gebhart/patrepeval huggingface dataset:
A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors (2007)

An array of cell-surface antigens expressed by human cancers have been identified as targets for antibody-based therapies. The great majority of these antibodies do not have specificity for cancer but recognize antigens expressed on a range of normal cell types (differentiation antigens). Over the past two decades, our group has analyzed thousands of mouse monoclonal antibodies for cancer specificity and identified a battery of antibodies with limited representation on normal human cells. The most tumor-specific of these antibodies is 806, an antibody that detects a unique epitope on the epidermal growth factor receptor (EGFR) that is exposed only on overexpressed, mutant, or ligand-activated forms of the receptor in cancer. In vitro immunohistochemical specificity analysis shows little or no detectable 806 reactivity with normal tissues, even those with high levels of wild-type (wt)EGFR expression. Preclinical studies have demonstrated that 806 specifically targets a subset of EGFR expressed on tumor cells, and has significant anti-tumor effects on human tumor xenografts, primarily through abrogation of signaling pathways. The present clinical study was designed to examine the in vivo specificity of a chimeric form of mAb 806 (ch806) in a tumor targeting/biodistribution/pharmacokinetic analysis in patients with diverse tumor types. ch806 showed excellent targeting of tumor sites in all patients, no evidence of normal tissue uptake, and no significant toxicity. These in vitro and in vivo characteristics of ch806 distinguish it from all other antibodies targeting EGFR.
Carrageenin-Induced Edema in Hind Paw of the Rat as an Assay for Antiinflammatory Drugs (1962)

A method is presented for measuring the edema induced by injection of 0.05 ml of 1% solution of carrageenin, an extract of Chondrus, into the plantar tissues of the hind paw of the rat. Peak edema develops within the first 3 to 4 hours, and is inhibited by pretreatment of the animals by single oral doses of antiinflammatory agents, steroid or non-steroid. Log dose responses to drugs are linear and parallel, and yield potency ratios with relatively narrow confidence limits. The potency ratios obtained for aspirin, phenylbutazone and hydrocortisone are fairly close to the ratios of their respective daily doses in the treatment of rheumatic disease. A potent antihistaminic-antiserotonin compound, cyproheptadine, is without effect on carrageenin-induced edema.
Introduction to Adaptive Arrays (2011)

This second edition is an extensive modernization of the bestselling introduction to the subject of adaptive array sensor systems. With the number of applications of adaptive array sensor systems growing each year, this look at the principles and fundamental techniques that are critical to these systems is more important than ever before. Introduction to Adaptive Arrays, 2nd Edition is organized as a tutorial, taking the reader by the hand and leading them through the maze of jargon that often surrounds this highly technical subject. It is easy to read and easy to follow, as fundamental concepts are introduced with examples before more current developments and techniques are introduced. Problems at the end of each chapter serve both instructors and professional readers by illustrating and extending the material presented in the text. Both students and practicing engineers will easily gain familiarity with the modern contribution that adaptive arrays have to offer practical signal reception systems.
Heat Sterilization of Glucose-Containing Fluids for Peritoneal Dialysis: Biological Consequences of Chemical Alterations (1995)

G lucose solutions used for medical purposes are sterile. Sterilization is commonly performed through the addition of energy , either in the form of radiation or heat. It has been known for many years that such a treatment leads to derangement and breakdown of the glucose molecules (1,2). The degree of degradation, however, depends on several factors other than the mode of sterilization, such as storage time, pH, light, glucose concentration, catalyzing substances, and temperature. Reports in the past have pointed out that glucose degradation products are toxic to different cell species. One of the first reports concerning this was published more than lOO years ago. The paper published in 1887 inAnnales de l'Institute Pasteur by E. Roux demonstrated the killing of spores due to the carbohydrate fraction of a medium exposed to sunlight (3). In 1935 it was demonstrated that 20 different carbohydrate (including glucose) solutions exposed to ultraviolet radiation inhibited the growth of bacteria ( 4). Since then, many other reports have described toxicity for microorganisms (5-7). Later, side effects due to glucose degradation products were observed on plant cells (8) as well as mammalian cells (9). It has also been shown that the degradation products can cause chromosomal breaks in human lymphocytes (10). For many years the interest in glucose degradation has focused mainly on safety in food production, cell culture media, and fluids for intravenous injection. In spite of the fact that a patient on peritoneal dialysis is exposed to around 3000 L of fluid every year, very little attention to date has been paid to glucose degradation products in heatsterilized peritoneal dialysis fluids.
Low-Dose Continuous Infusion 5-Fluorouracil and Cisplatin (1989)

A study was performed to evaluate the combination of low-dose continuous infusion 5-fluorouracil (LDCI-FU) (300 mg/m2 daily for 28 days) and cisplatin (20 mg/m2 days 1-5 and 24-28). Patients were treated for 28 days with a subsequent 14-day rest period. A total of 24 patients were entered on the study and were evaluable for response and toxicity. All patients were previously untreated, with a median age of 61.5 years and median performance status of 70% (Karnofsky). Bidimensional measurable disease was required. Complete responses were noted in 2 of 24 (8%) patients lasting 8+ and 9 months. Partial responses were observed in 8 of 24 (33%), with a median duration of response of 6 months. Median survival for the 24 patients was 9+ months. Toxicities included nausea and vomiting (25%), hand-foot syndrome (21%), diarrhea (4%), myelosuppression (21%), neurotoxicity (13%), gastric ulceration (13%), mucositis (17%), nephrotoxicity (4%), and subclavian vein thrombosis (21%). This combination demonstrated antineoplastic activity; however, its efficacy parallels other trials utilizing both single agent 5-fluorouracil (5-FU) and different variations of the 5-FU/cisplatin in combination. The impact of this combination on survival and comparison to other regimens requires a randomized trial.
Butterfly-Plant Coevolution: Has Passiflora adenopoda Won the Selectional Race with Heliconiine Butterflies? (1971)

Hooklike trichomes of Passiflora adenopoda provide a specific, effectively absolute defense against heliconiine butterfly larvae, a major class of Passiflora herbivores. It is suggested that since mechanical defenses are usually more selective in their action against herbivores, they usually are evolved by a plant only after it has accumulated a series of chemical defenses.
P2X7 Blockade Attenuates Murine Lupus Nephritis by Inhibiting Activation of the NLRP3/ASC/Caspase 1 Pathway (2013)

Activation of the P2X7 signaling pathway accelerates murine LN by activating the NLRP3/ASC/caspase 1 inflammasome, resulting in increased IL-1β production and enhanced Th17 cell polarization. Thus, targeting of the P2X7 /NLRP3 pathway should be considered as a novel therapeutic strategy in patients with lupus.
Epitope mapping of recombinant HeLa SmB and B' peptides obtained by the polymerase chain reaction. (1990)

SmB and SmB' are the major antigenic proteins contained within small nuclear RNP particles that are recognized by both human SLE and MRL mouse anti-Sm sera. We amplified cDNA obtained from HeLa cells by using the polymerase chain reaction and identified two clones, U2 and L13, that encode SmB and SmB', respectively. The nucleotide sequences of these two clones were identical except for the insertion of a 145-bp sequence in U2 that contained an early in frame termination codon and a potential 3' consensus splice site. The predicted amino acid sequences of HeLa SmB and B' proteins were therefore identical except for the COOH terminal 2 (U2) and 11 (L13) amino acids. U2, L13, and four subclones of U2 (F-B, B-R, F-X, and X-B) were ligated to pATH vectors and expressed as trpE fusion proteins. Epitope mapping with 12 human SLE and 12 MRL/lpr mouse anti-SmB/B' sera revealed that antibodies directed against the X-B peptide accounted for most (65.5 +/- 15.4 and 63.2 +/- 25.3%), B-R intermediate levels (51.5 +/- 30.8 and 18 +/- 19.6%), and F-X none of the anti-SmB activity in human and mouse sera, respectively. Ten human and two mouse sera contained antibodies that cross-reacted with epitopes located within the proline-rich, COOH-terminal, 27-residue peptide encoded by B-R and the NH2-proximal F-B peptide. These observations suggest that a) the polymerase chain reaction is a powerful ancillary method to synthesize autoantigens, b) SmB and B' in HeLa cells are derived from alternative splicing of a common RNA transcript, and c) both SLE and MRL anti-SmB/B' sera recognize multiple epitopes (some shared and some unique) on these proteins.
Locality-sensitive binary codes from shift-invariant kernels (2009)

This paper addresses the problem of designing binary codes for high-dimensional data such that vectors that are similar in the original space map to similar bi-nary strings. We introduce a simple distribution-free encoding scheme based on random projections, such that the expected Hamming distance between the bi-nary codes of two vectors is related to the value of a shift-invariant kernel (e.g., a Gaussian kernel) between the vectors. We present a full theoretical analysis of the convergence properties of the proposed scheme, and report favorable experimental performance as compared to a recent state-of-the-art method, spectral hashing. 1
Identification of Common Ligand Binding Determinants of the Insulin and Insulin-like Growth Factor 1 Receptors (1997)

Insulin and insulin-like growth factor 1 (IGF-1) are peptides that share nearly 50% sequence homology. However, although their cognate receptors also exhibit significant overall sequence homology, the affinity of each peptide for the non-cognate receptor is 2-3 orders of magnitude lower than for the cognate receptor. The molecular basis for this discrimination is unclear, as are the molecular mechanisms underlying ligand binding. We have recently identified a major ligand binding site of the insulin receptor by alanine scannning mutagenesis. These studies revealed that a number of amino acids critical for insulin binding are conserved in the IGF-1 receptor, suggesting that they may play a role in ligand binding. We therefore performed alanine mutagenesis of these amino acids to determine whether this is the case. cDNAs encoding alanine-substituted secreted recombinant IGF-1 receptors were expressed in 293 EBNA cells, and the ligand binding properties of the expressed proteins were evaluated. Mutation of Phe701 resulted in a receptor with undetectable IGF-1 binding; alanine substitution of the corresponding amino acid of the insulin receptor, Phe714, produces a 140-fold reduction in affinity for insulin. Mutation of Asp8, Asn11, Phe58, Phe692, Glu693, His697, and Asn698 produces a 3.5-6-fold reduction in affinity for IGF-1. In contrast, alanine mutation of the corresponding amino acids of the insulin receptor with the exception of Asp12 produces reductions in affinity that are 50-fold or greater. The affinity of insulin for these mutants relative to wild type receptor was similar to that of their relative affinity for IGF-1 with two exceptions; the IC50 values for insulin binding to the mutants of Arg10, which has normal affinity for IGF-1, and His697, which has a 6-fold reduction in affinity for IGF-1, were both at least 2 orders of magnitude greater than for wild type receptor. The Kd values for insulin of the corresponding alanine mutants of the insulin receptor, Arg14 and His710, are 2-3 orders of magnitude greater than for wild type receptor. However, in contrast, the relative affinity of des(25-30)[PheB25 alpha-carboxamide]insulin for these IGF-1 receptor mutants is reduced only 4- and 50-fold, respectively.
Absorption enhancement in silicon-on-insulator waveguides using metal island films (1996)

We report the degree to which the resonances associated with metal island films can be used to enhance the sensitivity of very thin semiconductor photodetectors. The island films can couple incident light into the waveguide modes of the detector, resulting in increased absorption. To characterize the coupling, silver-, gold-, and copper-island layers were formed on the surface of a thin-film photodetector fabricated in the 0.16 μm thick silicon layer of a silicon-on-insulator (SOI) wafer. The copper islands gave the best result, producing more than an order of magnitude enhancement in the photocurrent for light of wavelength 800 nm. The enhancements appear to be due primarily to coupling between the metal island resonances and the waveguide modes supported by the SOI structure.
Caveolin-1 and mitochondrial SOD2 (MnSOD) function as tumor suppressors in the stromal microenvironment (2011)

We have recently proposed a new model for understanding tumor metabolism, termed: "The Autophagic Tumor Stroma Model of Cancer Metabolism". In this new paradigm, catabolism (autophagy) in the tumor stroma fuels the anabolic growth of aggressive cancer cells. Mechanistically, tumor cells induce autophagy in adjacent cancer-associated fibroblasts via the loss of caveolin-1 (Cav-1), which is sufficient to promote oxidative stress in stromal fibroblasts. To further test this hypothesis, here we created human Cav-1 deficient immortalized fibroblasts using a targeted sh-RNA knock-down approach. Relative to control fibroblasts, Cav-1 deficient fibroblasts dramatically promoted tumor growth in xenograft assays employing an aggressive human breast cancer cell line, namely MDA-MB-231 cells. Co-injection of Cav-1 deficient fibroblasts, with MDA-MB-231 cells, increased both tumor mass and tumor volume by ~4-fold. Immuno-staining with CD31 indicated that this paracrine tumor promoting effect was clearly independent of angiogenesis. Mechanistically, proteomic analysis of these human Cav-1 deficient fibroblasts identified > 40 protein biomarkers that were upregulated, most of which were associated with i) myofibroblast differentiation, or ii) oxidative stress/hypoxia. In direct support of these findings, the tumor promoting effects of Cav-1 deficient fibroblasts could be functionally suppressed (nearly 2-fold) by the recombinant over-expression of SOD2 (superoxide dismutase 2), a known mitochondrial enzyme that de-activates superoxide, thereby reducing mitochondrial oxidative stress. In contrast, cytoplasmic soluble SOD1 had no effect, further highlighting a specific role for mitochondrial oxidative stress in this process. In summary, here we provide new evidence directly supporting a key role for a loss of stromal Cav-1 expression and oxidative stress in cancer-associated fibroblasts, in promoting tumor growth, which is consistent with "The Autophagic Tumor Stroma Model of Cancer". The human Cav-1 deficient fibroblasts that we have generated are a new genetically tractable model system for identifying other suppressors of the cancer-associated fibroblast phenotype, via a genetic "complementation" approach. This has important implications for understanding the pathogenesis of triple negative and basal breasts cancers, as well as tamoxifen-resistance in ER+ breast cancers, which are all associated with a Cav-1 deficient "lethal" tumor micro-environment, driving poor clinical outcome.
Articular Cartilage Repair (1998)

Articular cartilage can tolerate a tremendous amount of intensive and repetitive physical stress. However, it manifests a striking inability to heal even the most minor injury. Both the remarkable functional characteristics and the healing limitations reflect the intricacies of its structure and biology. Cartilage is composed of chondrocytes embedded within an extracellular matrix of collagens, proteoglycans, and noncollagenous proteins. Together, these substances maintain the proper amount of water within the matrix, which confers its unique mechanical properties. The structure and composition of articular cartilage varies three-dimensionally, according to its distance from the surface and in relation to the distance from the cells. The stringent structural and biological requirements imply that any tissue capable of successful repair or replacement of damaged articular cartilage should be similarly constituted. The response of cartilage to injury differs from that of other tissues because of its avascularity, the immobility of chondrocytes, and the limited ability of mature chondrocytes to proliferate and alter their synthetic patterns. Therapeutic efforts have focused on bringing in new cells capable of chondrogenesis, and facilitating access to the vascular system. This review presents the basic science background and clinical experience with many of these methods and information on synthetic implants and biological adhesives. Although there are many exciting avenues of study that warrant enthusiasm, many questions remain. These issues need to be addressed by careful basic science investigations and both short- and long-term clinical trials using controlled, prospective, randomized study design.
Metabolism of the analgesic drug ULTRAM ® (tramadol hydrochloride) in humans: API-MS and MS/MS characterization of metabolites (2002)

1. Metabolism of the analgesic agent tramadol hydrochloride has been investigated after a single oral administration of tramadol to three male volunteers (100 mg/subject), and a urine pool (4-12h) was obtained. 2. Unchanged tramadol and a total of 23 metabolites, consisting of 11 Phase I metabolites (M1-11) and 12 conjugates (seven glucuronides, five sulphates), were profiled, characterized and tentatively identified in urine on the basis of API ionspray-MS and MS/MS data. 3. Of the metabolites, five (M1-5) had been previously identified. 4. The metabolites were formed via the following six metabolic pathways: (1) O-demethylation, (2) N-demethylation, (3) cyclohexyl oxidation, (4) oxidative N-dealkylation, (5) dehydration and (6) conjugation. 5. Pathways 1-3 appear to be major routes, forming seven O-desmethyl/N-desmethyl and hydroxycyclohexyl metabolites. 6. Pathways 1-3 in conjunction with pathway 6 produced seven glucuronides along with five sulphates. 7. In addition, the in vitro metabolism of tramadol was conducted using a human liver microsomal fraction in the presence of an NADPH-generating system. Unchanged tramadol (82% of the sample) plus eight metabolites (M1, M2, M4-6, tramadol-N-oxide (M31), OH-cyclohexyl-M1 (M32) and dehydrated tramadol-N-oxide), were profiled and tentatively identified on the basis of MS and MS/MS data.
The role of progestins in the treatment of breast cancer. (1983)

In unselected populations of women, the progestins medroxyprogesterone acetate (MPA) and megestrol acetate (MA) have produced response rates of 14% to 31% in metastatic breast cancer, sparking new investigative activity to define their proper role. One proposed mechanism of action for progestins is that they interfere with replenishment of the cytoplasmic estrogen receptor. Although not binding to estrogen receptors, progesterone has been shown to decrease the quantity of estrogen receptor in target tissue. Prediction of response of metastatic breast cancer to progestins largely follows the conventional rules established for the selection of additive hormonal therapy. Little difference is seen between appropriate doses of MPA and of MA in reports of prognostic factors associated with tumor response. The presence of hormone receptors in tumor tissue may be the most significant predictor for response to progestins. Tumors that contain both estrogen and progesterone receptors will respond to progestins in over 61% of instances, whereas those with only one type of hormone receptor will respond 20% to 30% of the time. Response to MPA or MA is probably independent of the presence of progesterone receptor. Response rates to MA of around 30% have been noted in patients who had previously responded to tamoxifen and then progressed. Previous exposure to chemotherapy does not appear to jeopardize chances for response to MA. A limited number of randomized trials of tamoxifen versus MA show no significant response difference between the two therapies in breast cancer patients with similar prognoses.
Metagenomics to Paleogenomics: Large-Scale Sequencing of Mammoth DNA (2005)

We sequenced 28 million base pairs of DNA in a metagenomics approach, using a woolly mammoth (Mammuthus primigenius) sample from Siberia. As a result of exceptional sample preservation and the use of a recently developed emulsion polymerase chain reaction and pyrosequencing technique, 13 million base pairs (45.4%) of the sequencing reads were identified as mammoth DNA. Sequence identity between our data and African elephant (Loxodonta africana) was 98.55%, consistent with a paleontologically based divergence date of 5 to 6 million years. The sample includes a surprisingly small diversity of environmental DNAs. The high percentage of endogenous DNA recoverable from this single mammoth would allow for completion of its genome, unleashing the field of paleogenomics.
주조 및 불연속 석출물 미세조직을 가지는 Mg-Al 합금의 인장 특성 및 열전도도 (2020)

The objective of this study was to investigate the tensile properties and thermal conductivities of Mg- 9.3%Al alloy in as-cast state and heat-treated state consisting of fully discontinuous precipitates (DPs), respectively. The fully DPs microstructure was obtained by solution treatment at 405℃ for 24 h, followed by furnace cooling to RT. The as-cast alloy showed a partially divorced eutectic β(Mg17Al12) phase particles formed along the α-(Mg) cell boundaries. The DPs had various apparent (α+β) interlamellar spacings, which is related to different transformation temperatures during the furnace cooling. The DPs microstructure exhibited better tensile strength than the as-cast one, resulting from the higher value of elongation in response to its more homogeneous microstructure. It is noticeable that the DPs microstructure had 12.4% higher thermal conductivity in average than the as-cast one between RT and 200℃. The XRD analyses revealed that the lower Al concentration in the α-(Mg) matrix may well be responsible for the better thermal conductivity of the DPs microstructure.
(Received August 03, 2020; Revised August 10, 2020; Accepted August 31, 2020)