gebhart/patrepeval huggingface dataset:
In Vitro and In Vivo Study of Poly(ethylene glycol) Conjugated Ibuprofen to Extend the Duration of Action (2011)

Ibuprofen–polyethylene glycol (PEG) conjugates (PEG-Ibu) were prepared and their potential as a prolonged release system was investigated. Two PEG-Ibu conjugates were synthesized from Ibuprofen and PEG with two different molecular weights by esterification in the presence of DCC and DMAP. The PEG-Ibu conjugates were characterized by FT-IR, 1H NMR, Mass spectroscopy and DSC analysis. The solubility study in aqueous system showed an increase in solubility of conjugates. The dissolution / hydrolysis studies showed a specific acid–base catalysis pattern dependent on the pH of the medium. This indicated a good chemical stability in aqueous buffer solution of acidic medium and the extended release behavior was found in both prodrugs after 9 hour. The results demonstrate that, in the same condition, the rate of hydrolysis for PEG4000-Ibu is slower than other. The Writhing induced by acetic acid experiment and paw edema test after oral administration showed that both conjugates had extended analgesic and anti-inflammatory effects compared with Ibuprofen. These results suggest that PEG-Ibu could be a promising NSAID prodrug with an extended pharmacological effect owing to delayed-release of parent drug.
Functional Avidity of Tumor Antigen-Specific CTL Recognition Directly Correlates with the Stability of MHC/Peptide Multimer Binding to TCR (2002)

Avidity of Ag recognition by tumor-specific T cells is one of the main parameters that determines the potency of a tumor rejection Ag. In this study we show that the relative efficiency of staining of tumor Ag-specific T lymphocytes with the corresponding fluorescent MHC class I/peptide multimeric complexes can considerably vary with staining conditions and does not necessarily correlate with avidity of Ag recognition. Instead, we found a clear correlation between avidity of Ag recognition and the stability of MHC class I/peptide multimeric complexes interaction with TCR as measured in dissociation kinetic experiments. These findings are relevant for both identification and isolation of tumor-reactive CTL.
Molecular dissection of multi-stage tumorigenesis in transgenic mice. (1994)

The epidemiology of cancer in humans and in animal models suggests that multiple genetic events are responsible for the genesis of malignant tumors. During development of many tumors, distinctive changes can be recognized: normal unaffected tissue, hyperplasia with a high incidence of proliferating cells, induction of tumor angiogenesis with the new growth of capillaries, solid tumors (neoplasia), and finally metastasis. The molecular analysis of tumorigenesis is often hampered by the unavailability of tissue specimens from the multiple stages. For this reason, the genetic reproducibility and the accessibility of tissue specimens have made transgenic mice a valuable tool to study the molecular events that are involved in the stepwise progression to the tumor phenotype. Many transgenic mouse models of human cancer, for example mammary epithelia, skin and liver, exhibit similar patterns of stepwise tumor development. In this review we discuss possible strategies to investigate the molecular events that are involved in multi-stage tumor development. Then we present in some detail the molecular dissection of tumor development in two transgenic models of fibrosarcomas of the skin, and a third transgenic mouse line that develops tumors of the beta cells in the islets of Langerhans (insulinomas). In particular, approaches to the molecular characterization of tumor cell proliferation and tumor angiogenesis are discussed.
Oligonucleotide N3′ → P5′ Thio-phosphoramidate Telomerase Template Antagonists as Potential Anticancer Agents (2003)

Human telomerase is a reverse transcriptase that is expressed in essentially all cancer cells, but not in the vast majority of normal somatic cells. Therefore, the specific inhibition of telomerase activity in tumors might have significant beneficial therapeutic effects. We have designed and evaluated oligonucleotide N3' --> P5' thio-phosphoramidates as telomerase template antagonists. In biochemical cell-free assays 11-13-mer thio-phosphoramidate oligonucleotides demonstrated sequence specific and dose dependent inhibition of telomerase with pico-molar IC50 values. Optimization of the oligonucleotide sequence and length resulted in the identification of a 13-mer-oligonucleotide thio-phosphoramidate GRN163 as a drug development candidate. In cell cultures GRN163 was able to inhibit telomerase activity in the absence of cationic lipid with approximately 1 microM IC50 values. Telomerase inhibition by GRN163 produced gradual telomere shortening, followed by cellular senescence and/or apoptosis of cancer derived cell lines.
High frequency oscillations (80–500 Hz) in the preictal period in patients with focal seizures (2009)

High frequencies in the range of 80-500 Hz are present during the preictal period and are more prominent in the SOZ. They do not change in a systematic way before seizure onset for the horizons we tested. The 80-500 Hz band may be used for the localization of seizure-onset areas but may be more difficult to use for seizure prediction purposes.
Androgen Induces Adaptation to Oxidative Stress in Prostate Cancer: Implications for Treatment with Radiation Therapy (2007)

Radiation therapy is a standard treatment for prostate cancer (PC). The postulated mechanism of action for radiation therapy is the generation of reactive oxygen species (ROS). Adjuvant androgen deprivation (AD) therapy has been shown to confer a survival advantage over radiation alone in high-risk localized PC. However, the mechanism of this interaction is unclear. We hypothesize that androgens modify the radioresponsiveness of PC through the regulation of cellular oxidative homeostasis. Using androgen receptor (AR)(+) 22rv1 and AR(-) PC3 human PC cell lines, we demonstrated that testosterone increased basal reactive oxygen species (bROS) levels, resulting in dose-dependent activation of phospho-p38 and pAKT, and increased expression of clusterin, catalase, and manganese superoxide dismutase. Similar data were obtained in three human PC xenografts; WISH-PC14, WISH-PC23, and CWR22, growing in testosterone-supplemented or castrated SCID mice. These effects were reversible through AD or through incubation with a reducing agent. Moreover, testosterone increased the activity of catalase, superoxide dismutases, and glutathione reductase. Consequently, AD significantly facilitated the response of AR(+) cells to oxidative stress challenge. Thus, testosterone induces a preset cellular adaptation to radiation through the generation of elevated bROS, which is modified by AD. These findings provide a rational for combined hormonal and radiation therapy for localized PC.
Multifrequency laser with reduced intracavity wave mixing (1999)

We demonstrate a ten-channel 100-GHz spacing, waveguide grating router multifrequency laser that has significantly reduced intracavity wave mixing. The mixing products for the improved design are now too small to cause significant laser fluctuations during simultaneous multichannel operation. This was accomplished by reducing the shared waveguide length to 150 μm. We provide evidence that a significant portion of the remaining wave mixing occurs in the intracavity waveguide grating arms.
RNA Viruses in Hymenopteran Pollinators: Evidence of Inter-Taxa Virus Transmission via Pollen and Potential Impact on Non-Apis Hymenopteran Species (2010)

Although overall pollinator populations have declined over the last couple of decades, the honey bee (Apis mellifera) malady, colony collapse disorder (CCD), has caused major concern in the agricultural community. Among honey bee pathogens, RNA viruses are emerging as a serious threat and are suspected as major contributors to CCD. Recent detection of these viral species in bumble bees suggests a possible wider environmental spread of these viruses with potential broader impact. It is therefore vital to study the ecology and epidemiology of these viruses in the hymenopteran pollinator community as a whole. We studied the viral distribution in honey bees, in their pollen loads, and in other non-Apis hymenopteran pollinators collected from flowering plants in Pennsylvania, New York, and Illinois in the United States. Viruses in the samples were detected using reverse transcriptase-PCR and confirmed by sequencing. For the first time, we report the molecular detection of picorna-like RNA viruses (deformed wing virus, sacbrood virus and black queen cell virus) in pollen pellets collected directly from forager bees. Pollen pellets from several uninfected forager bees were detected with virus, indicating that pollen itself may harbor viruses. The viruses in the pollen and honey stored in the hive were demonstrated to be infective, with the queen becoming infected and laying infected eggs after these virus-contaminated foods were given to virus-free colonies. These viruses were detected in eleven other non-Apis hymenopteran species, ranging from many solitary bees to bumble bees and wasps. This finding further expands the viral host range and implies a possible deeper impact on the health of our ecosystem. Phylogenetic analyses support that these viruses are disseminating freely among the pollinators via the flower pollen itself. Notably, in cases where honey bee apiaries affected by CCD harbored honey bees with Israeli Acute Paralysis virus (IAPV), nearby non-Apis hymenopteran pollinators also had IAPV, while those near apiaries without IAPV did not. In containment greenhouse experiments, IAPV moved from infected honey bees to bumble bees and from infected bumble bees to honey bees within a week, demonstrating that the viruses could be transmitted from one species to another. This study adds to our present understanding of virus epidemiology and may help explain bee disease patterns and pollinator population decline in general.
HIV-1 GP120-mediated immune suppression and lymphocyte destruction in the absence of viral infection. (1989)

The magnitude of immunologic defects observed in HIV-1-infected individuals before the development of overt AIDS is disproportionately high in comparison to the levels of infectious virus in these patients--suggesting that factors other than direct virus-induced cytopathology may be involved. With this in mind, we investigated the immunologic consequences of the interaction between purified HIV-1 gp120 and the CD4 molecules expressed by uncommitted as well as Ag-specific lymphocytes. HIV-1 gp120 exhibited a dose-dependent immunosuppressive effect on: 1) Ag-driven proliferation of cloned CD4+ lymphocytes, 2) OKT3-driven proliferation of cloned CD4+ lymphocytes, and 3) cytolytic activity of CD4+, EBV-specific CTL. Thus, HIV-1 gp120 can, in a manner similar to OKT4A antibodies, suppress T cell activation and the expression of cytolytic activities through its interaction with CD4. Additionally, activated CD4+ lymphoblasts can be rendered susceptible to immune cytolysis by virtue of their binding of purified gp120. This "targeting" of activated lymphoblasts can occur with levels of gp120 far below that which is needed to saturate all OKT4A-defined CD4 epitopes. Adsorbed gp120 could be demonstrated on the surface of these cells for up to 12 h, a sufficient time for interaction with host cytolytic elements. The data from these in vitro modeling experiments highlight one of many potential mechanisms of HIV-1 induced immunosuppression and lymphocyte destruction that can occur in the absence of infectious virus and that is based on the unique interaction between HIV-1 gp120 and its cellular receptor, CD4.
pDUAL: a transposon-based cosmid cloning vector for generating nested deletions and DNA sequencing templates in vivo. (1993)

We describe a transposon gamma delta-containing cosmid cloning vector, pDUAL (previously called pJANUS), and demonstrate an efficient strategy for isolating nested deletions in both large-scale and small-scale DNA sequencing efforts. This "deletion factory" strategy takes advantage of the ability of gamma delta (Tn1000) to generate deletions that extend from an end of the transposon into adjacent DNA when gamma delta transposes to new sites in the same DNA molecule. pDUAL contains the contraselectable (conditional lethal) sacB+ (sucrose sensitivity) and strA+ (streptomycin sensitivity) genes just outside each end of an engineered gamma delta and selectable kan+ (Kanr) and tet+ (Tetr) genes between the cloning site and sacB and strA, respectively. Selection on sucrose tetracycline medium yields deletions that extend from one gamma delta end for various distances into the cloned DNA, while selection on streptomycin kanamycin medium yields comparable deletions in the other direction. Both types of deletions are recoverable because the essential plasmid replication origin is embedded in the gamma delta component and is thereby retained in each deletion product. Pilot experiments with pDUAL clones showed that deletion end points can be mapped or selected by plasmid size and that both DNA strands of any single clone can be accessed for sequencing by using a pair of universal primers specific for sequences that are just interior to the gamma delta ends.
Gabor wavelet transform and application to problems in early vision (2003)

Some of the work on the use of Gabor wavelets, a nonorthogonal family of functions, in the analysis of image data is reviewed. Applications to low-level vision problems such as boundary detection, feature detection and localization, and shape recognition are illustrated. A brief introduction to the Gabor wavelet transformation is included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Predicting Diabetic Nephropathy in Insulin-Dependent Patients (1984)

We studied whether microalbuminuria (urinary albumin excretion rates of 15 to 150 micrograms per minute) would predict the development of increased proteinuria in Type I diabetes. We also studied the influence of glomerular filtration rate, renal blood flow, and blood pressure on the later development of proteinuria. Forty-four patients who had had Type I diabetes for at least seven years and who had albumin excretion rates below 150 micrograms per minute were studied from 1969 to 1976, and 43 were restudied in 1983. Of the 14 who initially had albumin excretion rates at or above 15 micrograms per minute, 12 had clinically detectable proteinuria (over 500 mg of protein per 24 hours) or an albumin excretion rate above 150 micrograms per minute at the later examination. Of the 29 who initially had albumin excretion rates below 15 micrograms per minute, none had clinically detectable proteinuria at the later examination, although four had microalbuminuria. Those whose condition progressed to clinically overt proteinuria had elevated glomerular filtration rates and higher blood pressures at the initial examination than did those in whom proteinuria did not develop. Renal blood flow was not elevated in these patients. We conclude that microalbuminuria predicts the development of diabetic nephropathy and that elevated glomerular filtration rates and increased blood pressure may also contribute to this progression.
A non-invasive spectral reflectance method for mapping blood oxygen saturation in wounds (2003)

Reflectance spectroscopy is a common technique used to analyze blood oxygen saturation in biological tissues. This study describes a non-invasive method for mapping blood oxygen saturation in wounds using reflectance measurements obtained from a hyperspectral imaging system. The maps illustrate changes in blood oxygen saturation with high spatial resolution. This allows observation into local blood oxygen supplies of tissue as opposed to common point measurement techniques such as pulse oximetry and optical fiber probing. To demonstrate this, an algorithm designed to calculate the blood oxygen saturation from narrow band reflectance images at 760 and 800 nm was used. The algorithm incorporates the contributions of absorption by oxy-(HbO/sub 2/) and deoxy-hemoglobin (Hb) at the oxygen (O/sub 2/) sensitive and O/sub 2/ insensitive wavelength. Results of the algorithms performance are presented to demonstrate that reflectance measurements can be used to determine the amount of blood O/sub 2/ saturation of a wound.
Quarter-Wavelength Printed Loop Antenna With an Internal Printed Matching Circuit for GSM/ DCS/PCS/UMTS Operation in the Mobile Phone (2009)

A small-size printed loop antenna with an internal printed matching circuit capable of GSM/DCS/PCS/UMTS operation in the mobile phone is proposed. The antenna comprises an 85-mm long folded loop strip and an internal printed matching circuit encircled therein and formed by a coupling strip and an inductive strip. The loop strip is excited by the coupling strip to generate a 0.25 lambda resonant mode at about 900 MHz for GSM operation. For the inductive strip, it effectively causes a wideband higher order mode at about 1900 MHz for DCS/PCS/UMTS operation. Further, the antenna shows a uniplanar structure and requires a very small printed area of 170 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> on the system circuit board of the mobile phone, making it easy to fabricate at low cost. Details of the proposed antenna and its radiation performances including the SAR (specific absorption rate) results are studied.
Chiral Heterocycles by Iminium Ion Cyclization (2004)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral Heterocycles by Iminium Ion Cyclization†Jacques Royer, Martine Bonin, and Laurent MicouinView Author Information Synthèse et Structure de Molécules d'Intérêt Pharmacologique, Faculté des Sciences Pharmaceutiques et Biologiques, UMR 8638 (CNRS-Université Paris-5), 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France Cite this: Chem. Rev. 2004, 104, 5, 2311–2352Publication Date (Web):March 3, 2004Publication History Received25 September 2003Published online3 March 2004Published inissue 1 May 2004https://pubs.acs.org/doi/10.1021/cr020083xhttps://doi.org/10.1021/cr020083xresearch-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views6937Altmetric-Citations379LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Condensation,Cyclization,Ions,Molecular structure,Stereoselectivity Get e-Alerts
Hypersensitive knockin mouse strains identify receptors and pathways for nicotine action. (2003)

Two series of knockin mouse strains have been constructed with point mutations that result in hypersensitive neuronal nicotinic acetylcholine receptors containing alpha 4- or alpha 7-subunits. The full expression of the stronger alleles produces neonatal excitotoxic lethality; however, mice with attenuated expression or milder alleles are viable, and display a range of hypersensitive responses to nicotine. To date, measurements have been made on nicotine-induced seizures, Straub tail, hypothermia, antinociception, electroencephalograms and cellular electrophysiological responses. These strains are helping to define the occurrence of these important receptor subtypes, and their role in the acute and chronic actions of nicotine. The hypersensitive strains may be useful for the development of nicotinic drug therapy.
Allosteric nucleic acid catalysts (2000)

Endowing nucleic acid catalysts with allosteric properties provides new prospects for RNA and DNA as controllable therapeutic agents or as sensors of their cognate effector compounds. The ability to engineer RNA catalysts that are allosterically regulated by effector binding has been propelled by the union of modular rational design principles and powerful combinatorial strategies.
Dengue virus replication in human hepatoma cells activates NF-kappaB which in turn induces apoptotic cell death (1997)

The severe outcome of the dengue (DEN) virus infection known as DEN hemorrhagic fever-DEN shock syndrome (DHF-DSS) is, in some cases, accompanied by liver injury. Councilman bodies observed in liver biopsies of DHF-DSS cases may correspond to hepatocytes in apoptosis. We show here that infection of the hepatoma cell line HepG2 with DEN type 1 virus induced cell death typical of apoptosis late in the virus cycle. The transcription factor NF-kappaB was activated concomitantly with viral protein synthesis and thus before the appearance of apoptotic cells. Inhibition of apoptosis was observed when DEN virus-infected cells were treated with NF-kappaB decoys, indicating the involvement of this transcription factor in induction of cell death. Thus, infected hepatocytes appear to be subject to apoptosis in vitro, and this may be a key element in the pathophysiology of hepatic failure associated with DHF-DSS.
Structural and kinetic basis for heightened immunogenicity of T cell vaccines (2005)

Analogue peptides with enhanced binding affinity to major histocompatibility class (MHC) I molecules are currently being used in cancer patients to elicit stronger T cell responses. However, it remains unclear as to how alterations of anchor residues may affect T cell receptor (TCR) recognition. We correlate functional, thermodynamic, and structural parameters of TCR-peptide-MHC binding and demonstrate the effect of anchor residue modifications of the human histocompatibility leukocyte antigens (HLA)-A2 tumor epitope NY-ESO-1(157-165)-SLLMWITQC on TCR recognition. The crystal structure of the wild-type peptide complexed with a specific TCR shows that TCR binding centers on two prominent, sequential, peptide sidechains, methionine-tryptophan. Cysteine-to-valine substitution at peptide position 9, while optimizing peptide binding to the MHC, repositions the peptide main chain and generates subtly enhanced interactions between the analogue peptide and the TCR. Binding analyses confirm tighter binding of the analogue peptide to HLA-A2 and improved soluble TCR binding. Recognition of analogue peptide stimulates faster polarization of lytic granules to the immunological synapse, reduces dependence on CD8 binding, and induces greater numbers of cross-reactive cytotoxic T lymphocyte to SLLMWITQC. These results provide important insights into heightened immunogenicity of analogue peptides and highlight the importance of incorporating structural data into the process of rational optimization of superagonist peptides for clinical trials.