gebhart/patrepeval huggingface dataset:
A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac (+) cells. (1981)

Abstract A monoclonal antibody termed anti-Tac monoclonal antibody, which is reactive with activated and functionally mature human T cells, was produced by a somatic cell fusion technique. The reactivity of anti-Tac monoclonal antibody against various kinds of cells was determined by a complement-dependent cytotoxicity test. Anti-Tac antibody was reactive with a proportion of normal human peripheral blood T cells activated by PHA (54.7 ± 6.5%, mean ± SEM), Con A (20.6 ± 4.8), PWM (29.2 ± 2.6), SLO (25.3 ± 6.0), and allogeneic ceils (41.0 ± 5.8) but not with freshly separated resting T cells, B cells, monocytes, or B cells activated by EBV or PWM. Among various leukemic cells and cell line cells, 5 human cultured T cells (CTC) cultured with T cell growth-promoting factor(s) were reactive with anti-Tac antibody, whereas 4 long-term T cell lines (MOLT-4, CCRF-CEM, RPMI 8402, HSB-2) that do not require T cell growth-promoting factor(s) for growth, 2 long-term B cell lines (PA-3, RPMI 8392), 5 EBV-transformed B cell lines, leukemic T cells from patients with acute lymphoblastic leukemia (3 cases) and from those with Sezary syndrome (5 cases), and leukemic B cells from patients with chronic lymphocytic leukemia (4 cases) were not killed by anti-Tac antibody and complement. T cells reactive with anti-Tac antibody appeared before the marked increase in 3H-thymidine uptake in cultured T cells stimulated by Con A. Irradiation with 2000 R or mitomycin C treatment of cells did not prevent the appearance of Tac (+) cells in Con A- or PWM-stimulated T cell cultures, whereas culture with cycloheximide prevented the appearance of Tac (+) cells. These results indicate that the expression of Tac antigen requires protein synthesis but not DNA synthesis and cell division. The relationship between this anti-Tac antibody and other monoclonal antibodies directed to human T cells is discussed.
Overexpression and surface localization of the Chlamydia trachomatis major outer membrane protein in Escherichia coli (1992)

The Chlamydia trachomatis major outer membrane protein (MOMP) is the quantitatively predominant surface protein which has important functional, structural and antigenic properties. We have cloned and overexpressed the MOMP in Escherichia coli. The MOMP is surface exposed in C. trachomatis and capable of eliciting protective antibodies in infected hosts, and therefore has potential as a candidate vaccine to prevent infection with this significant human pathogen. The recombinant MOMP clone, L2rMOMP, contained the entire MOMP gene including the encoded leader sequence. Large quantities of chlamydial MOMP were expressed, some of which was processed and translocated to the E. coli surface. Surface localization of the MOMP was demonstrated by the binding of anti-MOMP monoclonal antibodies to the surface of the induced clone, and was visualized by fluorescence and electron microscopy. The induction of MOMP expression had a rapidly lethal effect on the L2rMOMP E. coli clone. Although no genetic system exists for Chlamydia, development of a stable, inducible E. coli clone which overexpresses the chlamydial MOMP permits a study of the biological properties of the MOMP, including the contribution of the MOMP variable segments to the topographical interactions which determine the antigenic structure responsible for human immune response.
A contribution to the knowledge of iberian earthworms with the description of a new species (1988)

SUMMARY One new lumbricid species Allolobophora iberica (Oligochaeta) is reported. The new species has been found in the vicinities of Braganca (Portugal) and Bejar (Spain). The description of its external features and internal anatomy is followed by a comparison with A. mehadiensis (Rosa, 1895), the species it most resembles.
Synthesis of [1′,2′,5′,2-13C4]-2′-Deoxy-D-adenosine by a Chemoenzymatic Strategy to Enable Labelling of Any of the 215 Carbon-13 and Nitrogen-15 Isotopomers (2002)

Enzymatic trans-N-glycosylation has been selected as the method of choice by which to couple [13C1]-adenine to [13C3]-2-deoxy-D-ribose. The enzymatic pentosylation of the labelled adenine base was achieved in a two-step/one-pot reaction, starting from thymidine labelled in the sugar ring, but not at the thymine base. The efficiency of this thymidine phosphorylase catalysed (TP-catalysed) and purine nucleoside phosphorylase catalysed (PNP-catalysed) transamination reaction was demonstrated by a high yield (91%) and stereochemical purity of the obtained [1′,2′,5′,2-13C4]-2′-deoxy-D-adenosine. To verify that all carbon and nitrogen positions and combination of positions in both the adenine and the sugar could be substituted by 13C and 15N at a minimum of cost, each of the steps was optimised to convert the commercially available and isotopically highly enriched (99%) synthons (acetaldehyde, acetic acid, ammonia, benzylamine, formic acid, methylamine, potassium cyanide, potassium thiocyanate and sodium nitrite) as quantitatively as possible. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)
Engineering the variable region of therapeutic IgG antibodies (2011)

Since the first generation of humanized IgG1 antibodies reached the market in the late 1990s, IgG antibody molecules have been extensively engineered. The success of antibody therapeutics has introduced severe competition in developing novel therapeutic monoclonal antibodies, especially for promising or clinically validated targets. Such competition has led researchers to generate so-called second or third generation antibodies with clinical differentiation utilizing various engineering and optimization technologies. Parent IgG antibodies can be engineered to have improved antigen binding properties, effector functions, pharmacokinetics, pharmaceutical properties and safety issues. Although the primary role of the antibody variable region is to bind to the antigen, it is also the main source of antibody diversity and its sequence affects various properties important for developing antibody therapeutics. Here we review recent research activity in variable region engineering to generate superior antibody therapeutics.
Mining the network value of customers (2001)

One of the major applications of data mining is in helping companies determine which potential customers to market to. If the expected profit from a customer is greater than the cost of marketing to her, the marketing action for that customer is executed. So far, work in this area has considered only the intrinsic value of the customer (i.e, the expected profit from sales to her). We propose to model also the customer's network value: the expected profit from sales to other customers she may influence to buy, the customers those may influence, and so on recursively. Instead of viewing a market as a set of independent entities, we view it as a social network and model it as a Markov random field. We show the advantages of this approach using a social network mined from a collaborative filtering database. Marketing that exploits the network value of customers---also known as viral marketing---can be extremely effective, but is still a black art. Our work can be viewed as a step towards providing a more solid foundation for it, taking advantage of the availability of large relevant databases.
Increased rhodamine 123 uptake by carcinoma cells. (1985)

The total cellular content of the fluorescent mitochondrial-specific dye rhodamine 123 (Rh-123) was quantified by butanol extraction as a function of time of exposure and dose for a variety of cell lines. These results were compared with observations made by fluorescence microscopy on dye localization and mitochondrial morphology. There appeared to be two categories of cell types based on Rh-123 uptake: those which progressively accumulate the dye, such as Ehrlich ascites tumor cells, carcinoma-derived lines MCF-7, PaCa-2, EJ, HeLa, and normal fibroblast line CCL 64; and those which appear to equilibrate with the extracellular dye within 1 h of incubation in Rh-123 (1 microgram/ml) with a minimal level of uptake, such as the normal epithelial-derived lines CV-1 and MDCK and the transformed fibroblast line 64F3. Within the first category, the absolute value of uptake per cell correlated with the concentration of Rh-123 in the medium and with the period of exposure to the dye up to a point of apparent cellular saturation. The length of time required for apparent saturation depended on the cell type. In the second category equilibration was very early, and the total uptake was a function of the extracellular concentration of Rh-123. This probably does not represent a saturation level of dye content in the non-accumulating, low uptake cell lines. Fluorescence microscopy revealed that Rh-123 localization was initially mitochondrial-specific for all of the cell lines examined. Over time, alterations in mitochondrial morphology and cytoplasmic fluorescence were observed in the high uptake cell lines but not in the minimal uptake cell lines. Incubation of the high uptake HeLa cell line with the mitochondrial membrane potential inhibitor p-trifluoromethoxyphenylhydrazone substantially decreased Rh-123 uptake. These observations may indicate a transformation-related characteristic of carcinoma cell mitochondria. It may be possible to exploit the mechanism responsible for the progressive accumulation of Rh-123 by carcinoma-derived cell types for chemotherapeutic approaches to certain types of carcinomas.
Self Antigens Expressed by Solid Tumors Do Not Efficiently Stimulate Naive or Activated T Cells: Implications for Immunotherapy (1997)

Induction and maintenance of cytotoxic T lymphocyte (CTL) activity specific for a primary endogenous tumor was investigated in vivo. The simian virus 40 T antigen (Tag) expressed under the control of the rat insulin promoter (RIP) induced pancreatic beta-cell tumors producing insulin, causing progressive hypoglycemia. As an endogenous tumor antigen, the lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) was introduced also under the control of the RIP. No significant spontaneous CTL activation against GP was observed. However, LCMV infection induced an antitumor CTL response which efficiently reduced the tumor mass, resulting in temporarily normalized blood glucose levels and prolonged survival of double transgenic RIP(GP x Tag2) mice (137 +/- 18 d) as opposed to control RIP-Tag2 mice (88 +/- 8 d). Surprisingly, the tumor-specific CTL response was not sustained despite the facts that the tumor cells continued to express MHC class I and LCMV-GP-specific CTLs were present and not tolerized. Subsequent adoptive transfer of virus activated spleen cells into RIP(GP x Tag2) mice further prolonged survival (168 +/- 11 d), demonstrating continued expression of the LCMV-GP tumor antigen and MHC class I. The data show that the tumor did not spontaneously induce or maintain an activated CTL response, revealing a profound lack of immunogenicity in vivo. Therefore, repetitive immunizations are necessary for prolonged antitumor immunotherapy. In addition, the data suggest that the risk for induction of chronic autoimmune diseases is limited, which may encourage immunotherapy against antigens selectively but not exclusively expressed by the tumor.
Multiple HLA A11-restricted cytotoxic T-lymphocyte epitopes of different immunogenicities in the Epstein-Barr virus-encoded nuclear antigen 4 (1993)

Epstein-Barr virus (EBV), a ubiquitous herpesvirus, induces potent HLA class I-restricted cytotoxic T-lymphocyte (CTL) responses. Analyses of target antigen choice have shown that the very strong CTL responses which are often observed through the HLA A11 allele map are due almost entirely to a single transformation-associated EBV protein, the nuclear antigen EBNA4. Here, we sought to determine the number and relative immunogenicities of HLA A11-restricted epitopes within this 938-amino-acid protein. An initial screening with a series of recombinant vaccinia virus vectors encoding progressively truncated forms of EBNA4 was followed by peptide sensitization experiments using overlapping 14- or 15-mers from the entire sequence. These two approaches allowed the identification of five epitope regions located between residues 101 and 115, 416 and 429, 396 and 410, 481 and 495, and 551 and 564 of the EBNA4 molecule. CTL preparations from all seven HLA A11-positive donors tested had demonstrable reactivities against the 416-to-429 peptide, whereas reactivities against the other epitopes either tended to be lost on serial passage or, for some of the donors, were never detected. The immunodominance of the 416-to-429 epitope was further supported by peptide dilution assays using polyclonal effectors and by CTL cloning experiments. Analysis of the 416-to-429 region identified the nanomer 416-424 (IVTDFSVIK) as the cognate peptide. This peptide was able to sensitize targets to lysis by A11-restricted CTL clones at concentrations as low as 5 x 10(-14) M.
Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification (2014)

The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.
Phase II trial of beta-all-trans-retinoic acid for cervical intraepithelial neoplasia delivered via a collagen sponge and cervical cap. (1986)

Retinoids are effective suppressors of the phenotypic development of cancer in many animal systems, whether the process is initiated by chemical, physical or viral carcinogens. Cases of cervical intraepithelial neoplasia are excellent for studying the effectiveness of retinoids as chemopreventive agents because the process can be closely followed by serial colposcopic and pathologic (cytology or biopsy) means and changes in the condition safely monitored. We have previously conducted a phase I study of trans-retinoic acid (Tretinoin) given topically by a collagen sponge and cervical cap. A dose of 0.372% was selected for phase II trial. We have treated 20 patients with topical retinoic acid, and a complete response with total regression of disease was obtained in 50%. Systemic and cervical side effects were mild and vaginal side effects moderate but tolerable. These results provide a clinical basis for a randomized, double-blind phase III study to definitely answer the question of whether retinoic acid is an effective chemopreventive agent for cervical cancer.
Optical Molecular Imaging Agents for Cancer Diagnostics and Therapeutics (2006)

The National Cancer Institute has set the goal of eliminating suffering and death due to cancer by 2015. A key strategy to achieve this goal is to improve early detection and prevention using novel molecularly targeted cancer diagnostics and therapeutics. As we begin to better understand the cellular and molecular pathways of carcinogenesis, it is possible to identify and treat precursors to cancer before changes are detected at anatomical levels. Developing imaging techniques with the ability to detect molecular signatures will not only target these abnormalities for therapy at the earliest possible stages but will also prove useful in further unraveling the molecular origins of cancer. The ability to image noninvasively in real-time makes optical imaging well suited to early detection. Molecular characterization in combination with optical imaging provides a sensitive and specific method to detect and prevent the progression of precancerous lesions.
p16INK4A is a robust in vivo biomarker of cellular aging in human skin (2006)

The cell-cycle regulating gene, p16INK4A, encoding an inhibitor of cyclin-dependent kinases 4 and 6, is considered to play an important role in cellular aging and in premature senescence. Although there is an age-dependent increase of p16INK4A expression in human fibroblast senescence in vitro, no data are available regarding the age dependency of p16INK4A in vivo. To determine whether p16INK4A expression in human skin correlates with donor age, p16INK4A expression was analyzed by immunohistochemistry as well as the expression of the p16INK4A repressor BMI1. Samples from the age groups 0-20, 21-70, and 71-95 years were selected from a bank of healthy human skin. We show that the number of p16INK4A positive cells is significantly higher in elderly individuals compared to the younger age groups. The number of p16INK4A positive cells was found to be increased in both epidermis and dermis, compartments with strictly different proliferative activities. BMI1 gene expression was significantly down-regulated with increasing donor age, whereas no striking age differences were observed for Ki67. In immunofluorescence co-expression studies, Ki67-positive cells were negative for p16INK4A and BMI1-expressing cells also stained negatively for Ki67. In conclusion, we provide for the first time evidence that p16INK4A expression directly correlates with chronological aging of human skin in vivo. p16INK4A therefore is a biomarker for human aging in vivo. The data reported here suggest a model for changes in regulatory gene expression that drive aging in human skin.
Mutator Effects in Escherichia coli Caused by the Expression of Specific Foreign Genes (2005)

Certain genes from Lactococcus lactis and Pseudomonas aeruginosa, including the nfxB gene, generate a mutator phenotype in Escherichia coli. The results of this study, together with those of a previous study, support conservation of regulatory sequences in E. coli and P. aeruginosa and suggest that some efflux pumps prevent mutagenicity by exporting mutagenic products of metabolism.
Risk Factors for Chlamydia trachomatis Pelvic Inflammatory Disease among Sex Workers in Nairobi, Kenya (1996)

Among 302 female sex workers in Nairobi, Kenya, who were followed for 17.6 +/- 11.1 months, 146 had one or more infections with Chlamydia trachomatis; 102 had uncomplicated cervical infection only, 23 had C. trachomatis pelvic inflammatory disease (PID), and 21 had combined C. trachomatis and Neisseria gonorrhoeae PID. As determined by multivariate logistic regression analysis, risk factors for C. trachomatis PID included repeated C. trachomatis infection (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.4; P = .0004), antibody to C. trachomatis heat-shock protein 60 (OR, 3.9; CI, 1.04-14.5; P = .04), oral contraceptive use (OR, 0.28; 95% CI, 0.08-0.99; P = .048), and number of episodes of nongonococcal nonchlamydial PID (OR, 1.7; 95% CI, 1.1-2.7; P = .02). Among human immunodeficiency virus (HIV)-seropositive women, a CD4 lymphocyte count of <400/mm3 was an additional independent risk factor for C. trachomatis PID (OR, 21.7; 95% CI, 1.2-383; P = .036); among HLA-typed women, HLA-A31 was independently associated with C. trachomatis PID (OR, 5.6; 95% CI, 1.1-29.4; P = .043). The results suggest an immune-mediated pathogenesis for C. trachomatis PID.
Systems‐wide analysis and engineering of metabolic pathway fluxes in bio‐succinate producing Basfia succiniciproducens (2013)

Basfia succiniciproducens has been recently isolated as novel producer for succinate, an important platform chemical. In batch culture, the wild type exhibited a high natural yield of 0.75 mol succinate (mol glucose)⁻¹. Systems-wide ¹³C metabolic flux analysis identified undesired fluxes through pyruvate-formate lyase (PflD) and lactate dehydrogenase (LdhA). The double deletion strain B. succiniciproducens ΔldhA ΔpflD revealed a 45% improved product yield of 1.08 mol mol⁻¹. In addition, metabolic flux analysis unraveled the parallel in vivo activity of the oxidative and reductive branch of the TCA cycle in B. succiniciproducens, whereby the oxidative part mainly served for anabolism. The wild type re-directed surplus NADH via a cycle involving malic enzyme or via transhydrogenase, respectively, to supply NADPH for anabolism, because the fluxes through the oxidative PPP and isocitrate dehydrogenase, that also provide this cofactor, were not sufficient. This was not observed for the deletion mutants, B. succiniciproducens ΔpflD and ΔldhA ΔpflD, where PPP and isocitrate dehydrogenase flux alone matched with the reduced anabolic NADPH demand. The integration of the production performance into the theoretical flux space, computed by elementary flux mode analysis, revealed that B. succiniciproducens ΔldhA ΔpflD reached 62% of the theoretical maximum yield.
ChemInform Abstract: Recent Progress in O‐Glycosylation Methods and Its Application to Natural Products Synthesis (1993)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Nuclear Magnetic Resonance Solution Structures of Lacticin Q and Aureocin A53 Reveal a Structural Motif Conserved among Leaderless Bacteriocins with Broad-Spectrum Activity (2016)

Lacticin Q (LnqQ) and aureocin A53 (AucA) are leaderless bacteriocins from Lactococcus lactis QU5 and Staphylococcus aureus A53, respectively. These bacteriocins are characterized by the absence of an N-terminal leader sequence and are active against a broad range of Gram-positive bacteria. LnqQ and AucA consist of 53 and 51 amino acids, respectively, and have 47% identical sequences. In this study, their three-dimensional structures were elucidated using solution nuclear magnetic resonance and were shown to consist of four α-helices that assume a very similar compact, globular overall fold (root-mean-square deviation of 1.7 Å) with a highly cationic surface and a hydrophobic core. The structures of LnqQ and AucA resemble the shorter two-component leaderless bacteriocins, enterocins 7A and 7B, despite having low levels of sequence identity. Homology modeling revealed that the observed structural motif may be shared among leaderless bacteriocins with broad-spectrum activity against Gram-positive organisms. The elucidated structures of LnqQ and AucA also exhibit some resemblance to circular bacteriocins. Despite their similar overall fold, inhibition studies showed that LnqQ and AucA have different antimicrobial potency against the Gram-positive strains tested, suggesting that sequence disparities play a crucial role in their mechanisms of action.