gebhart/patrepeval huggingface dataset:
Crizotinib: ALK/Met inhibitor, oncolytic (2011)

There are a number of molecular abnormalities that can occur in normal cells to induce a malignant phenotype. Recently, the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) has been shown to have gain-of-function when partnered with different proteins. As an example, on chromosome 2p, with inversion, there is translocation with generation of EML4-ALK tyrosine kinase in lung cancer. In a phase I trial, EML4-ALK patients were selected to determine the response to a potent small molecule tyrosine kinase inhibitor crizotinib (previously identified as PF02341066). Dramatic durable responses were observed with crizotinib at 250 mg twice a day (orally). Interestingly, crizotinib also has activity against MET receptor tyrosine kinase. We have previously shown that MET can be overexpressed, sometimes mutated, or sometimes amplified in lung cancer. Thus, this review will emphasize the characteristics of crizotinib, and detail the clinical experience.
Immunoprotection against systemic candidiasis in mice (1995)

We have previously described an immunosuppressive B cell mitogenic (ISM) protein, p43, produced by Candida albicans, which plays an important role in the survival of the microorganism in the host. The N-terminal amino acid sequence of p43 was found to be different from all amino acid sequences registered in updated protein databanks. Immunization of BALB/c mice with p43 partially neutralized the biological effects of this protein, namely depletion of bone marrow pre-B and B cells, the increased numbers of total and large B and CD4+ lymphocytes, and the nonspecific polyclonal response of splenic IgG2a-, IgG2b- and IgM-secreting plaque forming cells.immunization of BALB/c mice with p43 fully protected the mice against the fungal infection. In contrast, immunization with C. albicans sonicates (Cs) was not protective. Our data indicated that specific antibodies against p43 protected, whereas those against Cs facilitated C. albicans infection. Thus, the ratio between anti-p43 and anti-Cs antibody titres was much lower in the non-protected mice (Cs-immunized and control non-immunized) than in p43-immunized mice. Moreover, passive administration of specific anti-p43 antibodies significantly protected against fungal infection, whereas passive administration of specific anti-Cs antibodies markedly increased the susceptibility to C. albicans Infection. These observations are discussed on the basis of alternative approaches of immunointervention.
A kinase-deficient TrkC receptor isoform activates Arf6–Rac1 signaling through the scaffold protein tamalin (2006)

Neurotrophins play an essential role in mammalian development. Most of their functions have been attributed to activation of the kinase-active Trk receptors and the p75 neurotrophin receptor. Truncated Trk receptor isoforms lacking the kinase domain are abundantly expressed during development and in the adult; however, their function and signaling capacity is largely unknown. We show that the neurotrophin-3 (NT3) TrkCT1-truncated receptor binds to the scaffold protein tamalin in a ligand-dependent manner. Moreover, NT3 initiation of this complex leads to activation of the Rac1 GTPase through adenosine diphosphate-ribosylation factor 6 (Arf6). At the cellular level, NT3 binding to TrkCT1-tamalin induces Arf6 translocation to the membrane, which in turn causes membrane ruffling and the formation of cellular protrusions. Thus, our data identify a new signaling pathway elicited by the kinase-deficient TrkCT1 receptor. Moreover, we establish NT3 as an upstream regulator of Arf6.
Magnesium Complexes of Bis(phosphinimine)methane and -methanide Ligands (2002)

Mg complexes of bis(phosphoranimine)methane and -methanide ligands have been characterized. Reaction of CH2(Ph2PNSiMe3)2with MeMgI and MeMgCl gave the crystalline products CH2(Ph2PNSiMe3)2MgI2 (1) and [HC(Ph2PNSiMe3)2Mg(μ-Cl)]2 (2), respectively. The related reaction of LiCH(Ph2PNSiMe3)2 with MeMgI afforded CH(Ph2PNSiMe3)2MgI(THF) (3). Crystallographic data for 1−3 confirm a significant Mg−C interaction in complexes containing bis(phosphoranimine)methanide ligands.
The TD50: a proposed general convention for the numerical description of the carcinogenic potency of chemicals in chronic-exposure animal experiments. (1984)

A generally accepted format for the numerical description of the carcinogenic potency of a particular chemical in a particular strain of animals is desirable so that statements from different sources about potency and attempts by different authors to correlate potency with particular laboratory measurements will be comparable. The choice of an appropriate standard format is to a certain extent arbitrary. In this paper we recommend that the TD50 (tumorigenic dose rate 50) be used. TD50 can be calculated for a single target site or combination of sites. The TD50, in analogy with the LD50, is defined as that chronic dose rate (in mg/kg body weight/day) which would halve the actuarially adjusted percentage of tumor-free animals at the end of a standard experiment time--the
Ghrelin Protects Against Ethanol-Induced Gastric Ulcers in Rats: Studies on the Mechanisms of Action (2002)

Ghrelin, the endogenous ligand for GH secretagogue receptors, has been reported to influence acid gastric secretion and motility, but its potential gastroprotective effect is unknown. The aims of this study were 1) to examine the effects of central and peripheral administration of ghrelin on ethanol-induced gastric ulcers in conscious rats, and 2) to investigate the possible roles of nitric oxide (NO), vagal nerve, and sensory fibers in the gastric effects of ghrelin. Ghrelin was administered either intracerebroventricularly or sc 30 min before ethanol, and mucosal lesions were examined macroscopically. Additionally, rats were either treated with the inhibitor of NO synthesis N(omega)-nitro-L-arginine methyl ester (L-NAME) or underwent bilateral cervical vagotomy or capsaicin-induced sensory denervation. Conventional histology and immunohistochemistry for ghrelin, gastrin, and somatostatin were performed on gastric specimens from representative rats. Central ghrelin (4-4,000 ng/rat) dose-dependently reduced ethanol-induced gastric ulcers by 39-77%. Subcutaneous ghrelin administration (80 micro g/kg) reduced ulcer depth only. L-NAME and capsaicin, but not vagotomy, prevented the gastroprotective effect of central ghrelin (4000 ng/rat). This is the first evidence that ghrelin exerts a potent central gastroprotective activity against ethanol-induced lesions. The gastroprotective effect of ghrelin is mediated by endogenous NO release and requires the integrity of sensory nerve fibers.
Feline Model of Acute Nipah Virus Infection and Protection with a Soluble Glycoprotein-Based Subunit Vaccine (2006)

Nipah virus (NiV) and Hendra virus (HeV) are paramyxoviruses capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. Case reports from outbreaks and previous challenge experiments have suggested that cats were highly susceptible to NiV infection, responding with a severe respiratory disease and systemic infection. Here we have assessed the cat as a model of experimental NiV infection and use it in the evaluation of a subunit vaccine comprised of soluble G glycoprotein (sG). Two groups of two adult cats each were inoculated subcutaneously with either 500 or 5,000 50% tissue culture infective dose(s) (TCID(50)) of NiV. Animals were monitored closely for disease onset, and extensive analysis was conducted on samples and tissues taken during infection and at necropsy to determine viral load and tissue tropism. All animals developed clinical disease 6 to 9 days postinfection, a finding consistent with previous observations. In a subsequent experiment, two cats were immunized with HeV sG and two were immunized with NiV sG. Homologous serum neutralizing titers were greater than 1:20,000, and heterologous titers were greater than 1:20,000 to 16-fold lower. Immunized animals and two additional naive controls were then challenged subcutaneously with 500 TCID(50) of NiV. Naive animals developed clinical disease 6 to 13 days postinfection, whereas none of the immunized animals showed any sign of disease. TaqMan PCR analysis of samples from naive animals revealed considerable levels of NiV genome in a wide range of tissues, whereas the genome was evident in only two immunized cats in only four samples and well below the limit of accurate detection. These results indicate that the cat provides a consistent model for acute NiV infection and associated pathogenesis and an effective subunit vaccine strategy appears achievable.
Über zweistufige Redoxsysteme, XXI1) Synthese vinyloger und azavinyloger Redoxsysteme mit Indolylresten als Endgruppen (1976)

Abstract Es werden Synthesen für die Polyene 1 H,n; 1 , n; 2 , n; 3H ,n und 3,n (n = 0‐5) beschrieben, die als Endgruppen in 3‐Stellung verknüpfte Indolreste tragen und Beispiele für zweistufige Redoxsysteme vom „Hybrid‐Typ”︁ sind. Außerdem wird über die Synthese von Azaderivaten sowie eines 3,3′‐Azoindazols berichtet. ‐ Ein Teil der Verbindungen läßt sich zum stabilen Radikalkation und zum Dikation oxidieren.
Electrochemical Reduction of Carbon Dioxide on Various Metal Electrodes in Low‐Temperature Aqueous  KHCO 3 Media (1990)

Electrochemical reduction was investigated on 32 metal electrodes in aqueous medium. The current efficiency of reduction on Ni, Ag, Pb, and Pd increases significantly with lowering the temperature. The ratio of reduction products are also changed by lowering temperature. Potential dependence of and on an Hg electrode supports the electron transfer mechanism for production. Formation of methane and ethylene is observed on almost all metal electrodes used, although the efficiency is mainly very low except for Cu. A periodic table for reduction, which is drawn based on the dependence of reduction products on various metals, suggests the existence of a systematic rule for the electrocatalytic reduction of on metal surfaces.
Memo Is a Copper-Dependent Redox Protein with an Essential Role in Migration and Metastasis (2014)

Memo is an evolutionarily conserved protein with a critical role in cell motility. We found that Memo was required for migration and invasion of breast cancer cells in vitro and spontaneous lung metastasis from breast cancer cell xenografts in vivo. Biochemical assays revealed that Memo is a copper-dependent redox enzyme that promoted a more oxidized intracellular milieu and stimulated the production of reactive oxygen species (ROS) in cellular structures involved in migration. Memo was also required for the sustained production of the ROS O2- by NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 1 (NOX1) in breast cancer cells. Memo abundance was increased in >40% of the primary breast tumors tested, was correlated with clinical parameters of aggressive disease, and was an independent prognostic factor of early distant metastasis.
Angiotensin's role in renal development. (1997)

All the components of the renin-angiotensin system (RAS) are highly expressed in the developing kidney in a unique spatial and temporal pattern that is associated with nephrogenesis, vascularization, and the proper architectural and functional development of this organ. Pharmacological inhibition of the RAS results in structural and functional developmental abnormalities of the kidneys in several animal species, including humans. Similarly, altered renal morphology and functional abnormalities have been described in mice with targeted inactivation of the angiotensinogen (Agt) and the angiotensin-converting enzyme (ACE) genes. In contrast, inactivation of angiotensin receptors have not resulted in renal morphological abnormalities, suggesting a redundancy at this level of the RAS cascade that prevents the development of renal pathology. More importantly, inactivation of the ACE or Ao genes results in a renal phenotype remarkably similar to that obtained with pharmacological inhibition of the RAS. Taken together, the available information suggests that angiotensin is necessary for normal kidney development and for the maintenance of the functional and structural integrity of the adult kidney.
Development of a Multiplexed Tumor-Associated Autoantibody-Based Blood Test for the Detection of Non–Small Cell Lung Cancer (2010)

We developed a six-autoantibody algorithm for detecting cases of NSCLC among several high-risk populations. Population-based validation studies are now required to assign the true value of this tool for identifying early-stage NSCLC.
Electrokinetic Bioprocessor for Concentrating Cells and Molecules (2004)

Bioprocessors for concentrating bioparticles, such as cells and molecules, are commonly needed in bioanalysis systems. In this microfluidic processor, a global flow field generated by ac electroosmosis transports the embedded particles to the regions near the electrode surface. The processor then utilizes electrophoretic and dielectrophoretic forces, which are effective in short range, to trap the target cells and molecules on the electrode surface. By optimizing the operating parameters, we have concentrated various biological objects in a large range of sizes, including Escherichia coli bacteria, lambda phage DNA, and single-stranded DNA fragments as small as 20 bases that have a radius of gyration of only 3 nm.
Evolving and Experimental Technologies in Medical Imaging (2006)

Medical images are created by detecting radiation probes transmitted through or emitted or scattered by the body. The radiation, modulated through interactions with tissues, yields patterns that provide anatomic and/or physiologic information. X-rays, gamma rays, radiofrequency signals, and ultrasound waves are the standard probes, but others like visible and infrared light, microwaves, terahertz rays, and intrinsic and applied electric and magnetic fields are being explored. Some of the younger technologies, such as molecular imaging, may enhance existing imaging modalities; however, they also, in combination with nanotechnology, biotechnology, bioinformatics, and new forms of computational hardware and software, may well lead to novel approaches to clinical imaging. This review provides a brief overview of the current state of image-based diagnostic medicine and offers comments on the directions in which some of its subfields may be heading.
Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. (1989)

We have demonstrated previously that mild intraischemic hypothermia confers a marked protective effect on the final histopathological outcome. The present study was carried out to evaluate whether this protective effect involves changes in the degree of local cerebral blood flow reductions, tissue accumulation of free fatty acids, or alterations in the extracellular release of glutamate and dopamine. Rats whose intraischemic brain temperature was maintained at 36 degrees C, 33 degrees C, or 30 degrees C were subjected to 20 minutes of ischemia by four-vessel occlusion combined with systemic hypotension. Levels of local cerebral blood flow, as measured autoradiographically, were reduced uniformly in all experimental animals at the end of ischemia by gas chromatography after tissue extraction and separation by thin layer chromatography. A massive ischemia-induced accumulation of individual free fatty acids was observed in animal groups whose intraischemic brain temperature was maintained at either 36 degrees C or 30 degrees C. Extracellular neurotransmitter levels were measured by microdialysis; the perfusate was collected before, during, and after ischemia. In rats whose intraischemic brain temperature was maintained at 36 degrees C, dopamine and glutamate increased significantly during ischemia and the early period of recirculation (by 500-fold and sevenfold, respectively). In animals whose brain temperature was maintained at 33 degrees C and 30 degrees C, the release of glutamate was completely inhibited, and the release of dopamine was significantly attenuated (by 60%). These results suggest that mild intraischemic hypothermia does not affect the ischemia-induced local cerebral blood flow reduction or free fatty acid accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Derivatives of p,p'-Diaminodiphenyl Sulfone1a (1945)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDerivatives of p,p'-Diaminodiphenyl Sulfone1aHans Heymann and Louis F. FieserCite this: J. Am. Chem. Soc. 1945, 67, 11, 1979–1986Publication Date (Print):November 1, 1945Publication History Published online1 May 2002Published inissue 1 November 1945https://pubs.acs.org/doi/10.1021/ja01227a035https://doi.org/10.1021/ja01227a035research-articleACS PublicationsRequest reuse permissionsArticle Views376Altmetric-Citations14LEARN 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
Bone Mineral Density in Sclerosteosis; Affected Individuals and Gene Carriers (2005)

Heterozygous carriers of sclerosteosis have BMD values consistently higher than the mean of healthy subjects without any of the bone complications encountered in homozygotes. This finding suggests that the production and/or activity of sclerostin can be titrated in vivo, leading to variable increases in bone mass without any unwanted skeletal effects, a hypothesis of obvious significance for the development of new therapeutics for osteoporosis.
Power dependence of upconversion luminescence in lanthanide and transition-metal-ion systems (2000)

We show theoretically with the simplest possible model that the intensity of an upconversion luminescence that is excited by the sequential absorption of n photons has a dependence on absorbed pump power P, which may range from the limit of ${P}^{n}$ down to the limit of ${P}^{1}$ for the upper state and less than ${P}^{1}$ for the intermediate states. The two limits are identified as the cases of infinitely small and infinitely large upconversion rates, respectively. In the latter case, the dependence of luminescence intensities from intermediate excited states on pump power changes with the underlying upconversion and decay mechanisms. In certain situations, energy-transfer upconversion and excited-state absorption can be distinguished by the measured slopes. The competition between linear decay and upconversion in the individual excitation steps of sequential upconversion can be analyzed. The influence of nonuniform distributions of absorbed pump power or of a subset of ions participating in energy-transfer upconversion is investigated. These results are of importance for the interpretation of excitation mechanisms of luminescent and laser materials. We verify our theoretical results by experimental examples of multiphoton-excited luminescence in ${\mathrm{Cs}}_{3}{\mathrm{Lu}}_{2}{\mathrm{Cl}}_{9}{:\mathrm{E}\mathrm{r}}^{3+},$ ${\mathrm{Ba}}_{2}{\mathrm{YCl}}_{7}{:\mathrm{E}\mathrm{r}}^{3+},$ ${\mathrm{LiYF}}_{4}{:\mathrm{N}\mathrm{d}}^{3+},$ and ${\mathrm{Cs}}_{2}{\mathrm{ZrCl}}_{6}{:\mathrm{R}\mathrm{e}}^{4+}.$
On-line selection of discriminative tracking features (2003)

We present a method for evaluating multiple feature spaces while tracking, and for adjusting the set of features used to improve tracking performance. Our hypothesis is that the features that best discriminate between object and background are also best for tracking the object. We develop an online feature selection mechanism based on the two-class variance ratio measure, applied to log likelihood distributions computed with respect to a given feature from samples of object and background pixels. This feature selection mechanism is embedded in a tracking system that adaptively selects the top-ranked discriminative features for tracking. Examples are presented to illustrate how the method adapts to changing appearances of both tracked object and scene background.
Synergy between TLR9 and NOD2 innate immune responses is lost in genetic Crohn's disease (2005)

NOD2 stimulation normally enhances innate immune responses to CpG DNA. This marked synergistic effect is lost in Crohn's disease patients homozygous for NOD2 mutations, with implications for TLR mediated intestinal homeostasis and inflammation.
MODELLING RESIDENCE TIME AS ADVECTION- DIFFUSION WITH ZERO-ORDER REACTION KINETICS (2000)

As an alternative to the particle tracking-based residence time calculations, a finite difference approach using the conventional advection-diffusion-reaction kinetics equation for describing the evolution of the residence time field is derived. Advection and mixing of water masses is accompanied with their ageing following a simple zero-order kinetics rule. The governing equations are solved by finite differences with special attention to the approximation of the advective terms. To reduce numerical errors in the presence of sharp gradients robust upwind schemes are implemented. The sample applications demonstrate the main features of the approach including steady-state flow in a channel with groins and aquatic vegetation patches, reservoir through-flow with superimposed wind effect, and time-periodic flow in a bay.
Deafness Complicating Antibiotic Therapy of Hepatic Encephalopathy (1970)

Five cases of ototoxicity associated with the oral administration of neomycin are reported. The absence of renal failure but the presence of low serum antibiotic levels in these cases suggests that with prolonged exposure even minimal absorption can be toxic. Additional observations suggest that the related drug paromomycin may be similarly dangerous.
Dihydrogen Reduction of Carboxylic Esters to Alcohols under the Catalysis of Homogeneous Ruthenium Complexes: High Efficiency and Unprecedented Chemoselectivity (2007)

The missing link: The presence of two N,P bridges in the ruthenium complexes used as catalysts for the title reaction is essential. Esters that contain isolated CC bonds are reduced to the corresponding unsaturated alcohols in high yields with high chemoselectivity (see example). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z701015_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.