gebhart/patrepeval huggingface dataset:
Multiple beam laser cell micropatterning system (2004)

The various cell mechanisms, including cell-cell interactions, in native tissue could be better understood by engineering a cell coculture with a micro environment that closely mimics the natural cell arrangement. To this end, we developed a cell micropatterning system that uses a weakly focused laser beam to trap individual cells at the center of the beam and propel them forward onto an appropriate substrate. The optimal methods of introducing different cell types to be patterned into the patterning system and preventing cells from randomly falling onto the pattern were issues to be addressed with this system. Here, we report the development of a multi-chamber, multi-beam laser cell micropatterning system, in which the delivery of specific cells into the beam can be controlled using secondary laser beams. This permits consecutive creation of a pattern involving multiple cell types at specific relative positions. As examples, various patterns of fibroblasts have been created on collagen coated coverslips. In addition, two asynchronously beating clusters of cardiomyocytes were connected with fibroblasts of cardiac origin, yielding a deeper insight into the electrophysiological role of fibroblasts in conduction of the action potentials among cardiomyocytes.
Hyperinsulinemia and Left Ventricular Geometry in a Work-Site Population in Japan (1996)

The present study was designed to test whether hyperglycemia or hyperinsulinemia influences left ventricular mass and geometry. An echocardiogram and 75-g oral glucose tolerance test were performed in 210 normotensive and 180 mildly to moderately hypertensive male workers in a bus company who were free from cardiac diseases and were not taking medication for hypertension and diabetes mellitus. When we divided subjects into four groups according to the left ventricular geometric pattern using left ventricular mass index of 110 g/m2 and relative wall thickness (ratio of 2 x posterior wall thickness to end-diastolic left ventricular diameter) of 0.44, body mass index and systolic blood pressure were higher in those with concentric hypertrophy and eccentric hypertrophy. In addition, hemoglobin A(Ic) level and the sum of fasting and 2-hour postload serum glucose levels were higher in subjects with concentric hypertrophy. In subjects without diabetes mellitus (n=336), 2-hour postload serum insulin level and the sum of fasting and 2-hour postload serum insulin levels tended to be higher in those with concentric hypertrophy and concentric remodeling. In multiple regression analysis, the sum of glucose levels (or hemoglobin A(Ic) level) in all subjects and the sum of insulin (or 2-hour postload insulin) levels in subjects without diabetes mellitus significantly correlated with relative wall thickness, independent of age, systolic blood pressure, and body mass index. Neither glucose nor insulin levels correlated with left ventricular mass index. Our results suggest that hyperglycemia and hyperinsulinemia may promote concentric changes in the left ventricle in normotensive and mildly to moderately hypertensive men.
Chk2 Phosphorylation of BRCA1 Regulates DNA Double-Strand Break Repair (2003)

The pathway determining malignant cellular transformation, which depends upon mutation of the BRCA1 tumor suppressor gene, is poorly defined. A growing body of evidence suggests that promotion of DNA double-strand break repair by homologous recombination (HR) may be the means by which BRCA1 maintains genomic stability, while a role of BRCA1 in error-prone nonhomologous recombination (NHR) processes has just begun to be elucidated. The BRCA1 protein becomes phosphorylated in response to DNA damage, but the effects of phosphorylation on recombinational repair are unknown. In this study, we tested the hypothesis that the BRCA1-mediated regulation of recombination requires the Chk2- and ATM-dependent phosphorylation sites. We studied Rad51-dependent HR and random chromosomal integration of linearized plasmid DNA, a subtype of NHR, which we demonstrate to be dependent on the Mre11-Rad50-Nbs1 complex. Prevention of Chk2-mediated phosphorylation via mutation of the serine 988 residue of BRCA1 disrupted both the BRCA1-dependent promotion of HR and the suppression of NHR. Similar results were obtained when endogenous Chk2 kinase activity was inhibited by expression of a dominant-negative Chk2 mutant. Surprisingly, the opposing regulation of HR and NHR did not require the ATM phosphorylation sites on serines 1423 and 1524. Together, these data suggest a functional link between recombination control and breast cancer predisposition in carriers of Chk2 and BRCA1 germ line mutations. We propose a dual regulatory role for BRCA1 in maintaining genome integrity, whereby BRCA1 phosphorylation status controls the selectivity of repair events dictated by HR and error-prone NHR.
Interaction between Heat Shock Proteins and Antimicrobial Peptides (2000)

Drosocin, pyrrhocoricin, and apidaecin, representing the short (18-20 amino acid residues) proline-rich antibacterial peptide family, originally isolated from insects, were shown to act on a target bacterial protein in a stereospecific manner. Native pyrrhocoricin and one of its analogues designed for this purpose protect mice from bacterial challenge and, therefore, may represent alternatives to existing antimicrobial drugs. Furthermore, this mode of action can be a basis for the design of a completely novel set of antibacterial compounds, peptidic or peptidomimetic, if the interacting bacterial biopolymers are known. Recently, apidaecin was shown to enter Escherichia coli and subsequently kill bacteria through sequential interactions with diverse target macromolecules. In this paper report, we used biotin- and fluorescein-labeled pyrrhocoricin, drosocin, and apidaecin analogues to identify biopolymers that bind to these peptides and are potentially involved in the above-mentioned multistep killing process. Through use of a biotin-labeled pyrrhocoricin analogue, we isolated two interacting proteins from E. coli. According to mass spectrometry, Western blot, and fluorescence polarization, the short, proline-rich peptides bound to DnaK, the 70-kDa bacterial heat shock protein, both in solution and on the solid-phase. GroEL, the 60-kDa chaperonin, also bound in solution. Control experiments with an unrelated labeled peptide showed that while binding to DnaK was specific for the antibacterial peptides, binding to GroEL was not specific for these insect sequences. The killing of bacteria and DnaK binding are related events, as an inactive pyrrhocoricin analogue made of all-D-amino acids failed to bind. The pharmaceutical potential of the insect antibacterial peptides is underscored by the fact that pyrrhocoricin did not bind to Hsp70, the human equivalent of DnaK. Competition assay with unlabeled pyrrhocoricin indicated differences in GroEL and DnaK binding and a probable two-site interaction with DnaK. In addition, all three antibacterial peptides strongly interacted with two bacterial lipopolysaccharide (LPS) preparations in solution, indicating that the initial step of the bacterial killing cascade proceeds through LPS-mediated cell entry.
Towards image realism with interactive update rates in complex virtual building environments (1990)

Two strategies, pre-computation before display and adaptive refinement during display, are used to combine interactivity with high image quality in a virtual building simulation. Pre-computation is used in two ways. The hidden-surface problem is partially solved by automatically pre-computing potentially visible sets of the model for sets of related viewpoints. Rendering only the potentially visible subset associated with the current viewpoint, rather than the entire model, produces significant speedups on real building models. Solutions for the radiosity lighting model are pre-computed for up to twenty different sets of lights. Linear combinations of these solutions can be manipulated in real time. We use adaptive refinement to trade image realism for interactivity as the situation requires. When the user is stationary we replace a coarse model using few polygons with a more detailed model. Image-level linear interpolation smooths the transition between differing levels of image realism.
Cytotoxicity of a replication-defective mutant of herpes simplex virus type 1 (1992)

Replication-defective mutants of herpes simplex virus type 1 (HSV-1) may prove useful as vectors for gene transfer, particularly to nondividing cells. Cgal delta 3 is an immediate-early gene 3 (IE 3) deletion mutant of HSV-1 that expresses the lacZ gene of Escherichia coli from the human cytomegalovirus immediate-early control region but does not express viral early or late genes. This vector was able to efficiently infect and express lacZ in cells refractory to traditional methods of gene transfer. However, 1 to 3 days postinfection, Cgal delta 3 induced cytopathic effects (CPE) in many cell types, including neurons. In human primary fibroblasts Cgal delta 3 induced chromosomal aberrations and host cell DNA fragmentation. Other HSV-1 strains that caused CPE, tested under conditions of viral replication-inhibition, included mutants of the early gene UL42, the virion host shutoff function, single mutants of IE 1, IE 2, and IE 3, and double mutants of IE 3 and 4 and IE 3 and 5. Inhibition of viral gene expression by UV irradiation of virus stocks or by preexposure of cells to interferon markedly reduced the CPE. We conclude from these studies that HSV-1 IE gene expression is sufficient for the induction of CPE, although none of the five IE gene products appear to be solely responsible. After infection of human fibroblasts with Cgal delta 3 at a low multiplicity of infection, we were able to recover up to 6% of the input virus 2 weeks later by a superinfection-rescue procedure, even though the virally transduced human cytomegalovirus-lacZ transgene was not expressed at this time. It is therefore likely that inhibition or inactivation of viral IE gene expression, either for establishing latency or for the long-term transduction of foreign genes by HSV-1 vectors, is essential to avoid the death of infected cells.
Examining The Consequences For Year 12 Course Choices (2005)

At the end of secondary school, most students complete a Year 12 certificate. The subjects that students choose to study for this certificate can have a major influence on the educational and career options open to them after finishing school. Dr Sue Thomson explains how particular subjects or subject combinations are more likely to act as gateways to higher education or to vocational education and training, while other combinations are more likely to lead to the workforce.
The Role of Calcium and Phosphorylation of Cytosolic Phospholipase A2 in Regulating Arachidonic Acid Release in Macrophages (1998)

Arachidonic acid release is induced in macrophages with diverse agonists including calcium ionophores, phorbol myristate acetate (PMA), okadaic acid, and the phagocytic particle, zymosan, and correlates with activation of cytosolic phospholipase A2 (cPLA2). The role of calcium and phosphorylation of cPLA2 in regulating arachidonic acid release was investigated. Zymosan induced a rapid and transient increase in [Ca2+]i. This in itself is not sufficient to induce arachidonic acid release since ATP and platelet activating factor (PAF), agonists that induce transient calcium mobilization in macrophages, induced little arachidonic acid release. Unlike zymosan, which is a strong activator of mitogen-activated protein kinase (MAPK), ATP and PAF were weak MAPK activators and induced only a partial and transient increase in cPLA2 phosphorylation (gel shift). However, ATP or PAF together with colony stimulating factor-1 (CSF-1) synergistically stimulated arachidonic acid release. CSF-1 is a strong MAPK activator that induces a rapid and complete cPLA2 gel shift but not calcium mobilization or arachidonic acid release. Arachidonic acid release was more rapid in response to CSF-1 plus ATP or PAF than zymosan and correlated with the time course of the cPLA2 gel shift. Although low concentrations of ionomycin induced a lower magnitude of calcium mobilization than ATP, the response was more sustained resulting in arachidonic acid release. A23187 and ionomycin induced weak MAPK activation, and a partial and transient cPLA2 gel shift. The MAPK kinase inhibitor, PD 98059 suppressed A23187-induced MAPK activation and cPLA2 gel shift but had little effect on arachidonic acid release. These results indicate that in macrophages a transient increase in [Ca2+]i and sustained phosphorylation of cPLA2 can act together to promote arachidonic acid release but neither alone is sufficient. A sustained increase in calcium is sufficient for inducing arachidonic acid release. However, PMA and okadaic acid induce arachidonic acid release without increasing [Ca2+]i, although resting levels of calcium are required, suggesting alternative mechanisms of regulation.
Psoralen and ultraviolet A effects on epidermal ornithine decarboxylase induction and DNA synthesis in the hairless mouse. (1984)

8-Methoxypsoralen (8-MOP), 3-carbethoxypsoralen (3-CP), and 5-methoxypsoralen (5-MOP), with and without ultraviolet A (UVA), were compared as inducers of epidermal ornithine decarboxylase (ODC) and modulators of epidermal DNA synthesis in vivo in female Skh:hairless-1 albino mice. Both 8- and 5-MOP plus UVA induced epidermal ODC. Peak ODC activity was induced 24 hours after treatment, and ODC activity was still elevated at 48 hours. These same treatments also suppressed epidermal DNA synthesis 4 hours after treatment, as measured by tritiated thymidine incorporation. The psoralen 3-CP, which lacks the DNA monoadducts, failed to induce epidermal ODC either alone or with UVA and stimulated rather than suppressed incorporation of the tritiated thymidine.
Neodymium-doped silica lasers in end-pumped fiber geometry (1973)

Fused SiO2 has been used as a new noncrystalline host for the fabrication of two types of neodymium-doped room-temperature lasers, one of which operates at 1.06-μm and the other at 1.08-μm wavelength. The lasers have the geometry of clad optical fibers, with active cores as small as 15-μm diameter by 1-cm length. They are end pumped at 0.590 and 0.5145 μm with a pulsed dye laser and an argon ion laser, respectively. Thresholds as low as 1–2 mW of absorbed pump power in a 40-μm-diam core have been obtained, and eventual pumping with high-radiance semiconductor optical sources appears feasible.
CCAAT Enhancer-binding Protein α Is a Molecular Target of 1,25-Dihydroxyvitamin D3 in MCF-7 Breast Cancer Cells (2008)

Numerous studies have shown that the active form of vitamin D, 1,25(OH)(2)D(3), can exert growth inhibitory effects on human breast cancer cells and mammary tumor growth. However, the molecular mechanisms remain to be fully delineated. This study demonstrates for the first time that CCAAT enhancer-binding protein alpha (C/EBPalpha), a member of the C/EBP family of transcription factors, is induced by 1,25(OH)(2)D(3) and is a potent enhancer of VDR transcription in MCF-7 breast cancer cells. 1,25(OH)(2)D(3) was found to induce C/EBPalpha as well as VDR expression in MCF-7 cells. C/EBPalpha was not detected in MDA-MB-231 cells that are poorly responsive to 1,25(OH)(2)D(3). Antiproliferative effects of 1,25(OH)(2)D(3) and induction of VDR were observed in MDA-MB-231 cells transfected with C/EBPalpha, and knockdown of C/EBPalpha suppressed VDR and antiproliferative effects of 1,25(OH)(2)D(3) in MCF-7 cells. Transfection of C/EBPalpha in MCF-7 cells resulted in a dose-dependent enhancement of hVDR transcription. Our studies show that C/EBPalpha can bind to Brahma (Brm), an ATPase that is a component of the SWI/SNF complex, and cooperate with Brm in the regulation of hVDR transcription in MCF-7 cells. Because the levels of VDR in MCF-7 breast cancer cells correlate with the antiproliferative effects of 1,25(OH)(2)D(3) and because C/EBPalpha has been suggested as a potential tumor suppressor in breast cancer, these findings provide important mechanisms whereby 1,25(OH)(2)D(3) may act to inhibit growth of breast cancer cells. These findings also identify C/EBPalpha as a 1,25(OH)(2)D(3) target in breast cancer cells and provide evidence for C/EBPalpha as a candidate for breast cancer treatment.
Evaluating in Vitro Culture Medium of Gut Microbiome with Orthogonal Experimental Design and a Metaproteomics Approach (2017)

In vitro culture based approaches are time- and cost-effective solutions for rapidly evaluating the effects of drugs or natural compounds against microbiomes. The nutritional composition of the culture medium is an important determinant for effectively maintaining the gut microbiome in vitro. This study combines orthogonal experimental design and a metaproteomics approach to obtaining functional insights into the effects of different medium components on the microbiome. Our results show that the metaproteomic profile respond differently to medium components, including inorganic salts, bile salts, mucin, and short-chain fatty acids. Multifactor analysis of variance further revealed significant main and interaction effects of inorganic salts, bile salts, and mucin on the different functional groups of gut microbial proteins. While a broad regulating effect was observed on basic metabolic pathways, different medium components also showed significant modulations on cell wall, membrane, and envelope biogenesis and cell motility related functions. In particular, flagellar assembly related proteins were significantly responsive to the presence of mucin. This study provides information on the functional influences of medium components on the in vitro growth of microbiome communities and gives insight on the key components that must be considered when selecting and optimizing media for culturing ex vivo microbiotas.
A Rapid Monoclonal Antibody-Based Enzyme Immunoassay (EIA) for the Quantitative Determination of Soluble Fibrin in Plasma (1992)

Soluble fibrin is considered as a molecular marker for intravascular fibrin formation, and impending thrombotic events. Most of the existing assays are less suitable for routine clinical applications and their specificity may be limited. We have developed a sandwich-type EIA with a fibrin-specific MoAb described by us before (Proc Natl Acad Sci 1989; 86: 8951) as the capture antibody. An other MoAb (G8; Thromb Haemostas 1988; 60: 145) with an epitope in the carboxyl-terminal sections of the fibrin alpha-chains, was labeled with peroxidase and used as the tagging antibody. The EIA is calibrated against plasma spiked with known concentrations of soluble fibrin. The time-to-result of the EIA is only 1.5 h. Concentrations as low as 0.5 micrograms soluble fibrin/ml plasma are readily measureable. Heparin has no effect on the results. Fibrinogen and fibrin(ogen) degradation products are not detected. The values of fibrinopeptide A and soluble fibrin values found with the "COA-SET soluble fibrin" assay correlated well with the soluble fibrin values found with our EIA i.e. r = 0.998 and 0.984, respectively. The run-to-run variabilities were 7.9% and 6.6% for samples with low and high soluble fibrin concentrations, respectively. The within-run variabilities were 2.5, 1.8, 4.0 and 4.6% for samples with 1, 0.5, 0.25 and 0.125 micrograms soluble fibrin/ml, respectively. The sensitivity, specificity, accuracy and short time-to-result make our EIA suitable for routine clinical applications and the monitoring of the effectivity of heparinization.
Key components to the recent performance increases of solution processed non-fullerene small molecule acceptors (2015)

Within the last year, the intensive development of π-conjugated small molecule acceptors has yielded viable alternatives to fullerene acceptors in state-of-the-art organic photovoltaic devices.
Serine Phosphorylation, Chromosomal Localization, and Transforming Growth Factor-β Signal Transduction by Human (1996)

The transforming growth factor-beta (TGF-beta) superfamily regulates a multitude of cellular and developmental events. TGF-beta family ligands signal through transmembrane serine/threonine kinase receptors whose downstream effectors are largely unknown. Using genetic data from the fruit fly, we have identified a downstream effector of TGF-beta-induced signaling. TGF-beta signaling protein-1 (BSP-1) is rapidly phosphorylated in response to TGF-beta. Localization of bsp-1 to chromosome 4q28 suggests a role in carcinogenesis. These data suggest that BSP-1 is the prototype of a new class of signaling molecules.
Vaccinia Virus Intermediate and Late Promoter Elements Are Targeted by the TATA-Binding Protein (2006)

Vaccinia virus replicates in the cytoplasm of the host cell and encodes its own RNA polymerase and transcription factors. The proteins that target the poxvirus RNA polymerase to intermediate- and late-class promoters have not been identified. In this study, representatives of the intermediate and late promoters were characterized at the nucleotide level to identify essential motifs. Both intermediate and late viral promoters are shown to have an essential element suggestive of TATA boxes, which are potential targets for the TATA-binding protein (TBP). Several approaches were used to test for TBP requirement in vaccinia virus transcription, including overexpression of TBP, expression of a dominant negative mutant of TBP, RNA interference, and expression of adenovirus E1A protein, which inactivates TBP. In each case, the results support an essential role for TBP in vaccinia virus intermediate- and late-gene transcription. These findings indicate that poxviruses have integrated TBP as a central feature into an otherwise heterologous transcription system. A model for transcriptional switching, in which both intermediate and late promoter elements are targeted by TBP that recruits viral transcription factors to assemble a functional complex on their cognate promoters and a dysfunctional, repressed complex on the other class, is proposed.
CROSSTALK BETWEEN NUCLEAR AND MITOCHONDRIAL GENOMES (1996)

This review focuses on molecular mechanisms that underlie the communication between the nuclear and mitochondrial genomes in eukaryotic cells. These genomes interact in at least two ways. First, they contribute essential subunit polypeptides to important mitochondrial proteins; second, they collaborate in the synthesis and assembly of these proteins. The first type of interaction is important for the regulation of oxidative energy production. Isoforms of the nuclear-coded subunits of cytochrome c oxidase affect the catalytic functions of its mitochondrially coded subunits. These isoforms are differentially regulated by environmental and developmental signals and probably allow tissues to adjust their energy production to different energy demands. The second type of interaction requires the bidirectional flow of information between the nucleus and the mitochondrion. Communication from the nucleus to the mitochondrion makes use of proteins that are translated in the cytosol and imported by the mitochondrion. Communication from the mitochondrion to the nucleus involves metabolic signals and one or more signal transduction pathways that function across the inner mitochondrial membrane. An understanding of both types of interaction is important for an understanding of OXPHOS diseases and aging.
Fingerprinting genomes using PCR with arbitrary primers (1990)

Simple and reproducible fingerprints of complex genomes can be generated using single arbitrarily chosen primers and the polymerase chain reaction (PCR). No prior sequence information is required. The method, arbitrarily primed PCR (AP-PCR), involves two cycles of low stringency amplification followed by PCR at higher stringency. We show that strains can be distinguished by comparing polymorphisms in genomic fingerprints. The generality of the method is demonstrated by application to twenty four strains from five species of Staphylococcus, eleven strains of Streptococcus pyogenes and three varieties of Oryza sativa (rice).