gebhart/patrepeval huggingface dataset:
Opsin/all-trans-Retinal Complex Activates Transducin by Different Mechanisms Than Photolyzed Rhodopsin (1996)

In rhodopsin, the 11-cis-retinal chromophore forms a complex with Lys296 of opsin via a protonated Schiff base. Absorption of light initiates the activation of rhodopsin by cis/trans photoisomerization of retinal. Thermal relaxation through different intermediates leads into the metarhodopsin states which bind and activate transducin (Gt) and rhodopsin kinase (RK). all-trans-Retinal also recombines with opsin independent of light, forming activating species of the receptor. In this study, we examined the mechanism by which all-trans-retinal activates opsin. To exclude other amines except active site Lys296 from formation of Schiff bases, we reductively methylated rhodopsin (PM-rhodopsin), which we then bleached to generate PM-opsin. Using spectroscopic methods and a Gt activation assay, we found that all-trans-retinal interacted with PM-opsin, producing a noncovalent complex that activated Gt. The residual nucleotide exchange in Gt catalyzed by opsin was approximately 1/250 lower relative to that of photoactivated rhodopsin (pH 8.0, 23 degrees C). Addition of equimolar all-trans-retinal led to an occupancy of one-tenth of the putative retinal binding site(s) of opsin and enhanced the Gt activation rate 2-fold. When the concentration of all-trans-retinal was increased to saturation, the Gt activation rate of the opsin/all-trans-retinal complex was approximately 1/33 lower compared to that of photoactivated rhodopsin. We conclude that all-trans-retinal can form a noncovalent complex with opsin that activates Gt by different mechanisms than photolyzed rhodopsin.
Engineered anti-CD70 antibody-drug conjugate with increased therapeutic index (2008)

An anti-CD70 antibody conjugated to monomethylauristatin F (MMAF) via a valine-citrulline dipeptide containing linker has been shown previously to have potent antitumor activity in renal cell cancer xenograft studies. Here, we generated a panel of humanized anti-CD70 antibody IgG variants and conjugated them to MMAF to study the effect of isotype (IgG1, IgG2, and IgG4) and Fcgamma receptor binding on antibody-drug conjugate properties. All IgG variants bound CD70+ 786-O cells with an apparent affinity of approximately 1 nmol/L, and drug conjugation did not impair antigen binding. The parent anti-CD70 IgG1 bound to human FcgammaRI and FcgammaRIIIA V158 and mouse FcgammaRIV and this binding was not impaired by drug conjugation. In contrast, binding to these Fcgamma receptors was greatly reduced or abolished in the variant, IgG1v1, containing the previously described mutations, E233P:L234V:L235A. All conjugates had potent cytotoxic activity against six different antigen-positive cancer cell lines in vitro with IC50 values of 30 to 540 pmol/L. The IgGv1 conjugate with MMAF displayed improved antitumor activity compared with other conjugates in 786-O and UMRC3 models of renal cell cancer and in the DBTRG05-MG glioblastoma model. All conjugates were tolerated to > or =40 mg/kg in mice. Thus, the IgG1v1 MMAF conjugate has an increased therapeutic index compared with the parent IgG1 conjugate. The improved antitumor activity of the IgG1v1 auristatin conjugates may relate to increased exposure as suggested by pharmacokinetic analysis. The strategy used here for enhancing the therapeutic index of antibody-drug conjugates is independent of the antigen-binding variable domains and potentially applicable to other antibodies.
Time course of recombinant protein secretion after liposome-mediated gene transfer in a rabbit arterial organ culture model. (1994)

The organ culture model is a feasible and efficient means for investigating the kinetics of arterial gene transfer. Transfection of pXGH5 results in significant levels of hGH for up to 3 weeks, despite anatomic evidence of only limited gene expression. These data thus support the notion that the magnitude and/or duration of gene expression may be disproportionately high, relative to anatomic assessment of transfection efficiency in the case of a transgene encoding for a secreted protein.
Hypoxia-Inducible Factor-1α Is a Key Regulator of Metastasis in a Transgenic Model of Cancer Initiation and Progression (2007)

Adaptation to hypoxia is a critical step in tumor progression and is, in part, regulated by the transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha). Xenograft models have been extensively used to characterize the role of HIF-1alpha in experimental cancers. Although these models provide an understanding of tumor growth at terminal stages of malignancy, they do not address tumor initiation or metastatic progression. To elucidate these roles, HIF-1alpha was conditionally deleted in the mammary epithelium of a transgenic mouse model for metastatic breast cancer. Conditional deletion of HIF-1alpha in the mammary epithelium resulted in delayed tumor onset and retarded tumor growth; this was correlated with decreased tumor cell proliferation. Tumors with conditional deletion of HIF-1alpha were also less vascular during early tumor progression. Perhaps most surprisingly, deletion of HIF-1alpha in the mammary epithelium resulted in decreased pulmonary metastasis. These results show that whereas HIF-1alpha is not required for the initiation of breast tumor growth or tumor cell metastasis, the transcriptional activity of HIF-1alpha is a significant positive regulator of tumor progression and metastatic potential.
Initial Experience of Assessing Esophageal Tissue Injury and Recovery Using Delayed-Enhancement MRI After Atrial Fibrillation Ablation (2009)

Our preliminary results indicate delayed-enhancement MRI can assess the extent and follow progression of esophageal wall injury after catheter ablation of atrial fibrillation. It appears that acute esophageal injury recovers within 1 week of the procedure.
Methanogen Diversity in Deep Subsurface Gas-Associated Water at the Minami-Kanto Gas Field in Japan (2007)

Methanogen diversity and methanogenic potential in formation water obtained from the Minami-kanto gas field in Japan were investigated by using 16S rRNA gene libraries and culture-based enrichment methods, respectively. This region is the largest gas field that produces natural gases of dissolved-in-water type in Japan. Although the microbial population density was below statistical quantification limits (1 × 104 cells ml−1), autofluorescent coccoid and rod-shaped cells indicative of methanogens were observed. The represented genera in the archaeal 16S rRNA genes libraries were comprised of Methanobacterium, Methanospirillum, Methanocalculus, Methanococcus, Methanolobus and Methanosaeta. The dominant archaeal sequences were related to the hydrogenotrophic methanogens in the genus Methanobacterium. Of the methanogenic substrates tested using the formation water-based medium,H2-CO2 yielded the highest methane production. These results strongly suggest that the formation water of the Pleistocene strata in the gas fields harbor viable hydrogenotrophic methanogens and have possibly been making a contribution to ongoing methanogenesis.
A new mammalian host cell with enhanced survival enables completely serum‐free development of high‐level protein production cell lines (2011)

With over 25 monoclonal antibodies (mAbs) currently approved and many more in development, there is considerable interest in gaining improved productivity by increasing cell density and enhancing cell survival of production cell lines. In addition, high costs and growing safety concerns with use of animal products have made the availability of serum-free cell lines more appealing. We elected to transfect the myeloma cell line Sp2/0-Ag14 with Bcl2-EEE, the constitutively active phosphomimetic mutant of Bcl2, for extended cell survival. After adaptation of the initial transfectants to serum-independent growth, a clone with superior growth properties, referred to as SpESF, was isolated and further subjected to iterative rounds of stressful growth over a period of 4 months. The effort resulted in the selection of a promising clone, designated SpESFX-10, which was shown to exhibit robust growth and resist apoptosis induced by sodium butyrate or glutamine deprivation. The advantage of SpESFX-10 as a host for generating mAb-production cell lines was demonstrated by its increased transfection efficiency, culture longevity, and mAb productivity, as well as by the feasibility of accomplishing the entire cell line development process, including transfection, subcloning, and cryopreservation, in the complete absence of serum.
Non-primate lentiviral vectors. (2003)

Feline and equine lentivirus-derived vector systems are yielding impressive preclinical results in tissue culture, animal and ex vivo human organ models. Improved basic scientific understanding of lentiviral life cycles is facilitating development of these vectors, and initial systems based on other lentiviruses have been constructed. In addition to further engineering of the individual platforms for safety and efficacy, important goals for the field are to compare different lentiviral vector systems rigorously in specific human targets, and to derive clinical grade packaging/producer cell lines. Further progress in fundamental virology will be critical. Species-specific lentiviral restriction has recently emerged as a dynamic subject relevant to lentiviral pathogenesis research and lentiviral vector-based gene therapy. This review summarizes recent results in this growing field and discusses elements of an agenda for furthering application of these vectors to human gene therapy.
Serum Chitotriosidase Activity Is Increased in Subjects With Atherosclerosis Disease (2003)

Serum chitotriosidase activity is significantly increased in individuals suffering from atherosclerosis disease and is related to the severity of the atherosclerotic lesion, suggesting a possible role as atherosclerotic extent marker.
Efficient Keyword Search Across Heterogeneous Relational Databases (2007)

Keyword search is a familiar and potentially effective way to find information of interest that is "locked" inside relational databases. Current work has generally assumed that answers for a keyword query reside within a single database. Many practical settings, however, require that we combine tuples from multiple databases to obtain the desired answers. Such databases are often autonomous and heterogeneous in their schemas and data. This paper describes Kite, a solution to the keyword-search problem over heterogeneous relational databases. Kite combines schema matching and structure discovery techniques to find approximate foreign-key joins across heterogeneous databases. Such joins are critical for producing query results that span multiple databases and relations. Kite then exploits the joins - discovered automatically across the databases - to enable fast and effective querying over the distributed data. Our extensive experiments over real-world data sets show that (1) our query processing algorithms are efficient and (2) our approach manages to produce high-quality query results spanning multiple heterogeneous databases, with no need for human reconciliation of the different databases.
Transluminal Placement of Endovascular Stent-Grafts for the Treatment of Descending Thoracic Aortic Aneurysms (1994)

These preliminary results demonstrate that endovascular stent-graft repair is safe in highly selected patients with descending thoracic aortic aneurysms. This new method of treatment will, however, require careful long-term evaluation.
Impaired class switch recombination (CSR) in Waldenstrom macroglobulinemia (WM) despite apparently normal CSR machinery (2005)

Analysis of clonotypic isotype class switching (CSR) in Waldenström macroglobulinemia (WM) and IgM monoclonal gammopathy of undetermined significance (MGUS) reveals a normal initial phase of B-cell activation as determined by constitutive and inducible expression of activation-induced cytidine deaminase (AID). Switch mu (Smu) analysis shows that large deletions are not common in WM or IgM MGUS. In CD40L/IL-4-stimulated WM cultures from 2 patients, we observed clonotypic IgG exhibiting intraclonal homogeneity associated with multiple hybrid Smu/Sgamma junctions. This suggests CSR had occurred within WM cells. Nevertheless, the estimated IgG/IgM-cell frequency was relatively low (1/1600 cells). Thus, for the majority of WM B cells, CSR does not occur even when stimulated in vitro, suggesting that the WM cell is constitutively unable to or being prevented from carrying out CSR. In contrast to WM, the majority of IgM MGUS clones exhibit intraclonal heterogeneity of IgH VDJ. Furthermore, most IgM MGUS accumulate more mutations in the upstream Smu region than do WM, making them unlikely WM progenitors. These observations suggest that switch sequence analysis may identify the subset of patients with IgM MGUS who are at risk of progression to WM.
Antibody to type I insulinlike growth factor receptor inhibits growth of Wilms' tumor in culture and in athymic mice. (1989)

The role of the type I insulinlike growth factor (IGF) receptor in regulating growth of Wilms' tumor (WT) was evaluated by examining the effect of antibody-mediated inhibition of this receptor on tumor growth in cell cultures and as heterotransplants in athymic mice. An antibody to the human type I IGF receptor (alpha IR-3) inhibited 125I-IGF-1 binding and prevented stimulation of thymidine incorporation by IGF-1 in vitro. Intraperitoneal administration of alpha IR-3 to nude mice bearing WT heterotransplants prevented tumor growth for 4 weeks and resulted in partial regression of established tumors. These data indicate the importance of IGF action in control of WT growth in vivo, and suggest potential therapeutic application using antigrowth factor receptor antibodies to block growth factor action.
Potent V2/V1a vasopressin antagonists with C-terminal ethylenediamine-linked retro-amino acids (1992)

We report the solid-phase synthesis and antagonistic potencies of 25 analogues (1-25) of [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-ethyl-D-tyrosine,4-valine]arginine-vasopressin (d(CH2)5D-Tyr(Et)2-VAVP) (A) and of the related Ile4 (D) and [D-Phe2,Ile4] (E) analogues, potent antagonists of the antidiuretic (V2-receptor) and of the vasopressor (V1a-receptor) responses to arginine-vasopressin (AVP). Six of these peptides (1, 13, 17, 19, 21, and 23) have the Pro-Arg-Gly-NH2 tripeptide side chain fully or partially replaced or extended by ethylenediamine (Eda). The remaining 19 peptides have L- or D-amino acids retrolinked to these six C-terminal Eda peptides. Peptides 1, 13, 17, and 19 all have the ring structure of (A). Their side-chain structures are as follows: 1, Eda; 13, Pro-Eda; 17, Pro-Arg-Eda; 19, Arg-Gly-Eda. Peptide 21 is the Pro-Arg-Eda analogue of D; peptide 23 is the Pro-Arg-Gly-Eda analogue of E. Peptide 2 is the retro-Arg analogue of 1. Its side-chain structure is Eda<--Arg. Peptides 3-6 are analogues of 2 which have the D-Tyr-(Et)2 residue replaced by L-Tyr(Et)2 (3), D-Phe2 (4), D-Ile2 (5), or D-Leu2 (6), respectively. Peptides 7-12 are analogues of 2 which have the C-terminal retro-Arg replaced in retrofashion by D-Arg (7), Gly (8), Orn (9), D-Orn (10), D-Lys (11), or Arg-Arg (12). Peptides 14-16 have D-Orn (14), D-Lys (15), and D-Arg (16) retrosubstituted to peptide 13. Peptides 18, 20, and 22 are the retro-Arg-substituted analogues of 17, 19, and 21, respectively. Peptides 24 and 25 have Val and D-Val in retrolinkage with 23, respectively. All 25 peptides were examined for agonistic and antagonistic potencies in AVP V2/V1a assays. With the exception of peptides 5 and 6, all exhibit potent anti-V1a antagonism, with anti-V1a pA2 values in the range 7.64-8.33.(ABSTRACT TRUNCATED AT 400 WORDS)
Correction of Defective Protein Trafficking of a Mutant HERG Potassium Channel in Human Long QT Syndrome (1999)

The chromosome 7-linked form of congenital long QT syndrome (LQT2) is caused by mutations in the human ether-a-go-go-related gene (HERG) that encodes the rapidly activating delayed rectifier potassium channel. One mechanism for the loss of normal channel function in LQT2 is defective protein trafficking, which results in the failure of the channel protein to reach the plasma membrane. Here we show that the N470D LQT2 mutant protein is trafficking-deficient when expressed at 37 degrees C in HEK293 cells, whereas at 27 degrees C its trafficking to the plasma membrane and channel function are markedly improved. We further show that the antiarrhythmic drug E-4031, which selectively blocks HERG channels, also corrects defective protein trafficking of the N470D mutant and can restore the generation of HERG current. Similar findings were obtained with the drugs astemizole and cisapride, as well as with high concentrations of glycerol. The effect of E-4031 on HERG protein trafficking was concentration-dependent and required low drug concentrations (saturation present at 5 microM), developed rapidly with drug exposure, and occurred post-translationally. These findings suggest that protein misfolding leading to defective trafficking of some HERG LQT mutations may be corrected by specific pharmacological strategies.
ZLIB Compressed Data Format Specification version 3.3 (1996)

This specification defines a lossless compressed data format. The data can be produced or consumed, even for an arbitrarily long sequentially presented input data stream, using only an a priori bounded amount of intermediate storage. The format presently uses the DEFLATE compression method but can be easily extended to use other compression methods. It can be implemented readily in a manner not covered by patents. This specification also defines the ADLER-32 checksum (an extension and improvement of the Fletcher checksum), used for detection of data corruption, and provides an algorithm for computing it.
Experiments in plant tissue culture (1982)

Part I. Background Information: 1. Culture of plant cells, tissues, and organs 2. Laboratory facilities 3. Aseptic techniques 4. Media composition and preparation Part II. Experimental: Callus and Callus-Derived Systems: 5. Initiation and maintenance of callus 6. Organogenesis 7. Cell suspensions 8. Somatic embryogenesis Part III. Experimental: Culture of Organs and Organized Systems: 9. Isolated roots 10. Micropropagation by bud proliferation 11. Anther and pollen cultures Part IV. Experimental: Isolated Cells: 12. Transdifferentiation of parenchyma cells to tracheary elements 13. Isolation and culture of protoplasts 14. Protoplast fusion and somatic hybridization Part V. Supplementary Topics: 15. Cryopreservation of germplasm 16. Production of secondary metabolites 17. Quantitation of procedures 18. Formulations of tissue culture media 19. Commercial sources of supplies Author index Subject index.
Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE3 and presented by HLA‐A1 (1999)

Thirty-nine tumor-bearing patients with metastatic melanoma were treated with 3 subcutaneous injections of the MAGE-3.A1 peptide at monthly intervals. No significant toxicity was observed. Of the 25 patients who received the complete treatment, 7 displayed significant tumor regressions. All but one of these regressions involved cutaneous metastases. Three regressions were complete and 2 of these led to a disease-free state, which persisted for more than 2 years after the beginning of treatment. No evidence for a cytolytic T lymphocyte (CTL) response was found in the blood of the 4 patients who were analyzed, including 2 who displayed complete tumor regression. Our results suggest that injection of the MAGE-3.A1 peptide induced tumor regression in a significant number of the patients, even though no massive CTL response was produced. Int. J. Cancer 80:219–230, 1999. © 1999 Wiley-Liss, Inc.
HIV-1 Nef impairs MHC class II antigen presentation and surface expression (2001)

HIV-1-infected cells can avoid cytotoxic T lymphocyte killing by Nef-mediated down-regulation of surface MHC I. Here, we show that HIV-1 Nef inhibits MHC II restricted peptide presentation to specific T cells and thus may affect the induction of antiviral immune responses. Nef mediates this effect by reducing the surface level of mature (i.e., peptide-loaded) MHC II while increasing levels of immature MHC II, which are functionally incompetent because of their association with the invariant chain. Nef was the only HIV-1 gene product to possess this capacity, which was also observed in the context of the whole HIV-1 genome. Other proteins of the endocytic pathway were not affected by Nef expression, suggesting that Nef effects on MHC II did not result from a general alteration of the endocytic pathway. Response patterns to previously characterized mutations of Nef differed for Nef-induced modulation of mature and immature MHC II. Furthermore, the doses of Nef required to observe each of the two effects were clearly different, suggesting that Nef could affect MHC II peptide presentation through distinct mechanisms. Cooperation between those mechanisms may enable Nef to efficiently inhibit MHC II function.
Closure of the Pericardium Using Expanded Polytetrafluoroethylene GORE-TEX®-Surgical Membrane: Clinical Experience (1987)

Complete closure of the pericardium after cardiac operation would have the advantage of avoiding injury of the heart and great vessels should repeat sternotomy prove to be necessary. In such situations, various pericardial closure techniques have been described. Synthetic materials produced severe scarring, while xenografts appeared to be satisfactory, although fibrous reactions and aseptic cystic formations have been reported recently. Between 1985 and 1986 we closed the pericardium with GORE-TEX-Surgical Membrane in a selected series of 72 patients aging 1 month to 76 years, median 24 years. Overall hospital mortality was 3/72 cases. In no instance was there a relationship between death occurrence and pericardial closure through Surgical Membrane. There were 5 cases each of low cardiac output and rethoracotomy because of bleeding. No cardiac tamponade occurred. Two patients had to be reoperated three and four weeks after primary repair. Surgical Membrane was explanted. Electron microscopy examination showed no cellular ingrowth in the low porosity membrane. No immunocompetent cellular compounds were present on either side of the graft. Follow-up interval averaged 13 months. No complication related to pericardial closure has occurred until now. The Surgical Membrane has the advantages of easy availability, of lack of reactions both between its surface and the underlying epicardium and with the rest of the pericardium. We believe its routine use should be encouraged mainly in patients with high probability of reoperation.
DMDexon 1 truncating point mutations: Amelioration of phenotype by alternative translation initiation in exon 6 (2009)

Mutations in the DMD gene result in two common phenotypes associated with progressive muscle weakness: the more severe Duchenne muscular dystrophy (DMD) and the milder Becker muscular dystrophy (BMD). We have previously identified a nonsense mutation (c.9G>A; p.Trp3X) within the first exon of the DMD gene, encoding the unique N-terminus of the 427-kDa muscle isoform of the dystrophin protein. Although this mutation would be expected to result in severe disease, the clinical phenotype is very mild BMD, with ambulation preserved into the seventh decade. We identify the molecular mechanism responsible for the amelioration of disease severity to be initiation of translation at two proximate AUG codons within exon 6. Analysis of large mutational data sets suggests that this may be a general mechanism of phenotypic rescue for point mutations within at least the first two exons of the DMD gene. Our results directly demonstrate, for the first time, the use of alternate translational initiation codons within the DMD gene, and suggest that dystrophin protein lacking amino acids encoded by the first five exons retains significant function.