gebhart/patrepeval huggingface dataset:
Identification of Kinases Regulating Prostate Cancer Cell Growth Using an RNAi Phenotypic Screen (2012)

As prostate cancer progresses to castration-resistant disease, there is an increase in signal transduction activity. Most castration-resistant prostate tumors continue to express the androgen receptor (AR) as well as androgen-responsive genes, despite the near absence of circulating androgen in these patients. The AR is regulated not only by its cognate steroid hormone, but also by interactions with a constellation of co-regulatory and signaling molecules. Thus, the elevated signaling activity that occurs during progression to castration resistance can affect prostate cancer cell growth either through the AR or independent of the AR. In order to identify signaling pathways that regulate prostate cancer cell growth, we screened a panel of shRNAs targeting 673 human kinases against LNCaP prostate cancer cells grown in the presence and absence of hormone. The screen identified multiple shRNA clones against known and novel gene targets that regulate prostate cancer cell growth. Based on the magnitude of effect on growth, we selected six kinases for further study: MAP3K11, DGKD, ICK, CIT, GALK2, and PSKH1. Knockdown of these kinases decreased cell growth in both androgen-dependent and castration-resistant prostate cancer cells. However, these kinases had different effects on basal or androgen-induced transcriptional activity of AR target genes. MAP3K11 knockdown most consistently altered transcription of AR target genes, suggesting that MAP3K11 affected its growth inhibitory effect by modulating the AR transcriptional program. Consistent with MAP3K11 acting on the AR, knockdown of MAP3K11 inhibited AR Ser 650 phosphorylation, further supporting stress kinase regulation of AR phosphorylation. This study demonstrates the applicability of lentiviral-based shRNA for conducting phenotypic screens and identifies MAP3K11, DGKD, ICK, CIT, GALK2, and PSKH1 as regulators of prostate cancer cell growth. The thorough evaluation of these kinase targets will pave the way for developing more effective treatments for castration-resistant prostate cancer.
Methylation Status of Genes in Non-Neoplastic Mucosa From Patients With Ulcerative Colitis-Associated Colorectal Cancer (2010)

RUNX3, MINT1, and COX-2 are potential biomarkers for detecting the presence of CRC in patients with UC. These genes should be evaluated as biomarkers for colorectal dysplasia.
Synthesis and biological evaluation of hydroxamate-based iron chelators (1991)

A new and versatile route to desferrioxamine B (DFO, 1) is described. Hydroxamate reagent 4 was elaborated in a series of high yield steps to the tert-butoxycarbonyl nitrile 11, which provided DFO in three transformations. The intermediate 11 could also be utilized in the preparation of DFO analogues which contain terminal N-acyl groups other than acetyl. The methodology was further employed in the syntheses of the DFO polyether analogues 2 and 3, beginning with the 3,6,9-trioxadecylation of N-(tert-butoxycarbonyl)-O-benzylhydroxylamine. Polyethers 2 and 3 are neutral molecules, which are somewhat more lipophilic than the parent DFO. Polyether hydroxamate 2 was shown to be nearly 3 times as effective as desferrioxamine at clearing iron in rats.
Inhibitory effect of methyl gallate and gallic acid on oral bacteria (2008)

This study examined the ability of methyl gallate (MG) and gallic acid (GA), the main compounds of gallo-tannins in Galla Rhois, to inhibit the proliferation of oral bacterial and the in vitro formation of Streptococcus mutans biofilms. The antimicrobial activities of these compounds were evaluated in vitro using the broth microdilution method and a beaker-wire test. Both MG and GA had inhibitory effects on the growth of cariogenic (MIC<8 mg/ml) and periodontopathic bacteria (MIC=1 mg/ml). Moreover, these compounds significantly inhibited the in vitro formation of S. mutans biofilms (MG, 1 mg/ml; GA, 4 mg/ml; P<0.05). MG was more effective in inhibiting bacterial growth and the formation of S. mutans biofilm than GA. In conclusion, MG and GA can inhibit the growth of oral pathogens and S. mutans biofilm formation, and may be used to prevent the formation of oral biofilms.
Characterization of virulence and PCR-DGGE profiles of Fusarium avenaceum from western Canadian Prairie Ecozone of Saskatchewan (2010)

Abstract Fusarium avenaceum isolates causing fusarium head blight (FHB) in wheat were collected from the Canadian Prairies and Mixed Wood Plains Ecozones. A total of 91 isolates were grouped into 15 phenotypes and 10 VCGs which formed seven ITS rDNA phylogenetic clades and three EF-1α PCR-DGGE groups. Variation in virulence within F. avenaceum isolates ranged from high to avirulent on wheat. In general, virulent isolates demonstrated greater host range and geographic distribution, while avirulent isolates had a limited spread. Virulent isolates demonstrated greater heat tolerance, colour plasticity and growth rate compared with avirulent isolates. Overall, data indicate that pathogen dynamics and outbreaks might be influenced by the abundance ratio of virulent/avirulent isolates related to climate characteristics of each agro-region. The characterization of F. avenaceum ‘sensu lato’ isolates, obtained from western and eastern ecozones, provided baseline information on the variation that exists for this FHB-causing species. Combined with environmental or ecological information, this knowledge could establish a consistent, long-term management of the pathogen.
Simulated Annealing in Crystallography (1991)

X-ray crystallography (see Refs. 1 , 2 for reviews) is an increasingly impor­ tant tool for understanding structure, function, and control of biological macromolecules. Developments in genetics, data collection, and computer hardware have produced an unprecedented growth of macromolecular crystallographic studies. X-ray crystallography produces large amounts of diffraction data, whose interpretation is entirely dependent upon the availability of powerful computers and sophisticated algorithms. After crystallization and data collection, several computational procedures are required to solve and refine the structure. These procedures include methods of phasing, density modification, chain tracing, refinement, and correction of errors. Many of these computational procedures can be formulate:d as nonlinear optimization problems: One tries to optimize a target function, usually thc discrcpancy bctween observed and computed diffraction data, as a function of certain parameters, such as phases, scale factors between structure factors, or parameters of an atomic model. Optimization problems in macromolecular crystallography suffer from the multiple minimum problem. A case in point is crystallographic refine­ ment, in which one wants to improve the agreement of an atomic model with the diffraction data. The high-dimensionality of the parameter space of the atomic model (typically three times the number of atoms) introduces many local minima of the target function; thus, gradient descent methods, such as conjugate gradient minimization or least-squares methods (3),
General Bayesian estimation for speckle noise reduction in optical coherence tomography retinal imagery (2010)

An important image post-processing step for optical coherence tomography (OCT) images is speckle noise reduction. Noise in OCT images is multiplicative in nature and is difficult to suppress due to the fact that in addition the noise component, OCT speckle also carries structural information about the imaged object. To address this issue, a novel speckle noise reduction algorithm was developed. The algorithm projects the imaging data into the logarithmic space and a general Bayesian least squares estimate of the noise-free data is found using a conditional posterior sampling approach. The proposed algorithm was tested on a number of rodent (rat) retina images acquired in-vivo with an ultrahigh resolution OCT system. The performance of the algorithm was compared to that of the state-of-the-art algorithms currently available for speckle denoising, such as the adaptive median, maximum a posteriori (MAP) estimation, linear least squares estimation, anisotropic diffusion and wavelet-domain filtering methods. Experimental results show that the proposed approach is capable of achieving state-of-the-art performance when compared to the other tested methods in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), edge preservation, and equivalent number of looks (ENL) measures. Visual comparisons also show that the proposed approach provides effective speckle noise suppression while preserving the sharpness and improving the visibility of morphological details, such as tiny capillaries and thin layers in the rat retina OCT images.
Effect of iodide on total antioxidant status of human serum (2000)

Free radicals and subsequent lipid peroxidation have been implicated in the pathogenesis of several degenerative and chronic diseases which are also treated frequently in spas. There are some data arising from previous studies which support an antioxidant or scavenging effect of iodide, being the essential ingredient of a therapeutically used local brine. The aim of the study was to test the antioxidant capacity of iodide in human serum. For this reason we measured the so-called Total Antioxidant Status determined by a colorimetric method, which reflects the protection against the attack of reactive oxygen species, including enzymic and non-enzymic antioxidants. Exogenous iodide applied as NaI, shows a significantly increased antioxidant capacity in comparison with NaCl at a concentration of 15 microM, which is quite comparable to the upper range of serum iodide levels achieved through balneo-therapeutical intervention. This result is in accordance with previous results from in vitro depolymerization experiments with hyaluronic acid. The antioxidant effect of 15 microM NaI has been found to be approaching the physiologically relevant concentration of ascorbic acid (50 microM).
Green Fluorescent Protein Retroviral Vectors: Low Titer and High Recombination Frequency Suggest a Selective Disadvantage (1997)

Green fluorescent protein (GFP) has been used as a reporter molecule for gene expression because it fluoresces green after blue-light excitation. Inclusion of this gene in a vector could allow rapid, nontoxic selection of successfully transduced cells. However, many attempts by our laboratory to isolate stable retroviral producer cell clones secreting biologically active vectors containing either the highly fluorescent S65T-GFP mutant or humanized GFP have failed. Vector plasmids containing various forms of GFP and the neomycin resistance gene were transfected into three different packaging cell lines and fluorescence was observed for several days, but stable clones selected with G418 no longer fluoresced. Using confocal microscopy, the brightest cells were observed to contract and die within a matter of days. RNA slot-blot analysis of retroviral producer supernatants showed no viral production from the GFP plasmid-transfected clones, although all clones derived after transfection with an identical retroviral construct not containing GFP produced virus. Genomic Southern analysis of the GFP-transduced clones showed a much higher probability of rearrangement of the priviral sequences than in the control non-GFP clones. Overall, 18/34 S65T-GFP clones and 17/33 humanized-GFP clones had rearrangements, whereas 2/15 control non-GFP clones had rearrangements. Hence, producer cells expressing high levels of these GFP genes seem to be selected against, with stable clones undergoing major rearrangements or other mutations that both abrogate GFP expression and prevent vector production. These observations indicate that GFP may not be an appropriate reporter gene for gene transfer applications in our vector/packaging system.
Direct Observation of Ballistic Transport in GaAs (1985)

We present the first direct evidence of hot electrons traversing ballistically a thin GaAs layer. The energy distribution of the hot electrons associated with the momentum in the direction of the current was measured with the use of a tunneling-hot-electron-transfer amplifier as an electron spectrometer. The width of the ballistic peak was found to be about 60 meV for hot electrons with excess energy of some 300 meV above the thermal electrons. Those values are close to the expected initial injection values.
Real-time vital optical imaging of precancer using anti-epidermal growth factor receptor antibodies conjugated to gold nanoparticles. (2003)

Recent developments in photonic technology provide the ability to noninvasively image cells in vivo; these new cellular imaging technologies have the potential to dramatically improve the prevention, detection, and therapy of epithelial cancers. Endoscope-compatible microscopies, such as optical coherence tomography and reflectance confocal microscopy, image reflected light, providing a three-dimensional picture of tissue microanatomy with excellent spatial resolution (1-10 micro m). However, their ability to image molecular biomarkers associated with cancer is limited. Here, we describe a new class of molecular specific contrast agents for vital reflectance imaging based on gold nanoparticles attached to probe molecules with high affinity for specific cellular biomarkers. The application of gold bioconjugates for vital imaging of precancers is demonstrated using cancer cell suspensions, three-dimensional cell cultures, and normal and neoplastic fresh cervical biopsies. We show that gold conjugates can be delivered topically for imaging throughout the whole epithelium. These contrast agents have potential to extend the ability of vital reflectance microscopies for in vivo molecular imaging. They can potentially enable combined screening, detection, and therapy of disease using inexpensive imaging systems; such tools could allow mass screening of diseases such as cancer in resource-poor settings.
Dimer structure of the ribosomal protein L7/L12 probed by energy transfer (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDimer structure of the ribosomal protein L7/L12 probed by energy transferA. P. G. M. Thielen, J. Antonie Maassen, Jan Kriek, and Wim MoellerCite this: Biochemistry 1984, 23, 26, 6668–6674Publication Date (Print):December 18, 1984Publication History Published online1 May 2002Published inissue 18 December 1984https://pubs.acs.org/doi/10.1021/bi00321a059https://doi.org/10.1021/bi00321a059research-articleACS PublicationsRequest reuse permissionsArticle Views21Altmetric-Citations9LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Differentiation of Embryonic Stem Cell Lines Generated from Adult Somatic Cells by Nuclear Transfer (2001)

Embryonic stem (ES) cells are fully pluripotent in that they can differentiate into all cell types, including gametes. We have derived 35 ES cell lines via nuclear transfer (ntES cell lines) from adult mouse somatic cells of inbred, hybrid, and mutant strains. ntES cells contributed to an extensive variety of cell types, including dopaminergic and serotonergic neurons in vitro and germ cells in vivo. Cloning by transfer of ntES cell nuclei could result in normal development of fertile adults. These studies demonstrate the full pluripotency of ntES cells.
Assembly of an active enzyme by the linkage of two protein modules (1997)

The feasibility of creating new enzyme activities from enzymes of known function has precedence in view of protein evolution based on the concepts of molecular recruitment and exon shuffling. The enzymes encoded by the Escherichia coli genes purU and purN, N10-formyltetrahydrofolate hydrolase and glycinamide ribonucleotide (GAR) transformylase, respectively, catalyze similiar yet distinct reactions. N10-formyltetrahydrofolate hydrolase uses water to cleave N10-formyltetrahydrofolate into tetrahydrofolate and formate, whereas GAR transformylase catalyses the transfer of formyl from N10-formyltetrahydrofolate to GAR to yield formyl-GAR and tetrahydrofolate. The two enzymes show significant homology (approximately 60%) in the carboxyl-terminal region which, from the GAR transformylase crystal structure and labeling studies, is known to be the site of N10-formyltetrahydrofolate binding. Hybrid proteins were created by joining varying length segments of the N-terminal region of the PurN gene (GAR binding region) and the C-terminal (N10-formyltetrahydrofolate binding) region of PurU. Active PurN/PurU hybrids were then selected for by their ability to complement an auxotrophic E. coli strain. Hybrids able to complement the auxotrophs were purified to homogeneity and assayed for activity. The specific activity of two hybrid proteins was within 100- to 1000-fold of the native purN GAR transformylase validating the approach of constructing an enzyme active site from functional parts of others.
Development of vacuum plasma sprayed thin-film SOFC for reduced operating temperature (2000)

The reduction of the operating temperature of planar solid oxide fuel cells (SOFCs) to an intermediate temperature regime of 650–800°C is an important objective in current development activities worldwide, in order to reduce production costs and improve long-term stability. In addition, existing conventional SOFC production processes must be further developed towards automated production lines, and new manufacturing processes with the potential for mass production must be established to meet the strict cost targets for the successful introduction of SOFCs in the strongly competitive energy market. DLR the German aerospace research centre has developed a novel planar thin-film SOFC concept which is based on advanced plasma spray processes. These manufacturing techniques allow the subsequent deposition of the entire membrane-electrode assembly (MEA) onto a porous metallic substrate within a very short process time, and has the potential to be developed into an automated continuous production process. By applying the plasma spray technology single cells were fabricated and characterised as having high performance in the temperature range 750–900°C and good long-term behaviour. Further development work will concentrate on the assembly of stacks with several large-scale cells with dimensions of 10 × 10 and 20 × 20 cm2, in order to obtain stack performance and durability results.
WNT signaling modulates the diversification of hematopoietic cells (2000)

WNT proteins compose a family of secreted signaling molecules that regulate cell fate and behavior. The possible influence of WNTs on hematopoietic cell fate was examined. Both hematopoietic progenitor cell (HPC)-enriched embryonic avian bone marrow cells and the quail mesodermal stem cell line QCE6 were used for these studies. Under optimized conditions, the bone marrow and QCE6 cells behaved identically and developed into red blood cells (RBCs), monocytes, macrophages, granulocytes, and thrombocytes. This broad range of blood cell phenotypes exhibited by QCE6 cells was dependent on their active expression of WNT11. However, when QCE6 cells were prevented from producing WNT11-by expression of a stably transfected WNT11 antisense transgene-the cultures were dominated by highly vacuolated macrophages. RBCs were absent from these cultures, and the presence of monocytes was greatly diminished. Exposure of these WNT11 antisense cells to soluble WNT11 or WNT5a restored the broad range of blood cell phenotypes exhibited by parental QCE6 cells. Overexpression of WNT protein in QCE6 cells further increased the prevalence of RBCs and monocytes and greatly diminished the appearance of macrophages. Accordingly, treatment of HPC-enriched bone marrow cultures with soluble WNT11 or WNT5a inhibited macrophage formation. Instead, monocytes and RBCs were the prevalent cells displayed by WNT-treated bone marrow cultures. Together, these data indicate that WNTs may play a major role in regulating hematopoietic cell fate.
Expression of VHIII-associated cross-reactive idiotype on human B lymphocytes. Association with staphylococcal protein A binding and Staphylococcus aureus Cowan I stimulation (1991)

It has been demonstrated that staphylococcal protein A (SPA) has an "alternative" binding site with specificity for human Ig H chain V region of the VHIII subgroup. Because the major mitogenic component of Staphylococcus aureus Cowan I (SAC) is SPA, it is possible that SAC stimulates a subpopulation of B cells expressing Ig of the VHIII H chain subgroup. In the present study, we have investigated further the relationship between SPA binding and the expression of VHI- or VHIII-associated cross-reactive idiotype (CRI) on the surface of tonsillar B lymphocytes enriched for the expression or nonexpression of the CRI, and we examined the Ig secreted by cell lines established from these populations of B cells by EBV transformation. The VHIII CRI (D12)-enriched population yielded 21 cell lines, with 67% of them secreting SPA-reactive Ig; in contrast, only 6% (1 of 16) of VHI CRI-expressing lines secreted SPA-reactive Ig. The CRI-negative B cell population yielded 54 cell lines, of which 20% secreted SPA-reactive Ig, as might be anticipated because a majority of VHIII Ig+ B cells will be CRI-. SAC stimulation of CRI+ and CRI- populations showed preferential stimulation of the D12 population. These data support the proposal that SAC stimulation of human B cells is mediated through binding of SPA by its alternative binding site to IgV regions of the VHIII subgroup.
Optic cup and disk extraction from retinal fundus images for determination of cup-to-disc ratio (2008)

The ratio of the optic cup to disc (CDR) in retinal fundus images is one of the principal physiological characteristics in the diagnosis of glaucoma. Currently the CDR is manually determined which can be subjective and limits its use in mass screening. To automatically extract the disc, a variational level set method is proposed in this paper. For the cup, two methods making use of color intensity and threshold level set are evaluated. A batch of 73 retinal images from the Singapore Eye Research Centre was used to assess the performance of the determined CDR to the clinical CDR, and it was found that the threshold and variational level set methods produced 97% accuracy in the determined CDR results, an 18% improvement over the color intensity method. The results indicate potential applicability of the methods for automated and objective mass screening for early detection of glaucoma.