gebhart/patrepeval huggingface dataset:
Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia (2001)

BCR/ABL, the oncoprotein responsible for chronic myeloid leukemia (CML), transforms hematopoietic cells through both Ras-dependent and -independent mechanisms. Farnesyl protein transferase inhibitors (FTIs) were designed to block mutant Ras signaling, but they also inhibit the growth of transformed cells with wild-type Ras, implying that other farnesylated targets contribute to FTI action. In the current study, the clinical candidate FTI SCH66336 was characterized for its ability to inhibit BCR/ABL transformation. When tested against BCR/ABL-BaF3 cells, a murine cell line that is leukemogenic in mice, SCH66336 potently inhibited soft agar colony formation, slowed proliferation, and sensitized cells to apoptotic stimuli. Quantification of activated guanosine triphosphate (GTP)-bound Ras protein and electrophoretic mobility shift assays for AP-1 DNA binding showed that Ras effector pathways are inhibited by SCH66336. However, SCH66336 was more inhibitory than dominant-negative Ras in assays of soft agar colony formation and cell proliferation, suggesting activity against targets other than Ras. Cell cycle analysis of BCR/ABL-BaF3 cells treated with SCH66336 revealed G2/M blockade, consistent with recent reports that centromeric proteins that regulate the G2/M checkpoint are critical farnesylated targets of FTI action. Mice injected intravenously with BCR/ABL-BaF3 cells developed acute leukemia and died within 4 weeks with massive splenomegaly, elevated white blood cell counts, and anemia. In contrast, nearly all mice treated with SCH66336 survived and have remained disease-free for more than a year. Furthermore, SCH66336 selectively inhibited the hematopoietic colony formation of primary human CML cells. As an oral, nontoxic compound with a mechanism of action distinct from that of ABL tyrosine kinase inhibition, FTI SCH66336 shows promise for the treatment of BCR/ABL-induced leukemia.
Asymmetric distribution of the Listeria monocytogenes ActA protein is required and sufficient to direct actin‐based motility (1995)

Listeria monocytogenes is a Gram-positive facultative intracytoplasmic bacterial pathogen that exhibits rapid actin-based motility in eukaryotic cells and in cell-free cytoplasmic extracts. The protein product of the actA gene is required for bacterial movement and is normally expressed in a polarized fashion on the bacterial surface. Here we demonstrate that the ActA protein is sufficient to direct motility in the absence of other L. monocytogenes gene products, and that polarized localization of the protein is required for efficient unidirectional movement. We have engineered a fusion protein combining ActA with the C-terminal domain of the LytA protein of Streptococcus pneumoniae, which mediates high-affinity binding to DEAE-cellulose and to choline moieties present in the S. pneumoniae cell wall. DEAE-cellulose fragments or S. pneumoniae coated uniformly with the ActA/LytA fusion protein nucleate actin filament growth in cytoplasmic extracts, but do not move efficiently. However, when ActA/LytA-coated S. pneumoniae is grown to polarize the distribution of the fusion protein, the bacteria exhibit unidirectional actin-based movement similar to the normal movement of L. monocytogenes.
Depolarization of laser radiation in a nonlinear medium (1993)

We consider the depolarization of multimode laser radiation in a nonlinear anisotropic medium. The multimodal structure of the radiation leads to the smoothing of irregularities in the polarization of the light that propagates through the medium. With respect to depolarization, the anisotropic medium is shown to behave as the isotropic one does when the intensity of the radiation is sufficiently high. The characteristic depolarization lengths in some media are evaluated.
Normalization of Genomic DNA Using Duplex-Specific Nuclease (2010)

An application of duplex-specific nuclease (DSN) normalization technology to whole-genome shotgun sequencing of genomes with a large proportion of repetitive DNA is described. The method uses a thermostable DSN from the Kamchatka crab that specifically hydrolyzes dsDNA. In model experiments on human genomic DNA, we demonstrated that DSN normalization of double-stranded DNA formed during C0t analysis is effective against abundant repetitive sequences with high sequence identity, while retaining highly divergent repeats and coding regions at base-line levels. Thus, DSN normalization applied to C0t analysis can be used to eliminate evolutionarily young repetitive elements from genomic DNA before sequencing, and should prove invaluable in studies of large eukaryotic genomes, such as those of higher plants.
Fourier reconstruction of non‐uniformly sampled, aliased data (2004)

The Fourier reconstruction algorithm can regularize many kinds of non‐uniformly sampled data. One significant problem in reconstruction of seismic data is aliasing. In this abstract we present an extension of Fourier reconstruction that can interpolate uniformly and non‐uniformly sampled, aliased seismic data. Like other spatial and wavenumber domain interpolation algorithms, our method makes use of the unaliased lower part of the spectrum.
Strategy for achieving selective killing of carcinomas. (1994)

Carcinomas are malignancies derived from epithelial cells that frequently respond poorly to conventional chemotherapy. Selective expression or transduction of toxin genes to carcinomas, i.e. molecular chemotherapy, may offer important advantages over conventional chemotherapy. As one approach to developing a means of selectively expressing toxin genes, the transcriptional regulatory sequences of a gene expressed in multiple carcinomas were used to direct expression of the herpes simplex virus thymidine kinase (HSVtk) coding sequences. The secretory leukoprotease inhibitor (SLPI) gene was found to be expressed in lung, breast, oropharyngeal, bladder, endometrial, ovarian and colorectal carcinomas. The tissue-specific transcriptional regulatory sequences were isolated and used to construct a chimeric gene in which the SLPI sequences directed HSVtk expression. SLPI-expressing carcinomas were reduced in number by transduction of the SLPI-directed toxin plasmid plus ganciclovir, but the same treatment had no effect on a cell line that did not express SLPI. These results suggest that SLPI-directed therapeutic genes could be used for directing toxicity to carcinoma tissues, especially if combined with other targeting strategies.
Computer analysis of retroviral pol genes: assignment of enzymatic functions to specific sequences and homologies with nonviral enzymes. (1986)

A computer analysis of the amino acid sequences from the putative gene products of retroviral pol genes has revealed a 150-residue segment that is homologous with the ribonuclease H of Escherichia coli. The segment occurs at the carboxyl terminus of the region assigned to the 90-kDa reverse transcriptase polypeptide. In contrast, a section nearer the amino terminus of this sequence can be aligned with nonretroviral polymerases. The order of activities in the pol gene is thus: polymerase-ribonuclease-endonuclease. On another note, all retroviral endonuclease sequences contain a consensus zinc-binding "finger." This should not be confused with the well-known zinc requirement of reverse transcriptases.
Asymmetric tandem organic photovoltaic cells with hybrid planar-mixed molecular heterojunctions (2004)

We demonstrate high-efficiency organic photovoltaic cells by stacking two hybrid planar-mixed molecular heterojunction cells in series. Absorption of incident light is maximized by locating the subcell tuned to absorb long-wavelength light nearest to the transparent anode, and tuning the second subcell closest to the reflecting metal cathode to preferentially absorb short-wavelength solar energy. Using the donor, copper phthalocyanine, and the acceptor, C60, we achieve a maximum power conversion efficiency of ηP=(5.7±0.3)% under 1 sun simulated AM1.5G solar illumination. An open-circuit voltage of VOC⩽1.2V is obtained, doubling that of a single cell. Analytical models suggest that power conversion efficiencies exceeding 6.5% can be obtained by this architecture.
Gradient generation by an osmotic pump and the behavior of human mesenchymal stem cells under the fetal bovine serum concentration gradient (2007)

This paper describes a method to generate a concentration gradient using an osmosis-driven pump, without the need for bulky peripheral devices, such as an electric syringe pump or a pneumatic pump. By the osmosis, the flow in the microfluidic channel can be controlled even to a very slow speed (nanolitre scale), which enables its application to generate the stable and wide (width = 4 mm) concentration gradient profile, even within a short flow path. A computational simulation was also performed to predict the local distribution of the solute concentration and velocity-pressure profile in the microfluidic chip. The performance of the osmosis-driven pump was evaluated by culturing human mesenchymal stem cells within the concentration gradient of fetal bovine serum. The effects of the gradient on attachment, viability and morphology of the cells were analyzed and quantified. The cell density in a higher serum concentration region was twice greater than that in the pure culture media. The compact, cost-effective, self-powered and osmosis-based gradient generation system can be useful for biomedical and chemical applications.
2-Cyclopenten-1-one, a New Inducer of Heat Shock Protein 70 with Antiviral Activity (1996)

The cytoprotective role of heat shock proteins (HSP) described in variety of human diseases, including ischemia, inflammation, and infection, suggests new therapeutic strategies relying upon the development of drugs that selectively turn on heat shock genes. Cyclopentenone prostaglandins, which contain an alpha, beta-unsaturated carbonyl group in the cyclopentane ring and possess antiviral activity against several RNA and DNA viruses, were shown to function as signal for HSP synthesis in a nonstressful situation in a variety of mammalian cells. We now report that 2-cyclopenten-1-one selectively induces the expression of the 70-kDa HSP (HSP70) in human cells, through cycloheximide-sensitive activation of heat shock transcription factor 1 (HSF1). The alpha, beta-unsaturated carbonyl group is the key structure triggering HSF1 activation. Induction is associated with antiviral activity during infection with vesicular stomatitis virus. These results identify the molecular structure of natural prostaglandins responsible for HSF1 activation and open new perspectives in the search for novel antiviral and cytoprotective drugs.
Spatial distributions of local illumination color in natural scenes (2015)

In natural complex environments, the elevation of the sun and the presence of occluding objects and mutual reflections cause variations in the spectral composition of the local illumination across time and location. Unlike the changes in time and their consequences for color appearance and constancy, the spatial variations of local illumination color in natural scenes have received relatively little attention. The aim of the present work was to characterize these spatial variations by spectral imaging. Hyperspectral radiance images were obtained from 30 rural and urban scenes in which neutral probe spheres were embedded. The spectra of the local illumination at 17 sample points on each sphere in each scene were extracted and a total of 1904 chromaticity coordinates and correlated color temperatures (CCTs) derived. Maximum differences in chromaticities over spheres and over scenes were similar. When data were pooled over scenes, CCTs ranged from 3000 K to 20,000 K, a variation of the same order of magnitude as that occurring over the day. Any mechanisms that underlie stable surface color perception in natural scenes need to accommodate these large spatial variations in local illumination color.
IMPACT OF RUNOFF ON SALT INTRUSION OF YANGTZE ESTUARY (2011)

Based on one-dimensional and two-dimensional mathematical coupling models of tidal current and salinity from Datong to Yangtze estuary, the impacting scope of salt intrusion are calculated when the runoff of Datong from 4,500m3/s to 30,000m3/s, and the maximum and average value of salinity at each representative point of the estuary are given. When flow of Datong is less than 10,000 m3/s, if projects of water transfer, pumping and diversion are not taken into account at the lower reaches of Datong, the maximum salinity at the downstream reaches of Xuliujing and the average salinity at the downstream reaches of Baimaosha will exceed drinking water criteria.
Radioiodinated Flavones for in Vivo Imaging of β-Amyloid Plaques in the Brain (2005)

In vivo imaging of beta-amyloid (A beta) peptide aggregates in the brain may lead to early detection of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of AD treatment. The purpose of this study was to develop novel amyloid imaging agents based on flavone as a core structure. Radioiodinated flavone derivatives were designed and synthesized. The binding affinities of flavone derivatives for A beta aggregates varied from 13 to 77 nM. When in vitro plaque labeling was carried out using post-mortem AD brain sections, all flavones intensely stained not only amyloid plaques but also cerebrovascular amyloids. In biodistribution studies using normal mice, they displayed high brain uptakes ranging from 3.2 to 4.1% ID/g at 2 min postinjection. The radioactivity washed out from the brain rapidly (0.5-1.9% ID/g at 30 min), which is highly desirable for amyloid imaging agents. The results in the study suggest that these classes of radioiodinated flavones may be useful candidates as potential imaging agents for amyloid plaques.
Autoreactive epitopes defined by diabetes-associated human monoclonal antibodies are localized in the middle and C-terminal domains of the smaller form of glutamate decarboxylase. (1993)

The gamma-aminobutyrate-synthesizing enzyme glutamate decarboxylase (GAD; L-glutamate 1-carboxy-lyase, EC 4.1.1.15) is a major target of autoantibodies associated with both early and late stages of pancreatic beta-cell destruction and development of type 1 diabetes. We have used five monoclonal anti-islet-cell antibodies (MICAs 1,2,3,4, and 6) derived from a newly diagnosed diabetic patient to probe the autoimmune epitopes in the enzyme. All the MICAs specifically recognized the smaller GAD protein, GAD65, and did not recognize the nonallelic GAD67 protein. A series of N-terminal, C-terminal, and internal deletion mutants, as well as protein footprinting, were used to identify the target regions in GAD65. Immunoprecipitation revealed two major native epitope areas in the GAD65 molecule. The first, defined by MICAs 1 and 3, is destroyed by deleting 41 amino acids at the C terminus but is also dependent on intact amino acids 244-295. This epitope (or epitopes) may span both middle and C-terminal domains of the protein. The second conformational epitope region, defined by MICAs 4 and 6, is dependent on intact amino acids 245-295 but is not affected by deletion of 110 amino acids at the C terminus and is therefore confined to domain(s) in the middle of the molecule. MICA 2 recognizes a linear epitope close to the C terminus. Thus, the N-terminal domain of GAD65, which differs most significantly from GAD67, does not harbor the MICA epitopes. Rather subtle amino acid differences in the middle and C-terminal domains define the GAD65-specific autoimmune epitopes. Analysis of sera from 10 type 1 diabetic patients suggests that MICAs 1, 3, 4, and 6 represent a common epitope recognition in this disease, whereas the MICA 2 epitope is rare. Furthermore, autoantibodies in some sera are restricted to the MICA 1/3 epitope, suggesting that this epitope may represent a single dominant epitope in the early phases of beta-cell autoimmunity.
PTPσ Is a Receptor for Chondroitin Sulfate Proteoglycan, an Inhibitor of Neural Regeneration (2009)

Chondroitin sulfate proteoglycans (CSPGs) present a barrier to axon regeneration. However, no specific receptor for the inhibitory effect of CSPGs has been identified. We showed that a transmembrane protein tyrosine phosphatase, PTPsigma, binds with high affinity to neural CSPGs. Binding involves the chondroitin sulfate chains and a specific site on the first immunoglobulin-like domain of PTPsigma. In culture, PTPsigma(-/-) neurons show reduced inhibition by CSPG. A PTPsigma fusion protein probe can detect cognate ligands that are up-regulated specifically at neural lesion sites. After spinal cord injury, PTPsigma gene disruption enhanced the ability of axons to penetrate regions containing CSPG. These results indicate that PTPsigma can act as a receptor for CSPGs and may provide new therapeutic approaches to neural regeneration.
Antitumor Agent Calixarene 0118 Targets Human Galectin-1 as an Allosteric Inhibitor of Carbohydrate Binding (2012)

Calix[4]arene compound 0118 is an angiostatic agent that inhibits tumor growth in mice. Although 0118 is a topomimetic of galectin-1-targeting angiostatic amphipathic peptide Anginex, we had yet to prove that 0118 targets galectin-1. Galectin-1 is involved in pathological disorders like tumor endothelial cell adhesion and migration and therefore presents a relevant target for therapeutic intervention against cancer. Here, (15)N-(1)H HSQC NMR spectroscopy demonstrates that 0118 indeed targets galectin-1 at a site away from the lectin's carbohydrate binding site and thereby attenuates lactose binding to the lectin. Flow cytometry and agglutination assays show that 0118 attenuates binding of galectin-1 to cell surface glycans, and the inhibition of cell proliferation by 0118 is found to be correlated with the cellular expression of the lectin. In general, our data indicate that 0118 targets galectin-1 as an allosteric inhibitor of glycan/carbohydrate binding. This work contributes to the clinical development of antitumor calixarene compound 0118.
Plasmalemmal proteins of cultured vascular endothelial cells exhibit apical-basal polarity: analysis by surface-selective iodination. (1986)

Vascular endothelium in vivo appears to function as a polarized epithelium. To determine whether cellular polarity exists at the level of the plasma membrane, we have examined cultured endothelial monolayers for evidence of differential distribution of externally disposed plasmalemmal proteins at apical and basal cell surfaces. Lactoperoxidase beads were used to selectively label the apical surfaces of confluent endothelial monolayers, the total surfaces of nonenzymatically resuspended cells, and the basal surfaces of monolayers inverted on poly-L-lysine-coated coverslips, while maintaining greater than 98% viability in all samples. Comparison of the SDS PAGE radioiodination patterns obtained for each surface revealed a number of specific bands markedly enriched on either apical or basal surface. This polarized distribution involved membrane-associated as well as integral membrane proteins and was observed in several strains of bovine aortic endothelial cells, as well as in both primary and passaged human umbilical vein endothelial cells. In contrast, two morphologically nonpolarized cell types, bovine aortic smooth muscle and mouse peritoneal macrophages, did not display differential localization of integral membrane proteins. Polarized distribution of integral membrane proteins was established before the formation of a confluent monolayer. When inverted (basal-side-up) monolayers were returned to culture, the apical-side-up pattern was reexpressed within a few days. These results demonstrate that cell surface-selective expression of plasmalemmal proteins is an intrinsic property of viable endothelial cells in vitro. This apical/basal asymmetry of membrane structure may provide a basis for polarized endothelial functions in vivo.
Significance of Neutrophil Activation in Reactional Lepromatous Leprosy: Effects of Thalidomide <i>in vivo</i> and <i>in vitro</i>. Activation in Adjuvant Disease (1978)

A proportion of circulating neutrophils is able to reduce nitroblue tetrazolium (NBT) &lt;i&gt;in vitro&lt;/i&gt;. Such cells show blue formazan precipitates in their cytoplasm (FP cells). The proportion of FP cells is raised in many bacterial infections because of increased oxido-reductive activity (activation). This may also be induced &lt;i&gt;in vitro&lt;/i&gt; by incubation with endo-toxin. We have previously reported that, while in lepromatous leprosy (LL) there was no activation, a significant elevation in proportion of FP cells took place in reactional lepromatous leprosy (RLL). RLL is reported to be a form of immune complex disease, therefore, neutrophils would be involved in tissue damage. Signs and symptoms of RLL are dramatically improved by thalidomide. We have now studied neutrophil activation in patients with RLL just before and during treatment with thalidomide. Clinical improvement produced by this drug took place before lowering the proportion of FP cells. Concomitant infectious processes induced activation even if patients were under thalidomide treatment. Thalidomide, tested &lt;i&gt;in vitro&lt;/i&gt;, did not affect spontaneous reduction of NBT by neutrophils, nor did it block endotoxin-induced activation. The therapeutic effect of thalidomide is not related to properties inhibiting neutrophil activation. RLL has features that resemble those of adjuvant disease (ADJ). The latter is induced in the rat by injecting killed mycobacteria suspended in an oily vehicle. Inflammatory lesions, owing mainly to delayed hypersensitivity, appear in joints, skin and eyes. Thalidomide has suppressive properties concerning the signs of ADJ. We now studied neutrophil activation in rats of two strains: one susceptible to ADJ and the other refractory. Neutrophils from rats of both strains were able to become activated by &lt;i&gt;in vitro&lt;/i&gt; incubation with endotoxin, latex particles and &lt;i&gt;Staphylococcus aureus&lt;/i&gt; suspensions. After injection of mycobacteria, rats from the refractory strain showed little or no ADJ or neutrophil activation, despite the presence of inflammation at the injected site and gross enlargement of draining lymph nodes. Susceptible rats had a very intense ADJ. There was also a significant increase in proportion of FP cells, but this took place shortly after injection of mycobacteria and before signs of ADJ or acme of local inflammation had taken place. Activation disappeared by the time that ADJ became apparent. Significant neutrophil activation did not occur when susceptible rats received the oily vehicle alone. Our findings do not support the hypothesis that tissue damage in RLL is due &lt;i&gt;solely&lt;/i&gt; to neutrophil action by a mechanism similar to that of immune complex disease. Activation may be in RLL as in ADJ a specific phenomenon induced by a lymphokine.