gebhart/patrepeval huggingface dataset:
HIV Integrase Inhibitors (2013)

This chapter presents the discovery, development and evolution of integrase strand transfer inhibitors. A brief overview of the first‐generation inhibitors raltegravir and elvitegravir serves to describe their landmark advancement of the field and also outline areas for further improvement. The remainder of the discussion revolves around the strategy in designing a series of carbamoylpyridines that ultimately led to the discovery of dolutegravir, an investigational integrase inhibitor in late‐stage clinical development. In addition, an intriguing approach to the development of a related compound, S/GSK744, as a long‐acting parenteral agent is presented. Finally, an exciting new area of non‐catalytic site integrase inhibitors is included.
Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas (2007)

Diffuse large B-cell lymphoma (DLBCL) consists of at least 2 phenotypic subtypes; that is, the germinal center B-cell-like (GCB-DLBCL) and the activated B-cell-like (ABC-DLBCL) groups. It has been shown that GCB-DLBCL responds favorably to chemotherapy and expresses high levels of BCL6, a transcription repressor known to play a causative role in lymphomagenesis. In comparison, ABC-DLBCL has lower levels of BCL6, constitutively activated nuclear factor-kappaB, and tends to be refractory to chemotherapy. Here, we report that the STAT3 gene is a transcriptional target of BCL6. As a result, high-level STAT3 expression and activation are preferentially detected in ABC-DLBCL and BCL6-negative normal germinal center B cells. Most importantly, inactivating STAT3 by either AG490 or small interference RNA in ABC-DLBCL cells inhibits cell proliferation and triggers apoptosis. These phenotypes are accompanied by decreased expression of several known STAT3 target genes, including c-Myc, JunB, and Mcl-1, and increased expression of the cell- cycle inhibitor p27. In addition to identifying STAT3 as a novel BCL6 target gene, our results define a second oncogenic pathway, STAT3 activation, which operates in ABC-DLBCL, suggesting that STAT3 may be a new therapeutic target in these aggressive lymphomas.
Two‐dimensional multi‐criterion segmentation of pulmonary nodules on helical CT images (1999)

A multi-criterion algorithm for automatic delineation of small pulmonary nodules on helical CT images has been developed. In a slice-by-slice manner, the algorithm uses density, gradient strength, and a shape constraint of the nodule to automatically control segmentation process. The multiple criteria applied to separation of the nodule from its surrounding structures in lung are based on the fact that typical small pulmonary nodules on CT images have high densities, show a distinct difference in density at the boundary, and tend to be compact in shape. Prior to the segmentation, a region-of-interest containing the nodule is manually selected on the CT images. Then the segmentation process begins with a high density threshold that is decreased stepwise, resulting in expansion of the area of nodule candidates. This progressive region growing approach is terminated when subsequent thresholds provide either a diminished gradient strength of the nodule contour or significant changes of nodule shape from the compact form. The shape criterion added to the algorithm can effectively prevent the high density surrounding structures (e.g., blood vessels) from being falsely segmented as nodule, which occurs frequently when only the gradient strength criterion is applied. This has been demonstrated by examples given in the Results section. The algorithm's accuracy has been compared with that of radiologist's manual segmentation, and no statistically significant difference has been found between the nodule areas delineated by radiologist and those obtained by the multi-criterion algorithm. The improved nodule boundary allows for more accurate assessment of nodule size and hence nodule growth over a short time period, and for better characterization of nodule edges. This information is useful in determining malignancy status of a nodule at an early stage and thus provides significant guidance for further clinical management.
Ring-Opening Polymerization-Mediated Controlled Formulation of Polylactide−Drug Nanoparticles (2009)

We report here a unique method for formulating doxorubicin-polylactide (Doxo-PLA) conjugate nanoparticles, known as nanoconjugates (NCs), through Doxo/(BDI)ZnN(TMS)(2)-mediated [(BDI) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)-imino)-2-pentene], chemo- and regioselective polymerizations of lactide (LA) followed by nanoprecipitation. When Doxo/(BDI)ZnN(TMS)(2) was mixed with 1-pyrenemethanol (Pyr-OH) and 1-pyrenemethylamine (Pyr-NH(2)) and the mixture was utilized for the polymerization of LA, remarkable chemoselectivity was observed. Pyr-OH was completely consumed and covalently linked to the terminus of the PLA, whereas the Pyr-NH(2) remained intact in the polymerization solution. When Doxo was used as the initiator to polymerize LA in the presence of (BDI)ZnN(TMS)(2), the polymerization was complete within hours, with nearly 100% Doxo-loading efficiency and 100% LA conversion. Doxo loading as high as 27% could be achieved at a LA/Doxo ratio of 10. Both the steric bulk of the chelating ligand and the metal catalyst had dramatic effects on the regioselectivity during the initiation step. When Doxo/(BDI)ZnN(TMS)(2) was mixed with succinic anhydride (SA) to mimic the initiation of Doxo/(BDI)ZnN(TMS)(2)-mediated LA polymerization, Doxo-14-succinic ester (Doxo-SE) was the predominate product. When the steric bulk of BDI was reduced or when the BDI ligand was removed, significant amounts of Doxo-4',14-bis-succinic ester (Doxo-2SE) and Doxo-4',9,14-trisuccinic ester (Doxo-3SE) were formed. The use of (BDI)MgN(TMS)(2) in such a reaction also resulted in reduced regioselectivity and formation of both Doxo-SE and Doxo-2SE. Doxo/(BDI)ZnN(TMS)(2)-mediated LA polymerizations yielded Doxo-PLA conjugates with well-controlled molecular weights and polydispersities (as low as 1.02). The nanoprecipitation of Doxo-PLA formed NCs less than 150 nm in size with narrow particle size distributions. The sustained release of Doxo from Doxo-PLA NCs was achieved without a burst release. This method may have widespread utility for controlled conjugation of hydroxyl-containing agents to polyesters and formation of corresponding nanoparticles.
Parasexual Interspecific Plant Hybridization (1972)

Interspecific plant hybrids have been produced by parasexual procedures. Protoplasts of Nicotiana glauca and N. langsdorffii were isolated, fused, and induced to regenerate into plants. The somatic hybrids were recovered from a mixed population of parental and fused protoplasts by a selective screening method that relies on differential growth of the hybrid on defined culture media. The biochemical and morphological characteristics of the somatically produced hybrid were identical to those of the sexually produced amphiploid.
An equivalent circuit model of a radial line planar antenna with coupling probes (2003)

Many communication systems require a microwave planar antenna with a gain in the range of 30 dB or more. Achieving this value of gain using a planar microstrip patch array with a conventional circuit-type feeding network faces difficulties. The paper concentrates on the planar radial antenna consisting of one central feed probe and a number of coupling probes arranged in rings feeding antenna elements. The usual design goal for this antenna is a loss-free, uniform (amplitude and phase) aperture illumination to obtain maximum gain. Realization of this illumination requires selecting proper positioning and length of the coupling probes. To achieve this task in a predictable manner, an approximate model for the feed network was developed by H. Miyashita and T. Katagi (see IEEE Trans. Antennas and Propag., vol.44, no.8, p.1158-65, 1996) assuming only interactions between the central probe and individual coupling probes. We describe a circuit model which takes into account mutual coupling between all of the coupling probes. The model is tested on the example of a 5-ring planar radial array as described by Miyashita and Katagi. The results show agreement with theoretical and experimental results presented by other researchers. The radiation pattern is sensitive to small changes in the length of the coupling probes.
Efficient, Aerobic, Ruthenium-Catalyzed Oxidation of Alcohols into Aldehydes and Ketones (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEfficient, Aerobic, Ruthenium-Catalyzed Oxidation of Alcohols into Aldehydes and KetonesIstván E. Markó, Paul R. Giles, Masao Tsukazaki, Isabelle Chellé-Regnaut, Christopher J. Urch, and Stephen M. BrownView Author Information Département de Chimie, Laboratoire de Chimie Organique Université Catholique de Louvain, Bâtiment Lavoisier Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium Zeneca Agrochemicals, Jealott's Hill Research Station Bracknell, Berkshire RG42 6ET, U.K. Zeneca Process Technology Department Huddersfield Works, P.O. Box A38, Leeds Road Huddersfield HD2 1FF, U.K. Cite this: J. Am. Chem. Soc. 1997, 119, 51, 12661–12662Publication Date (Web):December 24, 1997Publication History Received15 September 1997Published online24 December 1997Published inissue 1 December 1997https://pubs.acs.org/doi/10.1021/ja973227bhttps://doi.org/10.1021/ja973227brapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views4011Altmetric-Citations270LEARN 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 SUBJECTS:Alcohols,Aldehydes,Ketones,Oxidation,Oxidation reactions Get e-Alerts
SPAS-1 (stimulator of prostatic adenocarcinoma-specific T cells)/SH3GLB2: A prostate tumor antigen identified by CTLA-4 blockade (2008)

Discovery of immunologically relevant antigens in prostate cancer forms the basis for developing more potent active immunotherapy. We report here a strategy using the transgenic adenocarcinoma of mouse prostate (TRAMP) model, which allows for the functional identification of immunogenic prostate tumor antigens with relevance for human immunotherapy. Using a combination of active tumor vaccination in the presence of CTL-associated antigen 4 (CTLA-4) in vivo blockade, we elicited tumor-specific T cells used to expression clone the first T cell-defined TRAMP tumor antigen, called Spas-1 (stimulator of prostatic adenocarcinoma specific T cells-1). Spas-1 expression was increased in advanced primary TRAMP tumors. We show that the immunodominant SPAS-1 epitope SNC9-H(8) arose from a point mutation in one allele of the gene in TRAMP tumor cells, and that immunization with dendritic cells pulsed with SNC9-H(8) peptide resulted in protection against TRAMP-C2 tumor challenge. In humans, the Spas-1 ortholog SH3GLB2 has been reported to be overexpressed in prostate cancer metastases. Additionally, we identified a nonmutated HLA-A2-binding epitope in the human ortholog SH3GLB2, which primed T cells from healthy HLA-A2(+) individuals in vitro. Importantly, in vitro-primed T cells also recognized naturally processed and presented SH3GLB2. Our findings demonstrate that our in vivo CTLA-4 blockade-based T cell expression cloning can identify immunogenic cancer antigens with potential relevance for human immunotherapy.
Gene expression profiles in primary ovarian serous papillary tumors and normal ovarian epithelium: Identification of candidate molecular markers for ovarian cancer diagnosis and therapy (2004)

With the goal of identifying genes with a differential pattern of expression between ovarian serous papillary carcinomas (OSPCs) and normal ovarian (NOVA) epithelium and using this knowledge for the development of novel diagnostic and therapeutic markers for ovarian cancer, we used oligonucleotide microarrays with probe sets complementary to 12,533 genes to analyze the gene expression profiles of 10 primary OSPC cell lines, 2 established OSPC cell lines (UCI-101, UCI-107) and 5 primary NOVA epithelial cultures. Unsupervised analysis of gene expression data identified 129 and 170 genes that exhibited >5-fold upregulation and downregulation, respectively, in primary OSPC compared to NOVA. Genes overexpressed in established OSPC cell lines had little correlation with those overexpressed in primary OSPC, highlighting the divergence of gene expression that occurs as a result of long-term in vitro growth. Hierarchical clustering of the expression data readily distinguished normal tissue from primary OSPC. Laminin, claudin 3, claudin 4, tumor-associated calcium signal transducers 1 and 2 (TROP-1/Ep-CAM, TROP-2), ladinin 1, S100A2, SERPIN2 (PAI-2), CD24, lipocalin 2, osteopontin, kallikrein 6 (protease M), kallikrein 10, matriptase (TADG-15) and stratifin were among the most highly overexpressed genes in OSPC compared to NOVA. Downregulated genes in OSPC included transforming growth factor-beta receptor III, platelet-derived growth factor receptor alpha, SEMACAP3, ras homolog gene family member I (ARHI), thrombospondin 2 and disabled-2/differentially expressed in ovarian carcinoma 2 (Dab2/DOC2). Differential expression of some of these genes, including claudin 3, claudin 4, TROP-1 and CD24, was validated by quantitative RT-PCR and flow cytometry on primary OSPC and NOVA. Immunohistochemical staining of formalin-fixed, paraffin-embedded tumor specimens from which primary OSPC cultures were derived further confirmed differential expression of CD24 and TROP-1/Ep-CAM markers on OSPC vs. NOVA. These results, obtained with highly purified primary cultures of ovarian cancer, highlight important molecular features of OSPC and may provide a foundation for the development of new type-specific therapies against this disease.
Membrane potential changes during mitogenic stimulation of mouse spleen lymphocytes (1980)

By monitoring differences in accumulation of the lipophilic cation [(3)H]tetraphenylphosphonium in media containing low or high potassium concentrations [Lichtshtein, D., Kaback, H. R. & Blume, A. J. (1979) Proc. Natl. Acad. Sci. USA 76, 650-654], the membrane potential of lymphocytes from various sources has been estimated. On the basis of this method, the potential of normal mouse spleen lymphocytes (T and B cells) is -65 +/- 2 mV (mean +/- SEM, interior negative). During the course of mitogenic stimulation by concanavalin A, lipopolysaccharide, or fetal calf serum, the membrane potential of murine spleen lymphocytes changes systematically according to the following pattern: (i) early depolarization lasting 2-3 hr, (ii) repolarization over the next 7 hr, and (iii) a final hyperpolarization phase during the last 24-48 hr. During repolarization and hyperpolarization, moreover, there is a direct correlation between the membrane potential and DNA synthesis, as judged by [(3)H]thymidine incorporation. By using isolated T and B cells, it is observed that concanavalin A depolarizes T cells only, whereas lipopolysaccharide depolarizes B cells only. Thus, both mitogens exhibit the same specificity for depolarization as for mitogenic stimulation. On the basis of these observations, it is suggested that the transition of lymphocytes from a resting state to mitotic activity is initiated by depolarization of the plasma membrane.
Picornavirus IRESes and the poly(A) tail jointly promote cap-independent translation in a mammalian cell-free system (2000)

In eukaryotic cells, efficient translation of most cellular mRNAs requires the synergistic interplay between the m7GpppN cap structure and the poly(A) tail during initiation. We have developed and characterized a cell-free system from human HeLa cells that recapitulates this important feature, displaying more than one order of magnitude of translational synergism between the cap structure and the poly(A) tail. The stimulation of cap-dependent translation by the poly(A) tail is length-dependent, but not mediated by changes in mRNA stability. Using this system, we investigated the effect of the poly(A) tail on the translation of picornaviral RNAs, which are naturally polyadenylated but initiate translation via internal ribosome entry sites (IRESs). We show that translation driven by the IRESs of poliovirus (PV), encephalomyocarditis virus (EMCV), and hepatitis A virus is also significantly augmented by a poly(A) tail, ranging from an approximately 3-fold stimulation for the EMCV-IRES to a more than 10-fold effect for the PV IRES. These results raise interesting questions concerning the underlying molecular mechanism(s). The cell-free system described here should prove useful in studying these questions as well as providing a general biochemical tool to examine the translation initiation pathway in a more physiological setting.
Staining of living bacteria with rhodamine 123 (1984)

It is possible to stain live bacteria with rhodamine 123 (R123).The stained fluorescent cells still keep the ability to replicate (Staphylococcus aureus, Bordetella pertussis) and to swim (e.g., Salmonella minnesota).Dead cells or cells with a dissipated transmembrane potential showed markedly diminished fluorescence.Gram-negative strains were stained with different efficiency, presumably reflecting the different constitutions of the outer membrane.Table 1 Gram-positive bacteria treated with
SMAD4 as a Prognostic Marker in Colorectal Cancer (2005)

More than 50% of patients with Dukes C colorectal cancer have disease recurrence and die within 5 years after surgical removal of their primary tumor. It is currently not possible to distinguish patients with good and bad prognosis. SMAD4 is an important tumor suppressor gene that mediates transforming growth factor-beta superfamily signaling and is located in chromosome 18q21, a region with frequent genetic losses in these tumors. Allelic imbalance in 18q has been linked to poor prognosis in a subset of colorectal cancer patients. Therefore, we generated a tissue microarray containing triplicate tumor samples from 86 Dukes C patients and used immunohistochemistry to assess the relative expression level of SMAD4 and its value as a prognostic marker. In addition, SMAD4 was screened for mutations and two polymorphic microsatellite markers were used to assess the presence of allelic imbalance in these tumors. Patients with tumors expressing high SMAD4 levels had significantly better overall (P < 0.025) and disease-free (P < 0.013) survival than patients with low levels. This identifies SMAD4 as a prognostic marker for Dukes C colorectal cancer. Although all tumors with absent SMAD4 staining showed allelic imbalance in 18q21, tumors with 18q21 allelic imbalance as a group showed no difference in SMAD4 levels compared with tumors without allelic imbalance, suggesting that additional mechanisms of SMAD4 down-regulation exist. In addition, although SMAD4 mutations were found in five tumors, they were not associated with shorter survival. In conclusion, the level of expression of SMAD4 was found to be a more sensitive marker than 18q21 allelic imbalance and SMAD4 mutations, which were of no prognostic significance for these patients.
P2–259: Discrimination between Alzheimer's disease patients and healthy subjects: Resting FDG–PET data (2006)

The pattern of brain activation in a region is dependent on the integrity of the neuronal and synaptic connections of a region. Thus the level of brain activation will lead to a spatial pattern of relatively higher and lower activation. Thus brain imaging data can be treated as a spatial pattern, and a statistical pattern recognition method can be used to map different patterns to different group membership. To investigate if machine learning methods can classify subjects between Alzheimer's disease and healthy control (HC) subjects. We applied the Support Vector Machine (SVM) algorithm to perform classification of group membership using resting glucose metabolism images obtained using positron emission tomography (PET). There were 17 AD and 12 age–matched HC. The average (standard deviation) age was 67.8 (10.1) and 66.8 (9.8) years for the HC and AD patients, respectively. The average Mini Mental State Exam score was 29.4 (0.6) and 11 (6.7) for the HC and AD patients, respectively. Values of the resting glucose metabolism were obtained using regions of interest (ROI) in the visual cortex, lateral temporal cortex, medial temporal lobe, inferior temporal lobe, ventral and dorso–lateral frontal lobe, anterior cingulate, and posterior cingulate. We found statistically significant differences in the temporal lobe, inferior parietal region, posterior cingulate and medial and frontal lobe areas. The analysis suing the SVM had two phases: during the training, the classifier algorithm finds the set of regions by which the two groups can be best distinguished from each other. In the test phase, given the FDG–PET values from a new subject the classifier predicts the subject's group membership. Our approach leads to two outputs: the classification of group membership, and the discriminating regions upon which the classification is based on. This method can be expanded to discriminate among 3 or more groups. The method is very promising as a tool to assist in the classification of subjects to patient populations.