gebhart/patrepeval huggingface dataset:
The contributions of oestrogen receptor isoforms to the development of papillary and anaplastic thyroid carcinomas (2007)

Oestrogen (E2) is known to promote the proliferation of thyroid papillary carcinoma cells (KAT5). However, the molecular mechanism responsible is not well understood. In the study reported herein, the localization of ER alpha (ERalpha) and beta (ERbeta) in KAT5 and anaplastic carcinoma cells (FRO) was studied by immunofluorescence staining and by immunoblotting the proteins in subcellular fractions. Cell proliferation and apoptosis were also determined together with the expression of relevant proteins. The pattern of the subcellular localization of ERalpha and ERbeta differed between papillary and anaplastic cancer. Upon E2 treatment, the level of ERalpha increased in the nuclei of papillary cancer cells but ERbeta remained unchanged. The level of mitochondrial ERbeta surpassed that of ERalpha in anaplastic cancer cells. The different locations of ERalpha and ERbeta in KAT5 and FRO agreed with the finding that E2 promoted the proliferation of KAT5 but inhibited or did not affect that of FRO cells, and with the proposed functions of these two receptors. E2 inhibited the level of Bax in the mitochondria of papillary cancer, followed by a decrease of cytochrome c and/or apoptosis-inducing factor (AIF) release from the mitochondria into the cytosol. However, in anaplastic cancer, E2 promoted the expression of Bax in the mitochondria and the release of cytochrome c and/or AIF from mitochondria into the cytosol. Our results may explain the differences in epidemiology and responses to anti-tumour therapy between papillary and anaplastic cancer in terms of the subcellular localization of ER isoforms. In conclusion, the findings provide evidence to support the observation that E2 is an important factor in the development of thyroid cancer. The subcellular localization of ERalpha and ERbeta may account for the different pathogenesis of thyroid papillary and anaplastic cancers.
Epigenetics of prostate cancer (2007)

Prostate cancer is the most common type of cancer other than skin cancer and the second leading cause of cancer death in men in the United States. Its exact causes are unknown. Several risk factors have been associated with prostate cancer including age, race, family history and diet. Epigenetic mechanisms including DNA methylation and histone modifications are important means of gene regulation and play essential roles in diverse biological and disease processes. Recently, frequent epigenetic aberrations such as DNA hypo- and hypermethylation and altered histone acetylation and methylation have been observed in prostate cancer affecting the expression and function of a large array of genes, leading to tumorigenesis, tumor progression and metastasis. In this chapter, we examined the current literature regarding epigenetic changes in prostate cancer and discuss the clinical potential of cancer epigenetics for the diagnosis and treatment of this disease.
Development of a reconstituted collagen tendon prosthesis. A preliminary implantation study. (1989)

A reconstituted collagen tendon prosthesis was developed and implanted in rabbit Achilles tendons. The prosthesis was prepared by extruding type-I collagen into fibers and crosslinking it either with glutaraldehyde or with dehydrothermal treatment followed by exposure to carbodiimide. A tendon prosthesis was assembled by coating a longitudinal array of the fibers with uncrosslinked collagen. In one leg of the rabbit, the Achilles tendon was replaced with the synthetic tendon; in the contralateral leg of the animal, the tendon was excised, devascularized, and anastomosed as an autogenous graft. The autogenous tendon grafts were seen to be infiltrated centrally by fibroblasts and capillaries ten weeks postoperatively and to have been partially replaced by repair tissue twenty weeks postoperatively. Three weeks after implantation, all collagen implants were noted to have been infiltrated with fibrous tissue. At ten weeks, reorganization of collagenous tissue was observed in and around the prostheses, and the carbodiimide-crosslinked implants had been resorbed and replaced by normal-appearing neotendon. The implants that had been treated with glutaraldehyde were resorbed more slowly and were surrounded by more inflammatory cells, compared with the prostheses that had been treated with carbodiimide. Neotendon in the glutaraldehyde-treated prostheses matured more slowly. When the implants were examined at intervals after the operation, their mechanical properties approached those of fresh tendon. The initial strength of the carbodiimide-treated implants was lower than that of the fresh autogenous grafts. Twenty weeks after implantation, the strength and modulus of the carbodiimide-treated implants approached those of fresh tendon.(ABSTRACT TRUNCATED AT 250 WORDS)
We know where you live (2012)

In the last few years, the increasing interest in location-based services (LBS) has favored the introduction of geo-referenced information in various Web 2.0 applications, as well as the rise of location-based social networks (LBSN). Foursquare, one of the most popular LBSNs, gives incentives to users who visit (check in) specific places (venues) by means of, for instance, mayorships to frequent visitors. Moreover, users may leave tips at specific venues as well as mark previous tips as done in sign of agreement. Unlike check ins, which are shared only with friends, the lists of mayorships, tips and dones of a user are publicly available to everyone, thus raising concerns about disclosure of the user's movement patterns and interests. We analyze how users explore these publicly available features, and their potential as sources of information leakage. Specifically, we characterize the use of mayorships, tips and dones in Foursquare based on a dataset with around 13 million users. We also analyze whether it is possible to easily infer the home city (state and country) of a user from these publicly available information. Our results indicate that one can easily infer the home city of around 78% of the analyzed users within 50 kilometers.
Effects of amino acid sequence, buffers, and ionic strength on the rate and mechanism of deamidation of asparagine residues in small peptides. (1991)

The nonenzymatic rates of deamidation of Asn residues in a series of pentapeptides with the sequences VSNXV and VXNSV, where X is one of 10 different amino acids, were determined at neutral, alkaline, and acid pH values. The results demonstrate that in neutral and alkaline solutions the amino acid residue on the amino side of the Asn had little or no effect on the rate of deamidation regardless of its charge or size. The group on the carboxyl side of Asn affected the rate of deamidation significantly. Increasing size and branching in the side chain of this residue decreased the rate of deamidation by as much as 70-fold compared to glycine in the N-G sequence, which had the greatest rate of deamidation. In acidic solution, the rate of deamidation of the Asn residue was not affected by the amino acid sequence of the peptide. The products for each deamidation reaction were tested for the formation of isoAsp residues. In neutral and alkaline solutions, all products showed that the isoAsp:Asp peptide products were formed in about a 3:1 ratio. In acidic solution, the Asp peptide was the only deamidation product formed. All peptides in which a Ser residue follows the Asn residue were found to undergo a peptide cleavage reaction in neutral and alkaline solutions, yielding a tripeptide and a dipeptide. The rate of the cleavage reaction was about 10% of the rate of the deamidation pathway at neutral and alkaline pH values. The rates of deamidation of Asn residues in the peptides studied were not affected by ionic strength, and were not specific base catalyzed. General base catalysis was observed for small bases like ammonia. A model for the deamidation reaction is proposed to account for the observed effects.
Critical Role of the Linking Amide in CC-1065 and the Duocarmycins:  Implications on the Source of DNA Alkylation Catalysis (1998)

The preparation and evaluation of both enantiomers of 5 are described and it constitutes an analogue of CBI-TMI (4), the duocarmycins, and CC-1065 in which the amide linking the alkylation and DNA binding subunits has been replaced by a methylene. The agent proved remarkably stable to acid-catalyzed solvolysis consistent with alkylation subunit stabilization derived from a fully engaged vinylogous amide. It was found to exhibit an acid-catalyzed solvolysis half-life (t1/2) of 80 h, 824 h, and ca. 30 500 h (3.3 days, 34 days, and ca. 3.5 years) at pH 1, 2, and 3, respectively, and to be completely stable at pH 7. The removal of the linking amide resulted in a 105-fold loss in cytotoxic potency and the complete loss of DNA alkylation capabilities providing an agent that is >106× less effective than 4 and >102× less effective than even N-BOC-CBI or N-Ac-CBI. These observations highlight the critical importance of the linking amide and implicate a fundamental role in DNA alkylation catalysis. Thus, rather than enhancing DNA alkylation by facilitating C4 carbonyl protonation (acid catalysis), the removal of the linking amide abolished the capabilities for DNA alkylation. This is consistent with the intimate participation of the linking amide in catalysis derived from a DNA binding-induced conformation change that serves to disrupt the alkylation subunit cross-conjugated vinylogous amide stabilization activating the agents for nucleophilic attack.
Synthesis, Characterization, and Tunable Optical Properties of Hollow Gold Nanospheres (2006)

Nearly monodisperse hollow gold nanospheres (HGNs) with tunable interior and exterior diameters have been synthesized by sacrificial galvanic replacement of cobalt nanoparticles. It is possible to tune the peak of the surface plasmon band absorption between 550 and 820 nm by carefully controlling particle size and wall thickness. Cobalt particle size is tunable by simultaneously changing the concentration of sodium borohydride and sodium citrate, the reducing and capping agent, respectively. The thickness of the gold shell can be varied by carefully controlling the addition of gold salt. With successful demonstration of ensemble as well as single HGN surface-enhanced Raman scattering, these HGNs have shown great potential for chemical and biological sensing applications, especially those requiring nanostructures with near-IR absorption.
Association of hematopoietic cell phosphatase with c-Kit after stimulation with c-Kit ligand. (1993)

Protein tyrosine phosphorylation and dephosphorylation have been implicated in the growth and functional responses of hematopoietic cells. Recent studies have identified a novel protein tyrosine phosphatase, termed hematopoietic cell phosphatase (HCP) or PTP1C, that is predominantly expressed in hematopoietic cells. HCP encodes a cytoplasmic phosphatase that contains two src homology 2 (SH2) domains. Since SH2 domains have been shown to target the association of signal-transducing molecules with activated growth factor receptors containing intrinsic protein kinase activity, we assessed the association of HCP with two hematopoietic growth factor receptors, c-Kit and c-Fms. The results demonstrate that HCP transiently associates with ligand-activated c-Kit but not c-Fms and that this association occurs through the SH2 domains. In both colony-stimulating factor 1- and stem cell factor-stimulated cells, there is a marginal increase in tyrosine phosphorylation of HCP. Lastly, HCP can dephosphorylate autophosphorylated c-Kit and c-Fms in in vitro reactions. The potential role of HCP in stem cell factor signal transduction is discussed.
Cellular Mechanism of Intraabdominal Abscess Formation by Bacteroides fragilis (1998)

We investigated the cellular mechanism by which Bacteroides fragilis promotes the development of intraabdominal abscesses in experimental models of sepsis. B. fragilis, as well as purified capsular polysaccharide complex (CPC) from this organism, adhered to primary murine mesothelial cells (MMCs) in vitro. The binding of CPC to murine peritoneal macrophage stimulated TNF-alpha production, which when transferred to monolayers of MMCs elicited significant ICAM-1 expression by these cells. This response resulted in enhanced polymorphonuclear leukocyte attachment to MMCs that could be inhibited by Abs specific for TNF-alpha or ICAM-1. Mice treated with TNF-alpha- or ICAM-1-specific Abs failed to develop intraabdominal abscesses following challenge with purified CPC. These results illustrated the role of the CPC in promoting adhesion of B. fragilis to the peritoneal wall and coordinating the cellular events leading to the development of abscesses associated with experimental intraabdominal sepsis.
Floorplan design using a hierarchical neural learning algorithm (1991)

Presents a novel floorplanning approach realized by using a neural learning algorithm in a hierarchically organized way. The connection nets of functional modules are described by means of a neural net to obtain a global optimum solution, and the shape and dimensions of each module are simultaneously considered by means of subordinate neural nets to obtain the final floorplan which is a partition for general modules with arbitrary shape. With this hierarchical neural model, not only a fast solution but also a very tight floorplan can be attained. This approach is also suitable for the macrocell placement because of its similarity to the floorplanning. The simulation has been programmed in C and implemented on VAX/VMS environments.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Targeting Acyl-CoA:Diacylglycerol Acyltransferase 1 (DGAT1) with Small Molecule Inhibitors for the Treatment of Metabolic Diseases (2011)

Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in triglyceride synthesis. Findings from genetically modified mice as well as pharmacological studies suggest that inhibition of DGAT1 is a promising strategy for the treatment of obesity and type 2 diabetes. Here we characterize a tool DGAT1 inhibitor compound, T863. We found that T863 is a potent inhibitor for both human and mouse DGAT1 in vitro, which acts on the acyl-CoA binding site of DGAT1 and inhibits DGAT1-mediated triacylglycerol formation in cells. In an acute lipid challenge model, oral administration of T863 significantly delayed fat absorption and resulted in lipid accumulation in the distal small intestine of mice, mimicking the effects of genetic ablation of DGAT1. In diet-induced obese mice, oral administration of T863 for 2 weeks caused weight loss, reduction in serum and liver triglycerides, and improved insulin sensitivity. In addition to the expected triglyceride-lowering activity, T863 also lowered serum cholesterol. Hepatic IRS2 protein was dramatically up-regulated in mice treated with T863, possibly contributing to improved insulin sensitivity. In differentiated 3T3-L1 adipocytes, T863 enhanced insulin-stimulated glucose uptake, suggesting a possible role for adipocytes to improve insulin sensitivity upon DGAT1 inhibition. These results reveal novel mechanistic insights into the insulin-sensitizing effects of DGAT1 inhibition in mouse models. Taken together, our study provides a comprehensive evaluation of a small molecule inhibitor for DGAT1 and suggests that pharmacological inhibition of DGAT1 holds promise in treating diverse metabolic disorders.
G‐protein activation by putative antagonists at mutant Thr373Lys α2A adrenergic receptors (1999)

1. Replacement of a threonine by a lysine at position 373 in the C-terminal portion of the third intracellular loop of the human alpha2A-adrenergic receptor (alpha2A AR) has been reported to generate a constitutively active mutant receptor in analogy with similar mutations in the alpha1B and beta2 AR (Ren et al., 1993). In the present study, the mutant Thr373Lys alpha2A AR receptor was investigated by measuring the formation of inositol phosphates in either the absence or presence of mouse G(alpha)15 protein in Cos-7 cells. 2. Increased affinity, potency and/or efficacy for the agonists [(-)-adrenaline, UK 14304, clonidine, guanabenz and oxymetazoline] was observed, consistent with a precoupled mutant alpha2A AR: G-protein state. The basal inositol phosphates response was similar at the wild-type (wt) and mutant alpha2A AR, but was enhanced at the mutant alpha2A AR upon co-expression with the mouse G(alpha)15 protein. This enhanced response could not be attenuated in the presence of any of the tested alpha2 AR antagonists (10 microM), suggesting that inverse agonist activity did not occur at the mutant alpha2A AR. 3. Ligands that so far have been identified as antagonists at the wt alpha2A AR demonstrated either no intrinsic activity (MK 912, WB 4101, RS 15385, RX 811059 and RX 821002) or positive efficacy [Emax, % vs. 1 microM UK 14304: dexefaroxan (27+/-7), idazoxan (34+/-9), atipamezole (27+/-4), BRL 44408 (59+/-5) and SKF 86466 (54+/-9)] at the mutant alpha2A AR, but only in the presence of the mouse G(alpha)15 protein. The ligand potencies corresponded with their respective pKi values at the mutant alpha2A AR receptor. 4. The partial agonist effect of SKF 86466 was resistant to pertussis toxin treatment (100 ng ml(-1)) and not affected by co-expression of the rat G(alpha)i1 protein. It was virtually absent in the presence of 10 microM RS 15385. SKF 86466 was without intrinsic activity upon co-expression of the mouse G(alpha)q protein. 5. Some putative alpha2 AR antagonists exerted a partial agonist activity that was highly dependent on the presence of specific G-protein alpha-subunits, suggesting that these ligands cause selective G-protein activation at the mutant alpha2A AR.
GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis (2008)

Gene Ontology (GO) analysis has become a commonly used approach for functional studies of large-scale genomic or transcriptomic data. Although there have been a lot of software with GO-related analysis functions, new tools are still needed to meet the requirements for data generated by newly developed technologies or for advanced analysis purpose. Here, we present a Gene Ontology Enrichment Analysis Software Toolkit (GOEAST), an easy-to-use web-based toolkit that identifies statistically overrepresented GO terms within given gene sets. Compared with available GO analysis tools, GOEAST has the following improved features: (i) GOEAST displays enriched GO terms in graphical format according to their relationships in the hierarchical tree of each GO category (biological process, molecular function and cellular component), therefore, provides better understanding of the correlations among enriched GO terms; (ii) GOEAST supports analysis for data from various sources (probe or probe set IDs of Affymetrix, Illumina, Agilent or customized microarrays, as well as different gene identifiers) and multiple species (about 60 prokaryote and eukaryote species); (iii) One unique feature of GOEAST is to allow cross comparison of the GO enrichment status of multiple experiments to identify functional correlations among them. GOEAST also provides rigorous statistical tests to enhance the reliability of analysis results. GOEAST is freely accessible at http://omicslab.genetics.ac.cn/GOEAST/
The evolution of ‘sol–gel’ chemistry as a technique for materials synthesis (2015)

From its initial use to describe hydrolysis and condensation processes, the term ‘sol–gel’ is now used for a diverse range of chemistries.
<title>Spatial characteristics of laser pulsed plasma deposition of thin films</title> (1990)

Lately a new film deposition technique — pulsed lase19 plasma vapour deposition (LPVD) — has been rather actively studied One of the main macroscopic features of any thin film deposition technique is distribution of film material on substrate. But this aspect of LPVD technique has been given a little attention. This paper discusses thickness profiles of the films deposited on the substrates by excimer laser plasma vapour deposition (ELPVD). Suggestions have been made concerning improvement of uniformity of the films thickness. Amorphous carbon films obtained by ELPVD technique can be used as protection and anti—reflection coatings for IR optics elements.
Molecular cloning, sequencing, and mapping of EGR2, a human early growth response gene encoding a protein with "zinc-binding finger" structure. (1988)

Early growth response gene-1 (Egr-1) is a mouse gene displaying fos-like induction kinetics in diverse cell types following mitogenic stimulation. Egr-1 encodes a protein with "zinc-binding finger" structure. Zinc fingers are a protein structural motif that serve as DNA-binding domains in several transcriptional regulatory proteins. Using low-stringency hybridization with an Egr-1 cDNA probe, we identified a distinct human cDNA (designated EGR2 for early growth response gene-2), which is coregulated with EGR1 by fibroblast and lymphocyte mitogens; however, several stimuli that induce Egr-1 mRNA in PC12 (rat pheochromocytoma) cells do not induce Egr-2 mRNA. The cDNA sequence predicts a protein of 406 amino acids, including three tandem zinc fingers of the Cys2-His2 class. Strikingly, the deduced amino acid sequences of human EGR2 and mouse Egr-1 are 92% identical in the zinc finger region but show no similarity elsewhere. EGR2 maps to human chromosome 10 at bands q21-22. Structure-function analysis of EGR2 and EGR1 proteins should provide insight into the mechanisms linking signal transduction and transcriptional regulation of gene expression.
Property-based testing of privileged programs (2002)

Addresses the problem of testing security-relevant software, especially privileged (typically, setuid root) and daemon programs in UNIX. The problem is important, since it is these programs that are the source of most UNIX security flaws. For some programs, such as the UNIX sendmail program, new security flaws are still being discovered, despite being in use for many years. For special-purpose systems with fewer users, flaws are likely to remain undiscovered for even longer. Our testing process is driven by specifications we create for the privileged programs. These specifications simultaneously define the allowed behavior far these programs and identify problematic system calls, regions where the program is vulnerable, and generic security flaws. The specifications serve three roles in our testing methodology: as criteria against which a program is sliced, as oracles against which it is tested, and as a basis for generating useful tests. Slicing is employed to significantly reduce the size of the program to be tested. We show that a slice of a privileged program (rdist) with respect to its security specifications is quite small. We introduce the Tester's Assistant, a collection of tools to mechanize the process of testing security-related C programs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>