gebhart/patrepeval huggingface dataset:
Role of the Escherichia coli FadR regulator in stasis survival and growth phase-dependent expression of the uspA, fad, and fab genes (1996)

The increased expression of the uspA gene of Escherichia coli is an essential part of the cell's response to growth arrest. We demonstrate that stationary-phase activation of the uspA promoter is in part dependent on growth phase-dependent inactivation or repression of the FadR regulator. Transcription of uspA is derepressed during exponential growth in fadR null mutants or by including the fatty acid oleate in the growth medium of FadR+ cells. The results of DNA footprinting analysis show that FadR binds downstream of the uspA promoter in the noncoding region. Thus, uspA is a member of the fadR regulon. All the fad-lacZ fusions examined (fadBA, fadL, and fadD) are increasingly expressed in stationary phase with kinetics similar to that of the increased expression of uspA. In contrast, beta-galactosidase levels decrease during stationary phase in a fabA-lacZ lysogen, consistent with the role of FadR as an activator of fabA. The growth phase-dependent increased and decreased transcription of fad genes and fabA, respectively, is dependent on the status of the fadR gene. Cells carrying a mutation in the FadR gene (fadRS219N) that makes it nonderepressible exhibit a weak stationary-phase induction of uspA and fad genes. In addition, cells carrying fadRS219N survive long-term stasis poorly, indicating that FadR-dependent alterations in fatty acid metabolism are an integral and important part of the adaptation to stationary phase.
CTLA-4 Blockade Synergizes Therapeutically with PARP Inhibition in BRCA1-Deficient Ovarian Cancer (2015)

Immune checkpoint blockade has shown significant therapeutic efficacy in melanoma and other solid tumors, but results in ovarian cancer have been limited. With evidence that tumor immunogenicity modulates the response to checkpoint blockade, and data indicating that BRCA-deficient ovarian cancers express higher levels of immune response genes, we hypothesized that BRCA(-) ovarian tumors would be vulnerable to checkpoint blockade. To test this hypothesis, we used an immunocompetent BRCA1-deficient murine ovarian cancer model to compare treatment with CTLA-4 or PD-1/PD-L1 antibodies alone or combined with targeted cytotoxic therapy using a PARP inhibitor. Correlative studies were performed in vitro using human BRCA1(-) cells. We found that CTLA-4 antibody, but not PD-1/PD-L1 blockade, synergized therapeutically with the PARP inhibitor, resulting in immune-mediated tumor clearance and long-term survival in a majority of animals (P < 0.0001). The survival benefit of this combination was T-cell mediated and dependent on increases in local IFNγ production in the peritoneal tumor environment. Evidence of protective immune memory was observed more than 60 days after completion of therapy. Similar increases in the cytotoxic effect of PARP inhibition in the presence of elevated levels of IFNγ in human BRCA1(-) cancer cells support the translational potential of this treatment protocol. These results demonstrate that CTLA-4 blockade combined with PARP inhibition induces protective antitumor immunity and significant survival benefit in the BRCA1(-) tumor model, and support clinical testing of this regimen to improve outcomes for women with hereditary ovarian cancer.
Target chambers for megajoule laser facilities (2002)

The authors present a 5-m-radius, 2.5-cm-wall-thickness target chamber designed to withstand buckling, impulse, and pressure loads in a 1-2-MJ laser fusion facility. Although the maximum expected fusion yield is <30 MJ, yields up to approximately 500 MJ are possible without exceeding allowable stresses. No wall ablation is expected unless the energy in the target chamber exceeds 1.2 MJ; this minimizes damage to optics and diagnostics caused by condensation during low-yield shots. The facility can illuminate indirect drive targets with good uniformity when either all or only a portion of 288 beamlets are operational. Direct drive targets can be illuminated by up to 72 beamlets in a separate target chamber. Sacrificial silica debris shields, with approximately 10-torr precharge of incondensable gas in the beam tubes, are used for protection of the final optics. The target chamber room has a 1-2-m-thick water neutron shield.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Nitric Oxide Modulates the Catalytic Activity of Myeloperoxidase (2000)

Myeloperoxidase (MPO), an abundant protein in neutrophils, monocytes, and subpopulations of tissue macrophages, is believed to play a critical role in host defenses and inflammatory tissue injury. To perform these functions, an array of diffusible radicals and reactive oxidant species may be formed through oxidation reactions catalyzed at the heme center of the enzyme. Myeloperoxidase and inducible nitric-oxide synthase are both stored in and secreted from the primary granules of activated leukocytes, and nitric oxide (nitrogen monoxide; NO) reacts with the iron center of hemeproteins at near diffusion-controlled rates. We now demonstrate that NO modulates the catalytic activity of MPO through distinct mechanisms. NO binds to both ferric (Fe(III), the catalytically active species) and ferrous (Fe(II)) forms of MPO, generating stable low-spin six-coordinate complexes, MPO-Fe(III).NO and MPO-Fe(II).NO, respectively. These nitrosyl complexes were spectrally distinguishable by their Soret absorbance peak and visible spectra. Stopped-flow kinetic analyses indicated that NO binds reversibly to both Fe(III) and Fe(II) forms of MPO through simple one-step mechanisms. The association rate constant for NO binding to MPO-Fe(III) was comparable to that observed with other hemoproteins whose activities are thought to be modulated by NO in vivo. In stark contrast, the association rate constant for NO binding to the reduced form of MPO, MPO-Fe(II), was over an order of magnitude slower. Similarly, a 2-fold decrease was observed in the NO dissociation rate constant of the reduced versus native form of MPO. The lower NO association and dissociation rates observed suggest a remarkable conformational change that alters the affinity and accessibility of NO to the distal heme pocket of the enzyme following heme reduction. Incubation of NO with the active species of MPO (Fe(III) form) influenced peroxidase catalytic activity by dual mechanisms. Low levels of NO enhanced peroxidase activity through an effect on the rate-limiting step in catalysis, reduction of Compound II to the ground-state Fe(III) form. In contrast, higher levels of NO inhibited MPO catalysis through formation of the nitrosyl complex MPO-Fe(III)-NO. NO interaction with MPO may thus serve as a novel mechanism for modulating peroxidase catalytic activity, influencing the regulation of local inflammatory and infectious events in vivo.
The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation (2003)

ErbB2 is a receptor tyrosine kinase whose activity in normal cells depends on dimerization with another ligand-binding ErbB receptor. In contrast, amplification of c-erbB2 in tumors results in dramatic overexpression and constitutive activation of the receptor. Breast cancer cells overexpressing ErbB2 depend on its activity for proliferation, because treatment of these cells with ErbB2-specific antagonistic antibodies or kinase inhibitors blocks tumor cells in the G1 phase of the cell cycle. Intriguingly, loss of ErbB2 signaling is accompanied by a decrease in the phosphotyrosine content of ErbB3. On the basis of these results, it has been proposed that ErbB3 might be a partner for ErbB2 in promoting cellular transformation. To test this hypothesis and directly examine the role of the "kinase dead" ErbB3, we specifically ablated its expression with a designer transcription factor (E3). By infection of ErbB2-overexpressing breast cancer cells with a retrovirus expressing E3, we show that ErbB3 is an essential partner in the transformation process. Loss of functional ErbB2 or ErbB3 has similar effects on cell proliferation and cell cycle regulators. Furthermore, expression of constitutively active protein kinase B rescues the proliferative block induced as a consequence of loss of ErbB2 or ErbB3 signaling. These results demonstrate that ErbB2 overexpression and activity alone are insufficient to promote breast tumor cell division. Furthermore, we identify ErbB3's role, which is to couple active ErbB2 to the phosphatidylinositol 3-kinase/protein kinase B pathway. Thus, the ErbB2/ErbB3 dimer functions as an oncogenic unit to drive breast tumor cell proliferation.
A new zinc-62/copper-62 generator as a copper-62 source for PET radiopharmaceuticals. (1989)

A new 62Zn/62Cu generator system was designed to provide a readily available 62Cu source for positron emission tomographic radiopharmaceuticals, based on the differences of complex formation between Zn and Cu. Noncarrier added 62Cu was selectively eluted as a glycine complex from 62Zn-adsorbed cation-exchange resin (CG-120, Amberlite), when a glycine solution (200 mM) was used as the eluant. The elution efficiency and radionuclidic purity of 62Cu were 70% and greater than 99.9%, respectively. Copper in glycine solution showed rapid complex formation with dithiosemicarbazone, which is one of the established Cu-binding agents for bifunctional chelating radiopharmaceutical.
The Autonomic Nervous System in Cardiac Electrophysiology (2010)

The autonomic nervous system plays an integral role in the modulation of normal cardiac electrophysiology. This is achieved via a complex network of pre- and postganglionic sympathetic and parasympathetic fibers that synapse on extrinsic and intrinsic cardiac ganglia and ultimately directly innervate cardiac myocytes. Alterations in autonomic tone may induce changes in local cellular electrophysiology that may manifest clinically in a number of ways, ranging from changes in heart rate to changes in heart rhythm. These relationships between autonomic tone and the evolution of cardiac dysrhythmias are areas of evolving research, with increasing evidence for a key role for autonomic ganglia in the pathogenesis of atrial fibrillation and sympathetic nerves in the predilection toward ventricular tachycardia in areas of myocardial scar. In this review, we highlight what is known about the anatomy and physiology of the cardiac autonomic nervous system, the evidence supporting the relationship of autonomic tone to clinically significant arrhythmias, and a variety of mechanisms (eg, direct ion channel effects) and diagnostic tools that exist to help define this relationship. Further emphasized are potential future avenues of research needed to elucidate the relationship between changes in normal autonomic tone and the pathogenesis of cardiac arrhythmias.
Hedgehog-GLI signaling regulates the behavior of cells with stem cell properties in the developing neocortex (2003)

Stem cells are crucial for normal development and homeostasis, and their misbehavior may be related to the origin of cancer. Progress in these areas has been difficult because the mechanisms regulating stem cell lineages are not well understood. Here, we have investigated the role of the SHH-GLI pathway in the developing mouse neocortex. The results show that SHH signaling endogenously regulates the number of embryonic and postnatal mouse neocortical cells with stem cell properties, and controls precursor proliferation in a concentration-dependent manner in cooperation with EGF signaling. These findings identify a crucial mechanism for the regulation of the number of cells with stem cell properties that is unexpectedly conserved in different stem cell niches.
Effect of wafer back grinding on the mechanical behavior of multilayered low-k for 3D-stack packaging applications (2008)

To study the effect of back grinding on the mechanical properties of the active side of the die, low-k stacked wafers were grinded to four different thicknesses of 500 mum, 300 mum, 150 mum, and 75 mum by using a commercial grinding process. Nanoindentation and nanoscratch tests were performed using the Nanoindenter XP (MTS Corp. USA) on both the normal (no back grinding) and back grinded samples to analyze the failure loads, modulus, hardness and adhesive/cohesive strength, of the low-k stack. It is found that the back grinding process enhances the mechanical integrity of low-k stack as the back grinded low-k stack exhibited in terms of the higher failure load and cohesive and/or adhesive strength of grinded low-k stack than the normal low-k stack. The TEM cross-section analysis showed that the interfaces in the low-k stack of normal sample are wavy, whereas the interfaces in the low-k stack of back grinded samples are even, especially at the black diamond region. Significant densification of BD films is observed in the case of back grinded sample. Based on these results, it is believed that the thermo-mechanical stresses applied and/or generated during wafer back grinding process affect the microstructure and enhance the mechanical strength of the low-k stack.
Detection of DNA Adducts by Electron Capture Mass Spectrometry (1997)

ADVERTISEMENT RETURN TO ISSUEReviewNEXTDetection of DNA Adducts by Electron Capture Mass SpectrometryRoger W. GieseView Author Information Department of Pharmaceutical Sciences in the Bouvé College of Pharmacy and Health Professions, Barnett Institute, and Chemistry Department, Northeastern University, Boston, Massachusetts 02115 Cite this: Chem. Res. Toxicol. 1997, 10, 3, 255–270Publication Date (Web):March 17, 1997Publication History Received29 July 1996Published online17 March 1997Published inissue 1 March 1997https://pubs.acs.org/doi/10.1021/tx9601263https://doi.org/10.1021/tx9601263review-articleACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views249Altmetric-Citations38LEARN 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 SUBJECTS:Adducts,Electrophoresis,Genetics,Reaction products,Surface analysis Get e-Alerts
Hepatocyte function and extracellular matrix geometry: long‐term culture in a sandwich configuration (1989)

Adult rat hepatocytes cultured in a collagen sandwich system maintained normal morphology and a physiological rate of albumin secretion for at least 42 days. Hepatocytes cultured on a single layer of collagen gel essentially ceased albumin secretion within 1 wk but could recover function with the overlay of a second layer of collagen gel. This culture configuration more closely mimics the hepatocytes' in vivo environment and provides a simple method for their long‐term maintenance.— D unn , J. C. Y.; Y armush , M. L.; K oebe , H. G.; T ompkins , R. G. Hepatocyte function and extracellular matrix geometry: long‐term culture in a sandwich configuration. FASEB J. 3: 174‐177; 1989.
The Lysyl Oxidase Inhibitor, β-Aminopropionitrile, Diminishes the Metastatic Colonization Potential of Circulating Breast Cancer Cells (2009)

Lysyl oxidase (LOX), an extracellular matrix remodeling enzyme, appears to have a role in promoting breast cancer cell motility and invasiveness. In addition, increased LOX expression has been correlated with decreases in both metastases-free, and overall survival in breast cancer patients. With this background, we studied the ability of beta-aminopropionitrile (BAPN), an irreversible inhibitor of LOX, to regulate the metastatic colonization potential of the human breast cancer cell line, MDA-MB-231. BAPN was administered daily to mice starting either 1 day prior, on the same day as, or 7 days after intracardiac injection of luciferase expressing MDA-MB-231-Luc2 cells. Development of metastases was monitored by in vivo bioluminescence imaging, and tumor-induced osteolysis was assessed by micro-computed tomography (microCT). We found that BAPN administration was able to reduce the frequency of metastases. Thus, when BAPN treatment was initiated the day before, or on the same day as the intra-cardiac injection of tumor cells, the number of metastases was decreased by 44%, and 27%, and whole-body photon emission rates (reflective of total tumor burden) were diminished by 78%, and 45%, respectively. In contrast, BAPN had no effect on the growth of established metastases. Our findings suggest that LOX activity is required during extravasation and/or initial tissue colonization by circulating MDA-MB-231 cells, lending support to the idea that LOX inhibition might be useful in metastasis prevention.
Control of the Shape of Copper Metallic Particles by Using a Colloidal System as Template (1997)

In this paper we show that the use of colloidal assemblies as templates favors the control of the shape of nanoparticles. Cylindrical copper metallic particles having same size can be obtained in various parts of the phase diagram when the template is made of interconnected cylinders. A very low amount of cylinders (13%) is formed when the synthesis is performed in cylindrical reverse micelles. When the colloidal self-assembly is a mixture of several phases, various types of shapes can be obtained. In some cases, the polydispersity in size is so low that metallic particles are able to self-assemble in a hexagonal network. Multilayers can be observed and are arranged in a face centered cubic structure.
Topological Constraints Governing the Use of the Chicken HS4 Chromatin Insulator in Oncoretrovirus Vectors (2002)

The expression of integrated oncoretrovirus vectors is subject to the inhibitory effects of surrounding chromatin. A previous report from our laboratory indicated that such position effects can be overcome by flanking a reporter vector with the cHS4 chromatin insulator. To characterize this activity more thoroughly, we switched the promoter-gene combinations in the reporter vector and analyzed expression of these vectors flanked with the cHS4 fragment in both orientations following bone marrow transduction and transplantation in mice. The results indicate that the cHS4 fragment can function in both orientations and can insulate both the virus long-terminal-repeat (LTR) promoter and an internal phosphoglycerate kinase (Pgk) promoter. However, insulation of the LTR promoter diminished when the orientation of the cHS4 fragment placed the CTCF-binding core element immediately proximal to the U3 region, suggesting a minimal distance requirement. Moreover, placement of the cHS4 fragment in the U3 region of the 3' LTR dramatically decreased the level of expression from an internal Pgk promoter, presumably by blocking interaction with the 3' LTR enhancer. Finally, sorting studies suggest that the severity of position effects or autonomous promoter silencing increases as transduced progenitors differentiate into mature progeny. These findings have direct implications for the use of chromatin insulators such as cHS4 in oncoretrovirus vectors.
Endothelial cell marker expression in dysplastic lesions of the liver: an immunohistochemical study (2001)

Alterations in the hepatic microcirculation comparable to those observed in hepatocellular carcinoma are present in a significant proportion of dysplastic lesions of the liver and may be indirect markers of the process of liver carcinogenesis.
INACTIVATION OF LIPID‐CONTAINING VIRUSES BY HYDROPHOBIC PHOTOSENSITIZERS AND NEAR‐ULTRAVIOLET RADIATION (1979)

Abstract—The hydrophobic photosensitizers acridine and phenothiazine inactivate the lipid‐contnining viruses PM2,φ6, and herpes simplex when samples are illuminated with near‐UV radiation. φ23–1‐ a . which is insensitive to organic solvents and presumably contains no lipids. is not inactivated under comparable conditions. For acridinc, the inactivation of virus requires that oxygen be present and is inhibited by sodium azide, implicating the involvement of singlet oxygen. For phenothiazine, oxygen is not required for photosensitized inactivation. Treatment of PM2 with acridine and near‐UV light caused a complete disruption of the virion, as determined by sucrose gradient analysis of treated and untreated samples. These data and related observations suggest that lipid‐containing viruses are inactivated through photosensitized membrane damage.
The role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells. (1990)

We have examined cultures of neonatal human foreskin keratinocytes (HFKs) to determine the ligands and functions of integrins alpha 2 beta 1, and alpha 3 beta 1 in normal epidermal stratification and adhesion to the basement membrane zone (BMZ) in skin. We used three assay systems, HFK adhesion to purified extracellular matrix (ECM) ligands and endogenous secreted ECM, localization of integrins in focal adhesions (FAs), and inhibition of HFK adhesion with mAbs to conclude: (a) A new anti-alpha 3 beta 1 mAb, P1F2, localized alpha 3 beta 1 in FAs on purified laminin greater than fibronectin/collagen, indicating that laminin was the best exogeneous ligand for alpha 3 beta 1. However, in long term culture, alpha 3 beta 1 preferentially codistributed in and around FAs with secreted laminin-containing ECM, in preference to exogenous laminin. Anti-alpha 3 beta 1, mAb P1B5, detached prolonged cultures of HFKs from culture plates or from partially purified HFK ECM indicating that interaction of alpha 3 beta 1 with the secreted laminin-containing ECM was primarily responsible for HFK adhesion in long term culture. (b) In FA assays, alpha 2 beta 1 localized in FAs conincident with initial HFK adhesion to exogenous collagen, but not laminin or fibronectin. However, in inhibition assays, anti-alpha 2 beta 1 inhibited initial HFK adhesion to both laminin and collagen. Thus, alpha 2 beta 1 contributes to initial HFK adhesion to laminin but alpha 3 beta 1 is primarily responsible for long-term HFK adhesion to secreted laminin-containing ECM. (c) Serum or Ca2(+)-induced aggregation of HFKs resulted in relocation of alpha 2 beta 1 and alpha 3 beta 1 from FAs to cell-cell contacts. Further, cell-cell adhesion was inhibited by anti-alpha 3 beta 1 (P1B5) and a new anti-beta 1 mAb (P4C10). Thus, interaction of alpha 3 beta 1 with either ECM or membrane coreceptors at cell-cell contacts may facilitate Ca2(+)-induced HFK aggregation. (d) It is suggested that interaction of alpha 3 beta 1 with a secreted, laminin-containing ECM in cultured HFKs, duplicates the role of alpha 3 beta 1 in basal cell adhesion to the BMZ in skin. Further, relocation of alpha 2 beta 1 and alpha 3 beta 1 to cell-cell contacts may result in detachment of cells from the BMZ and increased cell-cell adhesion in the suprabasal cells contributing to stratification of the skin.