gebhart/patrepeval huggingface dataset:
Suppression of stress protein GRP78 induction in tumor B/C10ME eliminates resistance to cell mediated cytotoxicity. (1993)

Tumor cells undergo self-destruction when incubated with cytotoxic T-cells (CTL) consistent with the observation that suppression of target protein synthesis causes resistance to apoptosis. Resistance to CTL is also induced by stress, suggesting that pathways exist suppressing apoptosis. Here we examine whether stress induced lysis resistance to CTL and tumor necrosis factor alpha involves stress proteins GRP78 and GRP94. We show that inhibition of GRP78 synthesis by transfection of cells with grp78 antisense vector pRSV-78WO leads to inability to induce resistance to CTL or tumor necrosis factor alpha. Resistance induced in untransfected cells is reversible upon stress removal and correlates with GRP78 rephosphorylation, consistent with the notion that phosphorylated GRP78 is nonfunctional. The possibility that GRP78 plays a role in defense against CTL mediated apoptosis is supported by the finding that CTL but not CD4+ cells express a high level of unphosphorylated GRP78.
Facilitate Insight by Non-Invasive Brain Stimulation (2011)

Our experiences can blind us. Once we have learned to solve problems by one method, we often have difficulties in generating solutions involving a different kind of insight. Yet there is evidence that people with brain lesions are sometimes more resistant to this so-called mental set effect. This inspired us to investigate whether the mental set effect can be reduced by non-invasive brain stimulation. 60 healthy right-handed participants were asked to take an insight problem solving task while receiving transcranial direct current stimulation (tDCS) to the anterior temporal lobes (ATL). Only 20% of participants solved an insight problem with sham stimulation (control), whereas 3 times as many participants did so (p = 0.011) with cathodal stimulation (decreased excitability) of the left ATL together with anodal stimulation (increased excitability) of the right ATL. We found hemispheric differences in that a stimulation montage involving the opposite polarities did not facilitate performance. Our findings are consistent with the theory that inhibition to the left ATL can lead to a cognitive style that is less influenced by mental templates and that the right ATL may be associated with insight or novel meaning. Further studies including neurophysiological imaging are needed to elucidate the specific mechanisms leading to the enhancement.
Ping-pong amplification of a retroviral vector achieves high-level gene expression: human growth hormone production (1990)

Retroviral vectors offer major advantages for gene transfer studies but have not been useful for producing proteins in large quantities. This deficiency has resulted in part from interference to superinfection, which limits the numbers of active proviruses in cells. Recently, we found that these vectors amplify when they are added as calcium phosphate precipitates to cocultures of cells that package retroviruses into ecotropic and amphotropic host range envelopes. Helper-free virions from either cell type can infect the other without interference, resulting in theoretically limitless back-and-forth (ping-pong) vector replication. In initial studies, however, amplifications of a vector that contained the human growth hormone gene ceased when the hormone produced was 0.3% or less of cellular protein synthesis. This limit was caused by two factors. First, recombinant shutoff viruses that are replication defective and encode envelope glycoproteins form at a low probability during any round of the vector replication cycle and these spread in cocultures, thereby establishing interference. Single cells in shutoff cocultures therefore synthesize both ecotropic and amphotropic envelope glycoproteins, and they release promiscuous (presumably hybrid) virions. The probability of forming shutoff viruses before the vector had amplified to a high multiplicity was reduced by using small cocultures. Second, cells with large numbers of proviruses are unhealthy and their proviral expression can be unstable. Stable expresser cell clones were obtained by selection. Thereby, cell lines were readily obtained that stably produce human growth hormone as 4 to 6% of the total protein synthesis. A ping-pong retroviral vector can be used for high-level protein production in vertebrate cells.
Phenoxodiol, an experimental anticancer drug, shows potent antiangiogenic properties in addition to its antitumour effects (2005)

Phenoxodiol (2H-1-benzopyran-7-0,1, 3-[4-hydroxyphenyl], PXD) is a synthetic analogue of the naturally-occurring plant isoflavone and anticancer agent, genistein. PXD directly induces mitotic arrest and apoptosis in most cancer cells and is currently undergoing clinical trials, as a chemotherapeutic in ovarian and prostate cancers. We show here that PXD also exhibits potent antiangiogenic properties. Thus, it inhibited endothelial cell proliferation, migration and capillary tube formation and inhibited expression of the matrix metalloproteinase MMP-2, a major matrix degrading enzyme. Importantly, we demonstrate that PXD is functional in vivo since it inhibited the extent of capillary tube invasion in an in vivo model of angiogenesis. We show that phenoxodiol inhibits hallmarks of endothelial cell activation, namely TNF or IL-1 induced E-selectin and VCAM-1 expression and IL-8 secretion. However, PXD had no effect on unstimulated endothelial cells. We also describe that PXD inhibits the lipid kinase sphingosine kinase, which recently has been implicated in endothelial cell activation and angiogenesis as well as oncogenesis. Thus, our results suggest that PXD may be an effective anticancer drug targeting the two drivers of tumour growth--the proliferation of the tumour cells themselves and the angiogenic and inflammatory stimulation of the vasculature.
Developmental territories created by mutual antagonism between Wingless and Decapentaplegic (1996)

Drosophila appendages develop from imaginal discs which become subdivided into distinct regions during normal patterning. At least 3 axes of asymmetry are required to produce a chiral appendage such as a leg. The A/P compartments provide one axis of asymmetry in all discs. In leg and antennal discs, the anterior compartment becomes asymmetric in the D/V axis with decapentaplegic (dpp) expression defining dorsal anterior leg, and wingless (wg) expression defining ventral anterior leg. However, unlike wing discs, no D/V compartment has been demonstrated in legs or antennae. How are the dorsal anterior and ventral anterior territories defined and maintained? Here we show that wg inhibits dpp expression and dpp inhibits wg expression in leg and eye/antennal discs. This mutual repression provides a mechanism for maintaining separate regions of wg and dpp expression in a developing field. We propose the term 'territory' to describe regions of cells that are under the domineering influence of a particular morphogen. Territories differ from compartments in that they are not defined by lineage but are dynamically maintained by continuous morphogen signaling. We propose that the anterior compartment of the leg disc is divided into dorsal and ventral territories by the mutual antagonism between WG and DPP signaling.
High quality ultra thin CVD HfO/sub 2/ gate stack with poly-Si gate electrode (2002)

We have developed and demonstrated an in-situ rapid thermal CVD (RTCVD) process for the fabrication of high quality ultra thin CVD HfO/sub 2/ gate stack that is compatible with conventional self-aligned poly-Si gate technology. These poly-Si gated HfO/sub 2/ gate stack show excellent interface properties, EOT=10.4 /spl Aring/, and leakage current Jg=0.23 mA/cm/sup 2/ @Vg=-1 V which is several orders of magnitude lower than RTO SiO/sub 2/ with poly-Si gate. In addition, the HfO/sub 2/ gate stack is thermally stable in direct contact with n/sup +/-poly Si gate under typical dopant activation conditions. These films also show excellent reliability under high-field electrical stress. We have also fabricated and demonstrated NMOSFETs, and studied boron penetration in HfO/sub 2/ gate stack with p/sup +/-poly Si gate.
Regulation of microglial inflammatory response by histone deacetylase inhibitors (2003)

The activation of microglial cells is involved in the pathogenesis of a variety of neurodegenerative diseases, stroke and traumatic brain injuries. Recent studies suggest that protein acetylation can affect the extent of inflammatory responses. Our aim was to elucidate whether histone deacetylase inhibitors, inducers of protein hyperacetylation, regulate the inflammatory response in neural models of inflammation in vitro and whether neurone-glia interactions affect this regulation. Interestingly, we observed that histone deacetylase inhibitors, such as trichostatin A (TSA) and suberoylanilide hydroxamic acid, strongly potentiated the lipopolysaccharide (LPS)-induced inflammatory response in murine N9 and rat primary microglial cells as well in neural co-cultures and hippocampal slice cultures. TSA clearly potentiated the LPS-induced expression of interleukin (IL)-6 and inducible nitric oxide synthase mRNAs, as well as the secretion of cytokines IL-6, tumour necrosis factor-alpha and macrophage inflammatory protein (MIP)-2, and nitric oxide (NO). Co-culture and slice culture experiments showed that the presence of astrocytes and neurones did not stimulate or prevent the pro-inflammatory potentiation induced by histone deacetylase inhibitor in microglial cells. The potentiation of cytokine and NO responses was blocked by the nuclear factor kappa B (NF-kappa B) inhibitors caffeic acid phenethyl ester and helenalin, demonstrating that the NF-kappa B signalling pathway is involved. The DNA-binding activity of the NF-kappa B complex was strongly increased by LPS treatment but not enhanced by TSA. This suggests that potentiation of the inflammatory response is not dependent on the level of cytoplasmic NF-kappa B activation or DNA-binding activity but that site of action may be at the level of transcriptional regulation. Our results suggest that environmental stresses, ageing, diet and diseases that regulate protein acetylation status may also affect the inflammatory response.
Automatic alignment of geographic features in contemporary vector data and historical maps (2017)

With large amounts of digital map archives becoming available, the capability to automatically extracting information from historical maps is important for many domains that require long-term geographic data, such as understanding the development of the landscape and human activities. In the previous work, we built a system to automatically recognize geographic features in historical maps using Convolutional Neural Networks (CNN). Our system uses contemporary vector data to automatically label examples of the geographic feature of interest in historical maps as training samples for the CNN model. The alignment between the vector data and geographic features in maps controls if the system can generate representative training samples, which has a significant impact on recognition performance of the system. Due to the large number of training data that the CNN model needs and tens of thousands of maps needed to be processed in an archive, manually aligning the vector data to each map in an archive is not practical. In this paper, we present an algorithm that automatically aligns vector data with geographic features in historical maps. Existing alignment approaches focus on road features and imagery and are difficult to generalize for other geographic features. Our algorithm aligns various types of geographic features in document images with the corresponding vector data. In the experiment, our alignment algorithm increased the correctness and completeness of the extracted railroad and river vector data for about 100% and 20%, respectively. For the performance of feature recognition, the aligned vector data had a 100% improvement on the precision while maintained a similar recall.
Photochemistry on surfaces. 2. Intermolecular electron transfer on colloidal alumina-coated silica particles (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotochemistry on surfaces. 2. Intermolecular electron transfer on colloidal alumina-coated silica particlesPrashant V. Kamat and William E. FordCite this: J. Phys. Chem. 1989, 93, 4, 1405–1409Publication Date (Print):February 1, 1989Publication History Published online1 May 2002Published inissue 1 February 1989https://pubs.acs.org/doi/10.1021/j100341a046https://doi.org/10.1021/j100341a046research-articleACS PublicationsRequest reuse permissionsArticle Views123Altmetric-Citations13LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Application of Free Energy Perturbation Calculations to the Enantioselective Binding of Peptides toC3-Symmetric Synthetic Receptors (1996)

Free energy perturbation (FEP) is applied to the calculation of the enantioselectivity in binding of three peptide guest molecules to certain C3-symmetric synthetic receptors. The calculations are able to reproduce the observed trends in enantioselection with errors ≤0.7 kcal/mol, and the agreement with experiment is the best with those guests which form stronger complexes. We find that the weakly bound guests sample more conformational space in the receptor complex than do the more strongly binding guests. These results indicate that obtaining the necessary converged ensemble averages is more challenging for the more weakly binding guests because their complexes are structurally more poorly defined. Our simulations also suggest that the high enantioselectivities observed with our receptors arise in large part from the ability of the preferred guest peptides to form, on average, a greater number of hydrogen bonds with the receptor.
Nonrandom rearrangement of chromosome 14 at band q32.33 in human lymphoid malignancies with mature B-cell phenotype. (1989)

Chromosomes were studied in 61 patients with differentiated B-cell malignancies including 21 with non-Hodgkin's lymphoma (NHL), three with hairy cell leukemia (HCL), eight with Waldenström's macroglobulinemia (WM), and 29 with plasma cell disorder. Chromosomally abnormal clones were identified in 35 of 61 patients studied: all with NHL, all with HCL, three of eight with WM, and eight of 29 with plasma cell disorder. The most recurrent chromosomal abnormality, observed in 26 of the 35 patients whose chromosomes were abnormal, was a rearrangement involving chromosome 14, in which an additional segment was attached at band 32 in the long arm to form a 14q+ marker chromosome. This rearrangement was seen in 17 patients with NHL, three with HCL, one with WM, and five with plasma cell disorder. In NHL, the rearrangement correlates with histological subclasses: t(14;18) in all four patients with malignant lymphoma (ML)-follicular, mixed small cleaved and large cell; t(8;14) or its variant form, t(8;22), in all six with ML-small noncleaved cell; and t(11;14) in two of three with ML-diffuse, mixed small and large cell. A t(14;18) was also found in each patient with ML-diffuse, large cell, WM, and multiple myeloma, and a variant three-way translocation, t(5;18;14) (q13;q21;q32), in one with ML-diffuse, small cleaved cell. The donor sites for these 14q+ were assigned to oncogene loci: c-myc (8q24), bcl-1 (11q13), and bcl-2 (18q21). Moreover, the donor sites were also located near immunoglobulin light chain gene loci in each patient with leukemic ML-diffuse, mixed small and large cell, t(2;14) (p13;q32.3), and HCL, t(14;22)(q32.3;q11.2). These findings suggest that chimeric DNA formation, not only between an immunoglobulin gene and a certain oncogene, but also between the IgH gene and one of the IgL genes may be potentially relevant in malignant B-cell proliferation.
Chemical Characterization, Spatial Distribution and Function of a Lipoprotein (Murein-Lipoprotein) of the E. coli Cell Wall. The Specific Effect of Trypsin on the Membrane Structure (1969)

A decrease of the absorbance at 578 nm of a cell wall suspension of mid log phase E. coli occurs when the suspension is incubated with trypsin. The reaction is so rapid that 55% of the total decrease is obtained within the first 2 min [ratio of enzyme to total cell wall protein = 1: 50 (w/w), room temperature]. The rate of the reaction is specific for trypsin when compared with other proteases, different lipases, lysozyme and other glycosidases. A peptide bond especially sensitive to trypsin could be localized within the complex cell wall by the demonstration that the decrease of the absorbance is paralleled by the splitting of the protein from the murein. This protein could be shown to be a lipoprotein with a part of the lipid probably covalently bound to the protein. It is called murein-lipoprotein. The link between the lipoprotein and the murein is -lysine. After trypsin digestion lysine is the only additional amino acid remaining at the murein. The ratio of the amount of lysine to the known constituents of the murein demonsstrates that on the average one lipoprotein molecule is covalently bound to every tenth repeating unit of the murein (N-acetylglucosamine–N-acetylmuramic acid–l-alanine-d-glutamic acid–meso-diaminopimelic acid–d-alanine). After 3 min incubation with trypsin, the isolated lipoprotein molecules have a lysine to arginine ratio of 4:4 as compared with 5:4 in the native molecule. The lipoprotein has an unusual amino acid comosition since it contains about 65% polar amino acids and no glycine, cysteine, proline, phenylalanine, and histidine could be found. On a weight basis the lipoprotein accounts for more than 40% of the rigid layer. Since the murein is held together exclusively by covalent bonds one can get a fairly accurate idea of the distribution of the lipoprotein molecules in the cell wall. About 105 lipoprotein molecules per cell should be distributed 103 Å apart along the glycosidic chains of the murein. The lipoprotein has an important function in stabilizing the total structure of the cell wall. It seems that cleavage of only one peptide bond adjacent to the lysine link between the lipoprotein and the murein causes the rapid decrease of the absorbance and as shown by electron microscopic exmination of ultrathin sections of trypsin treated cell walls, two separated membrane structures appear which otherwise are closely adjacent to one another.
Movement of zymosterol, a precursor of cholesterol, among three membranes in human fibroblasts. (1991)

Where examined, cholesterol is synthesized in the endoplasmic reticulum; however, its precursor, zymosterol, is found mostly in the plasma membrane. The novel implication of these disparate findings is that zymosterol circulates within the cell. In tracing its movements, we have now established the following: (a) in human fibroblasts, zymosterol is converted to cholesterol solely in the rough ER. (b) Little or no zymosterol or cholesterol accumulates in the rough ER in vivo. (c) Newly synthesized zymosterol moves to the plasma membrane without a detectable lag and with a half-time of 9 min, about twice as fast as cholesterol. (d) The pool of radiolabeled zymosterol in the plasma membrane turns over rapidly, faster than does intracellular cholesterol. Thus, plasma membrane zymosterol is not stagnant. (e) [3H]Zymosterol pulsed into intact cells is initially found in the plasma membrane. It is rapidly internalized and is then converted to [3H] cholesterol. Half of the [3H]cholesterol produced returns to the plasma membrane within 30 min of the initial [3H]zymosterol pulse. (f) Nascent zymosterol accumulates in a buoyant sterol-rich intracellular membrane before it reaches the plasma membrane. This membrane also acquires nascent cholesterol, exogenous [3H]zymosterol pulsed into intact cells, and [3H]cholesterol synthesized from the exogenous [3H] zymosterol. These results suggest that at least one sterol moves rapidly and in both directions among the rough endoplasmic reticulum, a sterol-rich intracellular membrane bearing nascent cholesterol, and the plasma membrane.
Grapheme-to-phoneme conversion using Long Short-Term Memory recurrent neural networks (2015)

Grapheme-to-phoneme (G2P) models are key components in speech recognition and text-to-speech systems as they describe how words are pronounced. We propose a G2P model based on a Long Short-Term Memory (LSTM) recurrent neural network (RNN). In contrast to traditional joint-sequence based G2P approaches, LSTMs have the flexibility of taking into consideration the full context of graphemes and transform the problem from a series of grapheme-to-phoneme conversions to a word-to-pronunciation conversion. Training joint-sequence based G2P require explicit grapheme-to-phoneme alignments which are not straightforward since graphemes and phonemes don't correspond one-to-one. The LSTM based approach forgoes the need for such explicit alignments. We experiment with unidirectional LSTM (ULSTM) with different kinds of output delays and deep bidirectional LSTM (DBLSTM) with a connectionist temporal classification (CTC) layer. The DBLSTM-CTC model achieves a word error rate (WER) of 25.8% on the public CMU dataset for US English. Combining the DBLSTM-CTC model with a joint n-gram model results in a WER of 21.3%, which is a 9% relative improvement compared to the previous best WER of 23.4% from a hybrid system.
The Role of Receptor Binding in Drug Discovery (1993)

Radioligand receptor binding has been used extensively to identify and characterize a host of receptors and enzymes targeting virtually every therapeutic area. Many drug discovery programs have been based on the utilization of radioligand receptor binding technology to identify lead compounds which interact with receptors likely to be important in neuronal, immunological, gastrointestinal, and cardiovascular function/dysfunction. There are several obvious advantages to using in vitro receptor binding as a first level screen when compared to in vivo pharmacometric screens. Scientifically, the structure activity data generated in binding assays is a direct reflection of the ligand/receptor interaction minus the complications which result from secondary events, bioavailability, and pharmacodynamic issues. Technically, the binding studies require only a small amount of test compound (< or = 1 mg), while whole animal studies routinely need gram quantities. Similarly, only a small amount of tissue is required, compared with the cost of purchase and maintenance of live animals for in vivo screening. Supply and labor costs are drastically reduced due to the limited volume and test tube based technology of receptor binding. For these reasons receptor binding assays have been utilized with considerable success to discover site specific lead compounds in virtually every therapeutic area.