-10A cells to adhere to the extracellular matrix and affected cell surface expression of integrins. Conclusions NR4A1 acts as an antimigratory factor in two normal mammary epithelial and two breast cancer cell lines tested. It is therefore possible that NR4A1 acts as an antimigratory factor in breast tumours, and further studies should be conducted to understand the mechanisms involved.
Usability of Human Factors Research in Design (2014)

There exists a disconnect between users of the science of human factors, that is, designers and practitioners, and producers of the science, that is, human factors researchers. Research results are primarily disseminated by articles published in scientific, peer reviewed journals, that are often targeted to other scientists, not designers or practitioners. Human factors standards and guidelines are intended for designers and human factors practitioners, but finding and accessing standards relevant to specific design problems is difficult as well. We convened this panel in order to focus on designers’ needs for human factors data, standards, and guidelines, and to seek solutions to what appears to be a communication problem between human factors researchers and the users of their results.
Development of Cr-Tolerant Cathodes of Solid Oxide Fuel Cells (2008)

We have shown that the Cr deposition process at (LSM) and (LSCF) cathodes of solid oxide fuel cells (SOFCs) is kinetically limited by the nucleation reaction between the gaseous Cr species and nucleation agents. In the case of the LSM electrode, the nucleation agent has been identified to be manganese species generated under cathodic polarization, and for the LSCF electrode, it is SrO species segregated at the electrode surface. Based on the mechanism proposed, we select (LNF) and (LBCF) perovskites. The results show that LNF and LBCF electrodes are highly tolerant toward the Cr deposition and are much more stable than LSM and LSCF cathodes under SOFC operating conditions in the presence of a Fe–Cr metallic interconnect.
Epstein-Barr virus nuclear antigen 2 induces FcRH5 expression through CBF1 (2006)

Fc-receptor homolog 5 (FcRH5) is a recently identified B-cell membrane protein of unknown function. In Burkitt lymphoma cell lines with chromosome 1q21 abnormalities, FcRH5 expression is deregulated, implicating FcRH5 in lymphomagenesis. Epstein-Barr virus infects and immortalizes B cells, and is implicated in the etiology of several tumors of B-cell origin. Overexpression of genes located on 1q21-25 has been proposed as a surrogate for Epstein-Barr virus in Burkitt lymphoma. We now report that Epstein-Barr virus nuclear antigen 2 (EBNA2) markedly induces the expression of the FcRH5 gene, encoded on chromosome 1q21. Induction occurred in the absence of other viral proteins and did not require de novo protein synthesis. EBNA2 lacks a DNA-binding domain and can target responsive genes through the host DNA binding protein CBF1. We show that induction of FcRH5 by EBNA2 is strictly CBF1 dependent, as it was abolished in CBF1-deficient cells. Accordingly, EBNA2 targeted CBF1 binding sites present in the FcRH5 promoter in vivo, as detected by chromatin immunoprecipitation. These results identify FcRH5 as a novel, direct target of EBNA2 that may contribute to the development of Epstein-Barr virus-associated tumors.
Discovery and Development of Simeprevir (TMC435), a HCV NS3/4A Protease Inhibitor (2014)

Hepatitis C virus is a blood-borne infection and the leading cause of chronic liver disease (including cirrhosis and cancer) and liver transplantation. Since the identification of HCV in 1989, there has been an extensive effort to identify and improve treatment options. An important milestone was reached in 2011 with the approval of the first-generation HCV NS3/4A protease inhibitors. However, new therapies are needed to improve cure rates, shorten treatment duration, and improve tolerability. Here we summarize the extensive medicinal chemistry effort to develop novel P2 cyclopentane macrocyclic inhibitors guided by HCV NS3 protease assays, the cellular replicon system, structure-based design, and a panel of DMPK assays. The selection of compound 29 (simeprevir, TMC435) as clinical candidate was based on its excellent biological, PK, and safety pharmacology profile. Compound 29 has recently been approved for treatment of chronic HCV infection in combination with pegylated interferon-α and ribavirin in Japan, Canada, and USA.
Efficient Transient Analysis of Power Grids (2007)

An efficient technique to establish a constant matrix with variable step-size multi-step formulas is presented for transient analysis of linear power grids. Instead of deriving new formulas with a constant leading coefficient, it is shown that, if the step change is relatively small, a constant matrix can also be obtained by carefully allocating the integration points and using the existing variable step-size multi-step formulas with proven accuracy and stability. Thus, with the technique proposed in this paper, LU decompositions are needed only for large step changes, and the computational efficiency of variable step methods can, therefore, be improved by effectively reducing the number of LU decompositions in transient analyses.
Improving Annealing via Directed Moves (2007)

Simulated annealing remains a widely-used heuristic for FPGA placement due, in part, to its ability to produce high-quality placements while accommodating complex objective functions and architectural constraints. In this work, we investigate the concept of "directed moves" during annealing as a means of improving upon the quality and run-time of the technique. We intersperse "intelligent" strategies for selecting and placing cells along with traditional, random moves during an anneal. This allows our annealer to converge more quickly and to attain better-quality placements with less statistical variability. Our results confirm that, for the same amount of computational effort, directed moves achieve 5% and 10% improvement in critical path delay and wire length, respectively, compared to traditional annealing perturbations.
RNase P branches out from RNP to protein: organelle-triggered diversification?: Figure 1. (2012)

RNase P is the enzyme that removes 5' leader sequences from precursor tRNAs. Remarkably, in most organisms, RNase P is a ribonucleoprotein particle where the RNA component is responsible for catalysis. In this issue of Genes & Development, Gutmann and colleagues (pp. 1022-1027) report the first organism, Arabidopsis thaliana, to employ protein-only RNase P in both its nucleus and organelles. An intriguing possibility is that replacement of RNase P ribonucleoprotein particles (RNPs) by proteins may have been triggered by the acquisition of organelles.
Long-Term Infection and Vertical Transmission of a Gammaretrovirus in a Foreign Host Species (2012)

Increasing evidence has indicated natural transspecies transmission of gammaretroviruses; however, viral-host interactions after initial xeno-exposure remain poorly understood. Potential association of xenotropic murine leukemia virus-related virus (XMRV) in patients with prostate cancer and chronic fatigue syndrome has attracted broad interests in this topic. Although recent studies have indicated that XMRV is unlikely a human pathogen, further understanding of XMRV xenoinfection would allow in vivo modeling of the initial steps of gammaretroviral interspecies transmission, evolution and dissemination in a new host population. In this study, we monitored the long-term consequences of XMRV infection and its possible vertical transmission in a permissive foreign host, wild-derived Mus pahari mice. One year post-infection, XMRV-infected mice showed no notable pathological changes, while proviral DNA was detected in three out of eight mice. XMRV-infected mice remained seropositive throughout the study although the levels of gp70 Env- and p30 capsid-specific antibodies gradually decreased. When vertical XMRV transmission was assessed, no viremia, humoral immune responses nor endogenization were observed in nine offspring from infected mothers, yet one offspring was found PCR-positive for XMRV-specific sequences. Amplified viral sequences from the offspring showed several mutations, including one amino acid deletion in the receptor binding domain of Env SU. Our results therefore demonstrate long-term asymptomatic infection, low incidence of vertical transmission and limited evolution of XMRV upon transspecies infection of a permissive new host, Mus pahari.
ChemInform Abstract: Synthesis of CNS‐Active Pyran, Thiopyran, and Piperidine Anellated Oxacarbabenzomorphanes. (1988)

Abstract The unsaturated ketone (I) undergoes cyclocondensation with 4‐thiacyclohexanone (II) to form the tetracyclic compound (III).
In situ hybridization mapping of a 500-kDa calcium-sensing protein gene (LRP2) to human chromosome region 2q31→q32.1 and porcine chromosome region 15q22→q24 (1995)

Recently, a 500-kDa protein, with homology to the rat Gp330 glycoprotein, was found to be expressed on the surface of human parathyroid, placental cytotrophoblast, and renal proximal tubule cells. The protein has been implicated to function as a sensor of extracellular calcium on parathyroid and placental cytotrophoblast cells. We report here in situ hybridization mapping of the corresponding gene, designed as low-density lipoprotein receptor related protein-2 and symbolized as LRP2, to human chromosome region 2q31-->q32.1 and porcine chromosome region 15q22-->q24. The results are discussed in a comparative mapping context.
Heteroprotein Complex Coacervation: Bovine β-Lactoglobulin and Lactoferrin (2013)

Lactoferrin (LF) and β-lactoglobulin (BLG), strongly basic and weakly acidic bovine milk proteins, form optically clear coacervates under highly limited conditions of pH, ionic strength I, total protein concentration C(P), and BLG:LF stoichiometry. At 1:1 weight ratio, the coacervate composition has the same stoichiometry as its supernatant, which along with DLS measurements is consistent with an average structure LF(BLG2)2. In contrast to coacervation involving polyelectrolytes here, coacervates only form at I < 20 mM. The range of pH at which coacervation occurs is similarly narrow, ca. 5.7-6.2. On the other hand, suppression of coacervation is observed at high C(P), similar to the behavior of some polyelectrolyte-colloid systems. It is proposed that the structural homogeneity of complexes versus coacervates with polyelectrolytes greatly reduces the entropy of coacervation (both chain configuration and counterion loss) so that a very precise balance of repulsive and attractive forces is required for phase separation of the coacervate equilibrium state. The liquid-liquid phase transition can however be obscured by the kinetics of BLG aggregation which can compete with coacervation by depletion of BLG.
Osmium‐ and Ruthenium‐Based Phosphorescent Materials: Design, Photophysics, and Utilization in OLED Fabrication (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Microwave near-field sensor for contactless gas pressure determination (2016)

In this contribution, a sensor concept for the contact-less detection of pressure fluctuations in its near-field is presented. The sensor consists of a microstrip patch antenna operating at microwave frequencies. A changing pressure of a non-conducting gas or liquid detunes the antenna by a variation of the dielectric properties. Due to the contactless approach and the compact design, the sensor is a versatile measurement instrument for the use in a wide field of application. Simulations and measurements with carbon dioxide at different pressures state the operational behavior of the sensor.
Bimetallic Effects in Homopolymerization of Styrene and Copolymerization of Ethylene and Styrenic Comonomers:  Scope, Kinetics, and Mechanism (2008)

This contribution describes the homopolymerization of styrene and the copolymerization of ethylene and styrenic comonomers mediated by the single-site bimetallic "constrained geometry catalysts" (CGCs), (mu-CH2CH2-3,3'){(eta(5)-indenyl)[1-Me2Si(tBuN)](TiMe2)}2 [EBICGC(TiMe2)2; Ti2], (mu-CH2CH2-3,3'){(eta(5)-indenyl)[1-Me2Si(tBuN)](ZrMe2)}2 [EBICGC(ZrMe2)2; Zr2], (mu-CH2-3,3'){(eta(5)-indenyl)[1-Me2Si(tBuN)](TiMe2)}2 [MBICGC(TiMe2)2; C1-Ti2], and (mu-CH2-3,3'){(eta(5)-indenyl)[1-Me2Si(tBuN)](ZrMe2)}2 [MBICGC(ZrMe2)2; C1-Zr2], in combination with the borate activator/cocatalyst Ph3C+ B(C6F5)4- (B1). Under identical styrene homopolymerization conditions, C1-Ti2 + B1 and Ti2 + B1 exhibit approximately 65 and approximately 35 times greater polymerization activities, respectively, than does monometallic [1-Me2Si(3-ethylindenyl)(tBuN)]TiMe2 (Ti1) + B1. C1-Zr2 + B1 and Zr2 + B1 exhibit approximately 8 and approximately 4 times greater polymerization activities, respectively, than does the monometallic control [1-Me2Si(3-ethylindenyl)(tBuN)]ZrMe2 (Zr1) + B1. NMR analyses show that the bimetallic catalysts suppress the regiochemical insertion selectivity exhibited by the monometallic analogues. In ethylene copolymerization, Ti2 + B1 enchains 15.4% more styrene (B), 28.9% more 4-methylstyrene (C), 45.4% more 4-fluorostyrene (D), 41.2% more 4-chlorostyrene (E), and 31.0% more 4-bromostyrene (F) than does Ti1 + B1. This observed bimetallic chemoselectivity effect follows the same general trend as the pi-electron density on the styrenic ipso carbon (D > E > F > C > B). Kinetic studies reveal that both Ti2 + B1 and Ti1 + B1-mediated ethylene-styrene copolymerizations follow second-order Markovian statistics and tend to be alternating. Moreover, calculated reactivity ratios indicate that Ti2 + B1 favors styrene insertion more than does Ti1 + B1. All the organozirconium complexes (C1-Zr2, Zr2, and Zr1) are found to be incompetent for ethylene-styrene copolymerization, yielding only mixtures of polyethylene and polystyrene. Model compound (mu-CH2CH2-3,3'){(eta(5)-indenyl)[1-Me2Si(tBuN)][Ti(CH2Ph)2]}2 {EBICGC[Ti(CH2Ph)2]2; Ti2(CH2Ph)4} was designed, synthesized, and structurally characterized. In situ activation studies with cocatalyst B(C6F5)3 suggest an eta(1)-coordination mode for the benzyl groups, thus supporting the proposed polymerization mechanism. For ethylene-styrene copolymerization, polar solvents are found to increase copolymerization activities and coproduce atactic polystyrene impurities in addition to ethylene-co-styrene, without diminishing the comonomer incorporation selectivity. Both homopolymerization and copolymerization results argue that substantial cooperative effects between catalytic sites are operative.
Ghost modes and resonant effects in AlGaN-InGaN-GaN lasers (1999)

Many diode laser structures, including those based on group-III nitride system, contain passive waveguide layers of higher refractive index than in the adjacent layers. Modes of such passive waveguides ("passive" modes) can interact with an active layer mode ("active" mode), giving rise to two kinds of normal modes or "supermodes" of a laser structure. Away from resonance, one of them is localized predominantly in the active region ("lasing" mode), while the other ones are located mostly in passive waveguides ("ghost" modes). The lasing mode is the mode at which laser generation occurs. The lossy ghost modes are parasitic modes of a laser structure that can consume energy from the active region. Resonant coupling occurs when the lasing mode and a ghost mode are in phase synchronism. In the paper, the concept of ghost modes is applied to InGaN-based diode lasers. The values for critical thickness are calculated for p-GaN cap layer and for n-GaN buffer/substrate layer for a particular multilayer laser structure. The typical thickness of 0.5 /spl mu/m of AlGaN-cladding layer is found to be insufficient to prevent rather strong coupling between the modes. Under the resonant coupling conditions, the modal gain is shown to be strongly suppressed, allowing no lasing at all.
Supplementary Data from Microvesicle-Mediated Delivery of Minicircle DNA Results in Effective Gene-Directed Enzyme Prodrug Cancer Therapy (2023)

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Translation can affect the antisense activity of RNase H1-dependent oligonucleotides targeting mRNAs (2017)

RNase H1-dependent antisense oligonucleotides (ASOs) can degrade complementary RNAs in both the nucleus and the cytoplasm. Since cytoplasmic mRNAs are actively engaged in translation, ASO activity may thus be affected by translating ribosomes that scan the mRNAs. Here we show that mRNAs associated with ribosomes can be cleaved using ASOs and that translation can alter ASO activity. Translation inhibition tends to increase ASO activity when targeting the coding regions of efficiently translated mRNAs, but not nuclear non-coding RNAs or less efficiently translated mRNAs. Increasing the level of RNase H1 protein eliminated the enhancing effects of translation inhibition on ASO activity, suggesting that RNase H1 recruitment to ASO/mRNA heteroduplexes is a rate limiting step and that translating ribosomes can inhibit RNase H1 recruitment. Consistently, ASO activity was not increased by translation inhibition when targeting the 3' UTRs, independent of the translation efficiency of the mRNAs. Contrarily, the activity of 3' UTR-targeting ASOs tended to be reduced upon translation inhibition, likely due to decreased accessibility. These results indicate that ASO activity can be affected by the translation process, and the findings also provide important information toward helping better ASO drug design.
Rapid Single-Shot Synthesis of the 217 Amino Acid-Long N-Terminal Domain of Pyocin S2 (2022)

Abstract The impermeable outer membrane of Pseudomonas aeruginosa is bypassed by antibacterial proteins known as S-type pyocins. Because of their properties, pyocins are investigated as a potential new class of antimicrobials against Pseudomonas infections. Their production and modification, however, remains challenging. To address this limitation, we employed automated fast-flow peptide synthesis (AFPS) for the rapid production of a pyocin S2 import domain. The N-terminal domain sequence (PyS2 NTD ) was synthesized in under 10 hours and purified to yield milligrams quantities of the desired product. To our knowledge, the 217 amino acid sequence of PyS2 NTD is among the longest peptides produced from a “single-shot” synthesis, i.e., made in a single stepwise route without the use of ligation techniques. Biophysical characterization of the PyS2 NTD with circular dichroism was consistent with the literature reports. Fluorescently labeled PyS2 NTD binds to P. aeruginosa expressing the cognate ferripyoverdine receptor (FpvA) and is taken up into the periplasm. This selective uptake was validated with confocal and super resolution microscopy, flow cytometry, and fluorescence recovery after photobleaching (FRAP). These modified, synthetic S-type pyocins domains can be used to probe import mechanisms of P. aeruginosa and leveraged to develop selective antimicrobial agents that bypass the outer membrane.
Comparison of intra-voxel spatial distributions of diffusion coefficients with intra-voxel spatial distributions of kurtosis coefficients (2023)

Previously, we have proposed the method for characterizing the intra-voxel spatial distribution of apparent diffusion coefficients (ADC) by using texture analysis and showed that texture features can provide different information from the conventional diffusion tensor imaging. In this study, we extended our method to the apparent kurtosis coefficients (AKC). We compared the features of the intra-voxel spatial distribution of ADC with that of AKC. We found that there is no significant difference in the spatial distribution of AKC from that of ADC, and a short scanning time with a single b-value may be sufficient to obtain information on diffusion distribution.
Adipose‐specific effect of rosiglitazone on vascular permeability and protein kinase C activation: novel mechanism for PPARγ agonist's effects on edema and weight gain (2006)

PPARgamma agonists, thiazolidinediones, cause fluid retention and edema due to unknown mechanisms. We characterized the effect of rosiglitazone (RSG), a thiazolidinedione, to induce vascular permeability, vascular endothelial growth factor (VEGF) expression, and protein kinase C (PKC) activation with edema and wt gain. In lean, fatty and diabetic Zucker rats, and endothelial insulin receptor knockout mice, RSG increased wt and vascular permeability, selectively in fat and retina, but not in heart or skeletal muscle. H2O content and wt of epididymal fat were increased by RSG and correlated to increases in capillary permeability in fat and body wt. RSG induced VEGF mRNA expression and PKC activation in fat and retina up to 2.5-fold. Ruboxistaurin, a PKCbeta isoform inhibitor, in the latter 2 wk of a 4-wk study, normalized vascular permeability in fat and decreased total wt gain, H2O content, and wt of fat vs. RSG alone but did not decrease VEGF expression, basal permeability, or food intake. Finally, RSG did not increase wt or vascular permeability in PKCbeta knockout vs. control mice. Thus, thiazolidinedione's effects on edema and wt are partially due to an adipose tissue-selective activation of PKC and vascular permeability that may be prevented by PKCbeta inhibition.