gebhart/patrepeval huggingface dataset:
Antibodies to the human 60 kDa heat-shock protein in patients with schizophrenia (1992)

Immune mechanisms are thought to be important in a subpopulation of patients with schizophrenia. We examined the specificity of neural antibodies in patients with schizophrenia to identify a possible antigen. Serum antibodies from patients with schizophrenia and control subjects were tested for binding to protein extracts of human neuroblastoma cells by western blot. Protein antigens were characterised by aminoterminal and internal aminoacid sequence analysis. 14 of 32 (44%) otherwise healthy patients with schizophrenia had antibodies to a neuroblastoma protein of molecular weight 60 kDa. By partial sequence analysis, this protein was identified as the 60 kDa human heat-shock protein (hsp) that is the P1 mitochondrial protein, and which is 50% homologous to the mycobacterial 65 kDa hsp. Antigens that crossreact with hsp65 have been implicated in the pathogenesis of adjuvant-induced arthritis in rats and autoimmune diabetes in mice. Of 100 normal subjects or disease controls, antibodies to hsp60 were found in only 8 patients, all of whom had active infectious or inflammatory disease. Our results support the presence of abnormal immune reactivity involving hsp60 in a subset of patients with schizophrenia. The immune response may be related to the pathogenesis of the disease.
Isolation and sequencing of a cDNA coding for the human DF3 breast carcinoma-associated antigen. (1988)

The murine monoclonal antibody (mAb) DF3 reacts with a high molecular weight glycoprotein detectable in human breast carcinomas. DF3 antigen expression correlates with human breast tumor differentiation, and the detection of a cross-reactive species in human milk has suggested that this antigen might be useful as a marker of differentiated mammary epithelium. To further characterize DF3 antigen expression, we have isolated a cDNA clone from a lambda gt11 library by screening with mAb DF3. The results demonstrate that this 309-base-pair cDNA, designated pDF9.3, codes for the DF3 epitope. Southern blot analyses of EcoRI-digested DNAs from six human tumor cell lines with 32P-labeled pDF9.3 have revealed a restriction fragment length polymorphism. Variations in size of the alleles detected by pDF9.3 were also identified in Pst I, but not in HindIII, DNA digests. Furthermore, hybridization of 32P-labeled pDF9.3 with total cellular RNA from each of these cell lines demonstrated either one or two transcripts that varied from 4.1 to 7.1 kilobases in size. The presence of differently sized transcripts detected by pDF9.3 was also found to correspond with the polymorphic expression of DF3 glycoproteins. Nucleotide sequence analysis of pDF9.3 has revealed a highly conserved (G + C)-rich 60-base-pair tandem repeat. These findings suggest that the variation in size of alleles coding for the polymorphic DF3 glycoprotein may represent different numbers of repeats.
Matrix metalloproteinases-2 and -9 are expressed in human neuroblastoma: contribution of stromal cells to their production and correlation with metastasis. (1998)

Neuroblastoma, the second most common solid childhood tumor, can be a highly invasive and metastatic form of cancer. To assess the role of matrix-degrading proteases in this cancer, we have examined the expression of matrix metalloproteinases (MMPs) and their corresponding tissue inhibitors of metalloproteinases (TIMPs) in 7 human neuroblastoma cell lines and 24 primary untreated tumors. MMP-2 (gelatinase A) and MMP-9 (gelatinase B) were the only two MMPs expressed. MMP-2 was detected predominantly in an inactive proform in all tumor cell lines and tumor tissue extracts. The lack of MMP-2 activation in cell lines was attributed to the absence of expression of a membrane-type MMP (MT1-MMP), which activates proMMP-2, and to the abundant expression of TIMPs, particularly TIMP-2. Immunohistochemical analysis of tumor tissue samples indicated that MMP-2 was present in both tumor cells and stromal cells. In contrast, MMP-9 was not expressed by neuroblastoma cell lines but was present in inactive and active forms in extracts from tumor tissues. Immunohistochemical analysis of positive specimens indicated that MMP-9 was predominantly present in stromal, vascular, and perivascular cells surrounding nests of tumor cells. There was no correlation between the levels of these MMPs and the MYCN copy number or the histopathological phenotype. However, there were higher levels of MMP-2 and MMP-9 in stage IV (metastatic) disease when compared with stages I and II (noninvasive and nonmetastatic) or IV-S (P < 0.05).
Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene (2005)

Rearrangements of the RET receptor tyrosine kinase gene generating RET/PTC oncogenes are specific to papillary thyroid carcinoma (PTC), the most frequent thyroid tumor. Here, we show that the RET/PTC1 oncogene, when exogenously expressed in primary normal human thyrocytes, induces the expression of a large set of genes involved in inflammation and tumor invasion, including those encoding chemokines (CCL2, CCL20, CXCL8, and CXCL12), chemokine receptors (CXCR4), cytokines (IL1B, CSF-1, GM-CSF, and G-CSF), matrix-degrading enzymes (metalloproteases and urokinase-type plasminogen activator and its receptor), and adhesion molecules (L-selectin). This effect is strictly dependent on the presence of the RET/PTC1 Tyr-451 (corresponding to RET Tyr-1062 multidocking site). Selected relevant genes (CCL20, CCL2, CXCL8, CXCR4, L-selectin, GM-CSF, IL1B, MMP9, UPA, and SPP1/OPN) were found up-regulated also in clinical samples of PTC, particularly those characterized by RET/PTC activation, local extrathyroid spread, and lymph node metastases, when compared with normal thyroid tissue or follicular thyroid carcinoma. These results, demonstrating that the RET/PTC1 oncogene activates a proinflammatory program, provide a direct link between a transforming human oncogene, inflammation, and malignant behavior.
Reduction in misfit dislocation density by the selective growth of Si1−xGex/Si in small areas (1990)

Si1−xGex and Si layers have been grown selectively in the exposed Si regions on oxide-patterned 〈100〉 oriented Si wafers using the chemical vapor deposition technique limited reaction processing. Misfit dislocation spacings at the heterointerface were measured using plan-view transmission electron microscopy in conjunction with a large-area thinning technique which allows for examination of 100–150 μm diameter areas. The dislocation density is reduced by at least a factor of 20 for small areas (lateral dimensions: tens of microns) bounded by oxide isolation when compared to adjacent large areas (millimeters) which are uninterrupted by the patterned oxide. The ability to selectively grow Si1−xGex on patterned wafers and the area-dependent reduction in dislocation density in as-grown films may be important considerations for future device applications using Si1−xGex strained layers.
Keratoacanthoma centrifugum marginatum: a diagnostic and therapeutic challenge. (2004)

A keratoacanthoma centrifugum marginatum (KACM) may pose a diagnostic and therapeutic challenge. Clinically and histologically, it may resemble mycobacterial or deep fungal infection or halogenoderma. Therapy can be challenging because the lesion can expand to a great size. We report on a patient with multiple lesions of KACM. The diagnostic difficulty and the therapeutic failure of imiquimod, intralesional methotrexate (MTX), and isotretinoin, as well as the therapeutic success of 5-fluorouracil (5-FU) cream, are discussed.
Production of Human or Humanized Antibodies in Mice (2012)

Mice are widely available laboratory animals that can easily be used for the production of antibodies against a broad range of antigens, using well-defined immunization protocols. Such an approach allows optimal in vivo affinity maturation of the humoral response. In addition, high-affinity antibodies arising in this context can readily be further characterized and produced as monoclonals after immortalizing and selecting specific antibody-producing cells through hybridoma derivation. Using such conventional strategies combined with mice that are either genetically engineered to carry humanized immunoglobulin (Ig) genes or engrafted with a human immune system, it is thus easy to obtain and immortalize clones that produce either fully human Ig or antibodies associating variable (V) domains with selected antigen specificities to customized human-like constant regions, with defined effector functions. In some instances, where there is a need for in vivo functional assays of a single antibody with a known specificity, it might be of interest to transiently express that gene in mice by in vivo gene transfer. This approach allows a rapid functional assay. More commonly, mice are used to obtain a diversified repertoire of antibody specificities after immunization by producing antibody molecules in the mouse B cell lineage from mouse strains with transgene Ig genes which are of human, humanized, or chimeric origin. After in vivo maturation of the immune response, this will lead to the secretion of antibodies with optimized antigen binding sites, associated to the desired human constant domains. This chapter focuses on two simple methods: (1) to obtain such humanized Ig mice and (2) to transiently express a human Ig gene in mice using hydrodynamics-based transfection.
Biomarkers for melanoma (2005)

Although recent studies have contributed greatly to the development of melanoma markers, it is anticipated that the application of gene expression profiling and proteomics techniques to melanocytic neoplasms will result in the identification of even more effective biomarkers for melanoma than those currently in clinical use.
Description of ultrashort pulse propagation in multimode optical fibers (2008)

The guided, single-mode propagation of ultrashort optical pulses is commonly described by a well studied and understood generalized nonlinear Schrödinger equation. Here we present and discuss an extended version for multimode optical fibers and waveguides including polarization effects, high-order dispersion, Kerr and Raman nonlinearities, self-steepening effects, as well as wavelength-dependent mode coupling and nonlinear coefficients. We then investigate the symmetry properties of the nonlinear coupling coefficients for the cases of step-index and circularly symmetric conventional fibers and for microstructured fibers with hexagonal symmetry. Finally, we study the computational complexity of the proposed algorithm.
P068 INVESTIGATION OF THE DISTRIBUTION AND ELIMINATION OF THE PEG COMPONENT OF CERTOLIZUMAB PEGOL IN RATS (2008)

Background: Certolizumab pegol is the first PEGylated Fc-free anti-tumour necrosis factor alpha (TNF) agent. The polyethylene glycol (PEG) component of certolizumab pegol comprises two 20 kDa chains of PEG attached to the Fab' via a single linker. The quantitative measurement of high molecular weight PEG has previously been difficult. Objective: To develop a method by which the tissue distribution and excretion of PEG in rats can be readily determined. Methods: PEG was measured in tissues, urine and faeces by proton nuclear magnetic resonance ( 1 H NMR) spectroscopy. Firstly, female Lewis rats were dosed at 100 mg/kg subcutaneously (sc) with either certolizumab pegol or an anti-rat TNF PEGylated Fab' (TN3). At six timepoints up to 84 days, various tissues (brain, mandibular and mesenteric lymph nodes, liver, spleen, kidneys, lungs, heart) were removed and assessed for the amount of PEG they contained. In a second 84-day study, urine and faeces were collected from rats in metabolism cages after one 400 mg/kg sc dose of certolizumab pegol. Results: PEG did not accumulate in any one specific organ. The distribution of the TN3 PEGylated Fab' was similar to certolizumab pegol, suggesting that TNF binding is not a major mediator of PEG distribution in tissues. Urine analyses showed the excretion was maximal on Day 6 and then declined in a first-order manner; by Day 84 the mean cumulative amount excreted was 65%. Using a first-order increase/decrease model, the total urinary excretion was 73% and the half-life was 23 days. PEG was also detected in faeces up to Day 42, with 18% of total excretion by this route. The total mean recovery was thus 91% of the administered dose. The molecular weight of the excreted PEG was estimated by SDS PAGE to be 40 kDa.
Cytokine detection by antibody-based proximity ligation (2004)

Efficient and precise detection techniques, along with extensive repertoires of specific binding reagents, will be needed to meet the challenges of proteome analyses. The recently established proximity ligation mechanism enables sensitive high-capacity protein measurements by converting the detection of specific proteins to the analysis of DNA sequences. Proximity probes containing oligonucleotide extensions are designed to bind pairwise to target proteins and to form amplifiable tag sequences by ligation when brought in proximity. In our previous report, both the ligatable arms and the protein binders were DNA molecules. We now generalize the method by providing simple and convenient protocols to convert any polyclonal antibodies or matched pair of monoclonal antibodies to proximity probe sets through the attachment of oligonucleotide sequences. Sufficient reagent for >100,000 proximity ligation assays can be prepared from 1 microg of antibody. The technique is applied to measure cytokines in a homogenous test format with femtomolar detection sensitivities in 1-microl samples, and we exemplify its utility in situations when only minute sample amounts are available.
Voice Response Systems Technology (1984)

Voice output technology has attained levels of surprising sophistication and quality at reasonable costs. Examined in this article are two methods of generating synthetic speech: phoneme and reconstructed voice systems. Applications, on both levels, are discussed. Accompanying the article are a glossary, directory, list of sources for further reading, as well as an introduction to IOCS, a leader in voice output systems.
Hydrogen Sensing and Sensitivity of Palladium-Decorated Single-Walled Carbon Nanotubes with Defects (2010)

Individual single-walled carbon nanotubes (SWCNTs) become sensitive to H2 gas when their surfaces are decorated with Pd metal, and previous reports measure typical chemoresistive increases to be approximately 2-fold. Here, thousand-fold increases in resistance are demonstrated in the specific case where a Pd cluster decorates a SWCNT sidewall defect site. Measurements on single SWCNTs, performed both before and after defect incorporation, prove that defects have extraordinary consequences on the chemoresistive response, especially in the case of SWCNTs with metallic band structure. Undecorated defects do not contribute to H2 chemosensitivity, indicating that this amplification is due to a specific but complex interdependence between a defect site’s electronic transmission and the chemistry of the defect−Pd−H2 system. Dosage experiments suggest a primary role is played by spillover of atomic H onto the defect site.
Antibodies against phosphatidylinositol and inositol monophosphate specifically inhibit tumour necrosis factor induction by malaria exoantigens. (1992)

The active component of the exoantigens of malarial parasites which stimulates macrophages to secrete tumour necrosis factor (TNF) has been shown to depend upon a phospholipid, the activity of which was blocked by phosphatidylinositol (PI) and inositol monophosphate (IMP) in competitive inhibition studies. Antisera made against the exoantigens of Plasmodium yoelii, which inhibited their induction of TNF, were found by an ELISA assay to contain antibody against several other phospholipids. However, the inhibitory antibody was removed specifically by adsorption with liposomes containing PI, but not other phospholipids. Furthermore, PI was the only phospholipid in non-liposomal form which induced the production of inhibitory antisera. Mice immunized with IMP, but not inositol, also produced inhibitory antisera. When incorporated into liposomes several other phospholipids did give rise to inhibitory antibodies but, in contrast to the antisera against parasite exoantigens, PI and IMP, the inhibitory activity was removed by adsorption with heterologous phospholipid liposomes, suggesting that it was directed against a common determinant, presumably the phosphate ester head group. Inhibitory antibodies in the antisera tested were predominantly IgM and titres were not increased after repeated injections. Antisera raised against PI, IMP or the cross-reacting phospholipid liposomes also inhibited TNF secretion by macrophages stimulated by exoantigens of the human parasites P. falciparum and P. vivax, but not by bacterial lipopolysaccharide. These findings confirm our conclusion that exoantigens from these different species contain phosphate bound to inositol in their TNF-inducing moiety.
Use of colicin e3 for biological containment of microorganisms (1996)

The genetic determinant of the lethal antibiotic colicin E3 was cloned under the control of a tightly regulated promoter in the absence of the gene for its cognate inhibitor. Combination of this killing cassette with a stringent regulatory element provided a substrate-dependent conditional suicide system that was exploited for the biological containment of a Pseudomonas putida strain. The lethality of a single gene copy and the distinct and universal cellular target of the antibiotic suggest colicin E3 as an ideal candidate for combination with other lethal functions to design highly efficient containment systems for microorganisms.
Quantitative IR spectrophotometry of peptide compounds in water (H2O) solutions. II. Amide absorption bands of polypeptides and fibrous proteins in α‐, β‐, and random coil conformations (1990)

Infrared spectra of poly(D,L-alanine), poly(L-glutamic acid), poly(L-lysine), silk fibroin, and tropomyosin have been registered for various conformations of the polypeptide chain. Assuming additivity of the main- and side-chain absorption, spectral parameters of amide I and II absorption bands corresponding to alpha-, beta-, and random coil conformations have been derived. The amide I band parameters for H2O and D2O have been compared.
Aggregation of Cartilage Proteoglycans (1974)

Abstract Viscosimetric and centrifugal analyses of nasal and tracheal proteoglycan preparations indicate that: a, the proteoglycan molecules from both cartilages have very similar physical properties (limiting viscosity numbers of 140 and 145 ml per g and s0 values of 25 and 20 S, respectively); b, about 80% of the proteoglycan molecules in each preparation can form aggregates; and c, the aggregates are much larger in nasal than in tracheal preparations (s0 values of 93 and 43 S, respectively). Hyaluronic acid is present at a concentration of 0.4 to 0.8% (w/w) in nasal proteoglycan aggregate preparations. Evidence is presented which suggests that the hyaluronic acid-proteoglycan interactions described by Hardingham and Muir ((1972) Biochim. Biophys. Acta 279, 401) are involved in aggregate formation and that the relative sizes of the aggregates are probably determined by the relative sizes of the hyaluronic acid molecules. Mild proteolysis of proteoglycan aggregates with papain removes the chondroitin sulfate and keratan sulfate from the aggregates while leaving about 25% of the total protein still bound to hyaluronic acid. This bound protein fraction was separated from the hyaluronic acid by chromatography on Sephadex G-200 with 4 m guanidine hydrochloride as the solvent. Polyacrylamide gel electrophoresis indicated that this fraction contains two proteins (molecular weights approximately 40,000 and 65,000) both of which are reduced to smaller peptide fragments when treated with β-mercaptoethanol. The two proteins retain their ability to bind to hyaluronic acid. The interactions between the proteins and the hyaluronic acid in the intact aggregates partially protect the hyaluronic acid from digestion with bacterial chondroitinase.
Gametic Imprinting in Mammals (1995)

Embryonic development in mammals is distinct from that in other vertebrates because it depends on a small number of imprinted genes that are specially expressed from either the maternal or paternal genome. Why mammals are uniquely dependent on sexual reproduction and how this dependency is dictated at a molecular level are questions that have been intensively investigated during the past 2 years. Gene inactivation experiments have confirmed predictions that imprinted genes regulate embryonic and placental growth and that DNA methylation is part of the imprinting mechanism. Despite these considerable achievements, the reason why imprinted hemizygosity is used as a mechanism to regulate the intrauterine growth of mammalian embryos remains elusive.
Flow Cytometric Analysis of Doxorubicin Accumulation in Cells From Human and Rodent Cell Lines (1989)

The correlation between intracellular accumulation of doxorubicin (DOX) and drug cytotoxicity was studied in cells from seven cell lines of rodent and human origin. We used three Chinese hamster ovary cell lines (AuxB1, CHRC5, and UV20), two murine tumor cell lines (KHT-LP1 and EMT6/Ro), and two human tumor cell lines (MGH-U1 and DLD-1). Intracellular DOX was measured by its fluorescence intensity with flow cytometry, and drug cytotoxicity was quantified with clonogenic assays. When data for all of the cell lines were combined, cell killing was correlated with the intracellular concentration of DOX (r = -.88). For the cell line AuxB1 and its DOX-resistant subline CHRC5, in which cells express high levels of P-glycoprotein, the relationship between cell survival and the intracellular concentration of DOX was stronger than that for the other cell lines. These results suggest that differences in intracellular accumulation of DOX account for much of the heterogeneity in response to the drug in cells from different cell lines, although additional mechanisms also contribute to variation in drug sensitivity. Flow cytometric analysis of intracellular DOX fluorescence is a simple assay that should be tested in cells from human tumors as a possible predictor of tumor response. For a given cell line, this technique also provides a rapid way to monitor the development of drug resistance after multiple courses of chemotherapy.
Bone Morphogenetic Protein 2 and Retinoic Acid Accelerate in Vivo Bone Formation, Osteoclast Recruitment, and Bone Turnover (2005)

Reconstruction of craniofacial defects presents a substantial biomedical burden, and requires complex surgery. Interestingly, children after age 2 years and adults are unable to heal large skull defects. This nonhealing paradigm provides an excellent model system for craniofacial skeletal tissueengineering strategies. Previous studies have documented the in vivo osteogenic potential of adipose-derived stromal (ADS) cells and bone marrow-derived stromal (BMS) cells. This study investigates the ability to accelerate in vivo osteogenesis on ex vivo recombinant human bone morphogenetic protein 2 (BMP-2) and retinoic acid stimulation. Mouse osteoblasts, ADS cells, and BMS cells were seeded onto apatite-coated PLGA scaffolds, stimulated with rhBMP-2 and retinoic acid ex vivo for 4 weeks, and subsequently implanted into critically sized (4 mm) calvarial defects. Samples were harvested after 2, 4, 8, and 12 weeks. Areas of complete bony bridging were noted as early as 2 weeks in vivo; however, osteoclasts were attracted to the scaffold as identified by calcitonin receptor staining and tartrate-resistant acid phosphatase activity staining. Although the optimal method of in vitro osteogenic priming for mesenchymal cells remains unknown, these results provide evidence that BMP-2 and retinoic acid stimulation of multipotent cells ex vivo can subsequently induce significant quantities of bone formation within a short time period in vivo.