gebhart/patrepeval huggingface dataset:
Analysis of cavitation dynamics during pulsed laser tissue ablation by optical on-line monitoring (1996)

Flashlamp pumped mid-IR laser systems emitting in the 2-3-/spl mu/m wavelength range are widely used for various medical applications, especially for tissue ablation. Explosive evaporation is inevitably associated with this process due to the short pulse durations of these laser systems and the high absorption of tissue and water in this spectral regime. Tissue displacement and dissection occur in liquid environment as a consequence of the induced cavitation. Depending on the application these processes might enhance the tissue ablation but can also cause adverse tissue effects. The ablation dynamics were investigated by evaluating the change in reflected probe-light intensity re-emitted from the application fiber tip. The ablated cavity and the signal was correlated to fast-flash photographs of the event. Based on this reflection signal a water/tissue discrimination system is introduced which can widely support medical laser applications. In laser sclerostomy ab externo, for example, this approach can be used as a feedback system to automatically control the ablation process. With such a system, adverse effects to adjacent tissue in the anterior chamber of the eye can be minimized.
Expression of E1AF/PEA3, an Ets-related transcription factor in human non-small-cell lung cancers: Its relevance in cell motility and invasion (2001)

Cell invasion and metastasis characterize the malignant potential of non-small-cell lung cancers (NSCLCs). We have previously reported that E1AF, a member of the Ets-related transcription factor family, confers invasive phenotype on breast cancer and oral squamous-cell carcinoma cell lines. In our study, we analyzed the E1AF expression in cell lines and resected tumors of NSCLCs by Northern blot and in situ hybridization analyses and found that 15 of 17 cell lines and 12 of 19 tumors expressed E1AF mRNA while normal lung tissue and concomitant normal cells within tumors did not. To examine the biologic importance of E1AF in NSCLCs, we introduced the E1AF gene into VMRC-LCD and NCI-H226, NSCLC cell lines lacking E1AF expression, and examined cell motility and invasion activities. E1AF-transfected VMRC-LCD cells showed increased cell motility that was 2-fold that of parental and vector-transfected control cells (p < 0.01), and both cell motility and invasion were increased 1.6-fold in NCI-H226 (p < 0.01). Furthermore, hepatocyte growth factor (HGF), which is one of the most effective cell-scattering factors, stimulated the motile and invasive activities in E1AF-transfected VMRC-LCD and NCI-H226 cells but not in their parental or vector-transfected control cells. Ets-1 mRNA expression was found in E1AF-transfected VMRC-LCD cells but not in parental or vector-transfected cells. HGF further induced expression of the Ets-1 and urokinase-type plasminogen activator (uPA) genes specifically in E1AF-transfected cells. These findings suggest that E1AF plays a substantial role in the cell motility and invasion of NSCLCs.
Early warning analysis for social diffusion events (2010)

There is considerable interest in developing predictive capabilities for social diffusion processes, for instance enabling early identification of contentious “triggering” incidents that are likely to grow into large, self-sustaining mobilization events. Recently we have shown, using theoretical analysis, that the dynamics of social diffusion may depend crucially upon the interactions of social network communities, that is, densely connected groupings of individuals which have only relatively few links to other groups. This paper presents an empirical investigation of two hypotheses which follow from this finding: 1.) the presence of even just a few inter-community links can make diffusion activity in one community a significant predictor of activity in otherwise disparate communities and 2.) very early dispersion of a diffusion process across network communities is a reliable early indicator that the diffusion will ultimately involve a substantial number of individuals. We explore these hypotheses with case studies involving emergence of the Swedish Social Democratic Party at the turn of the 20th century, the spread of SARS in 2002-2003, and blogging dynamics associated with potentially incendiary real world occurrences. These empirical studies demonstrate that network community-based diffusion metrics do indeed possess predictive power, and in fact can be significantly more predictive than standard measures.
Thrombin-induced degranulation of cultured bone marrow-derived mast cells. (1984)

This study was undertaken to determine if a plasma protease such as thrombin, a highly specific procoagulant enzyme that has numerous effects on platelets, endothelial cells, and smooth muscle cells, could mediate mast cell activation processes. Our results indicate that at near physiologic levels, thrombin can rapidly trigger mast cell degranulation without activating the 5-lipoxygenase system.
Up-regulation of the connexin43+ GAP junction network in haemopoietic tissue before the growth of stem cells (1994)

The early developmental stages of haemopoiesis are thought to be regulated by paracrine growth factors and by the haemopoietic environment. Are gap junctions involved here? Gap junctions are structures in cell membranes allowing the direct transfer of ions and small molecules between adjacent cells and are known to be involved in development. We have found that although connexin43 gap junctions are rare (0.00016 +/- 0.0002/microns2 tissue) in normal adult mouse marrow their expression is 80-fold higher (0.0292 +/- 0.0147/microns2) in neonatal marrow. One difference between neonatal and adult haemopoietic tissue is that in the latter more haemopoietic cells are dividing. To test if more gap junctions were due to increased division we altered adult blood-formation by mobilizing or destroying end cells--granulocytes and red cells--or by forcing stem cells to divide by making them regenerate an ablated blood-forming system. Mobilizing end cells had no effect on the number or distribution of gap junctions in marrow but forced stem cell division caused a 100-fold increase in gap junction expression and did so before any recognizable haemopoietic cells formed. There were greater than normal numbers of gap junctions in radio-protected adult mouse marrow. The cells coupled by gap junctions are TE-7+ mesodermally derived fibroblasts, STRO-1+ stromal cells, and CD45+ and CD34+ haemopoietic cells. We propose that there is a latent network of Cx43+ gap junctions in normal quiescent marrow. In response to events that call for active division of stem cells this network is amplified and coupled to haemopoietic stem cells, perhaps enabling them to divide.
Prognostic effect of estrogen receptor status across age in primary breast cancer (2007)

Estrogen receptor (ER) status is considered as an important prognostic factor as well as a predictive factor for endocrine responsiveness in breast cancer. We analyzed the distribution of ER status across age and estimated variations in the prognostic impact of ER status related to patients' age and time since diagnosis. Overall, 26,944 patients with primary breast cancer diagnosed from 1989 to 2004 were included. The proportion of ER positive tumors increased over age from 51 to 82%. In multivariate analysis of overall survival, ER positive status was found to be a significantly positive prognostic factor over all age groups. This effect was limited to the first 5 years after diagnosis, RR: 2.08 (95% CI: 1.95-2.22, p < 0.0001). Overall survival during the following 5 years was slightly superior for women with ER negative tumors, RR of death: 0.89 (95% CI: 0.79-1.00, p = 0.049). Results were unchanged in patients who did not receive adjuvant systemic therapy (n = 6,272). Thus, positive ER status does not confer a negative impact on survival in young women as has been previously reported. The inferior prognosis for ER negative patients during the first 5 years after diagnosis changes into a slightly superior residual prognosis compared to ER positive patients independent of use of adjuvant systemic therapy. This may have an impact on future designing of guidelines for adjuvant endocrine therapy beyond 5 years.
Emission Results from the New Development of A Dedicated Hydrogen - Enriched Natural Gas Heavy Duty Engine (2005)

&lt;div class="htmlview paragraph"&gt;Steady state emissions testing on a dynamometer with an 11-liter heavy-duty engine have shown the ability to obtain tail pipe oxides of nitrogen (NO&lt;sub&gt;x&lt;/sub&gt;) emissions of 0.15 g/bhp and below. Equivalence ratios of 0.53 have been achieved over the operating range. The development of a dedicated hydrogen-enriched natural gas (HCNG) engine utilizes a mechanical means to extend the lean limit of combustion through a quiescent intake path. Hydrogen blend ratios of 30-40% have been employed.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Current manufactured natural gas heavy-duty engines use intake swirl as a means of extending the lean limit of combustion for reducing NO&lt;sub&gt;x&lt;/sub&gt; emissions. These engines have shown reductions in NO&lt;sub&gt;x&lt;/sub&gt; emissions with HCNG and lean burn however, are unable to meet 2007 goals. Principals at Collier Technologies, Inc (CTI) have been developing and operating HCNG engines for the past eleven years with dramatic results in NO&lt;sub&gt;x&lt;/sub&gt; and CO emissions. CTI, Hess Microgen and Daewoo Heavy Industries are cooperatively developing the next generation of HCNG heavy-duty engines to meet the stringent 2007 emission requirements.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Transit authorities are researching all possible methods to meet the pending 2007 EPA emissions standards for heavy-duty transportation. Including HCNG, hybrids, pure hydrogen ICE's and fuel cells.&lt;/div&gt;
Archaeal RNA ligase from thermoccocus kodakarensis for template dependent ligation (2016)

Nicking-sealing RNA ligases play a significant biological role in host defense and cellular repair, and have become an important molecular tool in biomedical engineering. Due to the propensity for RNA to form secondary structures, RNA modifying enzymes with elevated optimum temperatures are highly desired. Current characterized double stranded RNA ligases, such as the bacteriophage T4 RNA ligase 2, while possessing good template dependency, are not active at elevated temperatures. The few characterized RNA ligases from thermophiles exhibit high template independency. We synthesize and characterize here, KOD RNA ligase (KOD1Rnl), a thermostable and template dependent RNA ligase from the archaeon, Thermoccocus Kodakarensis. We disclose that a 13 time reduction in template independent ligation can be achieved with the addition of a single stranded DNase, such as RecJ. We also elucidate the effects of the presence of blood proteins on the activity of KOD1Rnl. Template dependent and thermostable RNA ligases, such as KOD RNA ligase, can be utilized in RNA detection, modification and sequencing.
U-90152, a potent inhibitor of human immunodeficiency virus type 1 replication (1993)

Bisheteroarylpiperazines are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). We describe a novel bisheteroarylpiperazine, U-90152 [1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4-[3-(1-methyl eth yl-amino)pyridinyl]piperazine], which inhibited recombinant HIV-1 RT at a 50% inhibitory concentration (IC50) of 0.26 microM (compared with IC50s of > 440 microM for DNA polymerases alpha and delta). U-90152 blocked the replication in peripheral blood lymphocytes of 25 primary HIV-1 isolates, including variants that were highly resistant to 3'-azido-2',3'-dideoxythymidine (AZT) or 2',3'-dideoxyinosine, with a mean 50% effective dose of 0.066 +/- 0.137 microM. U-90152 had low cellular cytotoxicity, causing less than 8% reduction in peripheral blood lymphocyte viability at 100 microM. In experiments assessing inhibition of the spread of HIV-1IIIB in cell cultures, U-90152 was much more effective than AZT. When approximately 500 HIV-1IIIB-infected MT-4 cells were mixed 1:1,000 with uninfected cells, 3 microM AZT delayed the evidence of rapid viral growth for 7 days. In contrast, 3 microM U-90152 totally prevented the spread of HIV-1, and death and/or dilution of the original inoculum of infected cells prevented renewed viral growth after U-90152 was removed at day 24. The combination of U-90152 and AZT, each at 0.5 microM, also totally prevented viral spread. Finally, although the RT amino acid substitutions K103N (lysine 103 to asparagine) and Y181C (tyrosine 181 to cysteine), which confer cross-resistance to several nonnucleoside inhibitors, also decrease the potency of U-90152, this drug retains significant activity against these mutant RTs in vitro (IC50s, approximately 8 microgramM).
Mutations in p53 are frequent in the preneoplastic stage of mouse mammary tumor development. (1993)

Preneoplastic lesions in the mammary gland represent a population of cells at increased risk of progression to tumors. Because p53 is the most commonly mutated gene in human breast cancer, we sought to determine whether mutations in p53 were present in preneoplastic lesions or were acquired during progression to overt tumors. In the mouse mammary gland, hyperplastic alveolar nodules (HAN) are the most common preneoplastic lesion. Analysis of the TM series of transplantable murine HAN outgrowths and tumors allowed the status of p53 to be determined at distinct stages of mammary tumorigenesis. Alterations in the p53 gene or in the pattern of p53 protein expression were observed in all five HAN outgrowth lines examined. Altered expression of p53 protein was detected in 3 of 5 TM HAN outgrowth lines as determined by immunohistochemistry. Overexpression of nuclear p53 was detected in only a fraction of the cells (10-50%) in TM3 and TM4 HAN outgrowths, whereas in tumors that arose from TM4 HAN outgrowths, the proportion of cells overexpressing p53 protein approached approximately 100%. Despite overexpression of p53 in TM3 HAN outgrowths, no tumors have developed in this line. The TM9 outgrowth line exhibited a different pattern of p53 expression by immunohistochemistry: p53 protein was overexpressed in the cytoplasm of virtually all cells in the HAN outgrowths but was localized to the nuclei of TM9 tumor cells. Direct sequencing of p53 transcripts from tumors and cell lines revealed various genetic changes: point mutations in exons 4 and 5 (TM2H, nonsense; TM4, missense); a deletion in exon 5 (TM4); and an insertion in exon 7 (TM3). Although p53 protein was overexpressed in TM9 tumors, it was shown to be wild-type both by immunoprecipitation and direct sequencing of the entire coding region of the cDNA. TM4 cells were homogeneous with respect to mutant p53 genotype and uniformly expressed p53 by immunohistochemical staining in vitro, but transplantation of TM4 cells to fat pads of BALB/c hosts resulted in HAN outgrowths in situ in which < 50% of the cells expressed the mutant p53 at detectable levels. In summary, mutation of the p53 gene and overexpression of p53 protein can occur in preneoplastic mammary epithelial cells, and those mutations are maintained in tumors that arise from the HAN. Conversely, expression of mutant p53 was decreased when cells were grown in situ, implicating the presence of cellular factors that can suppress p53 expression in vivo. These observations demonstrate that the p53 pathway may be a common target for mutation in murine mammary tumorigenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
Mechanisms of action of gabapentin. (1997)

The chemical structure of gabapentin (Neurontin) is derived by addition of a cyclohexyl group to the backbone of gamma-aminobutyric acid (GABA). Gabapentin prevents seizures in a wide variety of models in animals, including generalized tonic-clonic and partial seizures. Gabapentin has no activity at GABAA or GABAB receptors of GABA uptake carriers of brain. Gabapentin interacts with a high-affinity binding site in brain membranes, which has recently been identified as an auxiliary subunit of voltage-sensitive Ca2+ channels. However, the functional correlate of gabapentin binding is unclear and remains under study. Gabapentin crosses several lipid membrane barriers via system L amino acid transporters. In vitro, gabapentin modulates the action of the GABA synthetic enzyme, glutamic acid decarboxylase (GAD) and the glutamate synthesizing enzyme, branched-chain amino acid transaminase. Results with human and rat brain NMR spectroscopy indicate that gabapentin increases GABA synthesis. Gabapentin increases non-synaptic GABA responses from neuronal tissues in vitro. In vitro, gabapentin reduces the release of several mono-amine neurotransmitters. Gabapentin prevents pain responses in several animal models of hyperalgesia and prevents neuronal death in vitro and in vivo with models of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Gabapentin is also active in models that detect anxiolytic activity. Although gabapentin may have several different pharmacological actions, it appears that modulation of GABA synthesis and glutamate synthesis may be important.
Response of Pseudomonas aeruginosa to pyocyanin: mechanisms of resistance, antioxidant defenses, and demonstration of a manganese-cofactored superoxide dismutase (1992)

Pseudomonas aeruginosa produces a blue pigment, pyocyanin. Pyocyanin is a redox-active phenazine compound that kills mammalian and bacterial cells through the generation of reactive oxygen intermediates. We examined the mechanisms by which P. aeruginosa resists pyocyanin. [14C]pyocyanin was taken up by both Escherichia coli and P. aeruginosa, though more slowly by the latter. Cyanide-insensitive respiration, used as an indicator of intracellular superoxide and/or hydrogen peroxide production, was 50-fold less in pyocyanin-treated P. aeruginosa than in E. coli. P. aeruginosa showed less cyanide-insensitive respiration than E. coli upon exposure to other redox-active compounds (paraquat, streptonigrin, and plumbagin). Electron paramagnetic resonance spectrometry and spin trapping showed that P. aeruginosa generated less pyocyanin radical and superoxide than E. coli. Cell extracts from E. coli contained an NADPH:pyocyanin oxidoreductase which increased the rate of reduction of pyocyanin by NADPH. Conversely, cell extracts from P. aeruginosa contained no NADPH:pyocyanin oxidoreductase activity and actually decreased the rate of pyocyanin-mediated NADPH oxidation. Antioxidant defenses could also reduce the sensitivity of P. aeruginosa to pyocyanin. Under culture conditions of limited phosphate, both pyocyanin production and catalase activity were enhanced. Superoxide dismutase activity was also increased under low-phosphate conditions. When cells were grown in a high-phosphate succinate medium, P. aeruginosa formed a previously described iron-superoxide dismutase as well as a manganese-cofactored superoxide dismutase. These results demonstrate that P. aeruginosa resists pyocyanin because of limited redox cycling of this compound and that under conditions favoring pyocyanin production, catalase and superoxide dismutase activities increase.
Cell-surface-expressed T-cell antigen-receptor zeta chain is associated with the cytoskeleton. (1995)

The T-cell antigen receptor zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. zeta chain can associate with certain protein tyrosine kinases and retains the capacity to transduce signals independently of the other receptor subunits. Thus, zeta chain could couple cell-surface-expressed T-cell antigen receptors to the intracellular signal-transduction apparatus by its association with various intracellular molecules in addition to tyrosine kinases. In the process of searching for zeta chain-associated molecules we observed that after lysis of resting T cells with Triton X-100, zeta chain is localized in the detergent-insoluble fraction, in addition to its presence in the detergent-soluble fraction. Treatment of T cells with cytochalasin B, an actin-depolymerizing agent, leads to the complete dissociation of zeta chain from the Triton-insoluble fraction, suggesting a linkage between zeta chain and the cytoskeletal matrix. We have also determined that cytoskeletal-associated zeta chain is expressed on the cell surface. Furthermore, a tyrosine-phosphorylated 16-kDa zeta chain was detected only in the Triton-insoluble cytoskeletal fraction of resting T cells. zeta chain also maintains its association with the cytoskeleton when expressed in COS cells, inferring that the cytoskeletal elements involved in this linkage may be ubiquitous. Finally, we have localized a 42-amino acid region in the intracytoplasmic domain of zeta chain, which is crucial for maximal interaction between zeta chain and the cytoskeleton. Anchorage of cell-surface-expressed zeta chain to the cytoskeleton in resting T cells may facilitate recycling of receptor complexes and/or allow the transduction of external stimuli into the cell.
Activation of a Phosphotyrosine Phosphatase by Tyrosine Phosphorylation (1993)

Regulation of cell proliferation, differentiation, and metabolic homeostasis is associated with the phosphorylation and dephosphorylation of specific tyrosine residues of key regulatory proteins. The phosphotyrosine phosphatase 1D (PTP 1D) contains two amino terminally located Src homology 2 (SH2) domains and is similar to the Drosophila corkscrew gene product, which positively regulates the torso tyrosine kinase signal transduction pathway. PTP activity was found to be regulated by physical interaction with a protein tyrosine kinase. PTP 1D did not dephosphorylate receptor tyrosine kinases, despite the fact that it associated with the epidermal growth factor receptor and chimeric receptors containing the extracellular domain of the epidermal growth factor receptor and the cytoplasmic domain of either the HER2-neu, kit-SCF, or platelet-derived growth factor beta (beta PDGF) receptors. PTP 1D was phosphorylated on tyrosine in cells overexpressing the beta PDGF receptor kinase and this tyrosine phosphorylation correlated with an enhancement of its catalytic activity. Thus, protein tyrosine kinases and phosphatases do not simply oppose each other's action; rather, they may work in concert to maintain a fine balance of effector activation needed for the regulation of cell growth and differentiation.