gebhart/patrepeval huggingface dataset:
Chemical ionization mass spectrometry with lithium ion attachment to the molecule (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemical ionization mass spectrometry with lithium ion attachment to the moleculeToshihiro. Fujii, Miyoshi. Ogura, and Hitoshi. JimbaCite this: Anal. Chem. 1989, 61, 9, 1026–1029Publication Date (Print):May 1, 1989Publication History Published online1 May 2002Published inissue 1 May 1989https://pubs.acs.org/doi/10.1021/ac00184a022https://doi.org/10.1021/ac00184a022research-articleACS PublicationsRequest reuse permissionsArticle Views380Altmetric-Citations64LEARN 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
Lung organoids: current uses and future promise (2017)

Lungs are composed of a system of highly branched tubes that bring air into the alveoli, where gas exchange takes place. The proximal and distal regions of the lung contain epithelial cells specialized for different functions: basal, secretory and ciliated cells in the conducting airways and type II and type I cells lining the alveoli. Basal, secretory and type II cells can be grown in three-dimensional culture, with or without supporting stromal cells, and under these conditions they give rise to self-organizing structures known as organoids. This Review summarizes the different methods for generating organoids from cells isolated from human and mouse lungs, and compares their final structure and cellular composition with that of the airways or alveoli of the adult lung. We also discuss the potential and limitations of organoids for addressing outstanding questions in lung biology and for developing new drugs for disorders such as cystic fibrosis and asthma.
Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot–Marie–Tooth neuropathy (2009)

Dominant-intermediate Charcot-Marie-Tooth neuropathy (DI-CMT) is characterized by axonal degeneration and demyelination of peripheral motor and sensory neurons. Three dominant mutations in the YARS gene, encoding tyrosyl-tRNA synthetase (TyrRS), have so far been associated with DI-CMT type C. The molecular mechanisms through which mutations in YARS lead to peripheral neuropathy are currently unknown, and animal models for DI-CMTC are not yet available. Here, we report the generation of a Drosophila model of DI-CMTC: expression of the 3 mutant--but not wild type--TyrRS in Drosophila recapitulates several hallmarks of the human disease, including a progressive deficit in motor performance, electrophysiological evidence of neuronal dysfunction and morphological signs of axonal degeneration. Not only ubiquitous, but also neuron-specific expression of mutant TyrRS, induces these phenotypes, indicating that the mutant enzyme has cell-autonomous effects in neurons. Furthermore, biochemical and genetic complementation experiments revealed that loss of enzymatic activity is not a common feature of DI-CMTC-associated mutations. Thus, the DI-CMTC phenotype is not due to haploinsufficiency of aminoacylation activity, but most likely to a gain-of-function alteration of the mutant TyrRS or interference with an unknown function of the WT protein. Our results also suggest that the molecular pathways leading to mutant TyrRS-associated neurodegeneration are conserved from flies to humans.
Hyaluronan and hyaluronidase in genitourinary tumors (2008)

Genitourinary cancers are the most frequently diagnosed cancers in men and the fifth most common in women. Management of disease through accurate and cost effective early diagnostic markers, as well as identification of valid prognostic indicators, has contributed significantly to improved treatment outcomes. In this review, we will discuss the function, regulation and clinical utility of hyaluronan (HA), genes encoding its metabolic enzymes and receptors that mediate its cellular effects. Specific HA synthase (HAS) and hyaluronidase (HAase) genes encode the enzymes that produce HA polymers and oligosaccharides, respectively. Differential effects of these enzymes in progression of genitourinary tumors are determined by the relative balance between HAS and HAase levels, as well as the distribution of receptors. The genes are regulated in a complex fashion at the transcriptional and post-translational levels, but also by epigenetic events, alternative mRNA splicing, and subcellular localization. Importantly, the major tumor-derived HAase enzyme, HYAL-1, either alone or together with HA, is an accurate diagnostic and prognostic marker for genitourinary tumors.
Microstructural Organization of the Cingulum Tract and the Level of Default Mode Functional Connectivity (2008)

The default mode network is a functionally connected network of brain regions that show highly synchronized intrinsic neuronal activation during rest. However, less is known about the structural connections of this network, which could play an important role in the observed functional connectivity patterns. In this study, we examined the microstructural organization of the cingulum tract in relation to the level of resting-state default mode functional synchronization. Resting-state functional magnetic resonance imaging and diffusion tensor imaging data of 45 healthy subjects were acquired on a 3 tesla scanner. Both structural and functional connectivity of the default mode network were examined. In all subjects, the cingulum tract was identified from the total collection of reconstructed tracts to interconnect the precuneus/posterior cingulate cortex and medial frontal cortex, key regions of the default mode network. A significant positive correlation was found between the average fractional anisotropy value of the cingulum tract and the level of functional connectivity between the precuneus/posterior cingulate cortex and medial frontal cortex. Our results suggest a direct relationship between the structural and functional connectivity measures of the default mode network and contribute to the understanding of default mode network connectivity.
Synergistic Roles of Neuregulin-1 and Insulin-like Growth Factor-I in Activation of the Phosphatidylinositol 3-Kinase Pathway and Cardiac Chamber Morphogenesis (1999)

Cardiac chamber morphogenesis requires the coordinated growth of both cardiac muscle and endocardial cell lineages. Paracrine growth factors may modulate the coordinated cellular specification and differentiation during cardiac chamber morphogenesis, as suggested by the essential role of endothelial-derived growth factors, neuregulin-1, and insulin-like growth factor-I. Using the whole mouse embryo culture system for delivery of diffusible factors into the cardiac chamber, neuregulin-1 was shown to promote trabeculation of the ventricular wall. Another factor, insulin-like growth factor-I, had no apparent effect by itself. Combined treatment with neuregulin-1 and insulin-like growth factor-I strongly induced DNA synthesis of cardiomyocytes and expansion of both the ventricular compact zone and the atrioventricular cushions leading to chamber growth and maturation. In cultured cardiomyocytes, combined neuregulin-1 and insulin-like growth factor-I also had a synergistic effect to promote DNA synthesis and cellular growth, which were prevented by wortmannin, an inhibitor of phosphatidylinositol 3-kinase. Adenoviral delivery of dominant negative Rac1, which acts downstream of phosphatidylinositol 3-kinase, blocked the effect of combined neuregulin-1/insulin-like growth factor-I treatment. These studies support the concept that the interaction of neuregulin-1 and insulin-like growth factor-I pathways plays an important role in coordinating cardiac chamber morphogenesis and may occur through convergent activation of phosphatidylinositol 3-kinase.
Chimeric α 2 -,β 2 -Adrenergic Receptors: Delineation of Domains Involved in Effector Coupling and Ligand Binding Specificity (1988)

The alpha 2 and beta 2 adrenergic receptors, both of which are activated by epinephrine, but which can be differentiated by selective drugs, have opposite effects (inhibitory and stimulatory) on the adenylyl cyclase system. The two receptors are homologous with each other, rhodopsin, and other receptors coupled to guanine nucleotide regulatory proteins and they contain seven hydrophobic domains, which may represent transmembrane spanning segments. The function of specific structural domains of these receptors was determined after construction and expression of a series of chimeric alpha 2-,beta 2-adrenergic receptor genes. The specificity for coupling to the stimulatory guanine nucleotide regulatory protein lies within a region extending from the amino terminus of the fifth hydrophobic domain to the carboxyl terminus of the sixth. Major determinants of alpha 2- and beta 2-adrenergic receptor agonist and antagonist ligand binding specificity are contained within the seventh membrane spanning domain. Chimeric receptors should prove useful for elucidating the structural basis of receptor function.
Report on a working session on security in wireless ad hoc networks (2003)

© ACM, (2003). This is the author’s version of the work. It is posted here by permission of ACM for your personaluse. Not for redistribution. The definitive version was published in ACM SIGMOBILE Mobile Computing and Communications Review Volume 7 Issue 1, January 2003. http://doi.acm.org/10.1145/881978.882002 QC 20110712
Kinetic analysis of a protein antigen-antibody interaction limited by mass transport on an optical biosensor (1997)

Using BIAcore technology, we determined the rate constants for a protein antigen-antibody interaction that was mass transport limited on the optical biosensor. The antigen consisted of a soluble form of the human T-cell receptor CD4 (two amino terminal domains, D1D2) and the antibody was an anti-CD4 monoclonal from monkey engineered with the constant domains from human IgG1. High quality response data were obtained for this interaction by orienting the attachment of the antibody on the sensor surface and correcting for instrument artifacts with control experiments. Using numerical integration and global fitting, we demonstrate that a mass transport limited reaction was the only model of those tested that described well D1D2 binding to three different surface densities of the antibody. Statistical profiling techniques showed that the error space and correlation for the parameters in the non-linear model were essentially linear, but only when the model was simultaneously fitted to data from multiple surface densities. The "on" and "off" rate constants (1.2 x 10(-6) M-1 s-1 and 2.9 x 10(-4) s-1) determined from the kinetic analysis predict an equilibrium dissociation constant (KD = 0.24 +/- 0.01 nM) that agrees with the value measured in solution by titration calorimetry (KD = 0.2 +/- 0.1 nM). The results indicate that, although the D1D2-antibody reaction is partially controlled by mass transport on the optical biosensor, by optimizing the experimental design and analyzing data from multiple surface densities it is possible to determine accurate estimates of the intrinsic equilibrium and kinetic rate constants.
Substrate Specificity Is Determined by Amino Acid Binding Pocket Size in Escherichia coli Phenylalanyl-tRNA Synthetase (1994)

Alanine at position 294 (Ala294) within the motif 3 consensus of Escherichia coli phenylalanyl-tRNA synthetase alpha subunit has previously been implicated as a determinant of amino acid specificity. To characterize the role of Ala294, the catalytic effects of amino acid replacements at this position were tested with purified wild-type and mutant phenylalanyl-tRNA synthetases. We show that Ala294 is involved in amino acid binding and that it influences specificity as a determinant of binding pocket size. Replacement of Ala294 by either glycine or serine, thereby increasing or decreasing the size of the binding pocket, respectively, reduces affinity for phenylalanine. The Gly294 mutant shows a relaxed specificity toward synthetic para-halogenated phenylalanine analogues, the apparent dissociation constant Km increasing in direct relation to an increase of the van der Waals radius of the para group, thus confirming the role of position 294 in determining amino acid binding pocket size. For the substrate analogue p-chlorophenylalanine, attachment to tRNA and in vivo incorporation into cellular protein by the Gly294 mutant were demonstrated. Tyrosine activation was also improved with this mutant, but the resulting enzyme-Tyr-adenylate complex was rapidly hydrolyzed, indicating the presence of a proofreading mechanism in E. coli phenylalanyl-tRNA synthetase.
Cytokinin biosynthesis and interconversion (1997)

To maintain hormone homeostasis, the rate of cytokinin biosynthesis, interconversion, and degradation is regulated by enzymes in plant cells. Cytokinins can be synthesized via direct (de novo) or indirect (tRNA) pathways. In the de novo pathway, a cytokinin nucleotide is synthesized from 5′‐AMP and isopentenyl pyrophosphate; a key enzyme which catalyzes this synthesis has been isolated from plant tissues, slime mold, and some microorganisms. Studies on the in vitro synthesis of the isopentenyl side chain of cytokinin in tRNA demonstrated that the isopentenyl group was derived from mevalonate, and turnover of the cytokinin‐containing tRNA may serve as a minor source of free cytokinins in plant cells. The interconversion of cytokinin bases, nucleosides and nucleotides is a major feature of cytokinin metabolism; and enzymes that regulate the interconversion have been identified. The N 6 ‐side chain and purine moiety of cytokinins are often modified and some of the enzymes involved in the modifications have been isolated. Most of the cytokinin metabolites have been characterized but very few enzymes regulating their metabolism have been purified to homogeneity. It remains a significant challenge to isolate plant genes involved in the regulation of cytokinin biosynthesis, interconversion and degradation.
L-Lactic Acid as a Factor in the Attraction of Aedes aegypti (Diptera: Culicidae) to Human Hosts2 (1970)

L(+)-lactic acid in the concentrations given off by human hands was shown in olfactometer tests to be an attractant for avid female Aedes aegypti (L.). The amount recovered by rinsing the hands with acetone ranged from 258 to 1225 micrograms; the amount evaporating from the hands ranged from 23 to 133 micrograms per hour. The regression lines (micrograms lactic acid per percent mosquitoes trapped) obtained in 4 tests with each of 11 subjects were significant, but other factors also influenced individual differences in attractiveness. Vapors from authentic L(+)-lactic acid released from glass sample tubes at rates comparable to those released from hands were attractive either in combination with carbon dioxide (CO2) in filtered air, or alone in room air. However, the synergistic effect of CO2 on the response to lactic acid did not persist more than a few seconds after the mosquitoes left an atmosphere rich in CO3. Breath contained more L(+)-lactic acid than vapor from the hands but was less attractive, probably because it also contained an excess of moisture. D(—)-lactic acid was less attractive than L(+)- lactic acid at low concentrations and in direct competition at higher concentrations. A stocking treated with L(+)-lactic acid at 3.56 milligrams per square centimeter (about 1000–8000 times the amount on hands) was repellent, i.e., the treatment reduced the number of mosquitoes landing and biting. However, in the olfactometer, vapors from this stocking were attractive, at least at a distance of 45 centimeters. Application of a repellent (deet) to the hands did not reduce the amount of lactic acid vapor released.
Deformation Potentials in Silicon. III. Effects of a General Strain on Conduction and Valence Levels (1963)

Using a self-consistent perturbation theory developed in the first two papers of this series we have calculated the deformation potentials for a general strain for points of high symmetry ($\ensuremath{\Gamma}$, $X$, and $L$) in the conduction and valence bands of Si. We compare our calculated results with experimental values for (1) hydrostatic-pressure dependence of various energy gaps, (2) uniaxial-strain dependence of the splitting of the fourfold degenerate level at the top of the valence band, and (3) uniaxial strain dependence of the splitting of the degeneracy between equivalent valleys at the bottom of the conduction band. The agreement between theory and experiment ranges from fair to good.
A Personalized Approach to Managing Inflammatory Bowel Disease. (2016)

The management of inflammatory bowel disease (IBD) requires a personalized approach to treat what is a heterogeneous group of patients with inherently variable disease courses. In its current state, personalized care of the IBD patient involves identifying patients at high risk for rapid progression to complications, selecting the most appropriate therapy for a given patient, using therapeutic drug monitoring, and achieving the individualized goal that is most appropriate for that patient. The growing body of research in this area allows clinicians to better predict outcomes for individual patients. Some paradigms, especially within the realm of therapeutic drug monitoring, have begun to change as therapy is targeted to individual patient results and goals. Future personalized medical decisions may allow specific therapeutic plans to draw on serologic, genetic, and microbial data for Crohn's disease and ulcerative colitis patients.
An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to the Tropomyosin-Related Kinase Inhibitor LOXO-101 (2015)

TRK fusions have been deemed putative oncogenic drivers, but their clinical significance remained unclear. A patient with a metastatic soft-tissue sarcoma with an LMNA-NTRK1 fusion had rapid and substantial tumor regression with a novel, highly selective TRK inhibitor, LOXO-101, providing the first clinical evidence of benefit from inhibiting TRK fusions.
An Interior-Point Method for Large-Scale -Regularized Least Squares (2007)

Recently, a lot of attention has been paid to regularization based methods for sparse signal reconstruction (e.g., basis pursuit denoising and compressed sensing) and feature selection (e.g., the Lasso algorithm) in signal processing, statistics, and related fields. These problems can be cast as -regularized least-squares programs (LSPs), which can be reformulated as convex quadratic programs, and then solved by several standard methods such as interior-point methods, at least for small and medium size problems. In this paper, we describe a specialized interior-point method for solving large-scale -regularized LSPs that uses the preconditioned conjugate gradients algorithm to compute the search direction. The interior-point method can solve large sparse problems, with a million variables and observations, in a few tens of minutes on a PC. It can efficiently solve large dense problems, that arise in sparse signal recovery with orthogonal transforms, by exploiting fast algorithms for these transforms. The method is illustrated on a magnetic resonance imaging data set.
Evidence for a Stable Interaction of gp41 with Pr55Gagin Immature Human Immunodeficiency Virus Type 1 Particles (2000)

Assembly of infectious human immunodeficiency virus type 1 (HIV-1) virions requires incorporation of the viral envelope glycoproteins gp41 and gp120. Several lines of evidence have suggested that the cytoplasmic tail of the transmembrane glycoprotein, gp41, associates with Pr55(Gag) in infected cells to facilitate the incorporation of HIV-1 envelope proteins into budding virions. However, direct evidence for an interaction between gp41 and Pr55(Gag) in HIV-1 particles has not been reported. To determine whether gp41 is associated with Pr55(Gag) in HIV-1 particles, viral cores were isolated from immature HIV-1 virions by sedimentation through detergent. The cores contained a major fraction of the gp41 that was present on untreated virions. Association of gp41 with cores required the presence of the gp41 cytoplasmic tail. In HIV-1 particles containing a functional protease, a mutation that prevents cleavage of Pr55(Gag) at the matrix-capsid junction was sufficient for the detergent-resistant association of gp41 with the isolated cores. In addition to gp41, a major fraction of virion-associated gp120 was also detected on immature HIV-1 cores. Isolation of cores under conditions known to disrupt lipid rafts resulted in the removal of a raft-associated protein incorporated into virions but not the HIV-1 envelope proteins. These results provide biochemical evidence for a stable interaction between Pr55(Gag) and the cytoplasmic tail of gp41 in immature HIV-1 particles. Moreover, findings in this study suggest that the interaction of Pr55(Gag) with gp41 may regulate the function of the envelope proteins during HIV-1 maturation.
Mutated p53 as a molecular marker for the diagnosis of head and neck cancer (2002)

In total, 10-30% of patients with head and neck squamous cell carcinoma (HNSCC) develop local recurrences despite seemingly adequate tumour resection. This may result from minimal residual cancer (MRC): small numbers of tumour cells left behind in the surgical margins, undetectable by routine histopathology. In recent studies, p53 mutations have been considered as selective and sensitive DNA markers of cancer cells. There are two potential problems in using mutated-p53 DNA as a marker. Firstly, p53 mutations occur early in progression and might therefore detect unresected precursor lesions besides tumour cells. Secondly, DNA is a very stable biomolecule that might lead to false-positive results. These two potential problems have been evaluated in this study. Fifty patients with a radical tumour resection were included, of whom 30 showed a p53 mutation in the primary tumour. Histopathologically tumour-free surgical margins were quantitatively analysed for mutated p53 by molecular diagnosis (plaque assay) and subsequent (immuno)histopathology. p53 mutated DNA was detected in the surgical margins of 19/30 patients. Immunohistochemistry confirmed the presence of small tumour foci in 2/19 mutated p53-positive cases. In 7/19 cases, the tumour-specific p53 mutation was found in unresected dysplastic mucosal precursor lesions. Moreover, in a number of cases small p53-immunostained patches were detected, but the mutations found were never tumour-related. By screening contralateral exfoliated cells and plaque assays on RNA it was shown that detection of mutated-p53 DNA is prone to false-positive results. In conclusion, using p53 mutations as a marker, both MRC and unresected mutated p53-positive mucosal precursor lesions are detected within surgical margins. Molecular assessment of surgical margins using p53 mutations enables the selection of HNSCC patients at high risk for tumour recurrence, but tumour RNA seems at present to be a more specific biomolecule for analysis than tumour DNA.