gebhart/patrepeval huggingface dataset:
The selection of aptamers specific for membrane molecular targets (2010)

A growing number of RNA aptamers have been selected experimentally using the SELEX combinatorial approach, and these aptamers have several advantages over monoclonal protein antibodies or peptides with respect to their applications in medicine and nanobiotechnology. Relatively few successful selections have been reported for membrane molecular targets, in contrast to the situation with non-membrane molecular targets. This review compares the procedures and techniques used in selections against membrane proteins and membrane lipids. In the case of membrane proteins, the selections were performed against soluble protein fragments, detergent-membrane protein mixed micelles, whole cells, vesicles derived from cellular membranes, and enveloped viruses. Liposomes were used as an experimental system for the selection of aptamers against membrane lipids. RNA structure-dependent aptamer binding for rafts in lipid vesicles was reported. Based on the selected aptamers against DOPC and the amino acid tryptophan, a specific passive membrane transporter composed of RNA was constructed. The determination of the selectivity of aptamers appears to be a crucial step in a selection, but has rarely been fully investigated. The selections, which use whole cells or vesicles derived from membranes, can yield aptamers not only against proteins but also against membrane lipids.
Temperature regiocontrol of intramolecular cyclization of di-hydroxysecoacids (2004)

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Autocrine/paracrine mechanism of insulin‐like growth factor‐1 secretion, and the effect of insulin‐like growth factor‐1 on proteoglycan synthesis in bovine intervertebral discs (1996)

The present study was undertaken to investigate the effect of insulin-like growth factor-1 on proteoglycan synthesis and the autocrine/paracrine mechanism involving insulin-like growth factor-1 in the bovine coccygeal intervertebral disc. Insulin-like growth factor-1 stimulated proteoglycan synthesis in cultured cells of the nucleus pulposus of bovine intervertebral discs in a dose-dependent manner, and the effect was inhibited by an anti-insulin-like growth factor-1 monoclonal antibody. In situ hybridization histochemistry revealed the expression of insulin-like growth factor-1 mRNA in the cultured cells, and its production in these cells was demonstrated by radioimmunoassay. Insulin-like growth factor-1 receptor in the cultured cells was also demonstrated immunohistochemically. Scatchard analysis using an [125I]insulin-like growth factor-1 binding assay showed that the cells cultured in monolayer had a single type of insulin-like growth factor-1 receptor, whose affinity and number were estimated to be 7.38 x 10(8)/M and 9.27 x 10(4)/cell, respectively. These results suggest that insulin-like growth factor-1 stimulates proteoglycan synthesis in cells of the nucleus pulposus and that these cells in culture have an insulin-like growth factor-1 autocrine/paracrine mechanism. The expressions of insulin-like growth factor-1 mRNA and insulin-like growth factor-1 receptor in disc tissue were greater in cells of the nucleus pulposus of fetal bovine intervertebral discs than in those of the adult discs. These findings suggest that the action of autocrine/paracrine insulin-like growth factor-1 is more active in cells of the young nucleus pulposus than in cells of mature subjects.
Targeted radionuclide therapy: theoretical study of the relationship between tumour control probability and tumour radius for a32P/33P radionuclide cocktail (2008)

As revealed by previous theoretical studies, targeted radionuclide therapy (TRT) that relies on a single beta-emitting radioisotope is likely to be inappropriate for clinical scenarios such as disseminated malignancy. For a patient with a vast number of tumours and metastases of largely differing sizes a high level of therapeutical efficiency might be achieved only for a restricted range of tumour sizes. This is due to the limited range of beta-electrons in human tissue, essentially causing the therapeutical impact to vary tremendously with tumour size. The dependence of curability on the tumour dimension is expected to be significantly altered if a radionuclide cocktail, consisting of a long-range and a short-range beta-emitter, such as (32)P and (33)P, is involved in the treatment. In this study, a radiation transport simulation was performed, using the MCNP4c2 Monte Carlo code, in order to investigate the relationship between tumour control probability (TCP) and tumour size, associated with concurrent use of (32)P and (33)P. Two different models of intratumoural distribution of cumulated activity were taken into account. One simulated an ideal radionuclide uptake in tumour tissue and the other referred to a limited radiotracer penetration. The results were examined in comparison to tumours targeted with pure (32)P, (33)P and (131)I. For both uptake scenarios a considerable reduction of the overall variation of TCP and thus an increasing chance of achieving tumour cure was observed for tumour sizes ranging from microscopic dimensions up to macroscopic diameters, if the targeted radionuclide treatment relies on a (32)P/(33)P cocktail. It was revealed that particular attention has to be given to the ratio of the (32)P and (33)P specific cumulated activities (SCA) in the tumour, since this is a significant determinant of the resulting behaviour of tumour control probability as the tumour diameter varies. This study suggests that a 32P/33P approach is more applicable to diseases that involve a variety of tumours and metastases differing in size.
Leukocyte‐endothelial cell adhesion: avenues for therapeutic intervention (1999)

British Journal of Pharmacology (1999) 126 , 537–550; doi: 10.1038/sj.bjp.0702328
AGS67E, an Anti-CD37 Monomethyl Auristatin E Antibody–Drug Conjugate as a Potential Therapeutic for B/T-Cell Malignancies and AML: A New Role for CD37 in AML (2015)

CD37 is a tetraspanin expressed on malignant B cells. Recently, CD37 has gained interest as a therapeutic target. We developed AGS67E, an antibody-drug conjugate that targets CD37 for the potential treatment of B/T-cell malignancies. It is a fully human monoclonal IgG2 antibody (AGS67C) conjugated, via a protease-cleavable linker, to the microtubule-disrupting agent monomethyl auristatin E (MMAE). AGS67E induces potent cytotoxicity, apoptosis, and cell-cycle alterations in many non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) cell lines and patient-derived samples in vitro. It also shows potent antitumor activity in NHL and CLL xenografts, including Rituxan-refractory models. During profiling studies to confirm the reported expression of CD37 in normal tissues and B-cell malignancies, we made the novel discovery that the CD37 protein was expressed in T-cell lymphomas and in AML. AGS67E bound to >80% of NHL and T-cell lymphomas, 100% of CLL and 100% of AML patient-derived samples, including CD34(+)CD38(-) leukemic stem cells. It also induced cytotoxicity, apoptosis, and cell-cycle alterations in AML cell lines and antitumor efficacy in orthotopic AML xenografts. Taken together, this study shows not only that AGS67E may serve as a potential therapeutic for B/T-cell malignancies, but it also demonstrates, for the first time, that CD37 is well expressed and a potential drug target in AML.
Down syndrome--recent progress and future prospects (2009)

Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and is associated with a number of deleterious phenotypes, including learning disability, heart defects, early-onset Alzheimer's disease and childhood leukaemia. Individuals with DS are affected by these phenotypes to a variable extent; understanding the cause of this variation is a key challenge. Here, we review recent research progress in DS, both in patients and relevant animal models. In particular, we highlight exciting advances in therapy to improve cognitive function in people with DS and the significant developments in understanding the gene content of Hsa21. Moreover, we discuss future research directions in light of new technologies. In particular, the use of chromosome engineering to generate new trisomic mouse models and large-scale studies of genotype-phenotype relationships in patients are likely to significantly contribute to the future understanding of DS.
A Uniquely Stable Replication-Competent Retrovirus Vector Achieves Efficient Gene Delivery in Vitro and in Solid Tumors (2001)

A major obstacle in cancer gene therapy is the limited efficiency of in vivo gene transfer by replication-defective retrovirus vectors in current use. One strategy for circumventing this difficulty would be to use vectors capable of replication within tumor tissues. We have developed a replication-competent retrovirus (RCR) vector derived from murine leukemia virus (MuLV). This vector utilizes a unique design strategy in which an internal ribosome entry site-transgene cassette is positioned between the env gene and the 3' long terminal repeat (LTR). The ability of this vector to replicate and transmit a transgene was examined in culture and in a solid tumor model in vivo. The RCR vector exhibited replication kinetics similar to those of wildtype MuLV and mediated efficient delivery of the transgene throughout an entire population of cells in culture after an initial inoculation with 1 plaque-forming unit (PFU) of vector per 2000 cells. After injection of 6 x 10(3) PFU of vector into established subcutaneous tumors, highly efficient spread of the transgene was observed over a period of 7 weeks, in some cases resulting in spread of the transgene throughout the entire tumor. MuLV-based RCR vectors show significant advantages over standard replication-defective vectors in efficiency of gene delivery both in culture and in vivo. This represents the first example of the use of an RCR vector in an adult mammalian host, and their first application to transduction of solid tumors.
Attachment of Trypanosoma cruzi trypomastigotes to receptors at restricted cell surface domains (1991)

We have used glutaraldehyde-fixed target cells to study the attachment phase of cell invasion by live trypomastigotes of Trypanosoma cruzi, and determined that attachment is polarized and receptor-mediated. T. cruzi trypomastigotes bind much less efficiently to confluent epithelial cells, which are polarized, than to sparse epithelial cells. When the tight junctions of confluent epithelial cells are disrupted by removing Ca2+ from the incubation medium before glutaraldehyde fixation, binding of T. cruzi increases. T. cruzi also shows preference for attachment underneath cells or to the edges of cells. The binding occurs within a few minutes, is saturable, and is influenced by the parasite developmental stage. Fab fragment derived from monoclonal antibodies that immunoprecipitate a 160-kDa molecule present only on the surface of trypomastigotes inhibit adhesion to fixed and live cells. Future characterization of the target cell receptors for this molecule and the use of fixed target cells should facilitate studies of the mechanisms involved in the initial interaction of T. cruzi with its host cells.
Isolated demyelinating syndromes: comparison of different MR imaging criteria to predict conversion to clinically definite multiple sclerosis. (2000)

The four dichotomized MR imaging parameters proposed by Barkhof et al are more specific and accurate than the criteria proposed by Paty et al or Fazekas et al for predicting conversion to clinically definite multiple sclerosis.
Inhibition of 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin papilloma formation in mice by dehydroepiandrosterone and two synthetic analogs (1989)

Previous work has demonstrated that the adrenal steroid, dehydroepiandrosterone (3-beta-hydroxy-5-androsten-17-one, DHEA), has broad spectrum tumor chemopreventive activity in laboratory mice and rats, inhibiting the development of spontaneous breast cancer and chemically induced tumors of the lung, colon, skin, thyroid and liver. DHEA treatment produces specific side-effects, including estrogenic and androgenic action and an increase in liver weight, which could limit its use as a cancer chemopreventive drug. It is now shown that oral administration of the synthetic steroid 16 alpha-fluoro-5-androsten-17-one, which lacks the side-effects of DHEA treatment, to CD-1 mice inhibits 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin papilloma formation at both the initiation and promotion stage. The synthetic steroid is more potent as an inhibitor of papilloma formation than comparably administered DHEA.
T-cell receptor transgenic analysis of tumor-specific CD8 and CD4 responses in the eradication of solid tumors. (1999)

The role of tumor-specific CD8 and CD4 lymphocytes in rejecting solid tumors has been difficult to determine because of the lack of models in which tumor antigen, specific CD8 cells, and specific CD4 cells can be monitored and controlled. To investigate the minimal components required for the induction and maintenance of CTL activity sufficient to reject a solid tumor in vivo, we transfected the influenza hemagglutinin (HA) gene into a nonimmunogenic class I+/class II- murine malignant mesothelioma (MM) tumor line to generate an endogenous tumor antigen and used TCR transgenic mice with class I- or class II-restricted specificities for HA as sources of naive, tumor-specific T cells. The data show that the presence of a strong tumor antigen is not in itself sufficient to induce an effective CTL response, nor does the presence of a high frequency of precursor cells guarantee tumor rejection. We also show that tumor-specific CD4 cells, when CTL numbers are suboptimal, greatly enhance the eradication of tumor, confirming the importance of antigen-presenting cell presentation of tumor antigens to class II-restricted cells. These data confirm that T-cell receptor transgenic cells, combined with nominal tumor antigen transfection, represent powerful tools to analyze tumor-specific T-cell responses.
Analysis of the Passive Damping Losses in LCL-Filter-Based Grid Converters (2012)

Passive damping is the most adopted method to guarantee the stability of LCL-filter-based grid converters. The method is simple and, if the switching and sampling frequencies are sufficiently high, the damping losses are negligible. This letter proposes the tuning of different passive damping methods and an analytical estimation of the damping losses allowing the choice of the minimum resistor value resulting in a stable current control and not compromising the LCL-filter effectiveness. Stability, including variations in the grid inductance, is studied through root locus analysis in the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">z</i> -plane. The analysis is validated both with simulation and with experiments.
The (P, &#x03B1;, K) anonymity model for privacy protection of personal information in the social networks (2011)

The (P, α, K) anonymity model for privacy protection of personal information in the social networks is proposed in this paper. The hidden fields P and the hidden levels a are set according to the individual privacy needs of the users. Then make the released data to meet the privacy protection requirements through the Datafly algorithm and the clustering algorithm. The experimental data shows that the (P, α, K) model is better than the traditional K-anonymity model and L-Diversity modeling reducing the running time and reducing the loss of information.
AN APPROACH TO RESOLVING SEMANTIC HETEROGENEITY IN A FEDERATION OF AUTONOMOUS, HETEROGENEOUS DATABASE SYSTEMS (1993)

An approach to accommodating semantic heterogeneity in a federation of interoperable, autonomous, heterogeneous databases is presented. A mechanism is described for identifying and resolving semantic heterogeneity while at the same time honoring the autonomy of the database components that participate in the federation. A minimal, common data model is introduced as the basis for describing sharable information, and a three-pronged facility for determining the relationships between information units (objects) is developed. Our approach serves as a basis for the sharing of related concepts through (partial) schema unification without the need for a global view of the data that is stored in the different components. The mechanism presented here can be seen in contrast with more traditional approaches such as “integrated databases” or “distributed databases”. An experimental prototype implementation has been constructed within the framework of the Remote-Exchange experimental system.
The Co-crystal Structure of Staphylococcal Enterotoxin Type A With Zn2+ at 2.7 Å Resolution (1996)

Superantigens form complexes with major histocompatibility complex (MHC) class II molecules and T-cell receptors resulting in extremely strong immunostimulatory properties. Staphylococcus aureus enterotoxin A (SEA) belongs to a subgroup of the staphylococcal superantigens that utilizes Zn2+ in the high affinity interaction with MHC class II molecules. A high affinity metal binding site was described previously in SEA co-crystallized with Cd2+ in which the metal ion was octahedrally co-ordinated, involving the N-terminal serine. We have now co-crystallized SEA with its native co-factor Zn2+ and determined its crystal structure at 2.7 A resolution. As expected for a Zn2+ ion, the co-ordination was found to be tetrahedral. Three of the ligands are located on the SEA surface on a C-terminal domain beta-sheet, while the fourth varies with the conditions. Further analysis of the zinc binding event was performed using titration microcalorimetry, which showed that SEA binds Zn2+ with an affinity of KD = 0.3 microM in an entropy driven process. The differential Zn2+ co-ordination observed here has implications for the mechanism of the SEA-MHC class II interaction.
Absorptionsspektren und Fluoreszenzeigenschaften konzentrierter Lösungen organischer Farbstoffe (1957)

Abstract An wäßrigen Lösungen fluoreszierender Farbstoffionen wurde die Konzentrationsabhängigkeit der Absorptionsspektren gemessen. Die gefundene Abhängigkeit läßt sich auf die Bildung von Dimeren zurückführen. In der Mehrzahl der untersuchten Fälle ergaben sich für die Spektren der Dimeren zwei Maxima, deren Zustandekommen durch eine Aufspaltung des Absorptionsmaximums des Monomeren erklärt werden kann. Die Konzentrationsabhängigkeit der Fluoreszenzausbeute dieser Lösungen wurde ebenfalls untersucht.
Enzymes as chaperones and chaperones as enzymes (1998)

Chaperones and foldases are two groups of accessory proteins which assist maturation of nascent peptides into functional proteins in cells. Protein disulfide isomerase, a foldase, and ATP-dependent proteases, responsible for degradation of misfolded proteins in cells, both have intrinsic chaperone activities. Trigger factor and DnaJ, well known Escherichia coli chaperones, show peptidyl prolyl isomerase and protein disulfide isomerase activities respectively. It is suggested that the combination of chaperone and enzyme activities in one molecule is the result of evolution to increase molecular efficiency.
Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system (2007)

Gaucher's disease, a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy using recombinant GCD (Cerezyme) expressed in Chinese hamster ovary (CHO) cells. As complex glycans in mammalian cells do not terminate in mannose residues, which are essential for the biological uptake of GCD via macrophage mannose receptors in human patients with Gaucher's disease, an in vitro glycan modification is required in order to expose the mannose residues on the glycans of Cerezyme. In this report, the production of a recombinant human GCD in a carrot cell suspension culture is described. The recombinant plant-derived GCD (prGCD) is targeted to the storage vacuoles, using a plant-specific C-terminal sorting signal. Notably, the recombinant human GCD expressed in the carrot cells naturally contains terminal mannose residues on its complex glycans, apparently as a result of the activity of a special vacuolar enzyme that modifies complex glycans. Hence, the plant-produced recombinant human GCD does not require exposure of mannose residues in vitro, which is a requirement for the production of Cerezyme. prGCD also displays a level of biological activity similar to that of Cerezyme produced in CHO cells, as well as a highly homologous high-resolution three-dimensional structure, determined by X-ray crystallography. A single-dose toxicity study with prGCD in mice demonstrated the absence of treatment-related adverse reactions or clinical findings, indicating the potential safety of prGCD. prGCD is currently undergoing clinical studies, and may offer a new and alternative therapeutic option for Gaucher's disease.
Refractory periorbital edema in a 29-year-old man. (1992)

A 29-year-old man developed periorbital edema which was initially diagnosed as angioedema. Further clinical investigation by orbital CT and orbital biopsy showed this to be orbital pseudotumor. Immunofluorescence staining for major basic protein clearly demonstrated tissue eosinophilia and extracellular major basic protein deposition. Orbital pseudotumor can mimic angioedema or allergic rhinoconjunctivitis and should be familiar to allergists and primary care physicians. The demonstration of striking extracellular major basic protein in biopsy specimen implicates a role for eosinophils in the pathogenesis of this disease.
Evaluation of methylnaltrexone for the reduction of postoperative vomiting and nausea incidences. (1995)

We examined the effect of methylnaltrexone on the incidence of postoperative nausea and vomiting in a prospective double-blind placebo controlled study. One hundred and twenty female patients undergoing laparoscopic major gynecological surgery were allocated randomly to receive either 20 mg methylnaltrexone or placebo IV at the end of surgery. Postoperative nausea and vomiting was evaluated for 6 h after admission to the PACU and assessed by number of episodes and degree of severity. The incidences of nausea and vomiting for the placebo group were 27 and 18 percent, respectively. The corresponding values for the methylnaltrexone group were 20 and 10 percent. We conclude that methylnaltrexone did not prevent nor significantly reduced the incidence and severity of postoperative nausea and vomiting following a balanced anesthetic technique in gynecological procedures.
Streptavidin aptamers: Affinity tags for the study of RNAs and ribonucleoproteins (2001)

RNA affinity tags would be very useful for the study of RNAs and ribonucleoproteins (RNPs) as a means for rapid detection, immobilization, and purification. To develop a new affinity tag, streptavidin-binding RNA ligands, termed "aptamers," were identified from a random RNA library using in vitro selection. Individual aptamers were classified into two groups based on common sequences, and representative members of the groups had sufficiently low dissociation constants to suggest they would be useful affinity tools. Binding of the aptamers to streptavidin was blocked by presaturation of the streptavidin with biotin, and biotin could be used to dissociate RNA/streptavidin complexes. To investigate the practicality of using the aptamer as an affinity tag, one of the higher affinity aptamers was inserted into RPR1 RNA, the large RNA subunit of RNase P. The aptamer-tagged RNase P could be specifically isolated using commercially available streptavidin-agarose and recovered in a catalytically active form when biotin was used as an eluting agent under mild conditions. The aptamer tag was also used to demonstrate that RNase P exists in a monomeric form, and is not tightly associated with RNase MRP, a closely related ribonucleoprotein enzyme. These results show that the streptavidin aptamers are potentially powerful tools for the study of RNAs or RNPs.