gebhart/patrepeval huggingface dataset:
Role of interferon regulatory factor 1 in induction of nitric oxide synthase. (1994)

Interferon gamma (IFN-gamma) interacts synergistically with bacterial lipopolysaccharide (LPS) to induce transcription of iNOS, the isoform of nitric oxide synthase whose activity is independent of elevated Ca2+ and exogenous calmodulin. To define a cis-acting element mediating IFN-gamma-dependent synergy, we made deletions in iNOS promoter constructs fused to reporter genes, transfected RAW 264.7 macrophages, and treated the cells with IFN-gamma and/or LPS. This analysis implicated the region from positions -951 to -911, a cluster of four enhancer elements known to bind IFN-gamma-responsive transcription factors, including an interferon regulatory factor binding site (IRF-E) at nucleotides -913 to -923. Site-specific substitution of two conserved nucleotides within IRF-E in the context of the full-length iNOS promoter ablated IFN-gamma's contribution to synergistic enhancement of transcription. Electromobility shift assays performed with a probe containing IRF-E revealed the existence of a complex in nuclei of RAW 264.7 macrophages that was present only after treatment with IFN-gamma, which reacted specifically with anti-IRF-1 immunoglobulin G and which included a species migrating at 40-45 kD, consistent with the apparent molecular weight of murine IRF-1. Thus, the synergistic contribution of IFN-gamma to transcription of iNOS in RAW 264.7 macrophages requires that IRF-1 bind to IRF-E in the iNOS promoter. In conjunction with the work of Kamijo et al. (Kamijo, R., H. Harada, T. Matsuyama, M. Bosland, J. Gerecitano, D. Shapiro, J. Le, K. S. Im, T. Kimura, S. Green et al. 1994. Science [Wash. DC]. 263:1612), these findings identify iNOS as the first gene that requires IRF-1 for IFN-gamma-dependent transcriptional regulation.
Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma. (2002)

Vascular endothelial growth factors (VEGF) are secreted by many tumor types, and are believed to affect tumor growth by promoting angiogenesis through binding to their receptors present on vascular endothelium. Recently, mRNA for VEGF-C the ligand for VEGFR-3, was found to be up-regulated in colorectal adenocarcinoma (CRC). The aim of this work was to determine: 1) the distribution of VEGF-C and VEGFR-3 in CRC, and 2) the biological significance of such expression. Sections of formalin-fixed and paraffin-embedded tissues from 56 CRC were immunohistochemically stained for VEGF-C and VEGFR-3. The type and percent of positive cells was recorded. Survival analysis was performed using the Kaplan-Meier method. All CRC were positive for VEGF-C which was present in the cancer cells themselves, as well as in stromal cells. Normal colon epithelium was usually negative. Only ten (17%) of the 56 CRC completely lacked VEGFR-3 expression. VEGFR-3 immunoreactivity was detected in <25% of the cancer cells in 22 cases and in >25% of the cells in 34 cases. Expression of VEGFR-3 in >25% of the cancer cells was associated with significantly poorer overall survival (p<0.05), but not with lymph node metastasis or depth of tumor invasion. Our results suggest that VEGFs promote cancer growth not only by stimulating angiogenesis, but also by acting on receptors present on the cancer cells themselves.
Factors affecting the performance of a thin film magnetoresistive vector magnetometer (1982)

Thin nickel-iron films with uniaxial anisotropy are vacuum-deposited onto glass. A bridge-connected group of conductive meander patterns is formed by photo-lithography; the current flow in each pattern is aligned at 45° to the anisotropy axis and the magnetoresistors are subjected to bias fields perpendicular to this axis. External fields cause magnetic vector rotation, producing magnetoresistive changes which unbalance the bridge. Poles along the edges of each meander pattern strip generate a demagnetisation field. Its magnitude and direction can be calculated from the effective pole density, which changes with the film’s direction of magnetisation. The field is dependent on the geometry of the conducting strips. Calculation of the equilibrium magnetisation direction is based on the Stoner-Wohlfarth model, modified by the effects of the demagnetisation field. There is close correlation between theoretical and experimental results, particularly at higher bias levels where most of the film exists as a single domain. Vector magnetometers must have low sensitivity to orthogonal fields. Careful choice of pattern geometry and optimised bias fields in theory allow a zero orthogonal response, a prediction confirmed by experiment. The magnetometer has a linear response and the system noise is less than 1γ per Hz1/2.
Gene Overexpression: Uses, Mechanisms, and Interpretation (2012)

The classical genetic approach for exploring biological pathways typically begins by identifying mutations that cause a phenotype of interest. Overexpression or misexpression of a wild-type gene product, however, can also cause mutant phenotypes, providing geneticists with an alternative yet powerful tool to identify pathway components that might remain undetected using traditional loss-of-function analysis. This review describes the history of overexpression, the mechanisms that are responsible for overexpression phenotypes, tests that begin to distinguish between those mechanisms, the varied ways in which overexpression is used, the methods and reagents available in several organisms, and the relevance of overexpression to human disease.
Estrogen Receptor, Progesterone Receptor, and Glucocorticoid Receptor Expression in Normal Breast Tissue, Breast In Situ Carcinoma, and Invasive Breast Cancer (2010)

Glucocorticoids (GCs) are used in cancer treatment to induce programmed cell death in transformed cells of the hematopoietic system and to lessen side effects. Moreover, GCs have been described not only as inhibitors of some chemotherapy or radiation-induced apoptosis, but also as inhibitors of cancer progression by down-regulation or up-regulation of different gene expressions. Recently, it has been suggested that GCs can attenuate estrogen responses through induction of expression and activity of the sulfotransferase. The presence or absence of glucocorticoid receptor (GR) in normal and abnormal breast tissue is thus interesting, and the aim of this study was to analyze the expression of GR during the progression of breast tissue. We tested by immunohistochemistry the expression status of estrogen receptor (ER), progesterone receptor (PR), and GR in normal breast parenchyma (n=49), ductal intraepithelial neoplasia (DIN) 1a (n=9), DIN 1b-1c (n=15), DIN 2-3 (n=21), and invasive breast carcinoma (n=39). The evaluation of GR expression was made by using the Allred score. All the normal parenchyma, DIN 1a, DIN 1b, and DIN 1c were ER-positive (ER+) and PR-positive (PR+). Seventeen of 21 DIN 2-3 and 30 of 39 invasive carcinomas were ER+/PR+. The other samples were ER-negative (ER-) and PR-negative (PR-). Moreover, all the ER-/PR- samples were GR-negative. Interestingly, we found a significant correlation between the histologic grade and the GR-negative tumors, and a percentage of positive patients presented with nuclear immunoreaction to GR, which decreases significantly with tumor histologic grade. Understanding the role of GCs in breast carcinoma is thus essential before continuing the widespread use of GCs combined with antineoplastic drugs or agents in the clinical management of women with breast cancer.
Heterologous Protein Expression Is Enhanced by Harmonizing the Codon Usage Frequencies of the Target Gene with those of the Expression Host (2008)

Synonymous codon replacement can change protein structure and function, indicating that protein structure depends on DNA sequence. During heterologous protein expression, low expression or formation of insoluble aggregates may be attributable to differences in synonymous codon usage between expression and natural hosts. This discordance may be particularly important during translation of the domain boundaries (link/end segments) that separate elements of higher ordered structure. Within such regions, ribosomal progression slows as the ribosome encounters clusters of infrequently used codons that preferentially encode a subset of amino acids. To replicate the modulation of such localized translation rates during heterologous expression, we used known relationships between codon usage frequencies and secondary protein structure to develop an algorithm ("codon harmonization") for identifying regions of slowly translated mRNA that are putatively associated with link/end segments. It then recommends synonymous replacement codons having usage frequencies in the heterologous expression host that are less than or equal to the usage frequencies of native codons in the native expression host. For protein regions other than these putative link/end segments, it recommends synonymous substitutions with codons having usage frequencies matched as nearly as possible to the native expression system. Previous application of this algorithm facilitated E. coli expression, manufacture and testing of two Plasmodium falciparum vaccine candidates. Here we describe the algorithm in detail and apply it to E. coli expression of three additional P. falciparum proteins. Expression of the "recoded" genes exceeded that of the native genes by 4- to 1,000-fold, representing levels suitable for vaccine manufacture. The proteins were soluble and reacted with a variety of functional conformation-specific mAbs suggesting that they were folded properly and had assumed native conformation. Codon harmonization may further provide a general strategy for improving the expression of soluble functional proteins during heterologous expression in hosts other than E. coli.
Effect of Dose of Prostaglandin F2α on Steroidogenic Components and Oligonucleosomes in Ovine Luteal Tissue1 (2000)

To determine whether prostaglandin (PG) F(2alpha) had a dose-dependent effect upon secretion of progesterone, oligonucleosome formation, or loss of luteal weight, ewes on Day 9 or 10 of the estrous cycle were administered 0, 3, 10, or 30 mg PGF(2alpha) per 60 kg BW (i.v.), and luteal tissue was collected 9 and 24 h after injection. All doses of PGF(2alpha) decreased (P < 0. 05) concentrations of progesterone in sera by 9 h; however, in ewes treated with 3 mg PGF(2alpha), concentrations of progesterone were similar to control values at 24 h and higher (P < 0.05) than those in the 10- or 30-mg groups. Concentrations of progesterone in sera over all dose levels were highly correlated to luteal concentrations of mRNA encoding steroidogenic acute regulatory protein (P < 0.001), cytochrome P450 side-chain cleavage (P < 0.02), and 3beta-hydroxysteroid dehydrogenase (P < 0.01). Corpora lutea collected at 24 h from ewes treated with the 10- and 30-mg doses of PGF(2alpha) weighed less (P < 0.05) than those from controls. Oligonucleosomes were not present in luteal tissues from control ewes. Surprisingly, all doses of PGF(2alpha)-induced oligonucleosomes in a majority of animals at 9 h and in a majority of ewes treated with 10 and 30 mg of PGF(2alpha) at 24 h. In conclusion, 3 mg of PGF(2alpha) per 60 kg BW transiently decreased serum concentrations of progesterone and induced oligonucleosome formation, but did not result in reduced luteal weight. The 10- and 30-mg doses of PGF(2alpha) decreased secretion of progesterone and induced oligonucleosome formation and luteolysis.
Synthesis and Evaluation of Sulphonylhydrazones of Phthalimido Acetaldehyde as Anticancer Agents (1998)

Department of Anticancer Drug Development &amp; Chemotherapy, Chittaranjan National Cancer Institute, Calcutta-700 026 <em>Manuscript received 15 January 1996, revised 25 September 1996, accepted 6 March 1997</em> Synthesis and Evaluation of Sulphonylhydrazones of Phthalimido Acetaldehyde as Anticancer Agents.
Briaviolide Q, a New Briarane from the Cultured <i>Briareum violaceum</i> (2018)

A new briarane-type diterpenoid, briaviolide Q (1), along with a known analogue, excavatolide Z (2), were obtained from a cultured octocoral Briareum violaceum. Details of the isolation and structure determination of briarane 1 from spectroscopic data are presented in this paper. In RAW264.7 cells, a macrophage-like murine cell line, briarane 1 was found to inhibit the protein expression of pro-inflammatory inducible nitric oxide synthase (iNOS) in cells stimulated by lipopolysaccharide (LPS).
p38 Mitogen-activated Protein Kinase Down-regulates Nitric Oxide and Up-regulates Prostaglandin E2 Biosynthesis Stimulated by Interleukin-1β (1997)

The inflammatory cytokine interleukin 1beta (IL-1beta) induces both cyclooxygenase-2 (Cox-2) and the inducible nitric-oxide synthase (iNOS) with increases in the release of prostaglandins (PGs) and nitric oxide (NO) from glomerular mesangial cells. However, the intracellular signaling mechanisms by which IL-1beta induces iNOS and Cox-2 expression is obscure. Our current studies demonstrate that IL-1beta produces a rapid increase in p38 mitogen-activated protein kinase (MAPK) phosphorylation and activation. Serum starvation and SC68376, a drug which selectively inhibits p38 MAPK in mesangial cells, were used to investigate whether p38 MAPK contributes to the signaling mechanism of IL-1beta induction of NO and PG synthesis. Serum starvation and SC68376 selectively inhibited IL-1beta-induced activation of p38 MAPK. Both SC68376 and serum starvation enhanced NO biosynthesis by increasing iNOS mRNA expression, protein expression, and nitrite production. In contrast, both SC68376 and serum starvation suppressed PG release by inhibiting Cox-2 mRNA, protein expression, and PGE2 synthesis. These data demonstrate that IL-1beta phosphorylates and activates p38 MAPK in mesangial cells. The activation of p38 MAPK may provide a crucial signaling mechanism, which mediates the up-regulation of PG synthesis and the down-regulation of NO biosynthesis induced by IL-1beta.
Dual cancer-specific targeting strategy cures primary and distant breast carcinomas in nude mice (2005)

Limitations of current viral-based gene therapies for malignant tumors include lack of cancer-specific targeting and insufficient tumor delivery. To ameliorate these problems and develop a truly effective adenovirus gene-based therapy for cancer, we constructed a conditionally replication competent adenovirus (CRCA) manifesting the unique properties of tumor-specific virus replication in combination with production of a cancer-selective cytotoxic cytokine, melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), which embodies potent bystander antitumor activity. Cancer cell selective tropism was ensured by engineering the expression of the adenoviral E1A protein, necessary for viral replication, under the control of a minimal promoter region of progression elevated gene-3 (PEG-3), which functions selectively in diverse cancer cells with minimal activity in normal cells. In the E3 region of this CRCA, we introduced the mda-7/IL-24 gene, thereby mediating robust production of this cytokine as a function of adenovirus replication. Infection of this CRCA (designated Ad.PEG-E1A-mda-7) in normal mammary epithelial cells and breast cancer cells confirmed cancer cell selective adenoviral replication, mda-7/IL-24 expression, growth inhibition, and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 into human breast cancer xenografts in athymic nude mice completely eradicated not only the primary tumor but also distant tumors (established on the opposite flank of the animal) thereby implementing a cure. This dual cancer-specific targeting strategy provides an effective approach for treating breast and other human neoplasms with the potential for eradicating both primary tumors and metastatic disease. Additionally, these studies support the potential use of mda-7/IL-24 in the therapy of malignant cancers.
Ontology construction for information selection (2003)

Technology in the field of digital media generates huge amounts of non-textual information, audio, video, and images, along with more familiar textual information. The potential for exchange and retrieval of information is vast and daunting. The key problem in achieving efficient and user-friendly retrieval is the development of a search mechanism to guarantee delivery of minimal irrelevant information (high precision) while ensuring relevant information is not overlooked (high recall). The traditional solution employs keyword-based search. The only documents retrieved are those containing user specified keywords. But many documents convey desired semantic information without containing these keywords. One can overcome this problem by indexing documents according to meanings rather than words, although this will entail a way of converting words to meanings and the creation of ontology. We have solved the problem of an index structure through the design and implementation of a concept-based model using domain-dependent ontology. Ontology is a collection of concepts and their interrelationships, which provide an abstract view of an application domain. We propose a new mechanism that can generate ontology automatically in order to make our approach scalable. For this we modify the existing self-organizing tree algorithm (SOTA) that constructs a hierarchy from top to bottom. Furthermore, in order to find an appropriate concept for each node in the hierarchy we propose an automatic concept selection algorithm from WordNet called linguistic ontology. To illustrate the effectiveness of our automatic ontology construction method, we have explored our ontology construction in text documents. The Reuters21578 text document corpus has been used. We have observed that our modified SOTA outperforms hierarchical agglomerative clustering (HAC).
Polyclonal intravenous immunoglobulin for the treatment of severe sepsis and septic shock in critically ill adults: A systematic review and meta-analysis* (2007)

This meta-analysis demonstrates an overall reduction in mortality with the use of ivIg for the adjunctive treatment of severe sepsis and septic shock in adults, although significant heterogeneity exists among the included trials and this result was not confirmed when only high-quality studies were analyzed. These data warrant a well-designed, adequately powered, and transparently reported clinical trial.
Self-locking underactuated mechanism for robotic gripper (2017)

We describe the concept and first prototype of a novel mechatronic design of a robotic gripper, which aims at being mounted on a humanoid robot to achieve firm (i.e. locked) and robust grasps. Such grasps could ideally support complex multi-contact motions, such as ladder climbing, or manipulation of complex tools, with energy efficiency. For this purpose, we propose a solution by designing a smart self-locking underactuated mechanism mounted in parallel to actuators to be triggered automatically when the desired grasp is achieved. This design leverages adjustable power distribution between the gripper and the brake through a differential gear. The advantages of adaptive, firm grasping, and energy-saving capabilities of our gripper are experimentally demonstrated by a prototype gripper.
Single-dose pharmacokinetics and antibacterial activity of daptomycin, a new lipopeptide antibiotic, in healthy volunteers (1992)

Three separate single-dose studies were performed to define the disposition and pharmacokinetics of daptomycin in healthy volunteers. Daptomycin was administered as a single 14C-labeled dose (1.0 mg/kg of body weight) and as single doses between 0.5 and 6.0 mg/kg. All doses were intravenous. Antibacterial activity was determined from doses of 2.0, 3.0, 4.0, and 6.0 mg/kg against two strains of Staphylococcus aureus (one methicillin resistant) and one Enterococcus strain. After administration of 14C-labeled daptomycin, recovery of 14C in urine and feces accounted for 83% of the administered dose, with the greatest fraction (78%) appearing in the urine. Specific analysis for daptomycin in both urine and plasma indicated that metabolic products were present in urine, but total 14C in plasma consisted of daptomycin only. Doses between 0.5 and 6 mg/kg were linear, with a limited total body clearance (0.13 to 0.21 ml/min/kg) and a small volume of distribution (0.10 to 0.15 liter/kg). The small volume of distribution may be a factor of the high plasma protein binding (90 to 95%). Renal clearance made up 34 to 54% of total body clearance. Daptomycin demonstrated in vivo antibacterial activity against all three test strains, with the greatest activity observed against methicillin-resistant S. aureus. The predicted MIC for all three strains was approximately 13 micrograms/ml, corresponding to total (bound plus unbound) drug. On the basis of the drug's pharmacokinetics and antibacterial activity, doses of 4 to 6 mg/kg/day, possibly in divided doses, are predicted to be effective.
Spermidine Ameliorates Neurodegeneration in a Mouse Model of Normal Tension Glaucoma (2015)

The results from this study suggest that oral spermidine administration could be a useful treatment for retinal degenerative disorders including glaucoma.
Preparative isolation of the two forms of pig pancreatic pro-(carboxypeptidase A) and their monomeric carboxypeptidases A (1985)

A method is reported for the preparative isolation of the two forms of pro-(carboxypeptidase A) from pig pancreas: the monomer and the binary complex with pro-(proteinase E). This method, which is mainly based on chromatography on DEAE-Sepharose at pH 5.7, allows these proenzymes to be prepared more quickly and in safer conditions than with other reported methods. Undegraded and homogeneous carboxypeptidase A1 and A2 species (peptidyl-L-amino acid hydrolase, EC 3.4.17.1), in monomeric forms with high specific activity, are also obtained in high yield by controlled trypsin activation of either of the pro-(carboxypeptidases A) followed by chromatography on DEAE-Sepharose at pH 5.8 under dissociating conditions (7 M-urea).
Tumor Microenvironment and the Response to Anticancer Therapy (2002)

Human solid tumors are invariably less well oxygenated than normal tissues. This leads to resistance to radiotherapy and anticancer chemotherapy, as well as predisposing for increased tumor metastases. Prolonged hypoxia of the tumor tissue also leads to necrosis, and necrotic regions are also characteristic of solid tumors. These two characteristics-hypoxia and necrosis-represent clear differences between tumors and normal tissues and are potentially exploitable in cancer treatment. This review focuses on the phenomenon of tumor hypoxia and how hypoxia and its accompanying necrosis can be exploited in therapy. One such strategy is to use drugs that are toxic only under hypoxic conditions, and the first drug of this class to enter clinical testing, tirapazamine, is showing considerable promise. The second way to exploit hypoxia is to take advantage of the selective induction under hypoxia of the transcription factor HIF-1 (hypoxia-inducible factor 1). Gene therapy strategies based on this are in development. Finally, tumor hypoxia can be exploited using live obligate anaerobes that have been genetically engineered to express enzymes that can activate non-toxic prodrugs into toxic chemotherapeutic agents.