gebhart/patrepeval huggingface dataset:
Telomerase inhibitors for the treatment of cancer: the current perspective (2001)

Telomerase is a holoenzyme responsible for the maintenance of telomeres, the protein-nucleic acid complexes at the ends of eukaryotic chromosomes that serve to maintain chromosomal stability and integrity. Telomerase activity is essential for the sustained proliferation of most immortal cells, including cancer cells. Since the discovery that telomerase activity is detected in 85-90% of all human tumours and tumour-derived cell lines but not in most normal somatic cells, telomerase has become the focus of much attention as a novel and potentially highly-specific target for the development of new anticancer chemotherapeutics. Herein we review the current perspective for the development of telomerase inhibitors as cancer chemotherapeutics. These include antisense strategies, reverse transcriptase inhibitors and compounds capable of interacting with high-order telomeric DNA tetraplex ("G-quadruplex") structures, so as to prevent enzyme access to the necessary linear telomere substrate. Critical appraisal of each individual approach is provided together with highlighted areas of likely future development.
Drugs that target dynamic microtubules: A new molecular perspective (2011)

Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These "biological vectors" can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule-targeting drugs work.
Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection (2014)

Influenza hemagglutinin (HA) is the primary target of the humoral response during infection/vaccination. Current influenza vaccines typically fail to elicit/boost broadly neutralizing antibodies (bnAbs), thereby limiting their efficacy. Although several bnAbs bind to the conserved stem domain of HA, focusing the immune response to this conserved stem in the presence of the immunodominant, variable head domain of HA is challenging. We report the design of a thermotolerant, disulfide-free, and trimeric HA stem-fragment immunogen which mimics the native, prefusion conformation of HA and binds conformation specific bnAbs with high affinity. The immunogen elicited bnAbs that neutralized highly divergent group 1 (H1 and H5 subtypes) and 2 (H3 subtype) influenza virus strains in vitro. Stem immunogens designed from unmatched, highly drifted influenza strains conferred robust protection against a lethal heterologous A/Puerto Rico/8/34 virus challenge in vivo. Soluble, bacterial expression of such designed immunogens allows for rapid scale-up during pandemic outbreaks.
Characterization of a-Plane GaN/(Al,Ga)N Multiple Quantum Wells Grown via Metalorganic Chemical Vapor Deposition (2003)

The structural and optical properties of a 10-period (10.7 nm GaN)/(10.1 nm Al0.25Ga0.75N) multiple quantum well structure grown on an a-plane GaN template layer were investigated. Despite high threading dislocation density (∼3×1010 cm-2) and surface undulations, abrupt quantum well interfaces produced well-defined satellite peaks out to the second order in a symmetric high-resolution X-ray diffraction scan. Thorough analysis of X-ray diffraction measurements (kinematical analysis and dynamic simulations) provided accurate measurements of the quantum well dimensions and barrier composition. Room temperature photoluminescence emission from the structure exhibits quantum confinement consistent with quantum wells free of polarization-induced electric fields.
New Phototriggers:1Extending thep-Hydroxyphenacyl π−π* Absorption Range (2000)

[equation--see text] Introducing 3-methoxy or 3,5-dimethoxy substituents on the 4-hydroxyphenacyl (pHP) photoremovable protecting group has been explored with two excitatory gamma-amino acids, L-glutamic acid and gamma-amino butyric acid (GABA). These substituents significantly extend the absorption range of the pHP chromophore, e.g., the tail of absorption bands of 2a,b extend above 400 nm, well beyond the absorptions of aromatic amino acids and nucleotides. Irradiation releases the amino acids with rate constants of approximately 10(7) s(-)(1) and appearance efficiencies (Phi(app)) of 0.03-0.04. The photoproducts are formed through the pHP excited triplet and are primarily products of photoreduction and photohydrolysis. 1a,b also rearranged to the phenylacetic acid 3.
Mitochondrial Creatine Kinase in Contact Sites: Interaction with Porin and Adenine Nucleotide Translocase, Role in Permeability Transition and Sensitivity to Oxidative Damage (2001)

The creatine/phosphocreatine circuit provides an efficient energy buffering and transport system in a variety of cells with high and fluctuating energy requirements. It connects sites of energy production (mitochondria, glycolysis) with sites of energy consumption (various cellular ATPases). The cellular creatine/phosphocreatine pool is linked to the ATP/ADP pool by the action of different isoforms of creatine kinase located at distinct subcellular compartments. Octameric mitochondrial creatine kinase (MtCK), together with porin and adenine nucleotide translocase, forms a microcompartment at contact sites between inner and outer mitochondrial membranes and facilitates the production and export into the cytosol of phosphocreatine. MtCK is probably in direct protein-protein contact with outer membrane porin, whereas interaction with inner membrane adenine nucleotide translocase is rather mediated by acidic phopholipids (like cardiolipin) present in significant amounts in the inner membrane. Octamer-dimer transitions of MtCK as well as different creatine kinase substrates have a profound influence on controlling mitochondrial permeability transition (MPT). Inactivation by reactive oxygen species of MtCK and destabilization of its octameric structure are factors that contribute to impairment of energy homeostasis and facilitated opening of the MPT pore, which eventually lead to tissue damage during periods of ischemia/reperfusion.
FORMULATION AND EVALUATION OF ION ACTIVATED OCULAR GELS OF KETOROLAC TROMETHAMINE (2010)

In­situ gels are viscous polymer‐based liquids that exhibit sol‐to‐gel phase transition on the ocular surface due to change in a specific physico‐ chemical parameter like ionic strength, pH or temperature. A major problem in ocular therapeutics is the attainment of optimal drug concentration at the site of action, which is compromised mainly due to pre‐corneal loss resulting in only a small fraction of the drug being ocularly absorbed. The effective dose administered can be altered by prolonging the retention time of medication into the eye by using in situ gels, thereby preventing the tear drainage. The objective of the present study is to formulation and evaluation of the in situ ocular gelling systems (ion activated gelling systems) of Ketorolac tromethamine. These gelling systems involve the us e of Gelrite as polymer. The formulations were evaluated for clarity, pH measurement, gelling capacity, drug content estimation, rheological study, in vitro drug release, ocular irritancy studies (as per draize test) and ex‐ vivo corneal permeation studies using isolated goats cornea. The developed formulations showed sustained release of drug for upto 6 hrs. The formulations were found to be non‐irritating with no ocular damage.
Soybean Aphid Resistance in PI 243540 Is Controlled by a Single Dominant Gene (2008)

The soybean aphid ( Aphis glycines Matsumura) is a pest of soybean [ Glycine max (L.) Merr.] in many soybean growing countries of the world. Host plant resistance is a very useful component of an integrated pest management program to control an insect problem. A maturity group (MG) IV plant introduction (PI) 243540 showed strong antibiosis resistance against the Ohio biotype of the soybean aphid. The objective of this study was to determine the inheritance of soybean aphid resistance gene(s) in PI 243540. The F 1 , F 2 , and F 2 ‐derived F 3 families from a cross between an aphid susceptible cultivar Wyandot and resistant PI 243540 were screened in a greenhouse with the Ohio biotype of the soybean aphid. All F 1 plants were resistant to the soybean aphid and χ 2 analysis of segregation of 341 F 2 plants indicated a fit to a single dominant gene ratio of 3:1 ( P = 0.51). Segregation in 330 F 2:3 families fit an expected 1:2:1 ratio ( P = 0.40). Our results indicate that a single dominant gene controls the soybean aphid resistance in PI 243540. The simple inheritance of this gene should be helpful to quickly transfer the gene to susceptible elite cultivars using the backcross breeding approach.
Cytokine‐related syndrome following injection of anti‐CD3 monoclonal antibody: Further evidence for transient in vivo T cell activation (1990)

In vivo injection of the hamster anti-murine CD3 monoclonal antibody 145 2C11 into BALB/c mice induces a massive systemic release of several cytokines. Very high circulating levels of tumor necrosis factor are detected both by enzyme-linked immunosorbent assay and L-929 bioassay 90 min following a single injection of 10 micrograms/mouse 145 2C11. Peak circulating levels of exclusively T cell-derived products such as interferon-gamma, interleukin 2 and interleukin 3 are also detected 90 min to 8 h post-injection. Importantly, this cytokine release is transient since none of these cytokines are still present 12 to 24 h post-injection. In parallel to cytokine release, 145 2C11-treated mice (10 micrograms/mouse) exhibit somnolence, hypomotility (quantified by actimetry), hypothermia, diarrhea and piloerection. At this dosage, the physical reaction is not lethal and reverses in all mice by 48 h post-injection. Severe but again reversible anatomopathological changes are also observed: massive cellular depletion, necrosis and edema of lymphoid organs, leakage syndrome and inflammatory cell infiltrates of the lung, cell vacuolization, necrosis and vascular congestion of the liver. All these data are similar to the clinical and immunological manifestations of the OKT3-induced reaction in patients and, thus, provide an invaluable experimental tool to study its mechanisms and explore its prevention.
The collaboration of both humoral and cellular HER-2/neu-targeted immune responses is required for the complete eradication of HER-2/neu-expressing tumors. (2001)

HER-2/neu (neu) transgenic mice (neu-N mice), which express the nontransforming rat proto-oncogene, demonstrate immunological tolerance to neu that is similar to what is encountered in patients with neu-expressing breast cancer. We have shown previously that a significant increase in neu-specific T cells, but no induction of neu-specific antibody, is seen after neu-specific vaccination in neu-N mice. In contrast, a significant induction of both neu-specific T-cell and antibody responses is found in nontoleragenic FVB/N mice after vaccination. These mice are fully protected from a s.c. challenge with NT cells, a mammary tumor cell line derived from a spontaneous tumor that arose in a neu-N mouse, whereas neu-N mice are not. In this study, we demonstrate that CD4+ T cell-depleted FVB/N mice show no induction of neu-specific IgG after vaccination and are unable to reject an NT challenge (0 of 10 mice were tumor free). Conversely, the depletion of natural killer cells has no effect on vaccine-mediated tumor rejection (100% of mice were tumor free). In CD8+ T cell-depleted animals, where vaccine-induced neu-specific IgG titers were normal, NT growth was delayed, but only 10% of mice remained tumor free, demonstrating that neu-specific IgG alone is insufficient for protection from NT challenge. To directly assess the necessity for the combination of neu-specific cellular and humoral immune responses, severe combined immunodeficient mice were given an adoptive transfer of CTLs plus IgG derived from FVB/N mice. Animals that were given CTLs that recognized an irrelevant antigen plus neu-specific IgG developed tumors at a rate similar to CD8+ T cell-depleted FVB/N mice. Animals receiving an adoptive transfer of neu-specific CTLs plus control IgG derived from naive FVB/N mice were only partially protected from NT challenge (50% of animals were tumor free). However, only animals receiving the combination of neu-specific CTLs and neu-specific IgG were fully protected from NT challenge (100% of animals were tumor free). These studies specifically define the immunological requirements for the eradication of neu-expressing tumors in this model system, demonstrating that both cellular and humoral neu-specific responses are necessary for protection from an NT challenge. These data suggest that vaccines optimized to induce maximal T- and B-cell immunity to neu, and possibly to similar putative tumor-rejection antigens, may lead to more potent in vivo antitumor immunity.
Purification and characterization of different molecular forms of prostate-specific antigen in human seminal fluid (1995)

We have developed a new procedure for purifying prostate-specific antigen (PSA) from human seminal fluid. The method is based on ammonium sulfate precipitation, hydrophobic interaction chromatography, gel filtration, and anion-exchange chromatography. It can be completed within 2 days with a recovery of intact PSA of 30%. By anion-exchange chromatography, five isoforms of PSA (A, B, C, D, and E) can be separated. The major form (PSA-B) consists of the intact enzyme, as shown by the occurrence of only one band of 33 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing or nonreducing conditions, and by amino acid sequencing, which reveals only one amino-terminal sequence corresponding to the reported amino-terminal sequence of intact PSA. The specific absorbance of 1 g/L PSA-B at 280 nm was 1.61, and 80% of the PSA-B formed a complex with alpha 1-antichymotrypsin, indicating that it is enzymatically active. Three cleaved forms of PSA with different nicking sites and low enzymatic activity were separated from intact PSA by ion-exchange chromatography. In addition, we isolated a glycosylation variant, PSA-A, which showed a higher isoelectric point (pI = 7.2) than PSA-B (pI = 6.9) but similar enzymatic activity; this form accounts for 5-10% of total PSA. After treatment with sialidase, PSA-A and B had the same isoelectric point value (pI = 7.7).
Energy Scalable Universal Hashing (2005)

Message authentication codes (MACs) are valuable tools for ensuring the integrity of messages. MACs may be built around a universal hash function (NH) which was explored in the construction of UMAC. In this paper, we use a variation on NH called WH. WH reaches optimally in the sense that it is universal with half the hash length of NH and it achieves perfect serialization in hardware implementation. We achieved substantial power savings of up to 59 percent and a speedup of up to 7.4 times over NH. Moreover, we show how the technique of multihashing and the Toeplitz approach can be combined to reduce the power and energy consumption even further while maintaining the same security level with a very slight increase in the amount of the key material. At low frequencies, the power and energy reductions are achieved simultaneously while keeping the hashing time constant. We developed formulae for estimation of the leakage and dynamic power consumptions as well as the energy consumption based on the frequency and the Toeplitz parameter t. We introduce a powerful method for scaling WH according to specific energy and power consumption requirements. Our implementation of WH-16 consumes only 2.95 /spl mu/W at 500 kHz. It can therefore be integrated into a self-powered device.
Titanium-mediated methylene-transfer reactions. Direct conversion of esters into vinyl ethers (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTitanium-mediated methylene-transfer reactions. Direct conversion of esters into vinyl ethersS. H. Pine, R. Zahler, D. A. Evans, and R. H. GrubbsCite this: J. Am. Chem. Soc. 1980, 102, 9, 3270–3272Publication Date (Print):April 1, 1980Publication History Published online1 May 2002Published inissue 1 April 1980https://pubs.acs.org/doi/10.1021/ja00529a076https://doi.org/10.1021/ja00529a076research-articleACS PublicationsRequest reuse permissionsArticle Views2824Altmetric-Citations267LEARN 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 Get e-Alerts
<title>Simplified active contour model applied to bone structure segmentation in digital radiographs</title> (1998)

This paper describes a segmentation technique based on a new simplified active contour scheme. The method is a compromise between dynamic programming and the original `snake' solution. It follows a two-step procedure: the first step moves the contour points toward image features using a new potential vector field; the second step smoothes out the contour using a numeric filter to impose continuity and rigidity constraints on the contour model. This technique allows a natural definition of the active contour parameters in term of local curvature and rigidity of the contour. Since it performed particularly well in very noise images, the procedure is demonstrated for segmenting bone structures of the human spine from sagittal radiographs.
Pharmacokinetics and Pharmacodynamics of Acid-suppressive Agents in Patients with Gastroesophageal Reflux Disease (1993)

Key pharmacokinetic and pharmacodynamic aspects of gastric acid-suppressive agents in patients with gastroesophageal reflux disease (GERD) are discussed. The acid-suppressive potencies of the histamine H2-receptor antagonists vary widely because of differences in clearance and other factors. The durations of action of cimetidine, ranitidine, and famotidine are similar to the dosage intervals usually chosen (6, 8, and 12 hours, respectively). Single bedtime doses of these drugs will effectively treat duodenal ulcer disease, but GERD requires a different approach since its symptoms are not well controlled by partial (less than 24-hour) suppression of gastric acid. One way to achieve greater efficacy in treating GERD is to administer higher doses more frequently. Another approach is to adjust the dosage upward until symptoms disappear. The improved acid-suppression characteristic of the proton-pump inhibitors was quickly applied to GERD therapy. Unlike the H2 antagonists, omeprazole completely suppresses circadian peaks in acid secretion, and omeprazole performs better than ranitidine in clinical trials. The use of omeprazole is limited, however, by concerns over secondary elevation of serum gastrin and the association between achlorhydria and gastric carcinoma in rats. Omeprazole may offer cost advantages over other agents. Because the effective dosages of all these agents vary, individualized dosage-adjustment strategies are necessary. Pharmacists can help to optimize treatment by monitoring pharmacodynamic markers. With a flexible approach to drug and dosage selection, it should be possible to manage GERD in most patients in a cost-effective manner.
Mapping Ligand Binding Domains in Chimeric Fibroblast Growth Factor Receptor Molecules (1999)

Fibroblast growth factors (FGFs) mediate essential cellular functions by activating one of four alternatively spliced FGF receptors (FGFRs). To determine the mechanism regulating ligand binding affinity and specificity, soluble FGFR1 and FGFR3 binding domains were compared for activity. FGFR1 bound well to FGF2 but poorly to FGF8 and FGF9. In contrast, FGFR3 bound well to FGF8 and FGF9 but poorly to FGF2. The differential ligand binding specificity of these two receptors was exploited to map specific ligand binding regions in mutant and chimeric receptor molecules. Deletion of immunoglobulin-like (Ig) domain I did not effect ligand binding, thus localizing the binding region(s) to the distal two Ig domains. Mapping studies identified two regions that contribute to FGF binding. Additionally, FGF2 binding showed positive cooperativity, suggesting the presence of two binding sites on a single FGFR or two interacting sites on an FGFR dimer. Analysis of FGF8 and FGF9 binding to chimeric receptors showed that a broad region spanning Ig domain II and sequences further N-terminal determines binding specificity for these ligands. These data demonstrate that multiple regions of the FGFR regulate ligand binding specificity and that these regions are distinct with respect to different members of the FGF family.
Advanced satellite system architecture for VSATs with ISDN compatibility (1988)

This paper describes a future communications satellite system architecture concept which allows the use of Very Small Aperature Terminals (VSATs) of 1.2 m to 1.8 m diameter and which provides access according to the international Integrated Services Digital Network (ISDN) standard. This satellite system design could make dial-up integrated voice and data service available nationwide and perhaps worldwide. The paper gives a conceptual system design based on the year 1995 technology for the communications satellite, the earth terminal, and the ground-based master control station and interface to the terrestrial ISDN network.
Utilizing surplus timing for power reduction (2002)

Multiple Vdd's, multiple Vth's, and multiple transistor width for utilizing surplus timing in non-critical paths for power reduction is investigated. Theoretical models are developed from which rules of thumb for optimum Vdd's, Vth's, and W's are derived, as well as knowledge for future design.