gebhart/patrepeval huggingface dataset:
The operation mechanism of a charge modulation device (CMD) image sensor (1991)

The operational mechanism of the charge modulation device (CMD) as an image sensor is presented. A newly developed device simulator, the transistor analysis program for imagers calculating non-steady-state equations (TRINE) is used in this analysis. Comparison of the calculated results with measured data shows that the model predictions are consistent with measured electrical and optical characteristics within a range of 20%. The operational mechanism has been clarified, and the accuracy of the method proves that it is effective in quantitative device design. The discretization scheme of the cylindrical coordinate system used is also shown.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
SYNTHESIS AND ANTICANCER ACTIVITY OF 4-AMINO-5-OXO-8-(β-D-XYLOFURANOSYL) PYRIDO[2,3-d]PYRIMIDINE (2001)

4-Amino-5-oxo-8-(beta-D-xylofuranosyl)pyrido[2,3-d]pyrimidine (4) was recently synthesized and evaluated in our laboratories for anticancer activities. This compound showed potent in vitro inhibitory effects on the growth of HTB-81 prostate cancer cells and Daudi-lymphoma. In vivo studies showed that the compound could inhibit HTB-81 tumor growth in syngeneic mice by 93% at a daily dose of 8.5 mg/kg for 10 days.
Quantitative structure–activity studies of insect growth regulators: XIX. Effects of substituents on the aromatic moiety of dibenzoylhydrazines on larvicidal activity against the beet armyworm Spodoptera exigua (2001)

Larvicidal activity against the beet armyworm, Spodoptera exigua (Hübner), was measured after topical treatment for a series of N-tert-butyl-dibenzoylhydrazines having various substituents in the benzoyl (A-ring) moiety closer to the tert-butyl group, the other benzoyl (B-ring) moiety being unsubstituted. The effects of substituents on the larvicidal activity were analyzed using the classical quantitative structure-activity relationship (QSAR) procedure. Introduction of hydrophobic substituents with a small volume into any position was favourable to activity. The existence of electron-withdrawing substituents at ortho positions was also favourable to activity. For multi-substituted compounds, physico-chemically unknown unfavourable factors were suggested to remain after separating common substituent effects derived from QSAR for mono-substituted analogues. With the exception of the unsubstituted compound RH-5849, the effect of substituents in the A-ring moiety on the larvicidal activity was similar to those found with the lepidopteran rice stem borer, Chilo suppressalis (Walker). The larvicidal activity of RH-5849 against S exigua was significantly lower than the value predicted from the correlation between activities against S exigua and C suppressalis. Topical treatment with piperonyl butoxide, a synergist inhibiting oxidative metabolism, slightly enhanced the larvicidal activity of RH-5849 against S exigua.
Identification of Bacillus subtilis genes expressed early during sporulation (1989)

Labelled cDNA transcribed in vitro from early-sporulation RNA was enriched for sporulation-specific sequences by subtractive hybridization to an excess of vegetative RNA and used to probe libraries of Bacillus subtilis chromosomal DNA. From the initial collection of clones that coded for RNAs transcribed preferentially during sporulation, several were subcloned and studied in more detail. It was found that two clones contained sequences (dciA and dciB) that had an undetectable level of transcription during vegetative growth but had transcripts that started to appear no later than eight minutes after induction of sporulation. A third DNA segment (dciC) was expressed at a low level in vegetative cells and increased within four minutes after induction of sporulation. The effects of spoO mutations, i.e. mutations that prevent cells from reaching stage I of the sporulation process, were tested. Induction of the dciA and dciB transcripts was significantly reduced in strains carrying mutations in the spoOA and spoOH genes but not in a spoOB mutant strain. In addition, a product of the abrB locus, a locus in which mutations are known to partially overcome the pleiotropic effect of spoOA and spoOB mutations, seemed to be required for dciA and dciB expression.
Surfactant protein D in the female genital tract (2004)

Surfactant protein D (SP-D) plays a role in innate immunity against various pathogens and in vivo studies have demonstrated that SP-D also has anti-inflammatory properties. SP-D was originally demonstrated in alveolar type II cells, but recent studies have shown extrapulmonary expression of SP-D indicating a systemic role for the protein. This study describes the presence of SP-D in the female genital tract, the placenta and in amniotic fluid using immunohistochemistry and enzyme-linked immunosorbent assay. SP-D was observed in cells lining surface epithelium and secretory glands in the vagina, cervix, uterus, fallopian tubes and ovaries. In the placenta, SP-D was seen in all villous and extravillous trophoblast subpopulations. Endometrial presence of SP-D in non-pregnant women varied according to stage of the menstrual cycle and was up-regulated towards the secretory phase. It is suggested that endometrial SP-D may prevent intrauterine infection at the time of implantation and during pregnancy.
Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018)

Subcutaneous delivery of biotherapeutics has become a valuable alternative to intravenous administration across many disease areas. Although the pharmacokinetic profiles of subcutaneous and intravenous formulations differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use. The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from both health-economic and scientific perspectives. The article covers different indications, treatment settings, administration volumes, and injection devices. We focus on biotherapeutics in rheumatoid arthritis (RA), immunoglobulin-replacement therapy in primary immunodeficiency (PI), beta interferons in multiple sclerosis (MS), and monoclonal antibodies (mAbs) in oncology. While most subcutaneous biotherapeutics in RA, PI, and MS are self-administered at home, mAbs for oncology are still only approved for administration in a healthcare setting. Beside concerns around the safety of biotherapeutics in oncology, a key challenge for self-administration in this area is that doses and dosing volumes can be comparatively large; however, this difficulty has recently been overcome to some extent by the development of high-concentration solutions, the use of infusion pumps, and the coadministration of the dispersion enhancer hyaluronidase. Furthermore, given the increasing number of biotherapeutics being considered for combination therapy and the high dosing complexity associated with these, especially when administered intravenously, subcutaneous delivery of fixed-dose combinations might be an alternative that will diminish these burdens on healthcare systems.
Production of Monoclonal Antibodies for Affinity Purification of Bovine Mullerian Inhibiting Substance Activity (1984)

Two monoclonal antibodies (IG8 and IG10) specific for Mullerian inhibiting substance (MIS) were obtained from the fusion between myeloma cell line SP2/0 and spleen cells from an A/J mouse immunized with partially purified MIS. The resulting hybridomas were screened by a solid-phase RIA and two lines were selected and cloned. Both MAbs IG8 and IG10 subsequently demonstrated specificity for MIS by their ability to inhibit biologically active MIS by precipitation with a second antibody, directly block MIS activity in the organ culture assay, and adsorb and elute active MIS when coupled to a solid support. SDS-polyacrylamide gel electrophoresis of affinity purified MIS demonstrated a major band at 140 kD in unreduced gels and two bands with approximate molecular weights of 70 and 74 KD following reduction. Protein bands were localized either directly by silver staining or on immunoblots developed with radiolabeled anti-MIS MA.
Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans (1993)

Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra.
Regulation of ERBB3/HER3 signaling in cancer (2014)

ERBB3/HER3 is emerging as a molecular target for various cancers. HER3 is overexpressed and activated in a number of cancer types under the conditions of acquired resistance to other HER family therapeutic interventions such as tyrosine kinase inhibitors and antibody therapies. Regulation of the HER3 expression and signaling involves numerous HER3 interacting proteins. These proteins include PI3K, Shc, and E3 ubiquitin ligases NEDD4 and Nrdp1. Furthermore, recent identification of a number of HER3 oncogenic mutations in colon and gastric cancers elucidate the role of HER3 in cancer development. Despite the strong evidence regarding the role of HER3 in cancer, the current understanding of the regulation of HER3 expression and activation requires additional research. Moreover, the lack of biomarkers for HER3-driven cancer poses a big challenge for the clinical development of HER3 targeting antibodies. Therefore, a better understanding of HER3 regulation should improve the strategies to therapeutically target HER3 for cancer therapy.
Modular Neural Networks for Medical Prognosis: Quantifying the Benefits of Combining Neural Networks for Survival Prediction (1997)

This paper describes a medical application of modular neural networks (NNs) for temporal pattern recognition. In order to increase the reliability of prognostic indices for patients living with the acquired immunodeficiency syndrome (AIDS), survival prediction was performed in a system composed of modular NNS that classified cases according to death in a certain year of follow-up. The output of each NN module corresponded to the probability of survival in a given year. Inputs were the values of demographic, clinical and laboratory variables. The results of the modules were combined to produce survival curves for individuals. The NNs were trained by backpropagation and the results were evaluated in test sets of previously unseen cases. We showed that, for certain combinations of NN modules, the performance of the prognostic index, measured by the area under the receiver operating characteristic curve, was significantly improved (p 0.05). We also used calibration measurements to quantify the benefits of combining NN modules, and show why, when and how NNs should be combined for building prognostic models.
Thymidine kinase-mediated killing of rat brain tumors (1993)

Gene therapy has many potential applications in central nervous system (CNS) disorders, including the selective killing of tumor cells in the brain. A rat brain tumor model was used to test the herpes simplex virus (HSV)-thymidine kinase (TK) gene for its ability to selectively kill C6 and 9L tumor cells in the brain following systemic administration of the nucleoside analog ganciclovir. The HSV-TK gene was introduced in vitro into tumor cells (C6-TK and 9L-TK), then these modified tumor cells were evaluated for their sensitivity to cell killing by ganciclovir. In a dose-response assay, both C6-TK and 9L-TK cells were 100 times more sensitive to killing by ganciclovir (median lethal dose: C6-TK, 0.1 microgram ganciclovir/ml; C6, 5.0 micrograms ganciclovir/ml) than unmodified wild-type tumor cells or cultured fibroblasts. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to kill established brain tumors in rats as quantified by both stereological assessment of brain tumor volumes and studies of animal survival over 90 days. Rats with brain tumors established by intracerebral injection of wild-type or HSV-TK modified tumor cells or by a combination of wild-type and HSV-TK-modified cells were studied with and without ganciclovir treatments. Stereological methods determined that ganciclovir treatment eliminated tumors composed of HSV-TK-modified cells while control tumors grew as expected (p < 0.001). In survival studies, all 10 rats with 9L-TK tumors treated with ganciclovir survived 90 days while all untreated rats died within 25 days. Curiously, tumors composed of combinations of 9L and 9L-TK cells could be eliminated by ganciclovir treatments even when only one-half of the tumor cells carried the HSV-TK gene. While not completely understood, this additional tumor cell killing appears to be both tumor selective and local in nature. It is concluded that HSV-TK gene therapy with ganciclovir treatment does selectively kill tumor cells in the brain and has many potential applications in CNS disorders, including the treatment of cancer.
Estrogen receptor impairs interleukin-6 expression by preventing protein binding on the NF- B site (1997)

Interleukin-6 (IL-6) is a multifunctional cytokine thought to be a key factor in post-menopausal osteoporosis, given its ability to induce osteoclast maturation and its down regulation by estrogens. We have previously shown that the effects of TNFalphaand estradiol on the human IL-6 promoter were dependent on a region of the promoter containing a C/EBP site and a NF-kappaB site. To define the molecular mode of action of estrogens, we performed gel shift assays with this DNA fragment as a probe, and nuclear extracts from TNFalpha-induced HeLa, MCF7 and Saos2 cells. Several induced complexes specifically bound the probe. The use of various competitor DNA suggested that most of the complexes detected contained NF-kappaB factors, and that C/EBP site binding factors were important for the overall binding to the probe. Addition of in vitro translated human estrogen receptor (hER) impaired the binding of three complexes in HeLa cells and two complexes in MCF7 and Saos2 cells. Competition experiments suggested that the NF-kappaB site was necessary for the effect of hER. The use of antisera against NF-kappaB and C/EBP proteins showed that the target complexes of hER contained the c-rel proto-oncogene product and to a lesser extent, the RelA protein. Taken together, these data show that hER impairs TNFalphainduction of IL-6 by preventing c-rel and, to a lesser extent, RelA proteins binding to the NF-kappaB site of the IL-6 promoter.
Small early gastric cancer with special reference to macrophage infiltration. (1999)

The authors investigate the tumor-infiltrating cells in small early gastric cancer (EGC) (<10 mm) and describe the ultrastructural features and interactions of macrophages with tumor cells and other inflammatory cells. Sections from 20 small EGCs were stained by immunohistochemical methods for CD20, UCHL1, CD4, CD8, and CD68 (electron microscopic examination was used in 6 of the 20). In all of the tumors, CD68-positive macrophages accounted for most tumor-infiltrating cells, with UCHL1-positive T lymphocytes, eosinophils, and neutrophils being the next most frequent. We found only a few CD20-positive B lymphocytes. Electron microscopic analysis revealed macrophages with many phagocytic vesicles, cellular debris, and apoptotic bodies. These morphologic data show that macrophages are actively phagocytic. The tumor cells in contact with macrophages showed no cytopathic changes. These data do not support a macrophage-mediated cancer lysis like the ones reported in some systems in vitro. Contacts among macrophages and other inflammatory cells formed a recurrent ultrastructural hallmark and suggest a communication among varying inflammatory cell types during the precocious host response to gastric neoplasia.
Predicting the Effects of Amino Acid Substitutions on Protein Function (2006)

Nonsynonymous single nucleotide polymorphisms (nsSNPs) are coding variants that introduce amino acid changes in their corresponding proteins. Because nsSNPs can affect protein function, they are believed to have the largest impact on human health compared with SNPs in other regions of the genome. Therefore, it is important to distinguish those nsSNPs that affect protein function from those that are functionally neutral. Here we provide an overview of amino acid substitution (AAS) prediction methods, which use sequence and/or structure to predict the effect of an AAS on protein function. Most methods predict approximately 25-30% of human nsSNPs to negatively affect protein function, and such nsSNPs tend to be rare in the population. We discuss the utility of AAS prediction methods for Mendelian and complex diseases as well as their broader applications for understanding protein function.
Binding of the herpes simplex virus immediate-early gene product ICP4 to its own transcription start site (1987)

A gel electrophoresis DNA-binding assay was used to detect proteins from herpes simplex virus type 1-infected and uninfected cells that specifically bind the upstream region of immediate-early (IE) gene 3. The assay is based on the altered electrophoretic mobility of DNA-protein complexes relative to that of free DNA in native gels. A series of end-labeled overlapping DNA fragments spanning a region from -272 to +27 (relative to the 5' terminus of the IE gene 3 mRNA) were used as probes. Two complexes were identified (referred to as A and B) which were driven by different protein factors. Formation of the A complex required infected-cell proteins extracted at any time from 2 to 16 h postinfection; a 0.5 to 1 M NaCl extract of infected cells, and a DNA probe that contained the sequences from -4 to +27 (relative to the 5' terminus of IE gene 3 mRNA). The protein that drove the formation of the A complex is not related to transcription factors TFIIIA or Sp1 or their cognate binding domains since neither the 5S RNA gene nor the GC box of simian virus 40 could compete for proteins that induced formation of the A complex. Through the use of monoclonal antibodies, the complex was shown to contain the IE gene 3 product, ICP4. A more detailed localization of the DNA-binding site in vitro by using chemical footprinting revealed that binding occurs over the sequence from -10 to +3 relative to the mRNA terminus. The binding of ICP4 to its own transcription start site may explain the repression of IE gene transcription which attends the onset of early (beta) gene expression and suggests an autoregulatory mechanism for gene control in herpes simplex virus type 1. The B complex was readily detected in uninfected cells (of a number of different cell lines), as well as in infected cells, with a probe containing the IE consensus sequence TAATGARATTC (where R is a purine) and two nested copies of the Sp1 binding motif GGGCGG; however, complexes were also detected with probes that lack the IE consensus sequence but contain Sp1 sites. These data suggest that the B complex contains the promoter-specific factor Sp1, and competition experiments with the clustered Sp1 binding domains from simian virus 40 confirmed this idea.
Clinical investigations of Toll-like receptor agonists (2008)

Imiquimod was the first TLR agonist approved for treatment of anogenital warts, actinic keratosis and superficial basal cell carcinoma in humans. Several other agonists of TLRs 4, 7, 8 and 9 were also shown to be effective for treatment of infections and cancers and, furthermore, were used as adjuvants for vaccination. Based on safety and efficacy of the TLR agonists used to date, applications are likely to increase in the future.
A mutation downstream from the signal peptidase cleavage site affects cleavage but not membrane insertion of phage coat protein. (1981)

Morphogenesis of filamentous phage includes synthesis of the phage major coat protein in precursor form, its insertion into the host cell plasma membrane, its cleavage to the mature form of the protein, and its assembly there into virions. The M13 mutant am8H1R6 encodes a coat protein in which leucine replaces glutamic acid as residue 2 of the mature protein [Boeke, J. D., Russel, M. & Model, P. (1980) J. Mol. Biol. 144, 103-116]. The coat protein precursor produced by this variant is a poor substrate for the Escherichia coli signal peptidase both in vivo and in vitro. This pre-coat protein, which is eventually processed and assembled into viable phage particles, is associated with the membrane fraction of the infected cell. We conclude that the domain recognized by the signal peptidase extends beyond the signal peptide itself. Furthermore, membrane association and signal peptide cleavage can be separated temporally under conditions that permit membrane insertion, cleavage, and phage assembly.
Chemistry and biology of the anaphylatoxin related serum peptide system. I. Purification, crystallization and properties of classical anaphylatoxin from rat serum (1972)

Abstract Classical anaphylatoxin, which causes histamine liberation and lethal anaphylatoxin shock in the guinea pig, was purified from dextran‐treated rat serum leading to a 5000‐fold increase in specific activity. It was crystallized in a molecular homogenous state. Rat anaphylatoxin consists of one peptide unit with a molecular weight of 9500, as determined by gel chromatography. First, evidence is presented that the anaphylatoxin‐forming contact reaction of normal, fresh serum with hydrophilic, insoluble substances of high molecular weight, e.g. dextran, yeast or antigen‐antibody complexes, does not lead to a stable anaphylatoxin molecule exclusively, but to a group of peptides of similar physicochemical behavior. Only one of these peptides displays anaphylatoxin activity. The lack of significant chemotactic activity for neutrophil leucocytes is characteristic for this crystallized classical anaphylatoxin. This indicates that anaphylatoxin and chemotactic activities are two different biological principles.