gebhart/patrepeval huggingface dataset:
Studies on nucleic acid reassociation kinetics: reactivity of single-stranded tails in DNA-DNA renaturation. (1975)

The reassociation kinetics of Escherichia coli DNA were measured by S1 nuclease resistance and hydroxyapatite binding. While the reaction assayed by hydroxyapatite displays second order kinetics, the S1 nuclease measurements follow a non-second order from, as previously reported by Morrow (Ph.D. Dissertation, Stanford University. 1974). Much of the reaction measured with S1 nuclease occurs between single stranded regions of fragments already bearing duplex structures from previous collisions, and between such regions and totally free single strands. Experimental determinations indicate that the nucleation rate of single stranded regions on fragments also containing duplexes is inhibited by an average factor of 2 to 4.
Diphenyl Phosphonate Inhibitors for the Urokinase-Type Plasminogen Activator:  Optimization of the P4 Position (2006)

This paper describes the structure-activity relationship in a series of tripeptidyl diphenyl phosphonate irreversible urokinase plasminogen activator (uPA) inhibitors, originally derived from an arginyltripeptide. uPA is considered an interesting target in anticancer drug design. The selectivity of these inhibitors for uPA is enhanced by the optimization of the P4 position. The most interesting compound shows an IC(50) of 5 nM, with a selectivity index of more than 3000 toward other Arg/Lys-specific proteases such as tissue-type plasminogen activator, plasmin, factor Xa, and thrombin. A synthetic strategy for the preparation of small libraries of diphenyl phosphonate analogues of capped tripeptides is described. It is shown that uPA is irreversibly inhibited, and interactions with the active site were modeled. Finally, a diparacetamol phosphonate analogue was developed to circumvent the release of cytotoxic phenol.
Incorporation of Chlorella vulgaris and Spirulina maxima biomass in pasta products. Part 1: Preparation and evaluation (2010)

Microalgae pastas presented very appellative colours, such as orange and green, similar to pastas produced with vegetables, with nutritional advantages, showing energetic values similar to commercial pastas. The use of microalgae biomass can enhance the nutritional and sensorial quality of pasta, without affecting its cooking and textural properties.
Gene expression profiling of 49 human tumor xenografts from in vitro culture through multiple in vivo passages - strategies for data mining in support of therapeutic studies (2014)

This study provides strategies to aid selection of xenograft models for therapeutic studies. These data highlight the dynamic nature of xenograft models and emphasize the importance of maintaining passage consistency throughout experiments.
Immunotherapy for Melanoma: Current Status and Perspectives (2010)

Immunotherapy is an important modality in the therapy of patients with malignant melanoma. As our knowledge about this disease continues to expand, so does the immunotherapeutic armamentarium. Nevertheless, successful preclinical models do not always translate into clinically meaningful results. The authors give a comprehensive analysis of most recent advances in the immune anti-melanoma therapy, including interleukins, interferons, other cytokines, adoptive immunotherapy, biochemotherapy, as well as the use of different vaccines. We also present the fundamental concepts behind various immune enhancement strategies, passive immunotherapy, as well as the use of immune adjuvants. This review brings into discussion the results of newer and older clinical trials, as well as potential limitations and drawbacks seen with the utilization of various immune therapies in malignant melanoma. Development of novel therapeutic approaches, along with optimization of existing therapies, continues to hold a great promise in the field of melanoma therapy research. Use of anti-CTLA4 and anti-PD1 antibodies, realization of the importance of co-stimulatory signals, which translated into the use of agonist CD40 monoclonal antibodies, as well as activation of innate immunity through enhanced expression of co-stimulatory molecules on the surface of dendritic cells by TLR agonists are only a few items on the list of recent advances in the treatment of melanoma. The need to engineer better immune interactions and to boost positive feedback loops appear crucial for the future of melanoma therapy, which ultimately resides in our understanding of the complexity of immune responses in this disease.
Microfluidic Large-Scale Integration (2002)

We developed high-density microfluidic chips that contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large-scale integration. A key component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. We used these integrated microfluidic networks to construct the microfluidic analog of a comparator array and a microfluidic memory storage device whose behavior resembles random-access memory.
Detection of nucleosome–IgG immune complexes in ascites from mice transplanted with anti-DNA antibody-secreting hybridomas and in plasmas from MRL-lpr/lpr mice (1996)

Autoantibodies directed against chromatin components characterize lupus diseases. Immune complexes made of these autoantibodies bound to nucleosomes released from dead cells could play some pathogenic role. The aims of this study were to investigate if nucleosome-IgG complexes could contaminate IgG anti-DNA MoAb preparations, and if such complexes circulate in lupus diseases. A new method was set up using preformed nucleosome-IgG complexes. Complexes were adsorbed onto microplate through Fc binding and nucleosomal DNA was detected by internal incorporation of labelled nucleotide. Using this method, high amounts of complexes were found in ascites from mice transplanted with anti-DNA antibody-secreting hybridomas. In some ascites, nucleosome was found to be strongly associated with the MoAb, confirming that nucleosome-IgG complexes could contaminate monoclonal autoantibody preparations. In MRL-lpr/lpr mice, nucleosome-IgG complexes were detected at 16-24 weeks of age at a time when kidney lesions are rapidly worsening, raising the question of their pathogenic significance.
AMPK and cell proliferation – AMPK as a therapeutic target for atherosclerosis and cancer (2006)

AMPK is a serine/threonine protein kinase, which serves as an energy sensor in all eukaryotic cell types. Published studies indicate that AMPK activation strongly suppresses cell proliferation in non-malignant cells as well as in tumour cells. These actions of AMPK appear to be mediated through multiple mechanisms including regulation of the cell cycle and inhibition of protein synthesis, de novo fatty acid synthesis, specifically the generation of mevalonate as well as other products downstream of mevalonate in the cholesterol synthesis pathway. Cell cycle regulation by AMPK is mediated by up-regulation of the p53-p21 axis as well as regulation of TSC2-mTOR (mammalian target of rapamycin) pathway. The AMPK signalling network contains a number of tumour suppressor genes including LKB1, p53, TSC1 and TSC2, and overcomes growth factor signalling from a variety of stimuli (via growth factors and by abnormal regulation of cellular proto-oncogenes including PI3K, Akt and ERK). These observations suggest that AMPK activation is a logical therapeutic target for diseases rooted in cellular proliferation, including atherosclerosis and cancer. In this review, we discuss about exciting recent advances indicating that AMPK functions as a suppressor of cell proliferation by controlling a variety of cellular events in normal cells as well as in tumour cells.
Regulatory subunits of cyclic AMP-dependent protein kinase: presence in granules and secretion by exocrine and endocrine cells (1989)

Cyclic AMP-dependent protein kinase (cAPK) is the intracellular mediator of signal transduction events involving the adenylate cyclase-cyclic AMP system. A monoclonal antibody (MAb BB1) to the type II regulatory subunit (RII) of cAPK was used in a post-embedding immunogold-labeling procedure to determine the ultrastructural localization of RII in several different secretory cells of the rat. Label was present in nuclei, especially over the heterochromatin, and in the cytoplasm, particularly in areas containing rough endoplasmic reticulum. Immunolabeled RII was also present in secretory granules of the parotid gland, exocrine and endocrine pancreas, seminal vesicle, anterior and intermediate pituitary, and intestinal endocrine cells. Photoaffinity labeling of parotid saliva, pancreatic and seminal fluids with the cyclic AMP analogue, 32P-labeled-8-azido-cyclic AMP, revealed the presence of cyclic AMP-binding proteins with electrophoretic mobilities similar to those of authentic cAPK regulatory subunits. These results confirm our previous observations on the localization of cAPK regulatory subunits in the rat parotid using polyclonal antibodies, and extend them to a number of other exocrine and endocrine cells. The apparent widespread occurrence of cAPK subunits in secretory granules and secretory fluids suggests that cAPK may be involved in specific intragranular regulatory and/or phosphorylation events, or that it has an unidentified extracellular function.
Neoplastic Transformation of RK3E by Mutant β-Catenin Requires Deregulation of Tcf/Lef Transcription but Not Activation of c-myc Expression (1999)

Current models predict that beta-catenin (beta-cat) functions in Wnt signaling via activation of Tcf/Lef target genes and that its abundance is regulated by the adenomatous polyposis coli (APC) and glycogen synthase kinase 3beta (GSK3beta) proteins. In colon and other cancers, mutations in APC or presumptive GSK3beta phosphorylation sites of beta-cat are associated with constitutive activation of Tcf/Lef transcription. In spite of assumptions about its oncogenic potential, prior efforts to demonstrate that mutated beta-cat will induce neoplastic transformation have yielded equivocal results. We report here that mutated, but not wild-type, beta-cat proteins induced neoplastic transformation of RK3E, an adenovirus E1A-immortalized epithelial cell line. Analysis of the properties of mutant beta-cat proteins and studies with a dominant negative Tcf-4 mutant indicated that the ability of beta-cat to bind and activate Tcf/Lef factors is crucial for transformation. c-myc has recently been implicated as a critical Tcf-regulated target gene. However, c-myc was not consistently activated in beta-cat-transformed RK3E cells, and a dominant negative c-Myc mutant protein failed to inhibit beta-cat transformation. Our findings underscore the role of beta-cat mutations and Tcf/Lef activation in cancer and illustrate a useful system for defining critical factors in beta-cat transformation.
Synthesis of Hierarchical Hollow Silica Microspheres Containing Surface Nanoparticles Employing the Quasi-Hard Template of Poly(4-vinylpyridine) Microspheres (2011)

A facile method of preparing hierarchical hollow silica microspheres containing surface silica nanoparticles (HHSMs) through the sol-gel process of tetraethylorthosilicate employing a quasi-hard template of non-cross-linking poly(4-vinylpyridine) microspheres is proposed. The quasi-hard template contains the inherent catalyst of the basic pyridine group, and a few of the polymer chains can escape from the template matrix into the aqueous phase, which initiates the sol-gel process spontaneously both on the surface of the template used to prepare the hollow silica shell and in the aqueous phase to produce the surface silica nanoparticles. By tuning the weight ratio of the silica precursor to the quasi-hard template, HHSMs with a size of about 180 nm and a shell thickness ranging from 14 to 32 nm and surface silica nanoparticles ranging from 17 to 36 nm are produced initially through the deposition of surface silica nanoparticles onto the silica shell, followed by template removal either by calcination or solvent extraction. The synthesized HHSMs are characterized, and a possible mechanism for the synthesis of HHSMs is proposed.
Renal Pathology in Wagr Syndrome (1996)

The Wilms' tumor-aniridia-genital anomalies-mental retardation (WAGR) syndrome is associated with an increased risk for developing Wilms' tumor. A right nephrectomy was performed following the diagnosis of Wilms' tumor in a 2-year-old girl with WAGR syndrome and chromosome 11, del 11p13. Pathologic examination revealed intralobar nephrogenic rests and a peripelvic multicystic mass, sharply delineated from the adjacent typical intralobar nephrogenic rests and renal parenchyma, which may represent a cystic Wilms' tumor (cystic partially differentiated nephroblastoma). We studied the expression of the H19 gene by in-situ hybridization performed on paraffin sections of the kidney. H19 is an imprinted maternally-expressed gene that is not translated to protein and functions as a regulatory RNA molecule. It is tightly linked with the paternally-imprinted gene of insulin-like growth factor 2. While IGF2 presumably plays a role in tumorigenesis of Wilms' tumor, H19 is not expressed in the majority of Wilms' tumors. The expression of H19 in the intralobar nephrogenic rests was found to be prominent in the component of the blastema and markedly reduced with differentiation to tubular structures similar to the fetal kidney. The differential diagnosis of hyperplastic intralobar nephrogenic rests from a small Wilms' tumor arising in intralobar nephrogenic rests is difficult. Complete understanding of the chain of molecular events occurring in the evolution of Wilms' tumors may lead to the development of tumor markers to be used on paraffin sections and so help in the differential diagnosis of hyperplasia versus malignant transformation.
Genetic Analysis Of The Yeast Cytoskeleton (1987)

We have made rapid progress in recent years in identifying the genetic causes of many human diseases. However, despite this recent progress, our mechanistic understanding of these diseases is often incomplete. This is a problem because it limits our ...Read More
A conditional U5 snRNA mutation affecting pre-mRNA splicing and nuclear pre-mRNA retention identifies SSD1/SRK1 as a general splicing mutant suppressor (1999)

A combination of point mutations disrupting both stem 1 and stem 2 of U5 snRNA (U5AI) was found to confer a thermosensitive phenotype in vivo. In a strain expressing U5AI, pre-mRNA splicing was blocked before the first step through an inability of the mutant U5 snRNA to efficiently associate with the U4/U6 di-snRNP. Formation of early splicing complexes was not affected in extracts prepared from U5 snRNA mutant cells, while the capacity of these extracts to splice a pre-mRNA in vitro was greatly diminished. In addition, significant levels of a translation product derived from intron containing pre-mRNAs could be detected in vivo. The SSD1/SRK1 gene was identified as a multi-copy suppressor of the U5AI snRNA mutant. Single copy expression of SSD1/SRK1 was sufficient to suppress the thermosensitive phenotype, and high copy expression partially suppressed the splicing and U4/U6.U5 tri-snRNP assembly pheno-types. SSD1/SRK1 also suppressed thermosensitive mutations in the Prp18p and U1-70K proteins, while inhibiting growth of the cold sensitive U1-4U snRNA mutant at 30 degrees C. Thus we have identified SSD1/SRK1 as a general suppressor of splicing mutants.
2-Amino-5,6-dihydro-1,3-oxazines. The Reduction of Carboxylic Esters with Sodium Borohydride1 (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT2-Amino-5,6-dihydro-1,3-oxazines. The Reduction of Carboxylic Esters with Sodium Borohydride1Joseph A. Meschino and Carol H. BondCite this: J. Org. Chem. 1963, 28, 11, 3129–3134Publication Date (Print):November 1, 1963Publication History Published online1 May 2002Published inissue 1 November 1963https://pubs.acs.org/doi/10.1021/jo01046a046https://doi.org/10.1021/jo01046a046research-articleACS PublicationsRequest reuse permissionsArticle Views368Altmetric-Citations30LEARN 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
Cognitive bladder training in the community. (1996)

Following a study trip sponsored through a Cow & Gate scholarship award, the author of this article introduced a cognitive bladder training programme for children with daytime wetting problems. This article looks at how the programme was introduced and describes the components of the programme including educational tools, motivation and bio-feedback. As a result of the programme district-wide, multidisciplinary management guidelines have been introduced.
FluoMar, a Fluorous Version of the Marshall Resin for Solution-Phase Library Synthesis (2003)

[structure: see text] The fluorous counterpart of the Marshall resin, 4-(1H,1H,2H,2H-perfluorodecylsulfanyl)phenol (FluoMar), is prepared by S-alkylation of 4-mercaptophenol with C(8)F(17)CH(2)CH(2)I and employed in the synthesis of amide and diamide analogues. The final products are purified by solid-phase extraction (SPE) over FluoroFlash silica cartridges.
Interference rejection using time-dependent constant modulus algorithms (1989)

Traditional adaptive filters are implemented using timeindependent training-sequence directed techniques. In contrast, the technique prsentcd and evaluated in this paper is based on time-dependent blind weight adaptation. The corresponding adaptive filter is able to exploit properties found in cyclostationary and constant-modulus signals. The steepest-descent CMAs, originally applied to time-independent adaptive processing, arc generalized and applied here to timedependent adaptive filtering for interference rejection. By filtering frcquency-shifted versions of the received signal, CMA-based time-dependent adaptive filters make use of additional spectral information to improve the estimate of the signal-&interest. Cpmputer simulations show the potential of the proposed techntque.
Capsaicin Inhibits in Vitro and in Vivo Angiogenesis (2004)

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a natural product of Capsicum species, is known to induce excitation of nociceptive terminals involved in pain perception. Recent studies have also shown that capsaicin not only has chemopreventive properties against certain carcinogens and mutagens but also exerts anticancer activity. Here, we demonstrated the antiangiogenic activity of capsaicin using in vitro and in vivo assay systems. In vitro, capsaicin inhibited vascular endothelial growth factor (VEGF) -induced proliferation, DNA synthesis, chemotactic motility, and capillary-like tube formation of primary cultured human endothelial cells. Capsaicin inhibited both VEGF-induced vessel sprouting in rat aortic ring assay and VEGF-induced vessel formation in the mouse Matrigel plug assay. Moreover, capsaicin was able to suppress tumor-induced angiogenesis in chick chorioallantoic membrane assay. Capsaicin caused G(1) arrest in endothelial cells. This effect correlated with the down-regulation of the expression of cyclin D1 that led to inhibition of cyclin-dependent kinase 4-mediated phosphorylation of retinoblastoma protein. Signaling experiments show that capsaicin inhibits VEGF-induced p38 mitogen-activated protein kinase, p125(FAK), and AKT activation, but its molecular target is distinct from the VEGF receptor KDR/Flk-1. Taken together, these results demonstrate that capsaicin is a novel inhibitor of angiogenesis and suggest that it may be valuable to develop pharmaceutical drugs for treatment of angiogenesis-dependent human diseases such as tumors.
Antiestrogen ICI 164,384 reduces cellular estrogen receptor content by increasing its turnover. (1992)

The ability of estrogens to stimulate the transcriptional activity of the estrogen receptor can be inhibited by a diverse range of estrogen antagonists. Here we show that the antiestrogen ICI 164,384, N-(n-butyl)-11-[3,17 beta-dihydroxy-estra-1,3,5(10)-trien-7 alpha-yl]N-methylundecanamide, rapidly reduces the levels of receptor protein transiently expressed in cells without affecting receptor mRNA abundance. The reduction in the levels of receptor protein is dose dependent, reversible by estradiol, and mediated by the hormone-binding domain of the receptor. Pulse-chase experiments indicate that the half-life of the receptor is reduced from approximately 5 hr in the presence of estradiol to less than 1 hr by ICI 164,384. A similar reduction in estrogen receptor levels is demonstrated in human breast cancer cells treated with ICI 164,384. We discuss the possibility that the increased turnover of the receptor might be a consequence of impaired receptor dimerization.
In vitro Attachment of Endothelial Cells to Different Graft Materials (1996)

The purpose of this study was to compare the degree of endothelial cell attachment to different synthetic vascular graft materials. Human microvessel endothelial cells were labelled with indium-111-oxine, injected into 9 different vascular grafts and left to adhere for 40 min. Unattached cells were removed and radioactivity of the grafts measured. Grafts were flushed with 20 ml phosphate-buffered saline during 5 s to remove cells with poor attachment and radioactivity was measured again. Attachment differed between the grafts. In order of decreasing attachment the grafts were albumin-coated Dacron (47%), preclotted Dacron (35-44%), gelatin-coated Dacron (20%), gelatin-coated polyurethane (17%), collagen-coated Dacron (12%), preclotted expanded polytetrafluoroethylene (ePTFE; 3%). Albumin-coated Dacron showed the highest degree of cell attachment of ePTFE the lowest. Statistically significant differences exist between ePTFE and all other grafts and between albumin-coated and collagen-coated Dacron, gelatin-coated polyurethane and gelatin-coated Dacron.