gebhart/patrepeval huggingface dataset:
Molecular Basis of the Differences in Binding Properties of the Highly Related C-type Lectins DC-SIGN and L-SIGN to Lewis X Trisaccharide and Schistosoma mansoni Egg Antigens (2004)

The dendritic cell-specific C-type lectin DC-SIGN functions as a pathogen receptor that recognizes Schistosoma mansoni egg antigens through its major glycan epitope Galbeta1,4(Fucalpha1,3)GlcNAc (Lex). Here we report that L-SIGN, a highly related homologue of DC-SIGN found on liver sinusoidal endothelial cells, binds to S. mansoni egg antigens but not to the Lex epitope. L-SIGN does bind the Lewis antigens Lea, Leb, and Ley, similar as DC-SIGN. A specific mutation in the carbohydrate recognition domain of DC-SIGN (V351G) abrogates binding to all Lewis antigens. In L-SIGN Ser363 is present at the corresponding position of Val351 in DC-SIGN. Replacement of this Ser into Val resulted in a "gain of function" L-SIGN mutant that binds to Lex, and shows increased binding to the other Lewis antigens. These data indicate that Val351 is important for the fucose specificity of DC-SIGN. Molecular modeling and docking of the different Lewis antigens in the carbohydrate recognition domains of L-SIGN, DC-SIGN, and their mutant forms, demonstrate that Val351 in DC-SIGN creates a hydrophobic pocket that strongly interacts with the Fucalpha1,3/4-GlcNAc moiety of the Lewis antigens. The equivalent amino acid residue Ser363 in L-SIGN creates a hydrophilic pocket that prevents interaction with Fucalpha1,3-GlcNAc in Lex but supports interactions with the Fucalpha1,4-GlcNAc moiety in Lea and Leb antigens. These data demonstrate for the first time that DC-SIGN and L-SIGN differ in their carbohydrate binding profiles and will contribute to our understanding of the functional roles of these C-type lectin receptors, both in recognition of pathogen and self-glycan antigens.
A beta-cell-specific protein binds to the two major regulatory sequences of the insulin gene enhancer. (1988)

The selective transcription of the Rat insulin 1 gene is mainly dependent on a beta-cell-specific enhancer element located in the 5' flanking DNA. In analogy to many other viral and cellular enhancers, the insulin enhancer has been shown to be of a mosaic structure and the cis-acting elements of importance for the enhancer activity have been defined. Two short sequences are of crucial importance for the enhancer activity since mutation of either sequence leads to a decrease in activity (by a factor of approximately 10), and the double mutant eliminates all enhancer activity. This study shows that these two major cis-acting elements interact with beta-cell-specific proteins. These two enhancer modules carry an 8-base-pair homology and compete with each other for protein binding, suggesting that they interact with the same protein, designated insulin enhancer binding factor 1 (IEF 1). Since mutation of these sequences eliminates the enhancer activity and protein binding, we propose that IEF 1 is the key regulator controlling the selective activity of the insulin gene enhancer.
A Circuit for Safe Diagnostic Electrical Stimulation of the Human Brain (1980)

An electronic circuit for controlled electrical stimulation of the human brain has been designed to optimize safety in charge transfer from electrodes to brain and to eliminate the likelihood of unwanted currents from the neurostimulator resulting from component failure. The circuit schematics feature the following designs: (1) a highly accurate and versatile rate generator 0.5 p.p.s. to 99 in increments of 0.5 p.p.s., (2) symmetrically-biphasic lead and lag pulses of 100 musec duration, (3) photo-isolated driver amplifiers with accurate waveform, reproduction, (4) true biphasic passive-current regulators driven by an isolated battery supply voltage for switch-selectable currents of 0.25 to 5 ma or variable current regulation, (5) accurate current and voltage waveform monitors that isolate the stimulating electrodes from the monitors, and (6) capacity-coupled outputs to guarantee no net D.C. component at the end of each biphasic pulse. Relay-switching circuits are also shown that allow sequential stimulation and recording from one or several electrodes. This neurostimulator has been in use for over two years without evidence of electrolytic damage at identifiable electrode tips. The utility of simultaneous stimulation of several different electrodes at safe charge levels is described.
Insulinlike Growth Factor-I Gene Therapy Applications for Cartilage Repair (2000)

Cartilage function after resurfacing with cell-based transplantation procedures or during the early stages of arthritic disease may be bolstered by the addition of growth factor genes to the transplanted tissue. Insulinlike growth factor-I maintains chondrocyte metabolism in normal cartilage homeostasis and has been shown to improve cartilage healing in vivo. Given the relatively short half-life of insulinlike growth factor-I in biologic systems, however, maintenance of effective concentrations of this peptide has necessitated either very high initial doses or repeated treatment. Delivery of the insulinlike growth factor-I gene, using a deleted adenovirus vector, specifically targeting graftable articular chondrocytes, bone marrow-derived chondroprogenitor cells, or synovial lining cells, may provide more durable insulinlike growth factor-I fluxes to articular tissues. Cultured equine articular chondrocytes, mesenchymal stem cells, synovial explants, and synovial intimal cells were readily transfected with an E1-deleted adenoviral vector containing equine insulinlike growth factor-I coding sequence. Optimal viral concentrations for effective transduction were 100 multiplicities of infection in synoviocytes, 500 multiplicities of infection in chondrocytes, and 1000 multiplicities of infection in mesenchymal stem cells. Production of insulinlike growth factor-I ligand varied from 65 ng/mL to 246 ng/mL in medium from chondrocytes and synovial explants, respectively. For chondrocytes, these concentrations were sufficient to produce significant stimulation of cartilage matrix gene expression and subsequent proteoglycan production. Moreover, cells in infected cultures maintained a chondrocytic phenotype and continued to express elevated insulinlike growth factor-I levels during 28 days of monolayer culture. Minimal synthetic activity, other than insulinlike growth factor-I ligand synthesis, was evident in synovial cultures. These experiments suggest several avenues for insulinlike growth factor-I supplementation of articular cartilage, including preimplantation adenoviral-insulinlike growth factor gene transfer to chondrocytes or chondroprogenitor cells, and direct injection of adenoviral-insulinlike growth factor to transfect the synovial structures in situ.
Imple.mentation of an adaptive digital/RF predistorter using direct LUT synthesis (2004)

This paper proposes an integrated adaptive digital/RF look-up-tables (LUT) based predistorter for the linearization of RF power amplifiers (PA). The LUT content that feeds a linear vector modulator used for the realization of the inverse nonlinear function is directly deduced given baseband input and output signals of the PA. Measured output spectrum of a linearized 90-W peak LDMOS power amplifier reveal a significant reduction of the power emission at the adjacent channels of about 15 dB under IS95, single-carrier WCDMA. The noteworthy experimental results carried out in this work were obtained through the construction of a prototype using an envelope detector, a linear RF vector modulator, FPGA, DSP processors, and fast A/D and D/A converters.
Predicting therapeutic outcome in patients with diffuse histiocytic lymphoma treated with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP) (1982)

Seventy-five patients with diffuse histiocytic lymphoma (DHL) ranging in age from 33 to 94 years were treated with cyclophosphamide, Adriamycin, vincristine and prednisone (CHOP). Thirty-eight patients (51%) achieved complete remission, but nine of these patients relapsed after remission lasting one to 23 months (median time to relapse, four months). We used multivariate analysis to identify those characteristics that significantly affected treatment outcome. The chances for complete remission were adversely affected by DHL appearing after histologic conversion from another lymphoma (P = 0.006), the presence of systemic symptoms (P = 0.24), and not having the large noncleaved (LNC) histologic subtype (P = 0.40). The chance for relapse from complete remission was increased only by the presence of systemic symptoms (P = 0.042). Overall survival was adversely affected by the presence of bone marrow involvement (P = 0.002), having other than LNC histologic subtype (P = .010), and the presence of systemic symptoms (P = 0.043). It appears that patients whose DHL appears de novo and who also are symptom status A (70% long-term disease-free survival) or have the LNC histologic subtype (67% long-term disease-free survival) have an excellent outlook when treated with CHOP at the doses used in this study. However, patients with B symptoms (16% long-term disease-free survival), histologic conversion to DHL (8% long-term disease-free survival), previous chemotherapy (8% long-term disease-free survival), and bone marrow involvement (8% long-term disease-free survival) respond poorly and for these patients other treatments need to be identified. In addition, patients with B symptoms who achieve complete remission with CHOP are at high risk to relapse (59% relapse rate) and should be considered for "intensification" therapy after complete remission is documented.
AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy (2016)

Usher syndrome type III (USH3A) is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and sensorineural deafness. Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal localization of clarin-1, a transmembrane protein of unknown function. In this study, we used an AAV-based approach to express CLRN1 in the mouse retina in order to determine the pattern of its subcellular localization in different cell types. We found that all major classes of retinal cells express AAV-delivered CLRN1 driven by the ubiquitous, constitutive small chicken β-actin promoter, which has important implications for the design of future USH3 gene therapy studies. Within photoreceptor cells, AAV-expressed CLRN1 is mainly localized at the inner segment region and outer plexiform layer, similar to the endogenous expression of other usher proteins. Subretinal delivery using a full strength viral titer led to significant loss of retinal function as evidenced by ERG analysis, suggesting that there is a critical limit for CLRN1 expression in photoreceptor cells. Taken together, these results suggest that CLRN1 expression is potentially supported by a variety of retinal cells, and the right combination of AAV vector dose, promoter, and delivery method needs to be selected to develop safe therapies for USH3 disorder.
Synthesis of 3,6-Disubstituted-2-nitrotoruenes by Methylation of Aromatic Nitrocompounds with Dimethylsulfonium Methylide (2000)

Abstract 3,6-disubstituted-2-nitrotoluenes were obtained in moderate yield by methylation of 2,5-disubstituted nitrobenzenes with dimethylsulfonium methylide in DMSO-THF mixture.
Putting Recommender Systems to Work for Organizations (1998)

The issue we focus on here is how to make recommender systems work in organizations and for organizations. Moving from the Internet to Intranets requires shifting the primary focus from sharing recommendations to sharing knowledge and from community-building to community support. Moving recommender systems from the Internet onto Intranets also means turning leisure-ware into groupware, creating both new challenges and new opportunities.
Trivalent vaccine mixture protects against simultaneous challenge with M. hyopneumoniae, PCV2, and PRRS virus (2010)

Introduction and Objectives 3FLEX is the t rade n ame asso ciated w ith t he mixture o f I ngelvac C ircoFLEX, I ngelvac MycoFLEX, and Ingelvac PRRS MLV swine vaccines (Boehringer I ngelheim V etmedica, Inc., St J oseph, M issouri). Previous s tudies using s ingle-agent ch allenges h ad d emonstrated lack of i mmunologic i nterference am ong t hese antigens. This laboratory s tudy w as c onducted to evaluate the efficacy o f t he t rivalent vaccine mixture a gainst m ultiple i nfections by challenging pigs w ith all 3 relevant pathogens simultaneously.
Origin activation and formation of single-strand TG1-3 tails occur sequentially in late S phase on a yeast linear plasmid. (1993)

In order to understand the mechanisms leading to the complete duplication of linear eukaryotic chromosomes, the temporal order of the events involved in replication of a 7.5-kb Saccharomyces cerevisiae linear plasmid called YLpFAT10 was determined. Two-dimensional agarose gel electrophoresis was used to map the position of the replication origin and the direction of replication fork movement through the plasmid. Replication began near the center of YLpFAT10 at the site in the 2 microns sequences that corresponds to the 2 microns origin of DNA replication. Replication forks proceeded bidirectionally from the origin to the ends of YLpFAT10. Thus, yeast telomeres do not themselves act as origins of DNA replication. The time of origin utilization on YLpFAT10 and on circular 2 microns DNA in the same cells was determined both by two-dimensional gel electrophoresis and by density transfer experiments. As expected, 2 microns DNA replicated in early S phase. However, replication of YLpFAT10 occurred in late S phase. Thus, the time of activation of the 2 microns origin depended upon its physical context. Density transfer experiments established that the acquisition of telomeric TG1-3 single-strand tails, a predicted intermediate in telomere replication, occurred immediately after the replication forks approached the ends of YLpFAT10. Thus, telomere replication may be the very last step in S phase.
An evolutionarily conserved leucine-rich repeat protein CLERC is a centrosomal protein required for spindle pole integrity (2008)

The centrosome functions as the microtubule-organizing center (MTOC) and plays a vital role in organizing spindle poles during mitosis. The pair of centrioles, which are the core components of the centrosome, duplicate once per cell cycle, and this feature is essential for the establishment of spindle bipolarity. Here we describe the molecular characterization of a novel protein called CLERC (Centrosomal leucine-rich repeat and coiled-coil containing protein) which is a human ortholog of Chlamydomonas Vfl1 protein. CLERC is a protein of 1032 amino acids with a calculated molecular mass of 120 kDa and possesses leucine-rich repeat and coiled-coil domains. Database searches revealed that CLERC has homologs in a wide variety of eukaryotes and is evolutionarily conserved. Endogenous CLERC protein associated with the centrosomes throughout the cell cycle and accumulated during mitosis. RNAi-mediated depletion of CLERC blocked formation of normal mitotic spindles and led to multipolar spindles. Moreover, many of the spindle poles in CLERC depleted cells contained only one centriole, indicating that centrosomes split into fractions containing a single centriole. These data indicate that the major function of CLERC during mitosis is to maintain the structural integrity of centrosomes, thereby contributing to spindle bipolarity.
Phenotypic characterization of intestinal Escherichia coli of pigs during suckling, postweaning, and fattening periods (1995)

A highly discriminatory and standardized biochemical fingerprinting method was used to monitor the persistence and colonization of intestinal Escherichia coli isolated from the feces of four sows and their litters (four piglets from each) during the suckling, postweaning, and fattening periods. Altogether, 195 fecal samples were collected and 1,827 E. coli strains were tested (mean number of isolates tested per fecal sample per pig, 9.5). Strains were divided into similarity groups on the basis of their biochemical phenotypes (BPTs). The diversity of E. coli strains in each sample was measured with Simpson's index of diversity, and similarity between E. coli floras of piglets was calculated with a population similarity index. Each fecal sample contained several BPTs of E. coli, some of which dominated that population. The intestinal colonization of piglets consisted of successive waves of different E. coli BPTs, the tenure of which varied from a few days to 2 weeks. Most of these BPTs disappeared in the succeeding samples and were not recovered again from the same piglets. On the other hand, some E. coli strains which colonized piglets early during the suckling period persisted for a long period and were referred to as resident BPTs. Each piglet carried more than one resident BPT (mean of 2.4 BPTs per pig), some of which were also found in other piglets.(ABSTRACT TRUNCATED AT 250 WORDS)
ChemInform Abstract: 3‐NITRO‐2‐PYRIDINESULFENYL (NPYS) GROUP. A NOVEL SELECTIVE PROTECTING GROUP WHICH CAN BE ACTIVATED FOR PEPTIDE BOND FORMATION (1981)

Abstract Aus dem Chlornitropyridin (I) wird mit Thioharnstoff (II) das Pseudothiouronium‐Salz hergestellt, das zum Thiol hydrolysiert und schließlich mit Kaliumhexacyanoferrat(III) zum Disulfid (III) oxidiert wird.
Monoclonal Antibodies, Small Molecules, and Vaccines in the Treatment of Breast Cancer (2004)

The human epidermal growth factor receptor (HER, ErbB) family of receptors is considered an important therapeutic target, and various types of molecularly based small molecules, including monoclonal antibodies, protein tyrosine kinase inhibitors, and therapeutic vaccines, are in development as potential therapies for metastatic breast cancer. Trastuzumab (Herceptin; Genentech, Inc.; South San Francisco, CA), the first approved monoclonal antibody for HER-2 (ErbB-2)-overexpressing metastatic breast cancer, provided the proof of principle that targeting specific receptors results in clinical benefit. Other monoclonal antibodies and the small molecule dual protein tyrosine kinase inhibitors show great promise as treatments for metastatic breast cancer but require evaluation in clinical trials to assess their benefits. Therapeutic vaccines may have a role, particularly in early-stage disease, but they are associated with greater limitations and study design issues that make their evaluation difficult. Optimum combination therapy regimens with a variety of novel approaches that incorporate small molecule targeted therapies need to be developed, and the population most likely to benefit from targeted therapies needs to be identified.
A novel biologic function of serum amyloid A. Induction of T lymphocyte migration and adhesion (1995)

In the course of an inflammatory response, the concentration of serum amyloid A (SAA), a hepatocyte-derived acute phase protein, increases up to 1000-fold above the normal level. Although SAA was previously thought to be immunosuppressive, we recently reported that SAA is a potent chemoattractant for monocytes and neutrophils. The present study shows that recombinant human (rh) SAA also induces directional migration of T cells in vitro. Phenotypic analyses revealed that CD4+ and CD8+ T cell subsets were equally responsive to rhSAA, whereas CD45RA cells were also not selectively attracted by rhSAA. The T cell chemotaxis induced by rhSAA was inhibited by pretreatment of cells with pertussis toxin, suggesting the interaction of rhSAA with a G-protein-coupled receptor species. T cells pretreated with an optimal concentration of SAA exhibited enhanced adherence to human umbilical cord endothelial cell monolayers. Subcutaneous administration of rhSAA into huPBL-SCID mice caused the infiltration of human T lymphocytes at the injection sites by 4 h. These results suggest that SAA may play an important role in recruiting T lymphocytes, as well as neutrophils and monocytes into inflammatory lesions.
Electrostatic stabilization in four‐helix bundle proteins (1993)

Charge substitutions generated by site-directed mutagenesis at the termini of adjacent anti-parallel alpha-helices in a four-helix bundle protein were used to determine a precise value for the contribution of indirect charge-charge interactions to overall protein stability, and to simulate the electrostatic effects of alpha-helix macrodipoles. Thermodynamic double mutant cycles were constructed to measure the interaction energy between such charges on adjacent anti-parallel helices in the four-helix bundle cytochrome b562 from Escherichia coli. Previously, theoretical calculations of helix macrodipole interactions using modeled four-helix bundle proteins have predicted values ranging over an order of magnitude from 0.2 to 2.5 kcal/mol. Our system represents the first experimental evidence for electrostatic interactions such as those between partial charges due to helix macrodipole charges. At the positions mutated, we have measured a favorable interaction energy of 0.6 kcal/mol between opposite charges simulating an anti-parallel helix pair. Pairs of negative or positive charges simulating a parallel orientation of helices produce an unfavorable interaction of similar magnitude. The interaction energies show a strong dependence upon ionic strength, consistent with an electrostatic effect. Indirect electrostatic contacts do appear to confer a limited stabilization upon the association of anti-parallel packing of helices, favoring this orientation by as much as 1 kcal/mol at 20 mM K phosphate.
Colorectal adenomas and cancer: pathologic relationships. (1982)

The relationship of adenomatous polyps and hyperplastic polyps to carcinomas of the colon and rectum are discussed. There is a continuum of neoplastic alterations from adenomas to invasive carcinomas, which is defined. Clinically relevant prognostic factors in adenomas containing cancer are evaluated. Degree of differentiation, depth of invasion, and the relative amount of carcinoma are important factors.
Indocyanine Green Angiography in the Surgical Management of Cerebral Arteriovenous Malformations (2014)

ICG videoangiography is a quick and safe method of intraoperatively mapping the angioarchitecture of superficial AVMs, but it is less helpful for deep-seated lesions. This modality alone does not improve the identification of residual disease or clinical outcomes. Surgeon experience with extensive study of preoperative vascular imaging is paramount to achieving acceptable clinical outcomes. Formal angiography remains the gold standard for the evaluation of AVM obliteration.
Exploiting Surface Plasmon Resonance (SPR) Technology for the Identification of Fibroblast Growth Factor-2 (FGF2) Antagonists Endowed with Antiangiogenic Activity (2009)

Angiogenesis, the process of new blood vessel formation, is implicated in various physiological/pathological conditions, including embryonic development, inflammation and tumor growth. Fibroblast growth factor-2 (FGF2) is a heparin-binding angiogenic growth factor involved in various physiopathological processes, including tumor neovascularization. Accordingly, FGF2 is considered a target for antiangiogenic therapies. Thus, numerous natural/synthetic compounds have been tested for their capacity to bind and sequester FGF2 in the extracellular environment preventing its interaction with cellular receptors. We have exploited surface plasmon resonance (SPR) technique in search for antiangiogenic FGF2 binders/antagonists. In this review we will summarize our experience in SPR-based angiogenesis research, with the aim to validate SPR as a first line screening for the identification of antiangiogenic compounds.