gebhart/patrepeval huggingface dataset:
Transactivation of the Interleukin-1 Alpha Promoter by Human T-cell Leukemia Virus (1997)

The expression of interleukin-1 alpha (IL-1 alpha) appears to be tightly regulated, as the levels of constitutive expression in normal cells is extremely low. In contrast to normal hematopoietic cells, human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines constitutively produce high levels of IL-1 alpha mRNA and secret this cytokine into the culture medium. IL-1-alpha mRNA is also expressed in fresh leukemic cells of adult T-cell leukemia/lymphoma (ATLL) patients. HTLV-I-induced IL-1 alpha might explain some symptoms observed in ATLL. In this regard, molecular dissection of the IL-1 alpha gene transcriptional regulation is of primary importance. In this review, the transcriptional regulation of IL-1 alpha gene expression and the possible role of the NF-kappaB pathway are discussed in the light of our current understanding of IL-1 alpha gene regulation by HTLV-I and HTLV-II Tax proteins, which are viral transcriptional transactivators.
Comprehensive dictionary of physical chemistry (1992)

Part 1 Theory of the structure of matter: elementary particles atoms molecules principles of quantum mechanics and quantum chemistry spectroscopy photochemistry states of matter gases liquids solids. Part 2 Thermodynamics: principles of technical thermodynamics principles of statistical thermodynamics electrochemistry chemical kinetics colloid and surface chemistry.
Biosimilar therapeutics--what do we need to consider? (2008)

Patents for the first generation of approved biopharmaceuticals have either expired or are about to expire. Thus the market is opening for generic versions, referred to as 'biosimilars' (European Union) or 'follow-on protein products' (United States). Healthcare professionals need to understand the critical issues surrounding the use of biosimilars to make informed treatment decisions.The complex high-molecular-weight three-dimensional structures of biopharmaceuticals, their heterogeneity and dependence on production in living cells makes them different from classical chemical drugs. Current analytical methods cannot characterize these complex molecules sufficiently to confirm structural equivalence with reference molecules. Verification of the similarity of biosimilars to innovator biopharmaceuticals remains a key challenge. Furthermore, a critical safety issue, the immunogenicity of biopharmaceuticals, has been highlighted in recent years, confirming a need for comprehensive immunogenicity testing prior to approval and extended post-marketing surveillance.Biosimilars present a new set of challenges for regulatory authorities when compared with conventional generics. While the demonstration of a pharmacokinetic similarity is sufficient for conventional, small-molecule generic agents, a number of issues will make the approval of biosimilars more complicated. Documents recently published by the European Medicines Agency (EMEA) outlining requirements for the market approval of biosimilars provide much-needed guidance. The EMEA has approved a number of biosimilar products in a scientifically rigorous and balanced process. Outstanding issues include the interchangeability of biosimilars and innovator products, the possible need for unique naming to differentiate the various biopharmaceutical products, and more comprehensive labelling for biosimilars to include relevant clinical data.
Deregulation of cyclin E in breast cancer. (1995)

Cyclin E, a regulatory subunit of cyclin dependent kinase-2, is thought to be rate limiting for the G1/S transition during the mammalian cell cycle. Previously, we showed severe alterations in cyclin E protein expression in human mammary epithelial cell lines and in surgical material obtained from patients with various malignancies. To understand the functional basis of these alterations we analyse here the regulation of cyclin E in breast cancer cells. We find that while cyclin E protein and its associated kinase activity in normal cells are cell cycle regulated, in tumor cells it remains in an active complex throughout the cell cycle. We also analysed cyclin E for possible deletions which could result in its constitutive function and found two novel truncated variants in its coding region. These variant forms of cyclin E were detected in several normal and tumor cell lines and tissue specimens. However, Western blot analysis indicated that only the multiple isoforms of cyclin E protein were expressed in tumor but not the normal tissue specimen, suggesting post transcriptional regulation of cyclin E. Lastly, in vitro analyses indicated that these truncated variant forms of cyclin E are biochemically active in their ability to phosphorylate histone H1. Collectively these observations suggest the presence of more than one form of cyclin E mRNA in all cells, normal and tumor. Once translated in tumor cells, the protein products of these truncated forms could give rise to a constitutively active form of cyclin E containing complexes.
Neutrophil adhesion in leukocyte adhesion deficiency syndrome type 2. (1995)

We have previously reported a newly discovered congenital disorder of neutrophil adhesion, leukocyte adhesion deficiency syndrome type 2 (LAD II). The clinical manifestations of this syndrome are similar to those seen in the classic leukocyte adhesion deficiency syndrome, now designated type 1 (LAD I), but the two syndromes differ in the molecular basis of their adhesion defects. LAD I is caused by a deficiency in the CD18 integrin adhesion molecules while LAD II patients are deficient in expression of sialyl-Lewis X (SLeX), a carbohydrate ligand for selectins. In this report we demonstrate that neutrophils from a LAD II patient bind minimally or not at all to recombinant E-selectin, purified platelet P-selectin, or P-selectin expressed on histamine-activated human umbilical vein endothelial cells, but have normal levels of L-selectin and CD11b/CD18 integrin, and adhere to and migrate across endothelium when CD11b/CD18 is activated. We compare LAD I and LAD II patient neutrophil function in vitro, demonstrating that integrin and selectin adhesion molecules have distinct but interdependent roles in neutrophil adhesion during an inflammatory response.
The effect of estrone-progesterone treatment on cell proliferation kinetics of hormone-dependent GR mouse mammary tumors. (1975)

Hormone-dependent mammary tumors were induced in virgin GR mice by treatment with estrone and progesterone. Discontinuation of hormonal treatment was followed by regression of the tumor. This response to hormone treatment was also observed in the first transplant generation in inbred syngeneic hosts, but after several transplantations the tumor growth became hormone independent. The hormone dependence of the primary tumors and tumors after a single transplantation was demonstrated by growth curves. Furthermore, the cell proliferation kinetics has been investigated in a growing as well as in a regressing hormone-dependent tumor after a single transplantation from the same primary tumor. The experimental data consist of growth curves, percentage-labeled mitoses curves, and labeling indices. Since these data do not contain information concerning the localization of the cell loss in the cell cycle, they were analyzed by a computer method based on three mathematical models differing in respect to the mode of cell loss. All three models gave approximately the same estimates of the cell kinetic parameters in the growing as well as the regressing tumor. The results for the growing, hormone-dependent tumor showed a growth fraction of 62%, a cell production rate of 3.4%/hr, and a cell loss rate of 2.3%/hr. Regression of the tumor after hormonal deprivation was accompanied by a decrease in growth fraction to 18% and a decrease in the cell production rate to 0.9%/hr, while the cell loss rate was unchanged at 2.8%/hr. Furthermore, the discontinuation of hormonal treatment introduced an increase in the mean transit time of the cell cycle, particularly in the mean transit time of the G1 phase. The results might indicate that estrone and progesterone treatment stimulated growth of hormone-dependent GR mouse mammary tumors mainly by an increase of growth fraction and cell production rate.
Injectable PAMAM/ODex double-crosslinked hydrogels with high mechanical strength (2016)

In situ injectable double-crosslinked hydrogels containing thiol functionalized poly(amido-amine) dendrimers (Gn-PAMAM-NH<sub>2</sub>-X) and oxidized dextrans (ODex) were prepared under physiological conditions without using potentially cytotoxic cross-linkers. The double-crosslinked structure was created by Schiff's base reaction and the formation of disulfide bonds. The morphology of the hydrogels was characterized by scanning electron microscopy. The gelation time, swelling and rheological behaviors of the hydrogels were investigated. We also studied the adhesive strength and cytocompatibility of the hydrogels. The surface amino density, concentration and generation of PAMAM are the main factors affecting the gelation. Relatively high surface amino density contributes to quick gelation, whereas too great a surface amino may lead to the brittleness of the hydrogel. A moderate concentration of PAMAM (10% wt) is suitable for gelation considering its appropriate gelation time. Where surface amino density and the mass concentration of PAMAM-NH<sub>2</sub> were identical, PAMAM with less generation was prone to gelation. The injectable PAMAM/ODex hydrogels have double-crosslinked structures and a high crosslinking density which lead to their high storage modulus. The adhesive strength of the hydrogels is about 2.4 times of commercial available fibrin glue and these hydrogels are nontoxic to L929 mouse fibroblast cells. The L929 cells can attach easily to the surface of hydrogels and proliferate on them, which demonstrates these novel injectable hydrogels are biocompatible and have potential uses in tissue engineering.
Methods for extracting place semantics from Flickr tags (2009)

We describe an approach for extracting semantics for tags, unstructured text-labels assigned to resources on the Web, based on each tag's usage patterns. In particular, we focus on the problem of extracting place semantics for tags that are assigned to photos on Flickr, a popular-photo sharing Web site that supports location (latitude/longitude) metadata for photos. We propose the adaptation of two baseline methods, inspired by well-known burst-analysis techniques, for the task; we also describe two novel methods, TagMaps and scale-structure identification. We evaluate the methods on a subset of Flickr data. We show that our scale-structure identification method outperforms existing techniques and that a hybrid approach generates further improvements (achieving 85% precision at 81% recall). The approach and methods described in this work can be used in other domains such as geo-annotated Web pages, where text terms can be extracted and associated with usage patterns.
Fluid changes during pregnancy: use of bioimpedance spectroscopy (1995)

The increase in body water during pregnancy is responsible for the largest portion of weight gain and is of interest of clinical practitioners. However, assessing changes in body fluids is not easily accomplished during pregnancy. The purpose of this study was to examine the accuracy of bioelectrical impedance spectroscopy for estimating fluid volumes before, during, and after pregnancy. Ten healthy adult women were recruited for the study. Total body water (TBW) and extracellular fluid (ECF) volume were measured at baseline (preconception); 8-10, 24-26, and 34-36 wk of gestation; and 4-6 wk postpartum by deuterium oxide and NaBr dilution, respectively. Estimates of TBW and ECF were also obtained by bioimpedance spectroscopy (BIS). At baseline, mean values for dilution and BIS estimates of TBW and ECF were 33.2 +/- 4.6 (SD) vs. 31.6 +/- 6.2 liters and 15.2 +/- 1.3 vs. 16.9 +/- 2.3 liters, respectively. TBW and ECF estimated by BIS were not significantly different from the dilution values at any time point. These results suggest that BIS may be useful in estimating volumes of ECF and TBW during pregnancy.
Eosinophilic Esophagitis in Children: Symptoms, Histology and pH Probe Results (2004)

Solid food dysphagia was the most common feature of eosinophilic esophagitis in our patients. Alkalinization of the esophagus was found in all nine pH probe recordings of eosinophilic esophagitis patients and may represent a previously unreported characteristic of the condition.
Highlights of the Latest Advances in Research on CDK Inhibitors (2014)

Uncontrolled proliferation is the hallmark of cancer and other proliferative disorders and abnormal cell cycle regulation is, therefore, common in these diseases. Cyclin-dependent kinases (CDKs) play a crucial role in the control of the cell cycle and proliferation. These kinases are frequently deregulated in various cancers, viral infections, neurodegenerative diseases, ischemia and some proliferative disorders. This led to a rigorous pursuit for small-molecule CDK inhibitors for therapeutic uses. Early efforts to block CDKs with nonselective CDK inhibitors led to little specificity and efficacy but apparent toxicity, but the recent advance of selective CDK inhibitors allowed the first successful efforts to target these kinases for the therapies of several diseases. Major ongoing efforts are to develop CDK inhibitors as monotherapies and rational combinations with chemotherapy and other targeted drugs.
Appropriate biochemical parameters in first-trimester screening for Down syndrome (1999)

Meta-analysis was used to calculate maternal serum marker distribution parameters for Down syndrome risk estimation in the first trimester. Data from 44 series were combined: relating to pregnancy associated plasma protein (PAPP)-A in 18, free beta human chorionic gonadotrophin (hCG) in 17, alpha-fetoprotein (AFP) in 26 and unconjugated oestriol (uE3) in 9. All levels were expressed in multiples of the normal median (MOM) for gestational age. Individual PAPP-A levels were available for 439 first and second-trimester Down syndrome pregnancies. The median MOM value increased with gestation: 0.35 at 6-8 weeks (31 cases), 0.40 at 9-11 weeks (197), 0.62 at 12-14 weeks (113) and 0.94 thereafter (98). A cubic regression equation was fitted so it could be estimated for each week of gestation. For the other markers the median value in Down syndrome was estimated from the weighted mean across all first-trimester series: 1.98 MOM for free beta-hCG in 579 cases; 0.79 MOM for AFP in 243 and 0.74 MOM for uE3 in 226. Variance-covariance matrices were calculated directly in unaffected pregnancies and from the difference between affected and unaffected pregnancies in Down syndrome. Based on these parameters we estimate that screening at 9-11 weeks with PAPP-A and free beta-hCG will yield a 64.6 per cent detection rate for a 5 per cent false-positive rate. Adding a third marker will increase detection to 66.6 per cent for AFP and 68.6 per cent for uE3; using all four markers it increases to 70.1 per cent. Routine ultrasound nuchal translucency measurement in addition to serum testing will increase the rates to 86.4 per cent, 87.2 per cent, 87.9 per cent and 88.3 per cent, respectively.
Agrobacterium-Mediated Transformation of Subterranean Clover (Trifolium subterraneum L.) (1994)

We have developed a rapid and reproducible transformation system for subterranean clover (Trifolium subterraneum L.) using Agrobacterium tumefaciens-mediated gene delivery. Hypocotyl segments from seeds that had been allowed to imbibe were used as explants, and regeneration was achieved via organogenesis. Glucose and acetosyringone were required in the co-cultivation medium for efficient gene transfer. DNA constructs containing four genes encoding the enzymes phosphinothricin acetyl transferase, [beta]-glucuronidase (GUS), neomycin phosphotransferase, and an [alpha]-amylase inhibitor were used to transform subterranean clover. Transgenic shoots were selected on a medium containing 50 mg/L of phosphinothricin. Four commercial cultivars of subterranean clover (representing all three subspecies) have been successfully transformed. Southern analysis revealed the integration of T-DNA into the subterranean clover genome. The expression of the introduced genes has been confirmed by enzyme assays and northern blot analyses. Transformed plants grown in the glasshouse showed resistance to the herbicide Basta at applications equal to or higher than rates recommended for killing subterranean clover in field conditions. In plants grown from the selfed seeds of the primary transformants, the newly acquired gene encoding GUS segregated as a dominant Mendelian trait.
On optimal communication strategies for cooperative cognitive radio networking (2013)

This work is concerned with enhancement of spectrum-energy efficiency whereby a primary user (PU) engages secondary users (SUs) to relay its transmission in an energy-aware cognitive radio network, i.e., forming a cooperative cognitive radio network (CCRN). The cooperation framework in CCRN can be multiple two-hop relaying with or without PU's direct link transmission using an amplify-and-forward or decode-and-forward mode. In the energy-aware CCRN, an individual cooperating partner attempts to maximize its own utility. The partner selection and parameter optimization, led by the PU, are formulated as two Stackelberg games, namely a sum-constrained power allocation game for two-phase cooperation and a power control game for three-phase cooperation, respectively. Unique Nash Equilibrium is proved and achieved in analytical format for each game. The optimal communication strategy is chosen which achieves the maximum PU utility among different optimal communication strategies. Moreover, an implementation scheme is presented to perform the partner selection and parameter optimization based on the analytical results. Theoretical analysis and performance evaluation show that the proposed CCRN model is a promising framework under which the PU's utility is maximized, while the relaying SUs can attain acceptable utilities.
Molecular Cloning and Characterization of a Transcription Factor for the copia Retrotransposon with Homology to the BTB-Containing Lola Neurogenic Factor (1997)

By transfection experiments, we previously identified a 72-bp enhancer sequence within the Drosophila copia retrotransposon which is involved in the control of the transcription level of this mobile element in cells in culture. Gel shift assays with nuclear extracts from Drosophila hydei-derived DH-33 cells further demonstrated specific interactions of at least two nuclear factors with this enhancer sequence. Using this sequence as a probe for the screening of an expression cDNA library that we constructed from DH-33 cells RNA, we have isolated a cDNA clone encoding a 110-kDa protein with features common to those of known transcription factors; these include a two-zinc-finger motif at the C terminus, three glutamine-rich domains in the presumptive activation domain of the protein, and an N-terminal domain which shares homology with the Bric-à-brac, Tramtrack, and Broad-Complex BTB boxes. The precise DNA recognition sequence for this transcription factor has been determined by both gel shift assays and footprinting experiments with a recombinant protein made in bacteria. The functionality of the cloned element was demonstrated upon transcriptional activation of copia reporter genes, as well as of a minimal promoter coupled with the identified target DNA sequence, in cotransfection assays in cells in culture with an expression vector for the cloned factor. Southern blot and nucleotide sequence analyses revealed a related gene in Drosophila melanogaster (the lola gene) previously identified by a genetic approach as involved in axon growth and guidance. Transfection assays in cells in culture with lola gene expression vectors and in situ hybridization experiments with lola gene mutants finally provided evidence that the copia retrotransposon is regulated by this neurogenic gene in D.melanogaster, with a repressor effect in the central nervous systems of the embryos.
Variola virus immune evasion design: Expression of a highly efficient inhibitor of human complement (2002)

Variola virus, the most virulent member of the genus Orthopoxvirus, specifically infects humans and has no other animal reservoir. Variola causes the contagious disease smallpox, which has a 30-40% mortality rate. Conversely, the prototype orthopoxvirus, vaccinia, causes no disease in immunocompetent humans and was used in the global eradication of smallpox, which ended in 1977. However, the threat of smallpox persists because clandestine stockpiles of variola still exist. Although variola and vaccinia share remarkable DNA homology, the strict human tropism of variola suggests that its proteins are better suited than those of vaccinia to overcome the human immune response. Here, we demonstrate the functional advantage of a variola complement regulatory protein over that of its vaccinia homologue. Because authentic variola proteins are not available for study, we molecularly engineered and characterized the smallpox inhibitor of complement enzymes (SPICE), a homologue of a vaccinia virulence factor, vaccinia virus complement control protein (VCP). SPICE is nearly 100-fold more potent than VCP at inactivating human C3b and 6-fold more potent at inactivating C4b. SPICE is also more human complement-specific than is VCP. By inactivating complement components, SPICE serves to inhibit the formation of the C3/C5 convertases necessary for complement-mediated viral clearance. SPICE provides the first evidence that variola proteins are particularly adept at overcoming human immunity, and the decreased function of VCP suggests one reason why the vaccinia virus vaccine was associated with relatively low mortality. Disabling SPICE may be therapeutically useful if smallpox reemerges.
Exploring uptake mechanisms of oral nanomedicines using multimodal nonlinear optical microscopy (2012)

Abstract Advances in pharmaceutical nanotechnology have yielded ever increasingly sophisticated nanoparticles for medicine delivery. When administered via oral, intravenous, ocular and transcutaneous delivery routes, these nanoparticles can elicit enhanced drug performance. In spite of this, little is known about the mechanistic processes underlying interactions between nanoparticles and tissues, or how these correlate with improved pharmaceutical effects. These mechanisms must be fully understood before nanomedicines can be rationally engineered to optimise their performance. Methods to directly visualise these particulates within tissue samples have traditionally involved imaging modalities requiring covalent labelling of fluorescent or radioisotope contrast agents. We present CARS, second harmonic generation and two photon fluorescence microscopy combined as a multi‐modal label‐free method for pinpointing polymeric nanoparticles within the stomach, intestine, gall bladder and liver. We demonstrate for the first time that orally administered chitosan nanoparticles follow a recirculation pathway from the GI tract via enterocytes, to the liver hepatocytes and intercellular spaces and then to the gall bladder, before being re‐released into the gut together with bile. (© 2012 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)