gebhart/patrepeval huggingface dataset:
Construction, Affinity Maturation, and Biological Characterization of an Anti-tumor-associated Glycoprotein-72 Humanized Antibody (2006)

The tumor-associated glycoprotein (TAG)-72 is expressed in the majority of human adenocarcinomas but is rarely expressed in most normal tissues, which makes it a potential target for the diagnosis and therapy of a variety of human cancers. Here we describe the construction, affinity maturation, and biological characterization of an anti-TAG-72 humanized antibody with minimum potential immunogenicity. The humanized antibody was constructed by grafting only the specificity-determining residues (SDRs) within the complementarity-determining regions (CDRs) onto homologous human immunoglobulin germ line segments while retaining two mouse heavy chain framework residues that support the conformation of the CDRs. The resulting humanized antibody (AKA) showed only about 2-fold lower affinity compared with the original murine monoclonal antibody CC49 and 27-fold lower reactivity to patient serum compared with the humanized antibody HuCC49 that was constructed by CDR grafting. The affinity of AKA was improved by random mutagenesis of the heavy chain CDR3 (HCDR3). The highest affinity variant (3E8) showed 22-fold higher affinity compared with AKA and retained the original epitope specificity. Mutational analysis of the HCDR3 residues revealed that the replacement of Asn(97) by isoleucine or valine was critical for the affinity maturation. The 3E8 labeled with (125)I or (131)I showed efficient tumor targeting or therapeutic effects, respectively, in athymic mice with human colon carcinoma xenografts, suggesting that 3E8 may be beneficial for the diagnosis and therapy of tumors expressing TAG-72.
Characterization of specific high affinity receptors for human tumor necrosis factor on mouse fibroblasts. (1985)

Mouse L-929 fibroblasts, an established line of cells, are very sensitive to lysis by human lymphotoxin (hTNF-beta). Specific binding of a highly purified preparation of hTNF-beta to these cells was examined. Recombinant DNA-derived hTNF-beta was radiolabeled with [3H]propionyl succinimidate at the lysine residues of the molecule to a specific activity of 200 microCi/nmol of protein. [3H]hTNF-beta was purified by high performance gel permeation chromatography and the major fraction was found to be monomeric by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The labeled hTNF-beta was fully active in causing lysis of L-929 fibroblasts and bound specifically to high affinity binding sites on these cells. Scatchard analysis of the binding data revealed the presence of a single class of high affinity receptors with an apparent Kd of 6.7 X 10(-11) M and a capacity of 3200 binding sites/cell. Unlabeled recombinant DNA-derived hTNF-beta was found to be approximately 5-fold more effective competitive inhibitor of binding than the natural hTNF-beta. The binding of hTNF-beta to these mouse fibroblasts was also correlated with the ultimate cell lysis. Neutralizing polyclonal antibodies to hTNF-beta efficiently inhibited the binding of [3H]hTNF-beta to the cells. We conclude that the specific high affinity binding site is the receptor for hTNF-beta and may be involved in lysis of cells.
IL-1 receptor antagonist ameliorates inflammasome-dependent inflammation in murine and human cystic fibrosis (2016)

Dysregulated inflammasome activation contributes to respiratory infections and pathologic airway inflammation. Through basic and translational approaches involving murine models and human genetic epidemiology, we show here the importance of the different inflammasomes in regulating inflammatory responses in mice and humans with cystic fibrosis (CF), a life-threatening disorder of the lungs and digestive system. While both contributing to pathogen clearance, NLRP3 more than NLRC4 contributes to deleterious inflammatory responses in CF and correlates with defective NLRC4-dependent IL-1Ra production. Disease susceptibility in mice and microbial colonization in humans occurs in conditions of genetic deficiency of NLRC4 or IL-1Ra and can be rescued by administration of the recombinant IL-1Ra, anakinra. These results indicate that pathogenic NLRP3 activity in CF could be negatively regulated by IL-1Ra and provide a proof-of-concept evidence that inflammasomes are potential targets to limit the pathological consequences of microbial colonization in CF.
Generation of software tools from processor descriptions for hardware/software codesign (1997)

An experimental set of tools that generate instruction set simulators,assemblers, and disassemblers from a single description wasdeveloped to test if retargetable development tools would work forcommercial DSP processors and microprocessors. The processorinstruction set was described using a language called nML. TheTMS320C50 DSP processor and the ARM7 microprocessor weremodeled in nML. The resulting instruction set models executeabout 25,000 instructions per second, and compiled instruction setsimulation models execute about 150,000 instructions per second.The viability of this approach and the deficiencies of nML are discussed.
NMR‐based determination of the binding epitope and conformational analysis of MUC‐1 glycopeptides and peptides bound to the breast cancer‐selective monoclonal antibody SM3 (2002)

Mucin glycoproteins on breast cancer cells carry shortened carbohydrate chains. These partially deglycosylated mucin 1 (MUC-1) structures are recognized by the monoclonal antibody SM3, which is being tested for its diagnostic utility. We used NMR spectroscopy to analyze the binding mode and the binding epitope of peptide and glycopeptide antigens to the SM3 antibody. The pentapeptide PDTRP and the glycopentapeptide PDT(O-alpha-D-GalNAc)RP are known ligands of the monoclonal antibody. The 3D structures of the ligands in the bound conformation were determined by analyzing trNOESY build-up rates. The peptide was found to adopt an extended conformation that fits into the binding pocket of the antibody. The binding epitopes of the ligands were determined by saturation transfer difference (STD) NMR spectroscopy. The peptide's epitope is predominantly located in the N-terminal PDT segment whereas the C-terminal RP segment has fewer interactions with the protein. In contrast, the glycopeptide is interacting with SM3 utilizing all its amino acids. Pro1 shows the strongest binding effect that slightly decays towards Pro5. The GalNAc residue interacts mainly via the N-acetyl residue while the other protons show less interactions similar to that of Pro5. The glycopeptide in the bound state also has an extended conformation of the peptide with the carbohydrate oriented towards the N-terminus. Docking studies showed that peptide and glycopeptide fit the binding pocket of the mAb SM3 very well.
Melanoma Immunotherapy (2010)

Melanoma immunotherapy has been an area of intense research for decades, and this work is now yielding more tangible results for patients. Work has focused on 4 main areas: cytokine therapy, administration of immune-modulating antibodies, adoptive T-cell therapy, and vaccines. Cytokine therapy is an established treatment for advanced melanoma, and immune-modulating antibodies have recently emerged as an exciting new area of drug development with efficacy now established in a phase III trial. Adoptive T-cell therapy provides the proof of principle that T cells can attack and eliminate tumors. It has been challenging, however, to adapt this treatment for widespread use. Vaccines have generally yielded poor results, but intratumor pathogen-based strategies have shown encouraging results in recent trials, perhaps due to stronger immune stimulation. A review of the field of melanoma immunotherapy is provided here, with emphasis on those agents that have reached clinical testing. Novel strategies to induce the immune system to attack melanomas are reviewed. In the future, it is envisioned that immunotherapy will have further application in combination with cytotoxic and targeted therapies.
Inhibition of Development of Murine Melanoma Lung Metastases by Systemic Administration of Recombinant Platelet Factor 4 (1995)

These results support the testing of rPF4 as an angiostatic agent in the treatment of metastatic tumors.
Hybrid adaptive-optics visual simulator (2010)

We have developed a hybrid adaptive-optics visual simulator (HAOVS), combining two different phase-manipulation technologies: an optically addressed liquid-crystal phase modulator, relatively slow but capable of producing abrupt or discontinuous phase profiles; and a membrane deformable mirror, restricted to smooth profiles but with a temporal response allowing compensation of the eye's aberration fluctuations. As proof of concept, a phase element structured as discontinuous radial sectors was objectively tested as a function of defocus, and a correction loop was closed in a real eye. To further illustrate the capabilities of the device for visual simulation, we recorded extended images of different stimuli through the system by means of an external camera replacing the subject's eye. The HAOVS is specially intended as a tool for developing new ophthalmic optics elements, where it opens the possibility to explore designs with irregularities and/or discontinuities.
The biosynthesis and functionality of the cell-wall of lactic acid bacteria. (1999)

The cell wall of lactic acid bacteria has the typical gram-positive structure made of a thick, multilayered peptidoglycan sacculus decorated with proteins, teichoic acids and polysaccharides, and surrounded in some species by an outer shell of proteins packed in a paracrystalline layer (S-layer). Specific biochemical or genetic data on the biosynthesis pathways of the cell wall constituents are scarce in lactic acid bacteria, but together with genomics information they indicate close similarities with those described in Escherichia coli and Bacillus subtilis, with one notable exception regarding the peptidoglycan precursor. In several species or strains of enterococci and lactobacilli, the terminal D-alanine residue of the muramyl pentapeptide is replaced by D-lactate or D-serine, which entails resistance to the glycopeptide antibiotic vancomycin. Diverse physiological functions may be assigned to the cell wall, which contribute to the technological and health-related attributes of lactic acid bacteria. For instance, phage receptor activity relates to the presence of specific substituents on teichoic acids and polysaccharides; resistance to stress (UV radiation, acidic pH) depends on genes involved in peptidoglycan and teichoic acid biosynthesis; autolysis is controlled by the degree of esterification of teichoic acids with D-alanine; mucosal immunostimulation may result from interactions between epithelial cells and peptidoglycan or teichoic acids.
Secondary structure of human leukocyte interferon from Raman spectroscopy. (1985)

Raman spectra were taken of human alpha (leukocyte) interferon subtype A (HuIFN-alpha A) purified from extracts of transformed Escherichia coli. Quantitative analysis of the conformationally sensitive amide I band indicates that IFN (interferon)-alpha A is 75 +/- 5% helical and 7 +/- 4% beta-strand. An independent analysis of the amide III spectrum indicates 71 +/- 5% helix and 10 +/- 6% beta-strand. These results differ with a recently proposed three-dimensional model based on secondary structure predictions derived from sequence and with circular dichroism measurements. The Raman spectrum of IFN-alpha A is compared with the spectra of several other helical proteins: hemerythrin, intestinal calcium-binding protein, melittin, and insulin.
Multiple sclerosis is prevalent in the zoroastrians (Parsis) of India (1990)

Using Schumacher's classification, we determined the prevalence rate of clinically definite multiple sclerosis (MS) in the distinct but tiny Zoroastrian (largely Parsi) community in the adjacent cities of Bombay (latitude, 18.55 degrees) and Poona (Pune). On prevalence day, 16 clinically definite cases of MS were counted, 14 in Bombay and 2 in Poona, from a total Zoroastrian population of 50,053 and 3,399, respectively. The crude prevalence ratio was 26 per 100,000 for Bombay and 58 per 100,000 for Poona. The age-adjusted prevalence ratio for Bombay was 24 per 100,000, with 95% confidence limits of 13.1 to 40.3. These are much higher than the low rates believed to be prevalent in India, and are comparable with those found in parts of Europe and the United States.
Bisphosphonate-associated osteonecrosis of the jaw: a literature review and clinical practice guidelines. (2006)

Clinical guidelines for prevention and management have recently been published. Dental hygienists have a major role in patient education related to awareness of the potential drug effect and to preventive oral health education.
Isolation of crt mutants constitutive for transcription of the DNA damage inducible gene RNR3 in Saccharomyces cerevisiae. (1992)

Ribonucleotide reductase is an essential enzyme that catalyzes the rate limiting step for production of the deoxyribonucleotides required for DNA synthesis. It is encoded by three genes, RNR1, RNR2 and RNR3, each of which is inducible by agents that damage DNA or block DNA replication. To probe the signaling pathway mediating this DNA damage response, we have designed a general selection system for isolating spontaneous trans-acting mutations that alter RNR3 expression using a chromosomal RNR3-URA3 transcriptional fusion and an RNR3-lacZ reporter plasmid. Using this system, we have isolated 202 independent trans-acting crt (constitutive RNR3 transcription) mutants that express high levels of RNR3 in the absence of DNA damaging agents. Of these, 200 are recessive and fall into 9 complementation groups. In some crt groups, the expression of RNR1 and RNR2 are also elevated, suggesting that all three RNR genes share a common regulatory pathway. Mutations in most CRT genes confer additional phenotypes, among these are clumpiness, hydroxyurea sensitivity, temperature sensitivity and slow growth. Five of the CRT genes have been identified as previously cloned genes; CRT4 is TUP1, CRT5 is POL1/CDC17, CRT6 is RNR2, CRT7 is RNR1, and CRT8 is SSN6. crt6-68 and crt7-240 are the first ts alleles of RNR2 and RNR1, respectively, and arrest with a large budded, cdc terminal phenotype at the nonpermissive temperature. The isolation of crt5-262, an additional cdc allele of POL1/CDC17, suggests for the first time that directly blocking DNA replication can provide a signal to induce the DNA damage response. crt2 mutants show a defect in basal level expression of RNR1-lacZ reporter constructs. These are the first mutants isolated in yeast that alter the regulation of DNA damage inducible genes and the identification of their functions sheds light on the DNA damage sensory network.
131I-chTNT-1/B mAb: tumour necrosis therapy for malignant astrocytic glioma (2006)

Treatment of malignant glioma is therapeutically challenging. Despite improvements in neurosurgery, radiotherapy and chemotherapy, few patients diagnosed with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) (WHO grades 3 and 4, respectively) will live beyond 2 years. Poor survival is due to the highly invasive nature and protected location of these tumours. Most malignant gliomas cannot be completely resected or irradiated due to their ability to infiltrate diffusely into normal brain tissue. Brain tissue is protected from the systemic circulation via the blood-brain barrier (BBB), which impedes entry of water-soluble chemotherapeutic agents into the tumour at therapeutic concentrations. (131)I-chTNT-1/B mAb (Cotara) employs an innovative strategy to treat the invasive portion of the tumour and the core lesion. (131)I-chTNT-1/B mAb is a genetically engineered, radiolabelled, chimeric monoclonal antibody specific for a universal intracellular antigen (i.e., DNA/histone H1 complex) exposed in the necrotic core of malignant gliomas. This antigen provides an abundant, insoluble, non-diffusible anchor for the mAb. Once localised to necrotic regions of the tumour, (131)I-chTNT-1/B mAb delivers a cytotoxic dose of (131)I radiation to the core lesion. (131)I-chTNT-1/B mAb is delivered via convection-enhanced delivery in order to maximise coverage to the tumour and the invasive front of the glial tumour. The clinical experience to date with (131)I-chTNT-1/B mAb is presented.
Diode-pumped selfstarting passively modelocked neodymium-doped fibre laser (1993)

An Nd3+-fibre laser pumped by a single stripe laser diode has been passively modelocked using a semiconductor saturable absorber/end mirror as the mode-locking element. A 6 cm length of heavily doped fibre was used to minimise the effects of positive group velocity dispersion, and stable modelocking with pulses of 4 ps duration was obtained at the laser wavelength of 1053 nm.
Real-time in vivo imaging by high-speed spectral opticalcoherence tomography (2003)

An improved spectral optical coherence tomography technique is used to obtain cross-sectional ophthalmic images at an exposure time of 64 micros per A-scan. This method allows real-time images as well as static tomograms to be recorded in vivo.
Formation Fracturing with Foam (1974)

American Institute of Mining, Metallurgical, and Petroleum Engineers, Inc. Abstract Over sixty wells have been treated with hydraulic fracturing techniques with foam as the fracturing fluid. These foams contained as much as 95% gaseous phase; most treatments used foams with gas contents in the 65% to 85% range. Foam has several desirable properties for use as a fracturing properties for use as a fracturing fluid: high sand-carrying and sand-suspending capability, low fluid loss, low hydrostatic head, low pressure drops due to friction, quick fluid recovery, low formation damage, and no reduction of fracture conductivity due to fluid ingredients. Most applications of foam as a fracture fluid have been in low permeability gas reservoirs. Several permeability gas reservoirs. Several oil reservoirs have also been successfully treated, however. Cost of the treatment is approximately the same or slightly less than a treatment with conventional fluids of comparable volume and rate. Introduction Foams used as fracturing fluids are dispersions of gas, generally nitrogen, in a liquid, generally water, with a small amount of surfactant foaming agent added. Volumetric gas content (referred to as foam quality) is generally between 65% and 85%. Qualities as high as 95% have been used. Surfactant content is commonly 0.5% to 1% of liquid volume. Stability is increased by addition of more surfactant, whether foaming agent or gelling agent. Such foams are homogeneous mixtures with a narrow range of bubble size, mean bubble size less than 200 microns, and are stable for periods of several hours. During a fracture-treatment operation, the liquid phase passes through a blender and is mixed with sand and then passes through the injection pump which raises the pressure to required injection pressure. Surfactant foaming agent is added downstream of the injection pump and gas is introduced with a tee or lateral downstream from the surfactant. Foam is generated at the point of gas introduction (see Figure 1). The gas is transported to the site and stored in cryogenic tanks and added to the injection stream at line pressure. The foams used for fracturing are similar to those described previously by several investigators.
Ultrasensitive Stain for Proteins in Polyacrylamide Gels Shows Regional Variation in Cerebrospinal Fluid Proteins (1981)

A new silver stain for electrophoretically separated polypeptides can be rapidly and easily used and can detect as little as 0.01 nanogram of protein per square millimeter. When employed with two-dimensional electrophoresis, it should permit qualitative and quantitative characterization of protein distributions in body fluids and tissues. It has been used to demonstrate regional variations in cerebrospinal fluid proteins.
Overexpression of EGFR and c‐erbB2 causes enhanced cell migration in human breast cancer cells and NIH3T3 fibroblasts (1998)

Overexpression of EGFR and c-erbB2 frequently occurs in human breast cancers, correlating with poor prognosis. Here we show that overexpression of EGFR and c-erbB2 in cell lines increases cell migration, an important step in metastasis formation. The effect of EGFR on migration is dependent on the addition of EGF to the cells. In contrast, c-erbB2 seems to act independently of its ligand in these assays. Overexpression of this receptor is sufficient to induce cell migration. In addition, we investigated the involvement of a number of signal transduction pathways known to be activated by the EGFR. We found that inactivation of MAPKK results in a decreased migration, while inactivation of PI3K increases migration.
Accumulation of rifampicin by Escherichia coli and Staphylococcus aureus (1998)

A centrifugation method was used to investigate the accumulation of 14C-rifampicin by Staphylococcus aureus and Escherichia coli, and to characterize the mechanism of rifampicin transport into S. aureus. For both species, drug accumulation was rapid with the steady-state concentration (SSC) reached within 40 s of drug exposure. Rifampicin accumulation by S. aureus was temperature and pH dependent; the lower the experimental temperature and the lower the experimental pH, the lower was the concentration of rifampicin accumulated. Accumulation was unaffected by the presence of inhibitors of antibiotic efflux, carbonyl cyanide m-chlorophenylhydrazone (CCCP), dinitrophenol (DNP), or reserpine. Exposure to increasing concentrations of rifampicin suggested that the accumulation process was saturable above a rifampicin concentration of 0.2 mg/L. Michaelis-Menten kinetics gave an apparent Km and Vmax for rifampicin, calculated from a Lineweaver-Burk plot, of 0.05 mg/L (0.06 microM) and 3.8 ng rifampicin per second, respectively. However, calculations suggest that these values reflect those for binding of rifampicin to its target, RNA polymerase.
Immunologic Response to Early and Routine DTP Immunization in Infants (1984)

The effect of early immunization, prior to discharge from the newborn nursery, on subsequent immunity as determined by enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig) M and IgG antibody titers to filamentous hemagglutinin and lymphocytosis-promoting toxin (LPT) of Bordetella pertussis and by standard pertussis agglutinin titers was investigated. Eighteen infants received routine diphtheria-tetanus-pertussis (DTP) immunization at 2, 4, and 6 months of age; 17 other infants received routine immunization and an additional DTP immunization in the newborn nursery. Antibody was determined on samples of cord blood and whole blood obtained at 4, 6, and 9 months of age. IgM anti-filamentus hemagglutinin was significantly higher at 4 and 6 months of age in the group that received early immunization (P less than .05). There was no significant difference in IgM anti-LPT, IgG anti-filamentus hemagglutinin, IgG anti-LPT, or pertussis agglutinin antibodies. Six control infants had high cord IgG anti-LPT titers. These six infants had significantly lower antibody titers to LPT at 6 and 9 months of age when compared with control with control infants with lower cord titers. Thirteen infants in the early immunization group with lower cord IgG anti-LPT titers achieved significantly lower titers at 9 months of age than the 12 comparable infants in the control group.