gebhart/patrepeval huggingface dataset:
Tyrosine mutations within the alpha platelet-derived growth factor receptor kinase insert domain abrogate receptor-associated phosphatidylinositol-3 kinase activity without affecting mitogenic or chemotactic signal transduction. (1991)

A phosphatidylinositol-3 (PI-3) kinase activity of unknown biological function associates with tyrosine kinase-containing proteins, including a number of growth factor receptors after ligand stimulation. In the beta platelet-derived growth factor (beta PDGF) receptor, phosphorylation of a specific tyrosine residue within the kinase insert domain was required for its interaction with this enzyme. We show that substitutions of phenylalanine for tyrosine residue 731 or 742 within the kinase insert domain of the alpha PDGF receptor do not impair PDGF-induced tyrosine phosphorylation of the receptor or of an in vivo substrate, phospholipase C-gamma. Moreover, phosphatidylinositol turnover in response to ligand stimulation is unaffected. However, both lesions markedly impair receptor association with PI-3 kinase. Antiphosphotyrosine antibody-recoverable PI-3 kinase was also dramatically reduced in PDGF-stimulated cells expressing either mutant receptor. Since neither mutation abolished PDGF-induced mitogenesis or chemotaxis, we conclude that alpha PDGF receptor-associated PI-3 kinase activity is not required for either of these major PDGF signalling functions.
Neural transplant staining with DiI and vital imaging by 2-photon laser-scanning microscopy. (1996)

We are developing a multielectrode silicon "neuroprobe" for maintaining a long-term, specific, two-way electrical interface with nervous tissue. Our approach involves trapping a neuron (from an embryonic rat hippocampus) in a small well with a stimulation/recording electrode at its base. The well is covered with a grillwork through which the neuron's processes are allowed to grow, making synaptic contact with the host tissue, in our case a cultured slice from a rat hippocampus. Each neuroprobe can accommodate 15 neurons, one per well. As a first step in studying neurite outgrowth from the neuroprobe, it was necessary to develop new staining techniques so that neurites from the probe neurons can be distinguished from those belonging to the host, without interference from non-specific background staining. We virtually eliminated background staining through a number of innovations involving dye solubility, cell washing, and debris removal. We also reduced photobleaching and phototoxicity, and enhanced imaging depth by using a 2-photon laser-scanning microscope. We focused on using the popular membrane dye, DiI, however a number of other membrane dyes were shown to provide clear images of neural processes using pulsed illumination at 900 nm. These techniques will be useful to others wishing to follow over time the growth of neurons in culture of after transplantation in vivo, in a non-destructive way.
Direct measurement of changes in intracellular calcium transients during hypoxia, ischemia, and reperfusion of the intact mammalian heart. (1989)

In studies of ischemia and reperfusion, a major experimental problem has been the inability to measure intracellular ionized calcium ([Ca2+]i) in the intact heart. We have developed a new approach in which the bioluminescent calcium indicator aequorin is used to measure [Ca2+]i in the isolated, coronary-perfused ferret heart. Aequorin is loaded into subepicardial myocytes of the left ventricle, and the signals are recorded simultaneously along with isovolumic left ventricular (LV) pressure at a constant pacing rate. This system shows 1) no attenuation or change of time course of LV pressure development or coronary perfusion pressure after aequorin loading; 2) consistent responses to physiological interventions and drugs; 3) individual aequorin and pressure signals that do not require signal averaging for analysis; and 4) [Ca2+]i levels comparable with those reported in tissue or isolated myocyte cell preparations. During 5 minutes of hypoxia, diastolic [Ca2+]i and LV diastolic pressure increased while the systolic values of both [Ca2+]i and pressure decreased. The peak-to-peak systolic [Ca2+]i versus LV isovolumic pressure relation remained close to the control curve. In contrast, during 3 minutes of global ischemia, LV systolic and diastolic pressures fell rapidly, while [Ca2+]i increased substantially. The [Ca2+]i versus pressure relations for both systole and diastole shifted to the right, indicating desensitization of the contractile apparatus to [Ca2+]i. These results provide evidence that different primary mechanisms determine the systolic and diastolic responses to acute hypoxia versus ischemia. During hypoxia, changes in [Ca2+]i handling probably play a major role, while during ischemia, changes in the Ca2+ sensitivity of the myofilaments appear to be of primary importance in the modulation of contractile dysfunction.
Multi-user Quantum Cryptography on Optical Networks (1995)

Abstract Quantum cryptography has been shown to be an effective technology for the secure distribution of keys on point-to-point optical links. We show how the existing techniques can be extended to allow multi-user secure key distribution on optical networks. We demonstrate that using network configurations typical of those found in passive optical network architectures any of the current quantum key distribution protocols can be adapted to implement secure key distribution from any user to any other user. An important feature of these adapted protocols is that the broadcaster, or service provider on the network, does not have to be trusted by the two users who wish to establish a key.
Single-molecule analysis for molecular haplotyping (2004)

In the genome era, there is great hope that genetic approaches such as linkage equilibrium mapping can be used to study common human disorders using a case-control population association study design. Ideally, the parental chromosomes are marked so that chromosomal regions in the form of haplotypes are compared in these studies to increase the power of association. Determining the haplotypes in a diploid individual is a major technical challenge in genetic studies of complex traits. A molecular approach to haplotyping is therefore highly desirable. Recent advances in DNA preparation, separation, labeling, and image analysis provide hope that a strategy of using a three-dye system coupled with DNA distance measurements between alleles will yield haplotype information of sufficiently high quality for genetic studies. In this work, we present the outline of the major challenges one must meet in developing a robust strategy for SNP detection and molecular haplotyping using single molecule analysis.
Study of amplified spontaneous emission systems by the ray-tracing technique (1993)

An implementation of the ray-tracing method for the study of radiation properties, such as intensity and spatial coherence, of an amplified spontaneous emission system is presented. Simple relations that express the controlling effect of the refraction on the output radiation properties are derived. We use analytical expressions, along with detailed numerical calculations, in order to analyze the intensity and the spatial coherence of the output radiation measured in x-ray laser experiments.
High Performance Silicon Nanowire Field Effect Transistors (2003)

Silicon nanowires can be prepared with single-crystal structures, diameters as small as several nanometers and controllable hole and electron doping, and thus represent powerful building blocks for nanoelectronics devices such as field effect transistors. To explore the potential limits of silicon nanowire transistors, we have examined the influence of source-drain contact thermal annealing and surface passivation on key transistor properties. Thermal annealing and passivation of oxide defects using chemical modification were found to increase the average transconductance from 45 to 800 nS and average mobility from 30 to 560 cm2/V·s with peak values of 2000 nS and 1350 cm2/V·s, respectively. The comparison of these results and other key parameters with state-of-the-art planar silicon devices shows substantial advantages for silicon nanowires. The uses of nanowires as building blocks for future nanoelectronics are discussed.
The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence (2007)

Here we report that RNA interference against ATM inhibited p53 accumulation in cells expressing oncogenic STAT5 and cooperated with Rb inactivation to suppress STAT5A-induced senescence. Knocking down ATM was also effective to bypass E2F1-induced senescence and in combination with Rb inactivation, inhibited RasV12-induced senescence. Cells that senesced in response to ca-STAT5A or RasV12 accumulated DNA damage foci and activated ATM, ATR, Chk1, and Chk2, indicating that aberrant oncogene activation induces a DNA damage signaling response. Intriguingly, bypassing oncogene-induced senescence by inactivation of p53 and Rb did not eliminate the accumulation of oncogene-induced DNA damage foci (ODDI), suggesting a mechanism that may limit transformation in immortalized cells.
Interleukin-18 Enhances Atherosclerosis in Apolipoprotein E −/− Mice Through Release of Interferon-γ (2002)

We have previously shown that interferon-gamma (IFN-gamma) is a potent enhancer of atherogenesis. Interleukin-18 (IL-18) promotes inflammatory responses through release of IFN-gamma, although it can also exert direct actions on other inflammatory mediators. In this present study, we determined the effects of IL-18 on atherogenesis and the role of IFN-gamma in this response. Male apolipoprotein E(-/-) mice (apoE(-/-); aged 16 weeks, n=10/group) were fed a normal diet and injected intraperitoneally for 30 days with either recombinant IL-18 (30 ng/g/day) or saline. Atherosclerotic lesion size was quantified in 2 vascular beds: the ascending aorta and the aortic arch. IL-18 administration did not affect serum cholesterol concentrations or lipoprotein-cholesterol distribution; however, exogenous IL-18 administration increased lesion size 2-fold in both the ascending aorta (50 642 +/- 12 515 versus 112 399 +/- 13 227 microm(2) P=0.004; saline versus IL-18 groups, respectively) and the aortic arch (3.1 +/- 0.3% versus 6.2 +/- 0.9% area, P=0.006). Exogenous IL-18 promoted a 4-fold increase in the number of lesion-associated T lymphocytes (11 +/- 3 versus 50 +/- 5 cells; P<0.0001) and cells expressing major histocompatability complex class II (9 +/- 3 versus 40 +/- 6 cells; P=0.0002). To determine the role of IFN-gamma production in this response, exogenous IL-18 was administered to apoE(-/-) mice that were IFN-gamma deficient. These studies demonstrated that lack of endogenous IFN-gamma ablated the effects of IL-18 on atherosclerosis. Therefore, these data strongly implicates IL-18 in the atherogenic process and suggests that IL-18 increases lesion development through enhancement of an inflammatory response involving an IFN-gamma-dependent mechanism. The full text of this article is available at http://www.circresaha.org.
Video Epitomes (2005)

Recently, "epitomes" were introduced as patch-based probability models that are learned by compiling together a large number of examples of patches from input images. In this paper, we describe how epitomes can be used to model video data and we describe significant computational speedups that can be incorporated into the epitome inference and learning algorithm. In the case of videos, epitomes are estimated so as to model most of the small space-time cubes from the input data. Then, the epitome can be used for various modeling and reconstruction tasks, of which we show results for video super-resolution, video interpolation, and object removal. Besides computational efficiency, an interesting advantage of the epitome as a representation is that it can be reliably estimated even from videos with large amounts of missing data. We illustrate this ability on the task of reconstructing the dropped frames in video broadcast using only the degraded video.
Cytolytic T‐cell responses of cancer patients vaccinated with a MAGE antigen (2002)

'Cancer-germline' genes such as the MAGE gene family are expressed in many tumors and in male germline cells but not in normal tissues. They encode shared tumor-specific antigens, which have been used in therapeutic vaccination trials of metastatic melanoma patients. To establish whether there is a correlation between tumoral regressions and T-cell responses against the vaccine antigen, we evaluated the responses of patients vaccinated with a MAGE-3 antigenic peptide or a recombinant virus coding for the peptide. Blood lymphocytes were stimulated with antigenic peptide followed by detection with tetramer, T-cell cloning, and TCR analysis. In 4/9 regressor patients and in 1/14 progressors we found a low level, usually monoclonal cytolytic T lymphocyte response against the MAGE-3 peptide.
Improvement of Glucose Tolerance and Hepatic Insulin Sensitivity by Oligofructose Requires a Functional Glucagon-Like Peptide 1 Receptor (2006)

Nondigestible fermentable dietary fibers such as oligofructose (OFS) exert an antidiabetic effect and increase the secretion of glucagon-like peptide 1 (GLP-1). To determine the importance of GLP-1 receptor-dependent mechanisms for the actions of OFS, we studied high-fat-fed diabetic mice treated with OFS for 4 weeks in the presence or absence of the GLP-1 receptor antagonist exendin 9-39 (Ex-9). OFS improved glucose tolerance, fasting blood glucose, glucose-stimulated insulin secretion, and insulin-sensitive hepatic glucose production and reduced body weight gain. Ex-9 totally prevented the beneficial effects of OFS. Furthermore, GLP-1 receptor knockout mice (GLP-1R(-/-)) were completely insensitive to the antidiabetic actions of OFS. At the molecular level, the effects of OFS on endogenous glucose production correlated with changes of hepatic IRS (insulin receptor substrate)-2 and Akt phosphorylation in an Ex-9-dependent manner. As inflammation is associated with diabetes and obesity, we quantified nuclear factor-kappaB and inhibitor of kappaB kinase beta in the liver. The activity of both intracellular inflammatory effectors was reduced by OFS but, importantly, this effect could not be reverted by Ex-9. In summary, our data show that the antidiabetic actions of OFS require a functional GLP-1 receptor. These findings highlight the therapeutic potential of enhancing endogenous GLP-1 secretion for the treatment of type 2 diabetes.
All‐D‐magainin: chirality, antimicrobial activity and proteolytic resistance (1990)

All-D-magainin-2 was synthesized to corroborate experimentally the notion that the biological function of a surface-active peptide stems primarily from its unique amphiphilic alpha-helical structure. Indeed, the peptide exhibited antibacterial potency nearly identical to that of the all-L-enantiomer. Being highly resistant to proteolysis and non-hemolytic all-D-magainin might have considerable therapeutic importance.
Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I. (1995)

The human T-cell leukemia virus type I Tax protein trans-activates several cellular genes implicated in T-cell replication and activation. To investigate its leukemogenic potential, Tax was targeted to the mature T-lymphocyte compartment in transgenic mice by using the human granzyme B promoter. These mice developed large granular lymphocytic leukemia, demonstrating that expression of Tax in the lymphocyte compartment is sufficient for the development of leukemia. Furthermore, these observations suggest that human T-cell leukemia virus infection may be involved in the development of large granular lymphocytic leukemia.
Polyamines Induce Blood-Brain Barrier Disruption and Edema Formation in the Rat (1996)

Polyamines (PA) are derived from ornithine by the enzyme ornithine decarboxylase (ODC), which is activated very rapidly as acute and delayed responses to brain ischemia and trauma. Polyamines play a role in the disruption of the blood-brain barrier (BBB) in different pathological states. This study examined the effect of exogenous polyamines, administered intracerebrally (i.c.v.) or intracarotidly on BBB function. Putrescine, spermidine and spermine, given individually, were found to disrupt BBB integrity within 15 min of i.c.v. administration (p = 0.03; p = 0.0013; p = 0.042 vs saline treated rats, respectively). The effect was still evident after 1 h; however, since the saline treated rats also showed increased permeability of Evans blue at this time, there was no statistical difference between polyamines or saline treated rats 1 h post injection. When injected into the carotid artery, rapid increase in BBB permeability was found 1 min after putrescine and spermidine (p < 0.01 vs saline), with a slight decline at 15 min. A slower effect was noticed after spermine administration which reached significance only at 15 min. These results suggest a role for PA as mediators of vasogenic edema formation in the brain soon after brain injuries which induce increased production of these compounds.
Indole Derivatives as Potent Inhibitors of Larval Settlement by the Barnacle,Balanus amphitrite (1994)

A potent inhibitor of larval settlement by the barnacle, Balanus amphitrite, was isolated as 2,5,6-tribromo-1-methylgraimne from a marine invertebrate. In comparative tests on the activity of related compounds, such compounds as 2-methylgramine and 2-methyl-3-(morpholinomethyl)-indole exhibited potent inhibitory activity. The inhibitory activity toward larval settlement was found not to be due to toxicity but to a repellent effect.
Lehninger Principles of Biochemistry (5th edition) (2008)

We compared the meaning of experiencing and regulating pain in novices and expert meditators using qualitative interviews. We identified five phenomenological clusters describing relevant features implicated in pain response strategies and meditation. These clusters were organized along a pseudo-gradient, which captured meditation expertise and predicted self-reports related to a pain paradigm and psychometric scales associated with pain and its regulation. These findings advance our understanding of the metacognitive mechanisms and beliefs underlying mindfulness meditation and can inform pain treatment strategies.
Inhibition of PI3Kδ Reduces Kidney Infiltration by Macrophages and Ameliorates Systemic Lupus in the Mouse (2014)

Systemic lupus erythematosus (SLE) is a human chronic inflammatory disease generated and maintained throughout life by autoreactive T and B cells. Class I phosphoinositide 3-kinases (PI3K) are heterodimers composed of a regulatory and a catalytic subunit that catalyze phosphoinositide-3,4,5-P3 formation and regulate cell survival, migration, and division. Activity of the PI3Kδ isoform is enhanced in human SLE patient PBLs. In this study, we analyzed the effect of inhibiting PI3Kδ in MRL/lpr mice, a model of human SLE. We found that PI3Kδ inhibition ameliorated lupus progression. Treatment of these mice with a PI3Kδ inhibitor reduced the excessive numbers of CD4(+) effector/memory cells and B cells. In addition, this treatment reduced serum TNF-α levels and the number of macrophages infiltrating the kidney. Expression of inactive PI3Kδ, but not deletion of the other hematopoietic isoform PI3Kγ, reduced the ability of macrophages to cross the basement membrane, a process required to infiltrate the kidney, explaining MRL/lpr mice improvement by pharmacologic inhibition of PI3Kδ. The observations that p110δ inhibitor prolonged mouse life span, reduced disease symptoms, and showed no obvious secondary effects indicates that PI3Kδ is a promising target for SLE.
A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. (1983)

A syndrome similar to idiopathic parkinsonism developed after intravenous self-administration of an illicit drug preparation in which N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) might have been responsible for the toxicity. In the present study we show that intravenous administration of NMPTP to the rhesus monkey produces a disorder like parkinsonism (akinesia, rigidity, postural tremor, flexed posture, eyelid closure, drooling) that is reversed by the administration of L-dopa. NMPTP treatment decreases the release of dopamine and dopamine accumulates in swollen, distorted axons in the nigrostriatal pathway just above the substantia nigra, followed by severe nerve cell loss in the pars compacta of the substantia nigra and a marked reduction in the dopamine content of the striatum. The pathological and biochemical changes produced by NMPTP are similar to the well-established changes in patients with parkinsonism. Thus, the NMPTP-treated monkey provides a model that can be used to examine mechanisms and explore therapies of parkinsonism.
The Role of Pivot Stiffness on the Dynamic Force Coefficients of Tilting Pad Journal Bearings (2013)

Recent comprehensive experimental data showcasing the force coefficients of commercial size tilting pad journal bearings has brought to rest the long standing issue on the adequacy of the [K,C,M] physical model to represent frequency independent bearing force coefficients, in particular viscous damping. Most experimental works test tilting pad journal bearings (TPJBs) with large preloads, operating over a large wide range of rotor speeds, and with null to beyond normal specific loads. Predictions from apparently simple fluid film bearing models stand poor against the test data which invariably signals to theory missing pivot and pad flexibility effects, and most importantly, ignoring significant differences in bearing and pad clearances due to actual operation, poor installation and test procedures, or simply errors in manufacturing and assembly. Presently, a conventional thermo hydrodynamic bulk flow model for prediction of the pressure and temperature fields in TPJBs is detailed. The model accounts for various pivot stiffness types, all load dependent and best when known empirically, and allows for dissimilar pad and bearing clearances. The algorithm, reliable even for very soft pad-pivots, predicts frequency reduced bearing impedance coefficients and over a certain frequency range delivers the bearing stiffness, damping and virtual mass force coefficients. Good correlation of predictions against a number of experimental results available in the literature bridges the gap between a theoretical model and the applications. Predicted pad reaction loads reveal large pivot deflections, in particular for a bearing with large preloaded pads, with significant differences in pivot stiffness as a function of specific load and operating speed. The question on how pivot stiffness acts to increase (or decrease) the bearing force coefficients, in particular the dynamic stiffness versus frequency, remains since the various experimental data show contradictory results. A predictive study with one of the test bearings varies its pivot stiffness from 10% of the fluid film stiffness to an almost rigid one, 100 times larger. With certainty, bearings with nearly rigid pivot stiffness show frequency independent force coefficients. However, for a range of pad pivot stiffness, 1/10 to ten times the fluid film stiffness, TPJB impedances vary dramatically with frequency, in particular as the excitation frequency grows above synchronous speed. The bearing virtual mass coefficients become negative, thus stiffening the bearing for most excitation frequencies.