gebhart/patrepeval huggingface dataset:
Adenovirus type 5 and 7 capsid chimera: fiber replacement alters receptor tropism without affecting primary immune neutralization epitopes (1996)

The efficient uptake of adenovirus into a target cell is a function of adenovirus capsid proteins and their interaction with the host cell. The capsid protein fiber mediates high-affinity attachment of adenovirus to the target cell. Although the cellular receptor(s) for adenovirus is unknown, evidence indicates that a single receptor does not function as the attachment site for each of the 49 different serotypes of adenovirus. Sequence variation of the fiber ligand, particularly in the C- terminal knob domain, is associated with serotype-specific binding specificity. Additionally, this domain of fiber functions as a major serotype determinant. Fiber involvement in cell targeting and its function as a target of the host immune response make the fiber gene an attractive target for manipulation, both from the perspective of adenovirus biology and from the perspective of using adenovirus vectors for gene transfer experiments. We have constructed a defective chimeric adenovirus type 5 (Ad5) reporter virus by replacing the Ad5 fiber gene with the fiber gene from Ad7A. Using the chloramphenicol acetyltransferase reporter gene, we have characterized this virus with respect to infectivity both in vitro and in vivo. We have also characterized the role of antifiber antibody in the host neutralizing immune response to adenovirus infection. Our studies demonstrate that exchange of fiber is a strategy that will be useful in characterizing receptor tropism for different serotypes of adenovirus. Additionally, the neutralizing immune response to Ad5 and Ad7 does not differentiate between two viruses that differ only in their fiber proteins. Therefore, following a primary adenovirus inoculation, antibodies generated against fiber do not constitute a significant fraction of the neutralizing antibody population.
Inhibition of human and ovine acrosomal enzymes by tannic acid in vitro (2001)

The effect of tannic acid, a common flavonoid, on the acrosin and plasminogen activator activity and plasmin activity of human and ram spermatozoa was evaluated. Acrosin and plasminogen activator activity were determined by spectrophotometry using the chromogenic substrates N-alpha-benzoyl-DL-arginine para-nitroanilide-HCl (BAPNA) and H-D-valyl-L-leucyl-L-lysine-p-nitroanilide-2HCl (S-2251), respectively. In extracts from both human and ovine acrosomes, the activities of acrosin and plasminogen activators were susceptible to tannic acid inhibition. The inhibitory effect of tannic acid was observed at concentrations > 50 micromol l(-1) in a dose-dependent manner. In additional experiments, low concentrations of tannic acid significantly inhibited tissue-type plasminogen activator, urokinase-type plasminogen activator and plasmin activity in a concentration-dependent manner over the range 0.25-200 micromol l(-1). Tannic acid reduced the motility of ram spermatozoa at a concentration of 1000 micromol l(-1) after 2 and 3 h co-incubation with spermatozoa. The motility of human spermatozoa remained unchanged over the range 0.1-1000 micromol tannic acid l(-1) during 3 h co-incubation. These results indicate that tannic acid inhibited the activity of both acrosin and plasminogen activator and indicates a possible mechanism by which flavonoids exert their antifertility effects.
Direct Association of Csk Homologous Kinase (CHK) with the Diphosphorylated Site Tyr568/570 of the Activated c-KIT in Megakaryocytes (1997)

The Csk homologous kinase (CHK), formerly MATK, has previously been shown to bind to activated c-KIT. In this report, we characterize the binding of SH2(CHK) to specific phosphotyrosine sites on the c-KIT protein sequence. Phosphopeptide inhibition of the in vitro interaction of SH2(CHK)-glutathione S-transferase fusion protein/c-KIT from SCF/KL-treated Mo7e megakaryocytic cells indicated that two sites on c-KIT were able to bind SH2(CHK). These sites were the Tyr568/570 diphosphorylated sequence and the monophosphorylated Tyr721 sequence. To confirm this, we precipitated native CHK from cellular extracts using phosphorylated peptides linked to Affi-Gel 15. In addition, purified SH2(CHK)-glutathione S-transferase fusion protein was precipitated with the same peptide beads. All of the peptide bead-binding studies were consistent with the direct binding of SH2(CHK) to phosphorylated Tyr568/570 and Tyr721 sites. Binding of FYN and SHC to the diphosphorylated Tyr568/570 site was observed, while binding of Csk to this site was not observed. The SH2(CHK) binding to the two sites is direct and not through phosphorylated intermediates such as FYN or SHC. Site-directed mutagenesis of the full-length c-KIT cDNA followed by transient transfection indicated that only the Tyr568/570, and not the Tyr721, is able to bind SH2(CHK). This indicates that CHK binds to the same site on c-KIT to which FYN binds, possibly bringing the two into proximity on associated c-KIT subunits and leading to the down-regulation of FYN by CHK.
Surface-enhanced Raman Scattering (SERS) method and instrumentation for genomics and biomedical analysis (1999)

The development of a surface-enhanced Raman scattering (SERS) method and instrument for use in biomedical and genomics analysis is described. The technology uses DNA gene probes based on SERS labels for gene detection and DNA mapping. The detection method uses nanostructured metallic substrates as SERS-active platforms. The surface-enhanced Raman gene (SERGen) probes can be used to detect DNA targets via hybridization to DNA sequences complementary to these probes. The probes do not require the use of radioactive labels and have great potential to provide both sensitivity and selectivity. Advanced instrumental systems designed for point-source spectral measurements and for multi-spectral imaging (MSI) are described. The MSI concept allows recoding the entire SERS spectrum for every pixel on the two-dimensional hybridization platform in the field of view with the use of a rapid-scanning solid-state device, such as the acousto-optic tunable filter (AOTF). The usefulness of the SERGen approach and its applications in biomedical diagnostics, high-throughput analysis and DNA mapping and sequencing are discussed. Copyright © 1999 John Wiley & Sons, Ltd.
Synthesis and Properties of Highly Efficient Electroluminescent Green Phosphorescent Iridium Cored Dendrimers (2003)

A simple convergent procedure has been developed for the preparation of solution processable phosphorescent dendrimers with biphenyl-based dendrons and fac-tris(2-phenylpyridyl)iridium(III) cores. We found that the attachment point and branching of the dendrons are important for controlling the color of the light emission. Photoluminescence excitation measurements showed that energy could be transferred efficiently from the dendrons to the core. Solution photoluminescence quantum yield (PLQY) measurements of the dendrimers were of order 70%, showing that the attachment of the dendron did not decrease the luminescence efficiency of the core iridium complex. The PLQYs of the neat dendrimer films increased with generation with the second-generation dendrimer having a neat film PLQY of 31%, 11/2 times higher than the first-generation dendrimers and almost 3 times that of the nondendritic iridium complex, demonstrating the power of the dendrimer architecture to control intermolecular interactions. Electrochemical experiments showed that charge was injected directly into the core of the dendrimers.
VarySysDB: a human genetic polymorphism database based on all H-InvDB transcripts (2008)

Creation of a vast variety of proteins is accomplished by genetic variation and a variety of alternative splicing transcripts. Currently, however, the abundant available data on genetic variation and the transcriptome are stored independently and in a dispersed fashion. In order to provide a research resource regarding the effects of human genetic polymorphism on various transcripts, we developed VarySysDB, a genetic polymorphism database based on 187,156 extensively annotated matured mRNA transcripts from 36,073 loci provided by H-InvDB. VarySysDB offers information encompassing published human genetic polymorphisms for each of these transcripts separately. This allows comparisons of effects derived from a polymorphism on different transcripts. The published information we analyzed includes single nucleotide polymorphisms and deletion-insertion polymorphisms from dbSNP, copy number variations from Database of Genomic Variants, short tandem repeats and single amino acid repeats from H-InvDB and linkage disequilibrium regions from D-HaploDB. The information can be searched and retrieved by features, functions and effects of polymorphisms, as well as by keywords. VarySysDB combines two kinds of viewers, GBrowse and Sequence View, to facilitate understanding of the positional relationship among polymorphisms, genome, transcripts, loci and functional domains. We expect that VarySysDB will yield useful information on polymorphisms affecting gene expression and phenotypes. VarySysDB is available at http://h-invitational.jp/varygene/.
Von Willebrand Factor and Development of Diabetic Nephropathy in IDDM (1991)

We tested the hypothesis that dysfunction of vascular endothelium, indicated by an increase in plasma level of von Willebrand factor (vWF), is present in patients with insulin-dependent diabetes mellitus (IDDM) who develop diabetic nephropathy (DN). DN was classified as absent (urinary albumin excretion [UAE] rate less than 15 microgram/min), incipient (UAE rate 15-200 micrograms/min), or clinical (UAE rate greater than 200 micrograms/min). We followed a cohort of 59 patients for a median of 3 yr. At baseline, 52 patients had no DN, 6 had incipient DN, and 1 had clinical DN. At follow-up, 38 patients had no DN (group 1). Incipient DN had developed in 14 patients and worsened in 3 patients. Clinical DN had worsened in 1 patient. Together, these 18 patients comprised group 2. A decrease in UAE was observed in the remaining three patients with incipient DN at baseline (group 3). In group 1, vWF--measured by immunoelectrophoresis and expressed as a percentage of normal--increased slightly (median 10%, range -43 to 145, P = 0.009). In group 2, vWF increased in all patients (median 80%, range 14 to 206 [corrected], P = 0.0002 vs. baseline and group 1). In group 3, vWF decreased (median -19%, range -44 to -18). After correction for possible confounders, i.e., age, varying duration of follow-up, and initial level of vWF, the difference in vWF change between groups 1 and 2 remained significant (P = 0.009). Poor glycemic control at baseline, estimated by glycosylated hemoglobin, was a significant predictor of increases in vWF in both group 1 and groups 1 and 2 combined.(ABSTRACT TRUNCATED AT 250 WORDS)
TAP2‐defective RMA‐S cells present Sendai virus antigen to cytotoxic T lymphocytes (1993)

The murine antigen-processing-defective mutant cell line RMA-S is leaky in the presentation of certain endogenously synthesized minor histocompatibility and viral antigens to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL). The viral antigens include influenza virus nucleoprotein, vesicular stomatitis virus (VSV) nucleocapsid and Rauscher murine leukemia virus (MuLV) antigen. Here we demonstrate Sendai virus antigen presentation by the HAM2 (murine TAP2, transporter associated with antigen presentation type 2)-defective RMA-S cell line and compare antigen presentation after restoration of the defect by murine TAP1/2 gene transfection. Kinetic studies revealed that RMA-S cells required 2-3 h longer incubation and approximately 10 times higher doses of Sendai virus to reach the same level of killing as the RMA parental line. After transfection of RMA-S cells with the murine TAP1/2 gene, Sendai virus antigen presentation was restored to levels of the RMA wild-type line with regard to time of virus infection and dose of virus needed for sensitizing target cells. The presentation of Sendai virus antigen in RMA-S cells was sensitive to brefeldin A (BFA), suggesting that the presentation was mediated via the endogenous pathway. Our findings confirmed leakiness of antigen presentation in RMA-S cells and extended it to Sendai virus. The results underscored the role for intact expression of the TAP 1/2 molecules for efficient MHC class I-mediated antigen presentation.
Simultaneous In Situ Detection of DNA Fragmentation and RNA/DNA Oxidative Damage Using TUNEL Assay and Immunohistochemical Labeling for 8-Hydroxy-2'-Deoxyguanosine (8-OHdG) (2003)

Analysis of DNA fragmentation using Terminal deoxynucleotidyl Transferase (TdT)-mediated nick end-labeling (TUNEL) is a very sensitive technique for in situ detection of various types of DNA breaks in cells undergoing apoptosis and/ or necrosis (1–6). TUNEL technique is widely used, for instance, to study mechanisms underlying early development and morphogenesis (7–14), aging (15–24), cancer (25,5,25–35) and neurodegenerative diseases (36,20,21,36–44). TUNEL detects the DNA fragmentation, which represents the end point of DNA degradation in apoptosis but does not depict primary stimuli that caused irreversible disruption to the integrity of DNA. Oxidative stress is one of such primary stimuli and there is a great deal of research aimed at unraveling the molecular mechanisms underlying oxidative damage to DNA by so-called reactive oxygen species (ROS) and oxygen radicals. Oxidative damage has been implicated in a wide variety of neurodegenerative disorders including Alzheimer’s dementia, amyotrophic lateral sclerosis, Huntington’s disease and Parkinson’s disease (45–55). Formation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) is the most common modification of DNA caused by oxidative stress. Therefore, immunohistochemical quantification of 8-OHdG would be a valuable tool in determining the extent of oxidative DNA damage caused by ROS. On the other hand, methods analyzing the oxidative damage to the DNA, are not sufficient alone either, since they do not reveal whether oxidative stress will result in apoptosis and cell death or not. Thus, it appears that limitations of each individual assay may be overcome if both techniques are combined in a single assay that is applied to the same cytological of histological specimen.
The localization of the insulinâlike growth factor receptor 1 (IGFR-1) in benign and malignant breast tissue (1997)

Insulin-like growth factors (IGFs) play an important role in normal cellular growth and development and have been implicated in the regulation of tumour growth. Two receptors are recognized, IGFR-1 and IGFR-2, of which one, IGFR-1, is a transmembrane heterodimer structurally similar to the insulin receptor. Studies using ligand-binding assays have suggested that the proportion of human breast carcinomas expressing IGFR-1 varies between 39 and 93 per cent and all suggest a lower level of IGFR-1 expression in benign mammary epithelia. As there is this variation between studies and since no study appears to have examined the immunohistochemical localization of IGFR-1 within breast tissue, a series of 79 infiltrating ductal carcinomas, 11 infiltrating lobular carcinomas, three cases of pure ductal carcinoma in situ (DCIS), seven fibroadenomas, and eight normal breast specimens have been studied utilizing the monoclonal antibody αIR3. IGFR-1 localized to the epithelial component of 90 per cent of the carcinomas, with only cytoplasmic (21 per cent), only membrane (5 per cent), or a mixture of both cytoplasmic and membrane (64 per cent) staining patterns. In some tumours, distinct basolateral distribution of the receptor was observed. Invasive lobular carcinoma showed significantly less labelling than ductal (P=0·0009). There was a significant correlation between the level of IGFR-1 immunostaining with both oestrogen receptor (P<0·001) and progesterone receptor (P=0·0018) positivity within the malignant group. All normal mammary epithelium showed strong labelling, which was often at an intensity matching that of the most strongly labelled carcinoma and occasionally visualized as basolateral staining of the luminal cells. Weak to moderate staining of endothelial cells was also observed. It is concluded that IGFR-1 immunoreactivity is found in the majority of breast carcinomas, where it correlates most closely with oestrogen receptor status. The high intensity labelling of normal cells seen in this study contrasts with the low levels inferred from ligand-binding-based techniques and emphasizes the importance of the morphological approach in the investigation of novel molecules. © 1997 John Wiley & Sons, Ltd.
Gelatin and Gelatin−Hyaluronic Acid Nanofibrous Membranes Produced by Electrospinning of Their Aqueous Solutions (2006)

ADVERTISEMENT RETURN TO ISSUEPREVNoteGelatin and Gelatin−Hyaluronic Acid Nanofibrous Membranes Produced by Electrospinning of Their Aqueous SolutionsJunxing Li, Aihua He, Jianfen Zheng, and Charles C. HanView Author Information Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Joint Laboratory of Polymer Science and Materials, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China Cite this: Biomacromolecules 2006, 7, 7, 2243–2247Publication Date (Web):June 16, 2006Publication History Received5 April 2006Revised10 May 2006Published online16 June 2006Published inissue 1 July 2006https://pubs.acs.org/doi/10.1021/bm0603342https://doi.org/10.1021/bm0603342brief-reportACS PublicationsCopyright © 2006 American Chemical SocietyRequest reuse permissionsArticle Views2971Altmetric-Citations147LEARN 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:Animal derived food,Electrospinning,Fibers,Membranes,Solution chemistry Get e-Alerts
Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors. (2006)

The use of Tc(I)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-His6-(ZHER2:4)2 conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with 99mTc should be investigated further.
Inorganic Polyphosphate Modulates TRPM8 Channels (2009)

Polyphosphate (polyP) is an inorganic polymer built of tens to hundreds of phosphates, linked by high-energy phosphoanhydride bonds. PolyP forms complexes and modulates activities of many proteins including ion channels. Here we investigated the role of polyP in the function of the transient receptor potential melastatin 8 (TRPM8) channel. Using whole-cell patch-clamp and fluorescent calcium measurements we demonstrate that enzymatic breakdown of polyP by exopolyphosphatase (scPPX1) inhibits channel activity in human embryonic kidney and F-11 neuronal cells expressing TRPM8. We demonstrate that the TRPM8 channel protein is associated with polyP. Furthermore, addition of scPPX1 altered the voltage-dependence and blocked the activity of the purified TRPM8 channels reconstituted into planar lipid bilayers, where the activity of the channel was initiated by cold and menthol in the presence of phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P(2)). The biochemical analysis of the TRPM8 protein also uncovered the presence of poly-(R)-3-hydroxybutyrate (PHB), which is frequently associated with polyP. We conclude that the TRPM8 protein forms a stable complex with polyP and its presence is essential for normal channel activity.
Serological diagnosis of syphilis. PHLS Syphilis Serology Working Group. (2000)

The availability of an increasing number of enzyme immunoassays (EIAs) for detecting syphilis antibodies makes it appropriate to review approaches to syphilis serology and to assess the role of syphilis EIAs in routine diagnostic microbiology laboratories. This paper summarises the principles and practice of syphilis serology and provides recommendations on the use of laboratory tests for syphilis in UK diagnostic microbiology laboratories. The main recommendations are summarised in a testing algorithm. Treponemal EIAs are an appropriate alternative to the use of combined Venereal Disease Research Laboratories/rapid plasma reagin and Treponema pallidum haemagglutination assay (TPHA) tests for screening for syphilis. If a treponemal EIA is used for screening an alternative treponemal test, such as TPHA, should be used for confirmatory testing. The fluorescent treponemal antibody-absorbed test is probably best reserved for specimens giving discrepant results. Such specimens may be referred to the PHLS laboratories that provide confirmatory treponemal testing for reference testing and to facilitate collection of surveillance data on what remains an important public health problem.
Immunotherapeutic and antitumour potential of thalidomide analogues (2001)

The immunomodulatory drug thalidomide has been shown to be clinically useful in a number of conditions including various immunological disorders and cancers. Clinical activity in vivo is attributed to the wide ranging immunological and non-immunological properties possessed by this drug; these include anti-TNF-alpha, T-cell co-stimulatory, anti-angiogenic activities and also direct antitumour activity. Recently, the design of compounds based on the thalidomide structure has led to the synthesis of analogues with greatly enhanced immunological activity and with similarly decreased toxicity. These derivatives fail into at least two categories; selective cytokine inhibitory drugs (SelCID), which are phosphodiesterase Type 4 (PDE4) inhibitors and immunomodulatory drugs (IMiD), similar to thalidomide which act via unknown mechanism(s). These compounds are in the process of being characterised in laboratory studies and are also now being assessed in Phase I and Phase I/II clinical studies. In this review we will highlight the properties of these two novel classes of compound in terms of their effects on both immunological and non-immunological systems in vitro. We will also describe how these studies are enabling the characterisation and development of these compounds into clinically relevant drugs in widely varying diseases. To this end we will describe the various clinical studies of lead compounds that are in progress and speculate as to the potential and future development of these exciting compounds.