gebhart/patrepeval huggingface dataset:
Contrasting roles of tau and microtubule-associated protein 2 in the vinblastine-induced aggregation of brain tubulin. (1984)

Two different proteins, tau and microtubule-associated protein 2 (MAP 2), are able to stimulate tubulin polymerization into microtubules in vitro, but it is not certain if both proteins act by the same mechanism. We have examined the effects of tau and MAP 2 on the vinblastine-induced polymerization of tubulin into spiral filaments. In the presence of tau, vinblastine induced extensive aggregation of tubulin as shown by a large increase in turbidity. The increase in turbidity was accompanied by the formation of large numbers of spirals composed of a filament 40-60 A in diameter. The rate and extent of this aggregation into spirals were dependent on the concentrations of tubulin, tau, and vinblastine. Unlike normal microtubule assembly, this type of aggregation was not inhibited by colchicine or podophyllotoxin. In contrast, MAP 2, even at high concentrations, was less effective than tau at promoting the vinblastine-induced increase in turbidity of tubulin. In fact, MAP 2 strongly inhibited the effect of tau. These results indicate that tau and MAP 2 interact differently with the tubulin molecule in the presence of vinblastine and suggest that the two proteins may play different roles in regulating or promoting microtubule assembly. Vinblastine may thus be a useful probe in analyzing the modes of interactions of tau and MAP 2 with tubulin.
Antibodies specific for the human retinoblastoma protein identify a family of related polypeptides. (1991)

Even though the retinoblastoma gene is one of the best-studied tumor suppressor genes, little is known about its functional role. Like all tumor suppressor gene products, the retinoblastoma protein (pRB) is thought to inhibit some aspect of cell proliferation. It also appears to be a cellular target of several DNA tumor virus-transforming proteins, such as adenovirus E1A, human papillomavirus E7, or simian virus 40 large T antigen. To help in the analysis of pRB, we have prepared a new set of anti-human pRB monoclonal antibodies. In addition to being useful reagents for the study of human pRB, these antibodies display several unexpected properties. They can be used to distinguish different subsets of the pRBs on the basis of their phosphorylation states. Some are able to recognize pRB homologs in other species, including mice, chickens, and members of the genus Xenopus. In addition, some of these antibodies can bind directly to other cellular proteins that, like pRB, were originally identified through their association with adenovirus E1A. These immunologically cross-reactive proteins include the p107 and p300 proteins, and their recognition by antibodies raised against pRB suggests that several members of the E1A-targeted cellular proteins form a structurally and functionally related family.
Recent patents for Hedgehog pathway inhibitors for the treatment of malignancy (2009)

Most reported Hh pathway inhibitors act on the key signaling transducer Smoothened (SMO). Screening of compound libraries using reporter and binding assays have identified a broad diversity of chemical structures that interact with SMO. These screening approaches, followed by conventional medicinal chemistry, have delivered important clinical drug candidates, such as GDC-0449 and XL-139. In addition, modification of the naturally occurring Veratrum alkaloid cyclopamine has resulted in various active analogues, including clinical drug candidate IPI-926. Although there are recent scientific literature reports of small molecules acting downstream of SMO, there is limited patent literature on this mode of Hh pathway inhibition.
Homologous Plasmid Recombination Is Elevated in Immortally Transformed Cells (1989)

The levels of intramolecular plasmid recombination, following transfection of a plasmid substrate for homologous recombination into normal and immortally transformed cells, have been examined by two independent assays. In the first assay, recovered plasmid was tested for DNA rearrangements which regenerate a functional neomycin resistance gene from two overlapping fragments. Following transformation of bacteria, frequencies of recombinationlike events were determined from the ratio of neomycin-resistant (recombinant) colonies to ampicillin-resistant colonies (indicating total plasmid recovery). Such events, yielding predominantly deletions between the directly repeated sequences, were substantially more frequent in five immortal cell lines than in any of three normal diploid cell strains tested. Effects of plasmid replication or interaction with T antigen and of bacterially mediated rejoining of linear molecules generated in mammalian cells were excluded by appropriate controls. The second assay used limited coamplification of a control segment of plasmid DNA, and of the predicted recombinant DNA region, primed by two sets of flanking oligonucleotides. Each amplified band was quantitated by reference to a near-linear standard curve generated concurrently, and recombination frequencies were determined from the ratio of recombinant/control DNA regions. The results confirmed that recombinant DNA structures were generated within human cells at direct repeats in the transfected plasmid and were markedly more abundant in an immortal cell line than in the diploid normal cells from which that line was derived.
Isolation and initial characterization of mouse tumor cells resistant to porphyrin-mediated photodynamic therapy. (1991)

Photodynamic therapy (PDT)-resistant variants of the RIF-1 mouse tumor cell line have been isolated following a protocol of repeated porphyrin incubation and light treatments. Two porphyrin incubation procedures, employing either an extended (16 h) or a short (1 h) incubation, were used in order to obtain cell strains exposed to conditions with differing intracellular photosensitizer localization. Two clones from each PDT porphyrin incubation protocol were selected for in vitro and in vivo analyses based on degree of resistance and plating efficiency. Resistant variants had increased protein content and were larger than the parental RIF-1 cells. In vitro growth rates were similar for all cell strains. Both 16-h PDT-resistant variants exhibited modest resistance to ionizing radiation and one of the 16-h PDT-resistant variants demonstrated increased sensitivity to hyperthermia. The PDT-resistant variants did not exhibit a multidrug resistance phenotype nor did they have altered porphyrin uptake properties. The parental and resistant RIF cells had comparable basal levels of antioxidant enzymes, reduced glutathione and stress proteins, but the number of cells required to produce in vivo tumor growth in 50% of inoculated animals was increased for all PDT-resistant variants. The resistant cells exhibit a stable phenotype and should be useful in studies designed to define PDT mechanisms of action.
Role of MicroRNA-214–Targeting Phosphatase and Tensin Homolog in Advanced Glycation End Product-Induced Apoptosis Delay in Monocytes (2011)

Advanced glycation end products (AGEs) delay spontaneous apoptosis of monocytes and contribute to the development of inflammatory responses. However, the mechanism by which AGEs affect monocyte apoptosis is unclear. We studied the role of microRNA-214 (miR-214) and its target gene in AGE-induced monocytic apoptosis delay. Using microRNA (miRNA) microarray and stem-loop, quantitative RT-PCR assay, we studied genome-wide miRNA expression in THP-1 cells treated with or without AGEs. Significant upregulation of miR-214 was consistently observed in THP-1 and human monocytes treated with various AGEs, and AGE-induced monocytic miR-214 upregulation was likely through activation of receptor for AGEs. A striking increase in miR-214 was also detected in monocytes from patients with chronic renal failure. Luciferase reporter assay showed that miR-214 specifically binds to the phosphatase and tensin homolog (PTEN) mRNA 3'-untranslated region, implicating PTEN as a target gene of miR-214. PTEN expression is inversely correlated with miR-214 level in monocytes. Compared with normal monocytes, AGE-treated monocytes and monocytes from chronic renal failure patients exhibited lower PTEN levels and delayed apoptosis. Overexpression of pre-miR-214 led to impaired PTEN expression and delayed apoptosis of THP-1 cells, whereas knockdown of miR-214 level largely abolished AGE-induced cell survival. Our findings define a new role for miR-214-targeting PTEN in AGE-induced monocyte survival.
Inferring imagined speech using EEG signals: a new approach using Riemannian manifold features (2017)

The results reveal certain aspects that may affect the success of speech imagery classification from EEG signals, such as sound, meaning and word complexity. This can potentially extend the capability of utilizing speech imagery in future BCI applications. The dataset of speech imagery collected from total 15 subjects is also published.
Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson's disease (1997)

A total of 335 patients with early Parkinson's disease (PD) were enrolled in a multicenter, randomized, double-blind trial designed to assess the efficacy and safety of pramipexole. Entry was restricted to patients with idiopathic PD who were not receiving levodopa. Pramipexole was administered according to an ascending dose schedule up to 4.5 mg/d. During the 7-week dose-escalation phase, each subject was titrated to his or her maximally tolerated dose of study medication. This was followed by a 24-week period of maintenance therapy. The mean daily dose during the maintenance period was 3.8 mg. Pramipexole significantly reduced the severity of PD symptoms and signs compared with placebo, as measured by decreases in parts II (Activities of Daily Living) and III (Motor Examination) of the Unified Parkinson's Disease Rating Scale at week 24 compared with baseline (p < or = 0.0001). Differences between the active drug and placebo groups emerged at week 3 (1.5 mg/d) in the ascending-dose interval and persisted throughout the maintenance phase (p < or = 0.0001). The majority of patients completed the study (pramipexole 83%, placebo 80%). In the assessment of adverse events, nausea, insomnia, constipation, somnolence, and visual hallucinations occurred more frequently in the pramipexole treatment group compared with placebo patients. No clinically significant changes were noted in blood pressure or pulse rate. Overall, these results indicate that pramipexole is safe and effective in the treatment of early PD.
Binding of glucagon to lipid bilayers (1990)

At physiological pH and temperature, glucagon binds to liposomes composed of egg phosphatidylcholine and cholesterol (2:1 mol/mol) in a highly specific manner. The chemical reactivities of the functional groups were determined over the concentration range of 1.0 X 10(-6)-3.0 X 10(-8) M by the method of competitive labelling with 1-fluoro-2,4-dinitrobenzene as the labelling reagent. At concentrations above 3 X 10(-7) M, the amino terminal histidine and the two tyrosine residues showed a marked decrease in reactivity in the presence of liposomes, but the reactivity of the Lys-12 N epsilon-amino group was unaltered. At lower concentrations the Lys-12 reactivity also decreased markedly, owing to a change in the environment of this group. These results indicated that two different forms of glucagon existed over the concentration range studied. Both in the absence and presence of liposomes the Lys-12 N epsilon-amino groups showed a transition in reactivity at 1.8 X 10(-7) M. In the presence of liposomes the other functional groups also showed a transition in reactivity at 2 X 10(-7) M but the change was much smaller. The pattern of reactivities were consistent with the X-ray crystallographic structure of the type 2 glucagon trimer being the predominant species at 10(-6) M, with free monomeric glucagon occurring at 3 X 10(-8) M. A trimerization constant of 4 X 10(13) M-2 at pH 7.5 and 37 degrees C was determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Cutting Edge: Ku70 Is a Novel Cytosolic DNA Sensor That Induces Type III Rather Than Type I IFN (2011)

Cytosolic foreign DNA is detected by pattern recognition receptors and mainly induces type I IFN production. We found that transfection of different types of DNA into various untreated cells induces type III IFN (IFN-λ1) rather than type I IFN, indicating the presence of uncharacterized DNA sensor(s). A pull-down assay using cytosolic proteins identified that Ku70 and Ku80 are the DNA-binding proteins. The knockdown studies and the reporter assay revealed that Ku70 is a novel DNA sensor inducing the IFN-lambda1 activation. The functional analysis of IFNL1 promoter revealed that positive-regulatory domain I and IFN-stimulated response element sites are predominantly involved in the DNA-mediated IFNL1 activation. A pull-down assay using nuclear proteins demonstrated that the IFN-λ1 induction is associated with the activation of IFN regulatory factor-1 and -7. Thus, to our knowledge, we show for the first time that Ku70 mediates type III IFN induction by DNA.
Apolipoprotein-mediated removal of cellular cholesterol and phospholipids (1996)

It is widely believed that high density lipoprotein (HDL) protects against cardiovascular disease by removing excess cholesterol from cells of the artery wall. Recent cell culture studies have provided evidence that a major pathway for removing cholesterol and phospholipids from cells is mediated by the direct interactions of HDL apolipoproteins (apo) with plasma membrane domains. These interactions efficiently clear cells of excess sterol by targeting for removal pools of cholesterol that feed into the cholesteryl ester cycle. The precursors for this pathway in vivo are likely to be lipid-free or lipid-poor apolipoproteins generated either by dissociation from the surface of HDL particles or by de novo synthesis. Fibroblasts from subjects with a severe HDL deficiency syndrome called Tangier disease have a cellular defect that prevents apolipoproteins from removing both cholesterol and phospholipids from cells. This defect is associated with a near absence of plasma HDL, markedly below normal low density lipoprotein (LDL) levels, and the appearance of macrophage foam cells in tissues. Thus, an inability of nascent apoA-I to acquire cellular lipids results in a rapid clearance of apoA-I from the plasma, decreased production and increased clearance of LDL, and sterol deposition in tissue macrophages. Although the molecular properties of this pathway are still poorly understood, these studies imply that the apolipoprotein-mediated pathway for removal of cellular lipids is a major source of plasma cholesterol and phospholipids and plays an important role in clearing excess cholesterol from macrophages in vivo.
Glutamate antagonists limit tumor growth (2001)

Neuronal progenitors and tumor cells possess propensity to proliferate and to migrate. Glutamate regulates proliferation and migration of neurons during development, but it is not known whether it influences proliferation and migration of tumor cells. We demonstrate that glutamate antagonists inhibit proliferation of human tumor cells. Colon adenocarcinoma, astrocytoma, and breast and lung carcinoma cells were most sensitive to the antiproliferative effect of the N-methyl-d-aspartate antagonist dizocilpine, whereas breast and lung carcinoma, colon adenocarcinoma, and neuroblastoma cells responded most favorably to the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate antagonist GYKI52466. The antiproliferative effect of glutamate antagonists was Ca(2+) dependent and resulted from decreased cell division and increased cell death. Morphological alterations induced by glutamate antagonists in tumor cells consisted of reduced membrane ruffling and pseudopodial protrusions. Furthermore, glutamate antagonists decreased motility and invasive growth of tumor cells. These findings suggest anticancer potential of glutamate antagonists.
Investigation of signal correlation for spaced and co-located antennas on multipath hf links and implications for the design of SIMO and MIMO systems (2006)

MIMO (Multiple Output Multiple Input) systems employ both transmitting and receiving arrays and space-time coding methods in order to achieve significantly greater channel capacities. Since the data rate possible for digital HF systems is generally comparatively low, it would be very useful if the capacity improvements inherent in MIMO techniques could be exploited at HF. In order to assess this possibility and in order to gain some insight into the optimum design of HF MIMO systems, the characteristics of the digital HF channel are explored in relation to this utilization. To accomplish this a wideband HF simulator, based on a physical model and including time-varying electron density irregularities is employed and used to assess correlation of the received multi-component signal at spaced antennas for different multipath scenarios and ionosphere parameters. The optimum parameters and scenarios for employment of HF MIMO systems are then discussed.
Activation energy for electromigration in Cu films (1991)

Copper is a possible substitute for Al in very large scale integration interconnects because of its higher resistance to electromigration damage (EMD) and its lower electrical resistivity. In the present work, we report on electrical resistance measurements of the activation energy for EMD in Cu films as determined by an isothermal annealing method carried out under high vacuum conditions. Temperature measurement and control were accomplished by means of a Cu thin-film thermistor. The activation energy for EMD of evaporated Cu films was found to be 0.79±0.02 eV.
Formation of ring patterns surrounded by ripples by single-shot laser irradiation with ultrashort pulse width at the solid/liquid interface (2003)

A single pulse (pulse width: 200 fs) was irradiated onto a water/silicon interface. The processed surface had many ring patterns surrounded by sinusoidal patterns within the irradiated spot. The diameter of their rings ranged from 500 nm to 10 μm. It was proposed that the oscillation of a bubble at the interface emitted an acoustic wave around itself and that the melted silicon surface, deformed due to acoustic pressure, solidified instantaneously in the course of the propagation of the acoustic wave on the silicon surface.
Geometric surface processing via normal maps (2003)

We propose that the generalization of signal and image processing to surfaces entails filtering the normals of the surface, rather than filtering the positions of points on a mesh. Using a variational strategy, penalty functions on the surface geometry can be formulated as penalty functions on the surface normals, which are computed using geometry-based shape metrics and minimized using fourth-order gradient descent partial differential equations (PDEs). In this paper, we introduce a two-step approach to implementing geometric processing tools for surfaces: (i) operating on the normal map of a surface, and (ii) manipulating the surface to fit the processed normals. Iterating this two-step process, we efficiently can implement geometric fourth-order flows by solving a set of coupled second-order PDEs. The computational approach uses level set surface models; therefore, the processing does not depend on any underlying parameterization. This paper will demonstrate that the proposed strategy provides for a wide range of surface processing operations, including edge-preserving smoothing and high-boost filtering. Furthermore, the generality of the implementation makes it appropriate for very complex surface models, for example, those constructed directly from measured data.
Lipid Modification of Proteins through Sortase-Catalyzed Transpeptidation (2008)

A general chemoenzymatic method for the site-specific attachment of lipids to protein substrates is described. Sortase A is used to append short lipid-modified oligoglycine peptides to the C terminus of protein substrates bearing a five amino acid sortase A recognition sequence (LPETG). We demonstrate the attachment of a range of hydrophobic modifications in excellent yield (60-90%), including a simple step for removing the sortase enzyme postreaction. Lipoproteins prepared using these procedures were subsequently shown to associate with mammalian cells in a lipid tail-dependent fashion and localized to the plasma membrane and endosomes.
A new approach to primary strengthening of colostomy with Marlex mesh to prevent paracolostomy hernia. (1986)

A new procedure for preventing paracolostomy hernia is described. It has been used since 1979 in 43 patients and is effective in strengthening the colostomy outlet in its common location and affixing the intestine firmly to the aperture. Four years after operation, no hernia or prolapse has occurred in the patients who underwent this procedure.
Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy (2008)

Citicoline supplementation has been used to ameliorate memory disturbances in older people and those with Alzheimer's disease. This study used MRS to characterize the effects of citicoline on high-energy phosphate metabolites and constituents of membrane synthesis in the frontal lobe. Phosphorus ((31)P) metabolite data were acquired using a three-dimensional chemical-shift imaging protocol at 4 T from 16 healthy men and women (mean +/- SD age 47.3 +/- 5.4 years) who orally self-administered 500 mg or 2000 mg Cognizin Citicoline (Kyowa Hakko Kogyo Co., Ltd, Ibaraki, Japan) for 6 weeks. Individual (31)P metabolites were quantified in the frontal lobe (anterior cingulate cortex) and a comparison region (parieto-occipital cortex). Significant increases in phosphocreatine (+7%), beta-nucleoside triphosphates (largely ATP in brain, +14%) and the ratio of phosphocreatine to inorganic phosphate (+32%), as well as significant changes in membrane phospholipids, were observed in the anterior cingulate cortex after 6 weeks of citicoline treatment. These treatment-related alterations in phosphorus metabolites were not only regionally specific, but tended to be of greater magnitude in subjects who received the lower dose. These data show that citicoline improves frontal lobe bioenergetics and alters phospholipid membrane turnover. Citicoline supplementation may therefore help to mitigate cognitive declines associated with aging by increasing energy reserves and utilization, as well as increasing the amount of essential phospholipid membrane components needed to synthesize and maintain cell membranes.