gebhart/patrepeval huggingface dataset:
Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase-I: evidence for cell cycle-independent toxicity. (1996)

Camptothecin is an S-phase-specific anticancer agent that inhibits the activity of the enzyme DNA topoisomerase-I (topo-I). Irreversible DNA double-strand breaks are produced during DNA synthesis in the presence of camptothecin, suggesting that this agent should not be toxic to nondividing cells, such as neurons. Unexpectedly, camptothecin induced significant, dose-dependent cell death of postmitotic rat cortical neurons in vitro; astrocytes were more resistant. Aphidicolin, an inhibitor of DNA polymerase alpha, did not prevent camptothecin-induced neuronal death, while death was prevented by actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole as well as cycloheximide and anisomycin, inhibitors of RNA and protein synthesis, respectively. Camptothecin-induced neuronal death was apoptotic, as characterized by chromatin condensation, cytoplasmic shrinking, plasma membrane blebbing, and fragmentation of neurites. DNA fragmentation was also confirmed by the use of the in situ DNA end labeling assay. In addition, aurintricarboxylic acid, an inhibitor of the apoptotic endonuclease, partially protected against camptothecin-induced neuronal death. The toxicity of stereoisomers of a camptothecin analogue was stereospecific, demonstrating that toxicity was a result of inhibition of topo-I. The difference in sensitivity to camptothecin between neurons and astrocytes correlated with their transcriptional activity and level of topo-I protein expression. These data indicate important roles for topo-I in postmitotic neurons and suggest that topo-I inhibitors can induce apoptosis independent of DNA synthesis. We suggest a model based on transcriptionally mediated DNA damage, a novel mechanism of action of topo-I poisons.
Protease B of Saccharomyces cerevisiae: Isolation and Regulation of the PRB1 Structural Gene (1987)

We have isolated the structural gene, PRB1, for the vacuolar protease B of Saccharomyces cerevisiae from a genomic library by complementation of the prb1-1122 mutation. Deletion analysis localized the complementing activity to a 3.2-kilobase pair XhoI-HindIII restriction enzyme fragment. The fragment was used to identify a 2.3-kilobase mRNA. S1 endonuclease mapping indicated that the mRNA and the gene were colinear. No introns were detected. The mRNA is of sufficient size to encode a protein of about 69,000 molecular weight, a number much larger than either the mature enzyme (congruent to 30,000 protein molecular weight) or the sole reported precursor (congruent to 39,000 protein molecular weight). These results suggest that proteolytic processing steps beyond that thought to be catalyzed by protease A may be required to convert the initial glycosylated translation product into mature protease B. The PRB1 mRNA is made in substantial amounts only when the cells have exhausted the glucose supply and enter the diauxic plateau. There is an extended time lag between PRB1 transcription and expression of protease B activity. A deletion that removes about 83% of the coding region was constructed as a diploid heterozygote. Spores bearing the deletion germinate, grow at normal rates into colonies, and have no obvious phenotype beyond protease B deficiency.
Clinical validation of the tempus xT next-generation targeted oncology sequencing assay (2019)

We developed and clinically validated a hybrid capture next generation sequencing assay to detect somatic alterations and microsatellite instability in solid tumors and hematologic malignancies. This targeted oncology assay utilizes tumor-normal matched samples for highly accurate somatic alteration calling and whole transcriptome RNA sequencing for unbiased identification of gene fusion events. The assay was validated with a combination of clinical specimens and cell lines, and recorded a sensitivity of 99.1% for single nucleotide variants, 98.1% for indels, 99.9% for gene rearrangements, 98.4% for copy number variations, and 99.9% for microsatellite instability detection. This assay presents a wide array of data for clinical management and clinical trial enrollment while conserving limited tissue.
The Ferrous Iron-Responsive BqsRS Two-Component System Activates Genes That Promote Cationic Stress Tolerance (2015)

Clearing chronic infections is challenging due to the physiological resistance of opportunistic pathogens to antibiotics. Effective treatments are hindered by a lack of understanding of how these organisms survive in situ. Fe(II) is typically present at micromolar levels in soils and sedimentary habitats, as well as in CF sputum. All P. aeruginosa strains possess a two-component system, BqsRS, that specifically senses extracellular Fe(II) at low micromolar concentrations. Our work shows that BqsRS protects the cell against cationic perturbations to the cell envelope as well as low pH and reduction potential (Eh), conditions under which Fe(2+) is stable. Fe(II) can thus be understood as a proxy for a broader environmental state; the cellular response to its detection may help rationalize the resistance of P. aeruginosa to clinically important cationic antibiotics. This finding demonstrates the importance of considering environmental chemistry when exploring mechanisms of microbial survival in habitats that include the human body.
Crystal Structure of C5b-6 Suggests Structural Basis for Priming Assembly of the Membrane Attack Complex (2012)

The complement membrane attack complex (MAC) forms transmembrane pores in pathogen membranes. The first step in MAC assembly is cleavage of C5 to generate metastable C5b, which forms a stable complex with C6, termed C5b-6. C5b-6 initiates pore formation via the sequential recruitment of homologous proteins: C7, C8, and 12-18 copies of C9, each of which comprises a central MAC-perforin domain flanked by auxiliary domains. We recently proposed a model of pore assembly, in which the auxiliary domains play key roles, both in stabilizing the closed conformation of the protomers and in driving the sequential opening of the MAC-perforin β-sheet of each new recruit to the growing pore. Here, we describe an atomic model of C5b-6 at 4.2 Å resolution. We show that C5b provides four interfaces for the auxiliary domains of C6. The largest interface is created by the insertion of an interdomain linker from C6 into a hydrophobic groove created by a major reorganization of the α-helical domain of C5b. In combination with the rigid body docking of N-terminal elements of both proteins, C5b becomes locked into a stable conformation. Both C6 auxiliary domains flanking the linker pack tightly against C5b. The net effect is to induce the clockwise rigid body rotation of four auxiliary domains, as well as the opening/twisting of the central β-sheet of C6, in the directions predicted by our model to activate or prime C6 for the subsequent steps in MAC assembly. The complex also suggests novel small molecule strategies for modulating pathological MAC assembly.
Rollable and implantable intraocular pressure sensor for the continuous adaptive management of glaucoma (2013)

We designed and tested a new rollable and implantable medical device to directly and continuously measure intraocular pressure. Since high intraocular pressure is a leading risk factor for glaucoma, such a system could solve the difficulties encountered in the management of this condition. In fact, glaucoma is one among those pathologies that could most benefit of an adaptive patient-specific medicine device. The presented prototype was realized with standard industrial microelectronic technologies (Flip-Chip on Kapton flexible PCB) and off-the-shelf IC components. Detailed system description and measurements, obtained during in-vitro and laboratory characterizations, are reported.
Shock-wave imaging by density recovery from intensity measurements (2018)

A method for quantitative estimation of density variation in high-speed flow, which uses light as an interrogating tool, is described. The wavefront distortion of the interrogating beam induced by the compressible flow field is estimated quantitatively, in which the density gradient of the flow field is seen as refractive-index gradient by the probing beam. The distorted wavefront is measured quantitatively by using the cross-sectional intensities of the distorted wavefront along the optical axis. Iterative algorithms are developed using both deterministic (Gauss-Newton) and stochastic (ensemble Kalman filter) update strategies to recover unknown parameters such as the phase of the wavefront or the refractive index distribution in the flow directly from the measured intensities. With phase recovered in the first step, a ray tomography algorithm is used to obtain the refractive index and density distributions in the flow from the phase. Experiments are conducted to quantitatively visualize the shock-wave-induced flow field in a shock-tunnel facility. The reconstructed density cross sections, obtained using different reconstruction methods, are presented and compared with those obtained by solving the Navier-Stokes equation using computational fluid dynamic routines. It is observed that the iterative algorithms always outperform those depending on solution of the transport-of-intensity equation. In particular, when using the iterative algorithms, the stochastic search scheme outperforms the Gauss-Newton method.
Heat Transfer Characteristics in Partial Boiling, Fully Developed Boiling, and Significant Void Flow Regions of Subcooled Flow Boiling (1997)

Abstract Subcooled flow boiling covers the region beginning from the location where the wall temperature exceeds the local liquid saturation temperature to the location where the thermodynamic quality reaches zero, corresponding to the saturated liquid state. Three locations in the subcooled flow have been identified by earlier investigators as the onset of nucleate boiling, the point of net vapor generation, and the location where x = 0 is attained from enthalpy balance equations. The heat transfer regions are identified as the single phase heat transfer prior to ONB, partial boiling (PB), and fully developed boiling (FDB). A new region is identified here as the significant void flow (SVF) region. Available models for predicting the heat transfer coefficient in different regions are evaluated and new models are presented based on our current understanding. The results are compared with some of the experimental data available in the literature.
Simultaneous remote extraction of multiple speech sources and heart beats from secondary speckles pattern (2009)

The ability of dynamic extraction of remote sounds is very appealing. In this manuscript we propose an optical approach allowing the extraction and the separation of remote sound sources. The approach is very modular and it does not apply any constraints regarding the relative position of the sound sources and the detection device. The optical setup doing the detection is very simple and versatile. The principle is to observe the movement of the secondary speckle patterns that are generated on top of the target when it is illuminated by a spot of laser beam. Proper adaption of the imaging optics allows following the temporal trajectories of those speckles and extracting the sound signals out of the processed trajectory. Various sound sources are imaged in different spatial pixels and thus blind source separation becomes a very simple task.
Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: a juxtacrine system for adhesion and activation of neutrophils. (1991)

The adhesion of polymorphonuclear leukocytes (PMNs) to vascular endothelial cells (EC) is an early and fundamental event in acute inflammation. This process requires the regulated expression of molecules on both the EC and PMN. EC stimulated with histamine or thrombin coexpress two proadhesive molecules within minutes: granule membrane protein 140 (GMP-140), a member of the selectin family, and platelet-activating factor (PAF), a biologically active phospholipid. Coexpression of GMP-140 and PAF is required for maximal PMN adhesion and the two molecules act in a cooperative fashion. The component of adhesion mediated by EC-associated PAF requires activation of CD11/CD18 integrins on the PMN and binding of these heterodimers to counterreceptors on the EC. GMP-140 also binds to a receptor on the PMN; however, it tethers the PMN to the EC without requiring activation of CD11/CD18 integrins. This component of the adhesive interaction is blocked by antibodies to GMP-140 or by GMP-140 in the fluid phase. Experiments with purified GMP-140 indicate that binding to its receptor on the PMN does not directly induce PMN adhesiveness but that it potentiates the CD11/CD18-dependent adhesive response to PAF by a mechanism that involves events distal to the PAF receptor. Tethering of the PMN to the EC by GMP-140 may also be required for efficient interaction of PAF with its receptor on the PMN. These observations define a complex cell recognition system in which tethering of PMNs by a selectin, GMP-140, facilitates juxtacrine activation of the leukocytes by a signaling molecule, PAF. The latter event recruits the third component of the adhesive interaction, the CD11/CD18 integrins.
A molecular photonic wire (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA molecular photonic wireRichard W. Wagner and Jonathan S. LindseyCite this: J. Am. Chem. Soc. 1994, 116, 21, 9759–9760Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://pubs.acs.org/doi/10.1021/ja00100a055https://doi.org/10.1021/ja00100a055research-articleACS PublicationsRequest reuse permissionsArticle Views1838Altmetric-Citations426LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Active-site carbamate formation and reaction-intermediate-analog binding by ribulosebisphosphate carboxylase/oxygenase in the absence of its small subunits (1984)

Even though depleted of more than 90% of its small subunits, ribulose 1,5-bisphosphate carboxylase/oxygenase from Synechococcus ACMM 323 still formed a stable complex with 2-carboxyarabinitol 1,5-bisphosphate from which exchange of the activator CO(2) molecule was prevented. The stoichiometry between nonexchangeable CO(2) and large subunits was unchanged regardless of the presence or absence of small subunits. The small-subunit-depleted enzyme was also "activated" by exposure to CO(2) and Mg(2+), although it was necessary for the small subunits to be bound before this "activation" could be expressed. Binding of small subunits occurred rapidly, its rate depending on subunit concentration. The initial rate of "activation" was not slowed in the absence of small subunits but its extent at equilibrium was reduced. These observations are not consistent with an obligate role for the small subunits in the activation process. Their necessity in catalysis must stem from a more subtle involvement in the catalytic mechanism itself.
Diversity of Lactobacilli in the Oral Cavities of Young Women with Dental Caries (2006)

For nearly a century, lactobacilli (LB) in the oral cavity have been generally associated with dental caries. Here, we characterized the LB isolated from the saliva of 6 women with active caries using genetic-based taxonomical identification methods. From each subject, 30 isolates growing on Rogosa medium and presumed to be LB were analyzed. Of the 180 isolates, 176 were further characterized by biotyping, DNA melting points, DNA chromosomal fingerprinting, genotyping, and phylogenetic cluster assessment. We found a total of 30 unique genotypes of LB in the saliva of caries-active women, with each woman harboring between 2 and 8 distinct genotypes. Although Lactobacillus vaginalis, L. fermentum, and L. salivarius were found in 4 of 6 of the subjects, results from other studies using comparable methods show an entirely different array of LB associated with caries. These collective observations lead us to surmise that LB associated with dental caries are likely exogenous and opportunistic colonizers, arising from food or other reservoirs outside the oral cavity.
Safety Assessment of Poly I: C in NZB/NZW Mice (1975)

The present report confirms the findings by Steinberg et al. (9) that repeated intraperitoneal injections of poly I:C (3 mug/g, three times per wk, 40-52 doses) enhanced the incidence and severity of glomerular lesions that occur spontaneously in NZG/NZW mice and also increased the development of circulating antibody against nucleic acids. This effect was minimal when only six intraperitoneal doses were given in 1 mug/g amount at weekly intervals. Intranasal administration of poly I:C (0.2 mug/g, three times per wk, 40 doses) or six doses of the drug (1 mug/g weekly) caused no apparent potentiation of glomerular response. ICR/Ha mice, which do not suffer from the spontaneously occurring disease, were uneffected by poly I:C treatment except for occasional development of antibody against poly I:C or DNA.
Nerve‐induced and spontaneous redistribution of acetylcholine receptors on cultured muscle cells. (1977)

1. Theree-day-old cultures of myotomal muscle, obtained from embryos of Xenopus laevis, were stained with fluorescent conjugates of alpha-bungarotoxin and maintained in native toxin in order to ensure that ACh receptors subsequently inserted into the sarcolemma would not be stained. Neural tube cells were then added to the cultures. 2. When cultures were exmained 1-3 days later fluorescent stain was found to be associated with sites of nerve-muscle contact. In some cases the stain along the path of contact extended for greater distances than the patches of stain seen on non-contacted muscle cells. 3. The development of new areas of fluorescent stain at sites of nerve-muscle contact was confirmed by making successive observations on the same muscle cells over a period of a day. 4. Similar experiments on muscle cells not contacted by nerve revealed the formation of new receptor patches, usually in areas of cell growth. 5. The majority of fluorescent pathes on non-contacted muscle cells did not undergo changes in size or shape over the course of 1-2 days. However some examples of enlargement, shrinkage and disappearance were observed. 6. On the basis of these findings it is concluded that ACh receptors aggregate within the sarcolemma, spontaneously as well as in response to innervation. In the latter case extrajunctional receptors accumulate at the site of nerve contact thereby contributing to the development of high receptor density in the subneural muscle membrane. This process of receptors redistribution occurs in the absence of synaptic or contractile activity. 7. Possible mechanisms involved in the redistribution of ACh receptors are discussed in relation to those which appear to modulate ligand-induced changes in the distribution of lectin and immunoglobulin receptors.
Using Microsoft Outlook 2000 (1998)

From the Publisher:
Special Edition Using Microsoft Outlook 2000 provides all the information a user, administrator, or programmer needs to maximize their use of Microsoft Outlook 2000. While the book quickly covers the basics of Outlook, it focuses with much greater intensity on advanced information, contact, calendar, and e-mail management techniques -- for both the Internet E-mail Only version of Outlook as well as the Corporate/Workgroup variation. 
The book covers in great detail the use of Outlook on a LAN as a client for Microsoft Exchange Server, Microsoft Mail, and cc:Mail, and it offers expert advice on a multitude of ways to customize Outlook for maximum personal productivity. Special Edition Using Microsoft Outlook 2000 also includes an entire section on developing Outlook-based applications with custom fields, custom forms, VBScript, and other Office applications. Provides complete coverage of installing, configuring, using, administering, and programming Microsoft Outlook 2000
Time course and morphology of dopaminergic neuronal death caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (1995)

Mechanisms responsible for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine (DA) neuronal death remain unknown and in mice it is even unclear whether neuronal death does occur. In vitro studies suggest that 1-methyl-4-phenylpyridinium ion (MPP+), the active metabolite of MPTP, kills neurons by apoptosis. Herein, we investigated whether MPTP induces DA neuronal death in vivo in mice and whether the mechanism is that of apoptosis. C57/bl Mice received different doses of MPTP administered in four intraperitoneal injections every 2 hours and were sacrificed at different time points for analyses of tyrosine hydroxylase (TH) immunohistochemistry, silver staining, and Nissl staining within the mesencephalon. We found that MPTP induces neuronal destruction in the substantia nigra pars compacta (SNpc) and the ventral tegmental area (VTA). The active phase of degeneration began at 12 h postinjection and continued up to 4 days. During this period, there was a greater decrease in TH-defined neurons than in Nissl-stained neurons suggesting that MPTP can cause a loss in TH without necessarily destroying the neuron. Thereafter, neuronal counts by both techniques equalized and there was no further loss of DA neurons. Dying neurons showed shrunken eosinophilic cytoplasm and shrunken darkly stained nuclei. Double staining revealed degenerating neurons solely among TH positive neurons of SNpc and VTA. At no time point and at no dose of MPTP was apoptosis observed. In addition, in situ labelling revealed no evidence of DNA fragmentation. This study demonstrates that the MPTP mouse model replicates several key features of neurodegeneration of DA neurons in PD and provides no in vivo evidence that, using this specific paradigm of injection, MPTP kills DA neurons by apoptosis.
Silicone Breast Implants and the Risk of Connective-Tissue Diseases and Symptoms (1995)

In a large cohort study, we did not find an association between silicone breast implants and connective-tissue diseases, defined according to a variety of standardized criteria, or signs and symptoms of these diseases.