gebhart/patrepeval huggingface dataset:
Characterizing Early Events Associated with the Activation of Target Genes by 1,25-Dihydroxyvitamin D3 in Mouse Kidney and Intestine in Vivo (2007)

In this report, we explore the interaction of the vitamin D receptor (VDR) at regulatory sites within both the Cyp24a1 and the Trpv6 genes using chromatin immunoprecipitation techniques in a mouse model in vivo. We show that exogenous 1,25(OH)(2)D(3) induces rapid VDR and RXR (retinoid X receptor) binding to the Cyp24a1 gene in both the kidney and the intestine and to the Trpv6 gene in the intestine. Separate studies of Trpv6 in vitro suggest that VDR binding occurs directly to VDR response elements located -2 and -4 kb upstream of the TSS. VDR binding is dose-dependent, demonstrating EC(50) values that are comparable with those for the induction of both Cyp24a1 and Trpv6 mRNA. Importantly, interaction of the VDR with these targets results in rapid changes in histone 4 acetylation as well as the recruitment of RNA polymerase II. The presence of both VDR and RNA polymerase II at these sites declines between 3-6 h, whereas the changes observed in acetylation decrease more slowly. Finally, we show that whereas mediator protein 1 is recruited to the Cyp24a1 promoter in the intestine, this coactivator is apparently not required for Trpv6 activation. These studies provide the first evidence for 1,25(OH)(2)D(3)-induced VDR interaction at key target genes in vivo, revealing the consequences of that interaction on the Cyp24a1 and Trpv6 genes.
A CpG-Ficoll Nanoparticle Adjuvant for Anthrax Protective Antigen Enhances Immunogenicity and Provides Single-Immunization Protection against Inhaled Anthrax in Monkeys (2015)

Nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of APCs, have shown substantial promise for enhanced immunopotentiation. We investigated the adjuvant activity of synthetic oligonucleotides containing CpG-rich motifs linked to the sucrose polymer Ficoll, forming soluble 50-nm particles (DV230-Ficoll), each containing >100 molecules of the TLR9 ligand, DV230. DV230-Ficoll was evaluated as an adjuvant for a candidate vaccine for anthrax using recombinant protective Ag (rPA) from Bacillus anthracis. A single immunization with rPA plus DV230-Ficoll induced 10-fold higher titers of toxin-neutralizing Abs in cynomolgus monkeys at 2 wk compared with animals immunized with equivalent amounts of monomeric DV230. Monkeys immunized either once or twice with rPA plus DV230-Ficoll were completely protected from challenge with 200 LD50 aerosolized anthrax spores. In mice, DV230-Ficoll was more potent than DV230 for the induction of innate immune responses at the injection site and draining lymph nodes. DV230-Ficoll was preferentially colocalized with rPA in key APC populations and induced greater maturation marker expression (CD69 and CD86) on these cells and stronger germinal center B and T cell responses, relative to DV230. DV230-Ficoll was also preferentially retained at the injection site and draining lymph nodes and produced fewer systemic inflammatory responses. These findings support the development of DV230-Ficoll as an adjuvant platform, particularly for vaccines such as for anthrax, for which rapid induction of protective immunity and memory with a single injection is very important.
Biotechnology of plasma proteins : hemostasis, thrombosis and iron proteins (1991)

This volume presents data on the use of monoclonal antibodies in the diagnosis and therapy of thrombotic diseases. It describes the applications of DNA technology in the diagnosis of the causes of thrombotic or congenital haemostatic disorders.
T-cell receptor usage by melanoma-specific clonal and highly oligoclonal tumor-infiltrating lymphocyte lines. (1994)

Tumor-infiltrating lymphocytes (TIL) obtained from human melanomas can specifically lyse autologous tumor in vitro and mediate tumor regression in vivo. To develop more effective therapeutic reagents and to further understand the T-cell response to tumors, the diversity of T-cell receptors (TCRs) involved in melanoma antigen recognition has been studied. The TCR variable (V) genes, joining (J) segments, and N diversity regions used by five clonal lines and one highly oligoclonal, melanoma-specific, CD8+ TIL line were examined utilizing PCR amplification with V gene subfamily-specific primers and anchor PCR. The TIL lysed multiple allogeneic melanomas expressing matched surface major histocompatibility complex class I molecules. TCR analysis confirmed the clonal nature of the TIL lines; however, the TCR repertoire was diverse. Even among the three HLA-A2 restricted TIL (TIL 1200, TIL F2-2, and TIL-5), no common V gene usage was found. Comparison of the third complementarity-determining regions of the TCRs from the HLA-A2 restricted TIL revealed no homology. Results presented here identify T-cell clonotypes that recognize epitopes on highly prevalent, shared melanoma tumor-associated antigens presented in the context of HLA-B55, HLA-A1, and HLA-A2. These T cells and the antigens they recognize represent important components for the design of new immunotherapies for patients with advanced melanoma.
Snake Venomics ofBitis gabonica gabonica. Protein Family Composition, Subunit Organization of Venom Toxins, and Characterization of Dimeric Disintegrins Bitisgabonin-1 and Bitisgabonin-2 (2006)

The protein composition of the venom of the East African Gaboon viper (Bitis gabonica gabonica) was analyzed using RP-HPLC, N-terminal sequencing, MALDI-TOF peptide mass fingerprinting, and CID-MS/MS. In total, 35 proteins of molecular masses in the range of 7-160 kDa and belonging to 12 toxin families were identified. The most abundant proteins were serine proteinases (26.4%), Zn2+-metalloproteinases (22.9%), C-type lectin-like proteins (14.3%), PLA2s (11.4%), and bitiscystatin (9.8%). Other protein classes, that is, bradykinin-potentiating peptides, dimeric disintegrins, Kunitz-type inhibitor, DC-fragments, sv-VEGF, CRISP, and L-amino acid oxidase, comprised between 1.3 and 3.4% of the total venom proteome. Only 11 venom-secreted proteins matched any of the previously reported 22 partial or full-length venom gland transcripts. In addition, venome and transcriptome depart in their relative abundances of different toxin families. The proteomic characterization of purified B. gabonica gabonica proteins run under nonreducing and reducing SDS-PAGE conditions revealed their aggregation state and subunit composition. Multimeric proteins included heterodimeric disintegrins, homodimeric sv-VEGF-A, heterodimeric (alphabeta) and tetrameric (alphabeta)4 C-type lectins, and multimeric PIII Zn2+-metalloproteinases. Determination of the complete primary structure and subunit composition of the two major dimeric disintegrins, bitisgabonin-1 and bitisgabonin-2, showed that each comprised a distinct RGD- and MLD-bearing subunit and a common, N-terminal-blocked, RGD-containing subunit identical to the disintegrin domain of the PII Zn2+-metalloproteinase 4. Cell adhesion inhibition assays showed that bitisgabonin-1 (RGD-RGD) is a potent inhibitor of integrin alpha5beta1, whereas bitisgabonin-2 (MLD-RGD) is a better antagonist of integrins alpha4beta1 and alpha9beta1.
Fast and Offset-Leakage Insensitive Current-Mode Line Driver for Active Matrix Displays and Sensors (2009)

Current-programmed active matrix (AM) architectures that are independent of fabrication technology are attractive for display and sensor because of their ability to tolerate mismatches and nonuniformity caused by aging. However, the long settling time due to low current levels and large parasitic capacitance can be a significant limitation. In this paper, we present a fast current-mode line driver based on positive feedback which controls the effect of parasitic capacitance. The driver was fabricated in 0.8-mum 20-V CMOS technology. While the measured settling time of a conventional current source is around 2 ms for a 100-nA input current and 200-pF parasitic capacitance, it is less than 4 mus for the driver presented here. Moreover, an offset-leakage cancellation technique is implemented for the fabricated driver to reduce the effect of leakage and offset currents to few nA.
SNC 80 and Related &#948; Opioid Agonists (2004)

The discovery of the selective delta (delta) opioid agonists SNC 80 and BW373U86, which possess a diarylmethylpiperazine structure unique among opioids, was a major advance in the field of delta-opioid ligands. Much research has been performed to uncover the structure-activity relationships (SAR) of this class of ligands and also to compare the diarylmethylpiperazines with the traditional morphinan-based delta opioids. This review focuses on the development of the SAR of this unique series of ligands, and discusses questions which remain unanswered.
Major internal parasites interfering with cattle production in France, and experiments to control them by strategic treatments. A bibliographic review. (1981)

A summary of the cattle management systems and statistics in France is presented as a framework to examine the recently published results on the major internal parasites of cattle in France from numeric data on naturally infested animals. From these results the major or constant parasites are Fasciola, Dictyocaulus, Ostertagia and Cooperia; occasional but important parasites are Nematodirus, Neoascaris, Eimeria, OEsophagostomum and Cysticercus bovis. Pathology results focus on disease given by the most common nematode : Ostertagiasis. For prevention and control of infestations in farm practice with typical management procedures, results are presented in dairy cattle (Brittany and Normandy), and in beef cattle (Limousin).
Innate Immune Signaling by, and Genetic Adjuvants for DNA Vaccination (2013)

DNA vaccines can induce both humoral and cellular immune responses. Although some DNA vaccines are already licensed for infectious diseases in animals, they are not licensed for human use because the risk and benefit of DNA vaccines is still controversial. Indeed, in humans, the immunogenicity of DNA vaccines is lower than that of other traditional vaccines. To develop the use of DNA vaccines in the clinic, various approaches are in progress to enhance or improve the immunogenicity of DNA vaccines. Recent studies have shown that immunogenicity of DNA vaccines are regulated by innate immune responses via plasmid DNA recognition through the STING-TBK1 signaling cascade. Similarly, molecules that act as dsDNA sensors that activate innate immune responses through STING-TBK1 have been identified and used as genetic adjuvants to enhance DNA vaccine immunogenicity in mouse models. However, the mechanisms that induce innate immune responses by DNA vaccines are still unclear. In this review, we will discuss innate immune signaling upon DNA vaccination and genetic adjuvants of innate immune signaling molecules.
Preparation and characterization of thermosensitive PNIPAA-coated iron oxide nanoparticles (2008)

A new and facile approach was established to fabricate thermoresponsive poly(N-isopropylacrylamide) (PNIPAA) coated iron oxide nanoparticles in a non-aqueous medium. The morphology and structure of the nanoparticle-doped composite were analyzed by means of transmission electron microscopy (TEM), x-ray powder diffraction (XRD), and Fourier transformation infrared spectrometry (FTIR). The thermosensitivity of the composite was also investigated. Results indicated that the oil-soluble iron oxide nanoparticles encapsulated with PNIPAA, composed of an inorganic iron oxide core and biocompatible PNIPAA shell, were dispersed well in water and had a sphere-like shape. The PNIPAA-coated iron oxide nanoparticles with such a kind of core-shell structure showed excellent thermosensitivity. Namely, the aqueous suspension of PNIPAA-coated iron oxide nanoparticles dramatically changed from transparent to opaque as the temperature increased from room temperature to 38 °C, showing potential as optical transmittance switch materials and their significance in the fields of protein adsorption and purification controlled release, and drug delivery.
Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma (2001)

Airway hyperresponsiveness (AHR), goblet cell metaplasia, and mucus overproduction are important features of bronchial asthma. To elucidate the molecular mechanisms behind these pulmonary pathologies, we examined for genes preferentially expressed in the lungs of a murine model of allergic asthma by using suppression subtractive hybridization (SSH). We identified a gene called gob-5 that had a selective expression pattern in the airway epithelium with AHR. Here, we show that gob-5, a member of the calcium-activated chloride channel family, is a key molecule in the induction of murine asthma. Intratracheal administration of adenovirus-expressing antisense gob-5 RNA into AHR-model mice efficiently suppressed the asthma phenotype, including AHR and mucus overproduction. In contrast, overexpression of gob-5 in airway epithelia by using an adenoviral vector exacerbated the asthma phenotype. Introduction of either gob-5 or hCLCA1, the human counterpart of gob-5, into the human mucoepidermoid cell line NCI-H292 induced mucus production as well as MUC5AC expression. Our results indicated that gob-5 may play a critical role in murine asthma, and its human counterpart hCLCA1 is therefore a potential target for asthma therapy.
The Bisphosphonate YM529 Inhibits Osteolytic and Osteoblastic Changes and CXCR-4–Induced Invasion in Prostate Cancer (2005)

Bisphosphonates are useful for the treatment of prostate cancer bone metastasis. However, the role of bisphosphonate on the development of the osteoblastic component of prostate cancer bone metastases is not defined. In the present study, the third-generation bisphosphonate, YM529 (minodoronate), was tested for its effects on the osteolytic PC-3 and novel osteoblastic LNCaP-SF cell lines. YM529 inhibited both osteolytic and osteoblastic changes in an intratibial tumor injection murine model. In vitro, YM529 inhibited both the proliferation and the invasion of both prostate cancer cell lines. The stromal cell-derived factor-1 (or CXCL12)/CXCR-4 pathway is believed to play an important role in the development of prostate cancer bone metastases. Thus, we determined if YM529 affected this pathway. YM529 suppressed CXCR-4 expression in PC-3 and LNCaP-SF in vitro and in vivo and this was associated with decreased in vitro invasion. These results suggest that YM529 may inhibit cancer cell invasion into the bone matrix by repressing the expression of CXCR-4 in bone metastasis lesions.
Single gene and gene interaction effects on fertilization and embryonic survival rates in cattle (2009)

Decrease in fertility and conception rates is a major cause of economic loss and cow culling in dairy herds. Conception rate is the product of fertilization rate and embryonic survival rate. Identification of genetic factors that cause the death of embryos is the first step in eliminating this problem from the population and thereby increasing reproductive efficiency. A candidate pathway approach was used to identify candidate genes affecting fertilization and embryo survival rates using an in vitro fertilization experimental system. A total of 7,413 in vitro fertilizations were performed using oocytes from 504 ovaries and semen samples from 10 different bulls. Fertilization rate was calculated as the number of cleaved embryos 48 h postfertilization out of the total number of oocytes exposed to sperm. Survival rate of embryos was calculated as the number of blastocysts on d 7 of development out of the number of total embryos cultured. All ovaries were genotyped for 8 genes in the POU1F1 signaling pathway. Single-gene analysis revealed significant associations of GHR, PRLR, STAT5A, and UTMP with survival rate and of POU1F1, GHR, STAT5A, and OPN with fertilization rate. To further characterize the contribution of the entire integrated POU1F1 pathway to fertilization and early embryonic survival, a model selection procedure was applied. Comparisons among the different models showed that interactions between adjacent genes in the pathway revealed a significant contribution to the variation in fertility traits compared with other models that analyzed only bull information or only genes without interactions. Moreover, some genes that were not significant in the single-gene analysis showed significant effects in the interaction analysis. Thus, we propose that single genes as well as an entire pathway can be used in selection programs to improve reproduction performance in dairy cattle.
Effects of aging on quantitative structural properties of coronary vasculature and microvasculature in rats (1994)

To determine whether the alterations in coronary vascular resistance with aging have a structural basis, the quantitative properties of the intramural branches of the coronary circulation and capillary network were measured in Fischer 344 rats at 4, 12, 20, and 29 mo. Physiological measurements demonstrated that a severe impairment in cardiac pump function developed with age, leading to the occurrence of ventricular failure at 29 mo. Morphometrically, the length densities of resistance vessels from 6 to 20 microns in luminal diameter markedly decreased at 12 mo, and this change persisted at 20 and 29 mo. This phenomenon affected the inner, middle, and outer layers of the left ventricular wall. In contrast, capillary luminal volume percentage, capillary numerical density, and average diffusion distance for oxygen in the left and right myocardium were altered only at 20 mo, whereas values comparable to those at 4 mo were found at 12 and 29 mo. The preservation of these capillary characteristics in the heart was due to a significant amount of capillary proliferation. In conclusion, aging effects lead to rarefaction of coronary arterioles in the myocardium, which may impair coronary resistance and reserve without altering the capillary microvasculature and the oxygenation potential of the old and senescent heart.
Phenylalanine ammonia lyase production by gamma irradiated and analog-resistant mutants of Rhodotorula glutinis. (2000)

Mutants resistant to phenylalanine analogs (L-tyrosine, p-fluoro-D, L-phenylalanine (PFP) and trans-cinnamic acid) were isolated from a wild type strain of Rhodotorula glutinis A-97 by mutagenic treatment with gamma radiation and screened for phenylalanine ammonia lyase (PAL) production. One such mutant, gammaT11 (resistant to L-tyrosine), exhibited four times the PAL activity of the parent wild strain A-97. Mutant isolate gammaTFP5.6 which was selected as L-tyrosine and PFP resistant isolate, produced inducible PAL activity at levels 5.94-fold higher than the wild-type A-97 and 2.66-fold higher than its parent mutant isolate gammaT5 which was resistant to L-tyrosine. The mutant isolate gammaTC5d which was resistant to L-tyrosine and trans-cinnamic acid, exhibited 3.48 and 1.56-fold increase in PAL activity compared to the parent wild strain A-97 and its parent mutant isolate gammaT5, respectively. Different media have been examined for the induction of PAL.
131. Two ketones of the stilbœstrol group (1941)

The first page of this article is displayed as the abstract.
Piezoresistive Sensor with High Elasticity Based on 3D Hybrid Network of Sponge@CNTs@Ag NPs (2016)

Pressure sensors with high elasticity are in great demand for the realization of intelligent sensing, but there is a need to develope a simple, inexpensive, and scalable method for the manufacture of the sensors. Here, we reported an efficient, simple, facile, and repeatable “dipping and coating” process to manufacture a piezoresistive sensor with high elasticity, based on homogeneous 3D hybrid network of carbon nanotubes@silver nanoparticles (CNTs@Ag NPs) anchored on a skeleton sponge. Highly elastic, sensitive, and wearable sensors are obtained using the porous structure of sponge and the synergy effect of CNTs/Ag NPs. Our sensor was also tested for over 2000 compression–release cycles, exhibiting excellent elasticity and cycling stability. Sensors with high performance and a simple fabrication process are promising devices for commercial production in various electronic devices, for example, sport performance monitoring and man–machine interfaces.
PHARMACOLOGIC AND BIOCHEMICAL CONSIDERATIONS OF DIMETHYL SULFOXIDE (1975)

DMSO has multiple known pharmacological properties. In addition to those referred to include: cryoprotective action, radioprotective effect, influence on serum cholesterol in experimental hypercholesteremia, and platelet aggregation antagonism. How the multiple properties of this chemical affect therapy in clinical medicine must yet be explained. It is clear, however, that DMSO does affect biological systems, and that this influence has many clinical applications. Perhaps one of the most interesting and significant properties of DMSO is its ability to move other drugsthrough membranes. When mixed with DMSO, many drugs appear to be potentiated in their physiologic effect; thus smaller doses are required and less toxicity is demonstrated. In cancer chemotherapy, this value already has practical use. Some of the studies to be reported in this monograph will describe additional, almost unbelievable observations. Perhaps the mechanism of action of these clinical phenomena will be found in one or more of the pharmacological properties described. It would not be surprising, however, if we were to conclude with a resolution to search for new explantations of the mystery of DMSO, for it would appear that DMSO is really a new principle in medicine and cannot always be measured by existing standards.
Induction of protective immunity to monoclonal-antibody-defined Plasmodium falciparum antigens requires strong adjuvant in Aotus monkeys (1986)

Monoclonal antibodies to the major Plasmodium falciparum merozoite surface coat and rhoptry antigens were produced. A combination of the affinity-purified polypeptides with Freund complete adjuvant which was given three times completely protected an Aotus lemurinus azure (karotype VI) monkey against homologous challenge; however, immunization with the same polypeptides with a muramyl dipeptide derivative [MDP-Lys(L18)] did not protect a second Aotus monkey, even though comparable high antibody titers were induced.
Apoptosis Signal-regulating Kinase 1 (ASK1) Is an Intracellular Inducer of Keratinocyte Differentiation (2001)

Cells differentiate in response to various extracellular stimuli. This cellular response requires intracellular signaling pathways. The mitogen-activated protein (MAP) kinase cascade is a core signal transduction pathway that determines the fate of many kinds of cell. MAP kinase kinase kinase activates MAP kinase kinase, which in turn activates MAP kinase. Apoptosis signal-regulating kinase (ASK1) was identified as a MAP kinase kinase kinase involved in the stress-induced apoptosis-signaling cascade that activates the SEK1-JNK and MKK3/MKK6-p38 MAP kinase cascades. Expression of the constitutively active form of ASK1 (ASK1-DeltaN) in keratinocytes induced significant morphological changes and differentiation markers, transglutaminase-1, loricrin, and involucrin. A transient increase in p21(Cip1/WAF1) reduced DNA synthesis, and cell cycle analysis verified the differentiation. p38 MAP kinase inhibitors, SB202190 and SB203580, abolished the induction of differentiation markers, transglutaminase-1, loricrin, and involucrin. In turn, the induction of differentiation with ceramide in keratinocytes caused an increase in ASK1 expression and activity. Furthermore, normal human skin expresses ASK1 protein in the upper epidermis, implicating ASK1 in in vivo keratinocyte differentiation. We propose that the ASK1-p38 MAP kinase cascade is a new intracellular regulator of keratinocyte differentiation.