gebhart/patrepeval huggingface dataset:
[Epigenetics of prostate cancer]. (2010)

Prostate cancer is one of the most common malignant tumors in males, and its etiology and pathogenesis remain unclear. Epigenesis is involved in prostate cancer at all stages of the process, and closely related with its growth and metastasis. DNA methylation and histone modification are the most important manifestations of epigenetics in prostate cancer. The mechanisms of carcinogenesis of DNA methylation include whole-genome hypomethylation, aberrant local hypermethylation of promoters and genomic instability. DNA methylation is closely related to the process of prostate cancer, as in DNA damage repair, hormone response, tumor cell invasion/metastasis, cell cycle regulation, and so on. Histone modification causes corresponding changes in chromosome structure and the level of gene transcription, and it may affect the cycle, differentiation and apoptosis of cells, resulting in prostate cancer. Some therapies have been developed targeting the epigenetic changes in prostate cancer, including DNA methyltransferases and histone deacetylase inhibitors, and have achieved certain desirable results.
Photo Tours (2012)

This paper describes an effort to automatically create ``tours'' of thousands of the world's landmarks from geo-tagged user-contributed photos on the Internet. These photo tours take you through each site's most popular viewpoints on a tour that maximizes visual quality and traversal efficiency. This planning problem is framed as a form of the Traveling Salesman Problem on a graph with photos as nodes and transition costs on edges and pairs of edges, permitting efficient solution even for large graphs containing thousands of photos. Our approach is highly scalable and is the basis for the Photo Tours feature in Google Maps, which can be viewed at http://maps.google.com/phototours.
IBRUTinib: BRUTe force against bortezomib-resistant myeloma cells (2015)

This article refers to:Ibrutinib inhibits BTK-driven NF-κB p65 activity to overcome bortezomib-resistance in multiple myeloma
Chronic imipramine treatment reduces inhibitory properties of group II mGlu receptors without affecting their density or affinity. (2008)

An increasing body of evidence indicates an important role of the glutamatergic system in the pathophysiology of depression. Not only ionotropic but also metabotropic glutamate receptors (mGlu receptors) have been suggested to be involved in the mechanism of action of antidepressant drugs. Moreover, several mGlu receptor ligands possess a great antidepressant potential. Group II mGlu receptor antagonists have been shown to induce antidepressant-like effects in rodents. An influence of chronic antidepressant treatment on group II mGlu receptors has also been suggested. In our studies, we examined an influence of repeated (21-day) imipramine treatment on the density of group II mGlu receptors and affinity of mGlu2 and mGlu3 receptor radioligand [3H]-LY341495 for group II mGlu receptors in the rat brain hippocampus and frontal cortex. Moreover, we analyzed an influence of chronic imipramine administration on the ability of group II mGlu receptor agonist, 2R,4R-APDC, to inhibit forskolin-stimulated cAMP accumulation in the rat brain cortical slices. We found that inhibitory properties of group II mGlu receptors were diminished after chronic, but not acute imipramine administration. However, no changes in the density or affinity of the mGlu2 and mGlu3 receptor ligand for group II mGlu receptors were observed.
Anterior cingulate dysfunction: Implications for psychiatric disorders? (2003)

develop a more comprehensive theory of ACC function to explain the various patterns of symptoms, cognitive and emotional deficits, as well as neuroimaging findings, across a number of psychiatric disorders. We also make suggestions for the design and interpretation of future studies concerning the ACC in psychiatric disorders that may provide important new insights into the neurobiological basis of these disorders.
An In‐vitro Investigation of Selected Biological Activities of Hydrolysed Flaxseed (Linum usitatissimum L.) Proteins (2008)

Abstract A study was conducted to determine bioactivities of flaxseed ( Linum usitatissimum L.; variety: Valour) proteins and their hydrolysates. Isolated flaxseed proteins were treated with Flavourzyme ® at different levels of enzyme to substrate ratio (E/S) and hydrolysis time. The unhydrolysed proteins and hydrolysates were studied for angiotensin I‐converting enzyme inhibiting (ACEI) activity, hydroxyl radical (OH·) scavenging activity and bile acid binding ability. Flavourzyme catalysed hydrolysis generated hydrolysates with a 11.94–70.62% degree of hydrolysis (DH). The hydrolysates (0.67 mg/ml) had strong ACEI activity (71.59–88.29%). The maximum ACEI activity containing hydrolysate exhibited an IC 50 of 0.07 mg/ml (E/S: 1.5; Time: 12 h; DH: 11.94%). The OH· scavenging activity of the hydrolysates (0.5 mg/ml) was 12.48–22.08% with an IC 50 of 1.56 mg/ml in the sample possessing maximum activity (E/S: 47.5; Time 0.7 h; DH: 24.63%). Both these activities were greater in hydrolysates with lower DH and higher peptide chain length (PCL) than those with higher DH and lower PCL. Hydrolysed flaxseed proteins (0.67 mg/ml) had no bile acid binding ability. The unhydrolysed proteins had no ACEI or OH· scavenging activity but demonstrated bile acid binding ability.
Cross-linking of mRNA to initiation factor eIF-3, 24 kDa cap binding protein and ribosomal proteins SI, S3/3a, S6 and S11 within the 48S pre-initiation complex (1984)

Native small ribosomal subunits from rabbit reticulocytes contain all initiation factors necessary for the formation of the mRNA-containing 48S pre-initiation complex. The complex formed in the presence of Met-tRNAf and 125I-labelled globin mRNA was cross-linked with diepoxybutane, and the covalent mRNA-protein complexes were isolated under denaturating conditions. The proteins of the covalent complex were identified as the 110, 95 and 66/64 kDa subunits of eIF-3. In addition, the 24 kDa cap binding protein and the ribosomal proteins S1, S3/3a, S6 and S11 were found covalently linked to the mRNA. Ribosomal proteins S3/3a and S6 were also involved in the ribosomal mRNA-binding domain of reticulocyte polysomes.
Establishment of a pluripotent cell line derived from a medaka (Oryzias latipes) blastula embryo. (1994)

A pluripotent cell line, OLES1, was established from a blastula embryo of a small freshwater fish, medaka (Oryzias latipes). Cells of this cell line were small and round, and they grew actively and stably in culture as dense clusters. They exhibited a positive alkaline phosphatase activity upon histochemical staining. When the cells were treated with retinoic acid, differentiation into various types of cells, including melanocytes, dopa-positive precursors of melanocytes, and cells with a molecular marker of skeletal muscles, troponin T, was induced in vitro. The present study opens a way to establishing embryonic stem cell lines in fish.
A New Class of Steroids Inhibits Angiogenesis in the Presence of Heparin or a Heparin Fragment (1985)

Steroids that lack glucocorticoid or mineralocorticoid activity were found to inhibit angiogenesis in the presence of heparin or specific heparin fragments. This newly discovered steroid function appears to be governed by distinct structural configurations of the pregnane nucleus. These compounds are here named angiostatic steroids.
Significance of interleukin-13 receptor alpha 2-targeted glioblastoma therapy (2014)

Glioblastoma multiforme (GBM) remains one of the most lethal primary brain tumors despite surgical and therapeutic advancements. Targeted therapies of neoplastic diseases, including GBM, have received a great deal of interest in recent years. A highly studied target of GBM is interleukin-13 receptor α chain variant 2 (IL13Rα2). Targeted therapies against IL13Rα2 in GBM include fusion chimera proteins of IL-13 and bacterial toxins, nanoparticles, and oncolytic viruses. In addition, immunotherapies have been developed using monoclonal antibodies and cell-based strategies such as IL13Rα2-pulsed dendritic cells and IL13Rα2-targeted chimeric antigen receptor-modified T cells. Advanced therapeutic development has led to the completion of phase I clinical trials for chimeric antigen receptor-modified T cells and phase III clinical trials for IL-13-conjugated bacterial toxin, with promising outcomes. Selective expression of IL13Rα2 on tumor cells, while absent in the surrounding normal brain tissue, has motivated continued study of IL13Rα2 as an important candidate for targeted glioma therapy. Here, we review the preclinical and clinical studies targeting IL13Rα2 in GBM and discuss new advances and promising applications.
Expression of Recombinant Vaccinia Virus-derived Alphavirus Proteins in Mosquito Cells (1985)

A recombinant vaccinia virus strain which contains and expresses a 26S cDNA insert encoding Sindbis virus structural proteins (VV:3S) was used to infect a continuous line of Aedes albopictus mosquito cells. There were not visible cytopathic effects due to the virus infection and the cells continued to grow normally. However, examination of the proteins present in the cytoplasm of the infected cells with Sindbis virus-specific antisera revealed that Sindbis virus proteins were being synthesized and processed. These results are discussed with respect to vaccinia virus as a non-lethal expression vector to deliver and express eukaryotic genetic information in insect cell systems and using this system (VV:3S) to dissect various facets of togavirus-insect cell interactions.
Molecular Mechanisms of Ubiquitin-Dependent Membrane Traffic (2011)

Over the past 14 years, ubiquitination has emerged as a centrally important mechanism governing the subcellular trafficking of proteins. Ubiquitination, interaction with sorting factors that contain ubiquitin-binding domains, and deubiquitination govern the itineraries of cargo proteins that include yeast carboxypeptidase S, the epithelial sodium channel ENaC, and epidermal growth factor receptor. The molecular structures and mechanisms of the paradigmatic HECT and RING domain ubiquitin ligases, of JAMM- and USP-domain-deubiquitinating enzymes, and of numerous ubiquitin-binding domains involved in these pathways have been worked out in recent years and are described.
In Vitro Reactivation of Human Immunodeficiency Virus 1 from Latently Infected, Resting CD4+T Cells after Bacterial Stimulation (2000)

Microbial coinfections have been associated with transient bursts of human immunodeficiency virus (HIV) viremia in patients. In this study, we have investigated whether microbial coinfections can induce replication of HIV-1 in latently infected CD4(+) T cells derived from HIV-infected patients who are receiving highly active antiretroviral therapy and in whom plasma viremia is undetectable by sensitive assays. We demonstrate that supernatants from macrophages exposed to the bacterial product lipopolysaccharide can induce in vitro activation of HIV-1 from latently infected, resting CD4(+) T cells obtained from HIV-infected individuals. Depletion of proinflammatory cytokines from the supernatant markedly reduced-whereas depletion of ss chemokines increased--the ability of the supernatant to induce replication of HIV-1. Our results suggest that coinfection with microbial pathogens such as bacteria may induce viral replication in the latent viral reservoirs in vivo.
Mutations in the 5′ End of the Human Immunodeficiency Virus Type 1 Polypurine Tract Affect RNase H Cleavage Specificity and Virus Titer (2003)

The RNase H activity of retroviral reverse transcriptases (RTs) degrades viral genomic RNA after it has been copied into DNA, removes the tRNA used to initiate negative-strand DNA synthesis, and generates and removes the polypurine tract (PPT) primer used to initiate positive-strand DNA synthesis. The cleavages that remove the tRNA and that generate and remove the PPT primer must be specific to generate linear viral DNAs with ends that are appropriate for integration into the host cell genome. The crystal structure of human immunodeficiency virus type 1 (HIV-1) RT in a complex with an RNA/DNA duplex derived from the PPT revealed that the 5' end of the PPT deviates from traditional Watson-Crick base pairing. This unusual structure may play a role in the proper recognition of the PPT by HIV-1 RT. We made substitution mutations in the 5' end of the PPT and determined their effects on virus titer. The results indicated that single and double mutations in the 5' end of the PPT had modest effects on virus replication in a single-cycle assay. More complex mutations had stronger effects on virus titer. Analysis of the two-long-terminal-repeat circle junctions derived from infecting cells with the mutant viruses indicated that the mutations affected RNase H activity, resulting in the retention of PPT sequences on viral DNA. The mutants tested preferentially retained specific segments of the PPT, suggesting an effect on cleavage specificity. These results suggest that structural features of the PPT are important for its recognition and cleavage in vivo.
Adapting Operator Settings in Genetic Algorithms (1998)

In the majority of genetic algorithm implementations, the operator settings are fixed throughout a given run. However, it has been argued that these settings should vary over the course of a genetic algorithm run--so as to account for changes in the ability of the operators to produce children of increased fitness. This paper describes an investigation into this question. The effect upon genetic algorithm performance of two adaptation methods upon both well-studied theoretical problems and a hard problem from operations research, the flowshop sequencing problem, are therefore examined. The results obtained indicate that the applicability of operator adaptation is dependent upon three basic assumptions being satisfied by the problem being tackled.
A Bone Mimic Based on the Self-Assembly of Hydroxyapatite on Chemically Functionalized Single-Walled Carbon Nanotubes (2005)

We report the use of chemically functionalized single-walled carbon nanotubes (SWNTs) as a scaffold for the growth of artificial bone material. The mineralization of SWNTs functionalized with phosphonates and poly(aminobenzene sulfonic acid) (PABS) was investigated in the solution phase and as films on substrates. Microscopy studies showed that hydroxyapatite (HA) nucleated and crystallized on the surface of the functionalized SWNTs. The negatively charged functional groups on SWNTs attract the calcium cations and lead to self-assembly of HA. The thickness of the HA layers was found to be a function of the mineralization time. Mineralization of SWNT−PABS films led to well-aligned plate-shaped HA crystals and the thickness of the crystals reached 3 μm after 14 days of mineralization. The PABS- and phosphonates-functionalized SWNTs can be applied as supporting scaffold for bone therapy.
Evaluation of biological pathways involved in chemotherapy response in breast cancer (2008)

Our goal was to examine the association between biological pathways and response to chemotherapy in estrogen receptor (ER)-positive and ER-negative breast cancers separately. Gene set enrichment analysis including 852 predefined gene sets, was applied to gene expression data from 51 ER-negative and 82 ER-positive breast cancers that were all treated with a preoperative paclitaxel, 5-fluoruracil, doxorubicin and cyclophosphamide chemotherapy. Twenty-seven (53%) ER-negative and 7 (9%) ER-positive patients had pathologic complete response (pCR) to therapy. Among the ER-negative cancers, a proliferation gene signature (FDR q = 0.1), the Genomic Grade Index (FDR q = 0.044) and the E2F3 pathway (FDR q = 0.22, p = 0.07) signature were enriched in the pCR group. Among the ER-positive cancers, the proliferation signature (FDR q = 0.001) and the Genomic Grade Index (FDR q = 0.015) were also significantly enriched in cases with pCR. Ki67 expression, as single gene marker of proliferation, did not provide the same information as the entire proliferation signature. An ER-associated gene set (FDR q = 0.03) and a mutant p53-gene signature (FDR q = 0.0019) were enriched in ER-positive cancers with residual cancer. Proliferation- and genomic grade-related gene signatures are associated with chemotherapy sensitivity in both ER-negative and -positive breast cancers. Genes involved in the E2F3 pathway are associated with chemotherapy sensitivity among ER-negative cancers. The mutant p53-signature and expression of ER-related genes were associated with lower sensitivity to chemotherapy in ER-positive breast cancers only.
The myc gene family proteins and their role in transformation and differentiation. (1990)

Several genes within the mammalian genome share homology with the transforming gene, v-myc, of the avian myelocytic leukemia viruses. Of these, c-myc, Nmyc and Lmyc have been shown to possess transforming activity in vitro and each is found to be aberrantly expressed in a variety of tumours. In normal tissues, expression of Nmyc and Lmyc is restricted to embryonic development and a few adult tissues whereas c-myc and Bmyc are very widely expressed. The proteins encoded by the various myc genes share substantial sequence homology. c-, N and Lmyc proteins are all nuclear phosphoproteins that possess very short biological half lives and bind DNA. All three possess identifiable motifs present in a number of other nuclear proteins involved in transcriptional regulation, and the possible role of myc proteins in gene regulation is discussed. Some experiments, however, favour a different role for c-myc, in DNA replication. Whatever their precise molecular functions may be, it is clear that myc genes play an essential role in the regulation of cellular proliferation.
Antifreeze glycoprotein agents: structural requirements for activity (2011)

Antifreeze glycoproteins (AFGPs) are considered to be the most efficient means to reduce ice damage to cell tissues since they are able to inhibit growth and crystallization of ice. The key element of antifreeze proteins is to act in a non-colligative manner which allows them to function at concentrations 300-500 times lowers than other dissolved solutes. During the past decade, AFGPs have demonstrated tremendous potential for many pharmaceutical and food applications. Presently, the only route to obtain AFGPs involves the time consuming and expensive process of isolation and purification from deep-sea polar fishes. Unfortunately, it is not amenable to mass production and commercial applications. The lack of understanding of the mechanism through which the AFGPs inhibit ice growth has also hampered the realization of industrial and biotechnological applications. Here we report the structural motifs that are essential for antifreeze activity of AFGPs, and propose a unified mechanism based on both recent studies of short alanine peptides and structure activity relationship of synthesized AFGPs.
Near-optimal n-layer channel routing (1986)

In this paper we present two n-layer channel routing algorithms that guarantee successful routing of the channel for n greater than three. The first is linear and optimal given a VHV …HV assignment of layers. The second, using an HVH…VH layer assignment, is quasilinear and performs optimally on examples from the literature. Except in pathological cases, we expect the latter router to perform within one row of optimal. For comparison with published examples we implemented the second router in five and three layers. The five-layer implementation routed all examples optimally while the three-layer implementation routed the examples with the same or fewer rows than the published examples. With its n-layer capability this channel router will allow channel routing to be used when more than three layers are available. This router can also be used to evaluate the utility of additional layers.
Photothermal detection of local thermal effects during selective nanophotothermolysis (2003)

Photothermal (PT) technique was applied to the detection of laser-induced local thermal effects around absorbing nanoparticles into cells. The experiments demonstrated the capability of this technique for studying the threshold and the dynamic of thermal events around even a single particle in a broad temperature range, including monitoring of microbubble dynamic. PT technique shows promise for optimizing cancer-cell killing by incorporation of gold nanoparticles into the cells (selective “nanophotothermolysis”), as verified by electron microscopy and conventional viability tests.
Disialogangliosides GD2 and GD3 are involved in the attachment of human melanoma and neuroblastoma cells to extracellular matrix proteins. (1986)

Human melanoma cells express relatively large amounts of the disialogangliosides GD3 and GD2 on their surface whereas neuroblastoma cells express GD2 as a major ganglioside. Monoclonal antibodies (Mabs) directed specifically to the carbohydrate moiety of GD3 and GD2 inhibit melanoma and neuroblastoma cell attachment to various substrate adhesive proteins, e.g. collagen, vitronectin, laminin, fibronectin, and a heptapeptide, glycyl-L-arginyl-glycyl-L-aspartyl-L-seryl-L-prolyl-L-cysteine, which constitutes the cell attachment site of fibronectin. Cells that are preattached to a fibronectin substrate can also be induced to detach and round up in the presence of purified anti-ganglioside Mab. Moreover, when melanoma cells that contain both GD2 and GD3 are incubated with Mabs directed to both of these molecules an additive inhibition is observed. The specificity of this inhibition is demonstrated since Mabs of various isotypes directed to either protein or carbohydrate epitopes on a number of other major melanoma or neuroblastoma cell surface antigens have no effect on cell attachment. A study of the kinetics involved in this inhibition indicates that significant effects occur during the first 5 min of cell attachment, suggesting an important role for GD2 and GD3 in the initial events of cell-substrate interactions. The role of gangliosides in cell attachment apparently does not directly involve a strong interaction with fibronectin since we could not observe any binding of radiolabeled fibronectin or fragments of the molecule known to contain the cell attachment site to melanoma gangliosides separated on thin-layer chromatograms. An alternative explanation would be that gangliosides may play a role in the electrostatic requirements for cell-substrate interactions. In this regard, controlled periodate oxidation of terminal, unsubstituted sialic acid residues on the cell surface not only specifically destroys the antigenic epitopes on GD2 and GD3 recognized by specific Mabs but also inhibits melanoma cell and neuroblastoma cell attachment. In fact, the periodate-induced ganglioside oxidation and the inhibition of cell attachment are equally dose dependent. These data suggest that cell-substratum interactions may depend in part on the electrostatic environment provided by terminal sialic acid residues of cell surface gangliosides and possibly other anionic glycoconjugates.