gebhart/patrepeval huggingface dataset:
Novel Designs of Multivalent Anti-CD20 Humanized Antibodies as Improved Lymphoma Therapeutics (2008)

Multivalent antibodies, either monospecific or bispecific, may improve the efficacy of current therapeutic interventions involving a single monoclonal antibody (mAb). We have applied the Dock-and-Lock (DNL) method, a new platform technology for the site-specific and covalent assembly of modular components into stably tethered complexes of defined composition, to prepare a hexavalent, anti-CD20 antibody, designated Hex-hA20, which comprises six Fabs with one Fc. We show that Hex-hA20 retains the binding activity of all six Fabs, associates with CD20 in lipid rafts, affects antibody-dependent cell-mediated cytotoxicity, but not complement-dependent cytotoxicity, and inhibits proliferation of Daudi, Raji, and Ramos cells in vitro at subnanomolar concentrations without the need for a cross-linking antibody. In addition, Hex-hA20 induces strong homotypical adhesion and is inefficient in stimulating calcium mobilization. Thus, Hex-hA20 exhibits biological properties attributable to both type I and type II anti-CD20 mAbs, as exemplified by rituximab and tositumomab, respectively. Although Hex-hA20 has a short serum half-life, it shows antitumor efficacy in tumor-bearing mice comparable with veltuzumab at equivalent doses. The versatile DNL method was also applied to generate two other multivalent anti-CD20 antibodies without the Fc region, Tri-hA20 and Tetra-hA20, comprising three and four Fabs of veltuzumab, respectively. Similar to Hex-hA20, these were purified to near homogeneity and shown to have potent antiproliferative activity in vitro, thus indicating the need for clustering three or more CD20 molecules on the cell surface to induce growth inhibition.
Proton pump inhibitor therapy in gastro‐oesophageal reflux disease decreases the oesophageal immune response but does not reduce the formation of DNA adducts (2008)

Short-term PPI therapy in EO patients reduces the oesophageal cellular immune response, but does not change oxidative damage. PPI therapy may therefore not be effective in reducing the risk of oesophageal cancer in GERD patients.
Human serotonin 5‐HT7 receptor: cloning and pharmacological characterisation of two receptor variants (1997)

Two splice variants of the 5-HT7 receptor were identified in human brain that differ in the lengths of their intracellular carboxy terminal tail. Identification of the variants of this receptor is of particular interest since the 5-HT7 receptor is known to have a high affinity for a number of antidepressants and is localized in brain regions thought to be implicated in depression. The two isoforms are expressed in roughly equal amounts in various regions of the human brain. When expressed in NIH-3T3 cells, both variants encode functional 5-HT7 receptors, positively coupled to adenylyl cyclase. We suggest that both variants are derived from a single gene by alternative mRNA splicing. Furthermore, our results from Southern blot analysis studies suggest that additional 5-HT7 receptor genes may exist in human.
Linear Segmentation and Segment Significance (1998)

We present a new method for discovering a segmental discourse structure of a document while categorizing segment function. We demonstrate how retrieval of noun phrases and pronominal forms, along with a zero-sum weighting scheme, determines topicalized segmentation. Futhermore, we use term distribution to aid in identifying the role that the segment performs in the document. Finally, we present results of evaluation in terms of precision and recall which surpass earlier approaches.
Interaction between p53 and estradiol pathways in transcriptional responses to chemotherapeutics (2013)

Estrogen receptors (ERs) and p53 can interact via cis-elements to regulate the angiogenesis-related VEGFR-1 (FLT1) gene, as we reported previously. Here, we address cooperation between these transcription factors on a global scale. Human breast adenocarcinoma MCF7 cells were exposed to single or combinatorial treatments with the chemotherapeutic agent doxorubicin and the ER ligand 17β-estradiol (E2). Whole-genome transcriptome changes were measured by expression microarrays. Nearly 200 differentially expressed genes were identified that showed limited responsiveness to either doxorubicin treatment or ER ligand alone but were upregulated in a greater than additive manner following combined treatment. Based on exposure to 5-fuorouracil and nutlin-3a, the combined responses were treatment-specific. Among 16 genes chosen for validation using quantitative real-time PCR, seven (INPP5D, TLR5, KRT15, EPHA2, GDNF, NOTCH1, SOX9) were confirmed to be novel direct targets of p53, based on responses in MCF7 cells silenced for p53 or cooperative targets of p53 and ER. Promoter pattern searches and chromatin IP experiments for the INPP5D, TLR5, KRT15 genes supported direct, cis-mediated p53 and/or ER regulation through canonical and noncanonical p53 and ER response elements. Collectively, we establish that combinatorial activation of p53 and ER can induce novel gene expression programs that have implications for cell-cell communications, adhesion, cell differentiation, development and inflammatory responses as well as cancer treatments.
Adaptive high-precision control of positioning tables-theory and experiments (1994)

Positioning tables are widely used in industries, and precise control of their motion is difficult to achieve because of uncertainty in their load and friction parameters. In this paper, we describe the development and experimentation of a new adaptive controller for precise table motion control. The global stability of the controller and global convergence of tracking errors are proven using Lyapunov stability theory under mild conditions. The adaptive controller has been experimentally implemented and extensively tested on a belt-drive high-speed table, resulting in significant improvement over conventional PID controller.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ghrelin-induced growth hormone secretion in humans (2000)

Ghrelin is a novel growth hormone (GH) releaser acylated peptide that has recently been purified from stomach, and which potently binds to the GH secretagogue receptor. Ghrelin releases GH in vitro and in vivo in animal models, however its actions, potency and specificity in humans are unknown. In the present study, 12 healthy subjects were studied: 6 underwent four tests with ghrelin administered i.v. at the dose of 0 (placebo), 0.25, 0.5 and 1 microg/kg which corresponds to 0, 18, 37 and 75 microg total dose. A further 6 volunteers underwent two tests on different days with ghrelin at the dose of 3.3 or 6.6 microg/kg which corresponds to 250 microg and 500 microg total dose. Ghrelin-mediated GH secretion showed a dose-response curve, in which 1 microg/kg was the minimally effective dose in some individuals, but not as a group. On the contrary, the total doses of 250 microg and 500 microg elicited a powerful GH secretion, with a mean peak of 69.8+/-9.2 microg/l and 90.9+/-16.9 microg/l respectively, and areas under the curve of 4435+/-608 and 6125+/-1008 microg/l per 120 min respectively. All of them statistically significant vs placebo and vs the 1 microg/kg dose. Ghrelin administration also elicited a relevant dose-response mediated prolactin secretion suggesting no specificity of its actions. No relevant side effects were observed with ghrelin apart from a hyperhydrosis episode in two individuals tested with the higher ghrelin doses. In conclusion, ghrelin is a potent releaser of GH in normal individuals, with a dose-response pattern of operation. No saturating dose was observed.
Antibodies selected from combinatorial libraries block a tumor antigen that plays a key role in immunomodulation (2006)

We searched for cell-surface-associated proteins overexpressed on B cell chronic lymphocytic leukemia (CLL) to use as therapeutic antibody targets. Antibodies binding the immunosuppressive molecule CD200 were identified by cell panning of an antibody phage display library derived from rabbits immunized with primary CLL cells. B cells from 87 CLL patients exhibited 1.6- to 5.4-fold cell-surface up-regulation of CD200 relative to normal B cells. An effect of increased CD200 expression by CLL cells on the immune system was evaluated in mixed lymphocyte reactions. Addition of primary CLL but not normal B cells to macrophages and T cells downregulated the Th1 response, as seen by a 50-95% reduction in secreted IL-2 and IFN-gamma. Antibodies to CD200 prevented downregulation of the Th1 response in most B cell CLL samples evaluated, indicating abrogation of the CD200/CD200R interaction can be sufficient to restore the Th1 response. A disease-progression-associated shift of the immune response from Th1 to Th2 has been observed in numerous cancers. Because this cytokine shift is also believed to promote the induction of regulatory T cells, reverting the immune response to Th1 through direct targeting of the cancer cells may provide therapeutic benefits in CLL by encouraging a cytotoxic T cell response.
Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis (2014)

Overall, high generalised tumour inflammatory infiltrate could be a good prognostic marker for CRC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes to increase the robustness of the analyses.
Safer handling practice 2: putting theory into practice (2001)

Christine Brown Wilson explores practical strategies to support staff in implementing the theories and concepts of safer handling practice.
Crystal structure of the TSP-1 type 1 repeats (2002)

Thrombospondin-1 (TSP-1) contains three type 1 repeats (TSRs), which mediate cell attachment, glycosaminoglycan binding, inhibition of angiogenesis, activation of TGFbeta, and inhibition of matrix metalloproteinases. The crystal structure of the TSRs reported in this article reveals a novel, antiparallel, three-stranded fold that consists of alternating stacked layers of tryptophan and arginine residues from respective strands, capped by disulfide bonds on each end. The front face of the TSR contains a right-handed spiral, positively charged groove that might be the "recognition" face, mediating interactions with various ligands. This is the first high-resolution crystal structure of a TSR domain that provides a prototypic architecture for structural and functional exploration of the diverse members of the TSR superfamily.
Spectral analysis and discrimination by zero-crossings (1986)

We advance a coherent development of zero-crossing-based methods and theory appropriate for fast signal analysis. Quite a few ideas pertaining to zero-crossing counts found in the literature can be expressed and interpreted with the help of this more general setup. A central issue addressed in some detail is the fruitful connection which exists between zero-crossing counts and linear filtering. This connection is explored and interpreted with the help of a certain zero-crossing spectral representation, and is then applied in spectral analysis, detection, and discrimination. Zero-crossing counts in filtered time series are called higher order crossings. The theme of this work is that higher order crossings analysis provides a useful descriptive as well as an analytical tool that can in many respects match spectral analysis. To a great extent these two types of analysis are, in fact, equivalent, but each emphasizes a different point of view. Advantages offered by higher order crossings are great simplicity and a drastic data reduction.
Catalytic Dehydrogenative Cross-Coupling: Forming Carbon−Carbon Bonds by Oxidizing Two Carbon−Hydrogen Bonds (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTCatalytic Dehydrogenative Cross-Coupling: Forming Carbon−Carbon Bonds by Oxidizing Two Carbon−Hydrogen BondsCharles S. Yeung and Vy M. Dong*View Author Information Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6*E-mail: [email protected]Cite this: Chem. Rev. 2011, 111, 3, 1215–1292Publication Date (Web):March 9, 2011Publication History Received24 August 2010Published online9 March 2011Published inissue 9 March 2011https://pubs.acs.org/doi/10.1021/cr100280dhttps://doi.org/10.1021/cr100280dreview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views52222Altmetric-Citations3594LEARN 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:Catalysts,Coupling reactions,Cross coupling reaction,Hydrocarbons,Indoles Get e-Alerts
Prostate cancer proteomics: Current trends and future perspectives for biomarker discovery (2017)

The clinical and fundamental research in prostate cancer - the most common urological cancer in men - is currently entering the proteomic and genomic era. The focus has switched from one single marker (PSA) to panels of biomarkers (including proteins involved in ribosomal function and heat shock proteins). Novel genetic markers (such as Transmembrane protease serine 2 (TMPRSS2)-ERG fusion gene mRNA) or prostate cancer gene 3 (PCA3) had already entered the clinical practice, raising the question whether subsequent protein changes impact the evolution of the disease and the response to treatment. Proteomic technologies such as MALDI-MS, SELDI-MS, i-TRAQ allow a qualitative/quantitative analysis of the proteome variations, in both serum and tumor tissue. A new trend in prostate cancer research is proteomic analysis of prostasomes (prostate-specific exosomes), for the discovery of new biomarkers. This paper provides an update of novel clinical tests used in research and clinical diagnostic, as well as of potential tissue or fluid biomarkers provided by extensive proteomic research data.
Gbb/Bmp signaling is essential for maintaining germline stem cells and for repressingbamtranscription in theDrosophilatestis (2004)

Stem cells are responsible for replacing damaged or dying cells in various adult tissues throughout a lifetime. They possess great potential for future regenerative medicine and gene therapy. However, the mechanisms governing stem cell regulation are poorly understood. Germline stem cells (GSCs) in the Drosophila testis have been shown to reside in niches, and thus these represent an excellent system for studying relationships between niches and stem cells. Here we show that Bmp signals from somatic cells are essential for maintaining GSCs in the Drosophila testis. Somatic cyst cells and hub cells express two Bmp molecules, Gbb and Dpp. Our genetic analysis indicates that gbb functions cooperatively with dpp to maintain male GSCs, although gbb alone is essential for GSC maintenance. Furthermore, mutant clonal analysis shows that Bmp signals directly act on GSCs and control their maintenance. In GSCs defective in Bmp signaling, expression of bam is upregulated, whereas forced bam expression in GSCs causes the GSCs to be lost. This study demonstrates that Bmp signals from the somatic cells maintain GSCs, at least in part, by repressing bam expression in the Drosophila testis. dpp signaling is known to be essential for maintaining GSCs in the Drosophila ovary. This study further suggests that both Drosophila male and female GSCs use Bmp signals to maintain GSCs.
Targeting the epidermal growth factor receptor (EGFR) - a new therapeutic option in oncology? (2006)

The epidermal growth factor receptor (EGFR) is commonly overexpressed in a variety of solid tumours, and clinical trials indicate that this antigen has important roles in cancer aetiology and progression. EGFR thus provides a rational target for cancer therapies and a number of strategies influencing this receptor, and its downstream signal cascades, including monoclonal antibodies, tyrosine-kinase inhibitors, antisense oligonucleotides inhibiting EGFR synthesis and antibody-based immunoconjugates, have been evaluated. In particular, monoclonal antibodies targeting the receptor's extracellular domain and small molecules blocking tyrosine-kinase activation intracellularly have already shown some activity in clinical phase I-III trials. These two major classes of anti-EGFR therapeutics will be the main topic of this review. In the case of tyrosine-kinase inhibitors, amplification, high polysomy of the EGFR gene, high protein expression and mutations of the receptor were found to be significantly associated with better response to such treatment. However, many questions remain unanswered and future issues in the development of EGFR inhibitors will include the identification of biological predictors of response, combination with other therapies and also their use in earlier stages of cancer.
Asymmetric Hydrogenation Using Monodentate Phosphoramidite Ligands (2007)

Monodentate phosphoramidites are excellent ligands for Rh-catalyzed asymmetric hydrogenations of substituted olefins. Enantioselectivities between 95 and 99% were obtained in the asymmetric hydrogenation of protected alpha- and beta-dehydroamino acids and esters, itaconic acid and esters, aromatic enamides, aromatic enol esters, aromatic and aliphatic enol carbamates, and alpha-substituted cinnamic acids. An iridium catalyst Ir(L*)(COD)Cl was developed that contains only a single bulky phosphoramidite based on 3,3'-disubstituted BINOL or bisphenol as a chiral ligand. With this catalyst, acetylated dehydroamino acid esters could be hydrogenated with very good enantioselectivity. Most reactions have turnover frequencies of 250-1600 h (-1), depending upon the hydrogen pressure. The enantioselectivity is unaffected by the pressure over a wide range. Because of their modularity and easy synthesis, parallel ligand synthesis is possible. Results obtained with these library ligands deviate only slightly from those obtained with purified ligands. Using this instant ligand library protocol, DSM has developed catalysts for industrial processes. These MonoPhos ligands are currently used in production for pharmaceutical intermediates by DSM. It is possible to use catalysts based on a mixture of two different monodentate ligands, such as two different monodentate phosphoramidites or one phosphoramidite and one achiral phosphine ligand. Dependent upon the substrate, the "mixed" catalyst may lead to higher enantioselectivity and rate than the "homocatalysts".
Rover (1995)

article Free Access Share on Rover: a toolkit for mobile information access Authors: A. D. Joseph M.I.T. Laboratory for Computer Science, Cambridge, MA M.I.T. Laboratory for Computer Science, Cambridge, MAView Profile , A. F. de Lespinasse M.I.T. Laboratory for Computer Science, Cambridge, MA M.I.T. Laboratory for Computer Science, Cambridge, MAView Profile , J. A. Tauber M.I.T. Laboratory for Computer Science, Cambridge, MA M.I.T. Laboratory for Computer Science, Cambridge, MAView Profile , D. K. Gifford M.I.T. Laboratory for Computer Science, Cambridge, MA M.I.T. Laboratory for Computer Science, Cambridge, MAView Profile , M. F. Kaashoek M.I.T. Laboratory for Computer Science, Cambridge, MA M.I.T. Laboratory for Computer Science, Cambridge, MAView Profile Authors Info & Claims ACM SIGOPS Operating Systems ReviewVolume 29Issue 5Dec. 3, 1995pp 156–171https://doi.org/10.1145/224057.224069Published:03 December 1995Publication History 168citation1,459DownloadsMetricsTotal Citations168Total Downloads1,459Last 12 Months79Last 6 weeks26 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Staphylococcus aureus Mevalonate Kinase: Isolation and Characterization of an Enzyme of the Isoprenoid Biosynthetic Pathway (2003)

It has been proposed that isoprenoid biosynthesis in several gram-positive cocci depends on the mevalonate pathway for conversion of acetyl coenzyme A to isopentenyl diphosphate. Mevalonate kinase catalyzes a key reaction in this pathway. In this study the enzyme from Staphylococcus aureus was expressed in Escherichia coli, isolated in a highly purified form, and characterized. The overall amino acid sequence of this enzyme was very heterologous compared with the sequences of eukaryotic mevalonate kinases. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analytical gel filtration chromatography suggested that the native enzyme is a monomer with a molecular mass of approximately 33 kDa. The specific activity was 12 U/mg, and the pH optimum was 7.0 to 8.5. The apparent K(m) values for R,S-mevalonate and ATP were 41 and 339 micro M, respectively. There was substantial substrate inhibition at millimolar levels of mevalonate. The sensitivity to feedback inhibition by farnesyl diphosphate and its sulfur-containing analog, farnesyl thiodiphosphate, was characterized. These compounds were competitive inhibitors with respect to ATP; the K(i) values were 46 and 45 micro M for farnesyl diphosphate and its thio analog, respectively. Parallel measurements with heterologous eukaryotic mevalonate kinases indicated that S. aureus mevalonate kinase is much less sensitive to feedback inhibition (K(i) difference, 3 orders of magnitude) than the human enzyme. In contrast, both enzymes tightly bound trinitrophenyl-ATP, a fluorescent substrate analog, suggesting that there are similarities in structural features that are important for catalytic function.
Colonization of experimental murine breast tumours by Escherichia coli K-12 significantly alters the tumour microenvironment (2008)

The successful application of live bacteria in cancer therapy requires a more detailed understanding of bacterial interaction with the tumour microenvironment. Here, we analysed the effect of Escherichia coli K-12 colonization on the tumour microenvironment by immunohistochemistry and fluorescence microscopy in the murine 4T1 breast carcinoma model. We described the colonization of tumour-bearing mice, as well as the spatiotemporal distribution of E. coli K-12 in the 4T1 tumour tissue over a period of 14 days. The colonization resulted within 3 days in large avascular necrotic tissue, redistribution of hypoxic areas and an enhanced collagen IV deposition within the colonized tumour tissue, which changed the tumoral perfusion of systemically injected immunoglobulins. In addition, E. coli K-12 colonization led to the redistribution of tumour-associated macrophages, forming a granulation tissue around bacterial colonies, and also to an increase in TNFalpha and matrix metalloproteinase 9 expression. Colonization of 4T1 tumours by E. coli K-12 resulted in strong reduction of pulmonary metastatic events. These new insights will contribute to the general understanding of the tumour-microbe cross-talk and to the design of bacterial strains with enhanced anticancer efficiency.