gebhart/patrepeval huggingface dataset:
Protein kinase A activity is required for the budding of constitutive transport vesicles from the trans-Golgi network (1997)

We have examined the role played by protein kinase A (PKA) in vesicle-mediated protein transport from the trans-Golgi network (TGN) to the cell surface. In vivo this transport step was inhibited by inhibitors of PKA catalytic subunits (C-PKA) such as the compound known as H89 and a myristoylated form of the inhibitory peptide sequence contained in the thermostable PKA inhibitor. Inhibition by H89 occurred at an early stage during the transfer of vesicular stomatitis virus G glycoprotein from the TGN to the cell surface. Reversal from this inhibition correlated with a transient increase in the number of free coated vesicles in the Golgi area. Vesicle budding from the TGN was studied in vitro using vesicular stomatitis virus-infected, permeabilized cells. Addition to this assay of C-PKA stimulated vesicle release while it was suppressed by PKA inhibitory peptide, H89, and antibody against C-PKA. Furthermore, vesicle release was decreased when PKA-depleted cytosol was used and restored by addition of C-PKA. These results indicate a regulatory role for PKA activity in the production of constitutive transport vesicles from the TGN.
Tertiary alphabet for the observable protein structural universe (2016)

Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only ∼600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. We go on to show that universal TERMs provide an effective mapping between sequence and structure. We demonstrate that TERM-based statistics alone are sufficient to recapitulate close-to-native sequences given either NMR or X-ray backbones. Furthermore, sequence variability predicted from TERM data agrees closely with evolutionary variation. Finally, locations of TERMs in protein chains can be predicted from sequence alone based on sequence signatures emergent from TERM instances in the PDB. For multisegment motifs, this method identifies spatially adjacent fragments that are not contiguous in sequence-a major bottleneck in structure prediction. Although all TERMs recur in diverse proteins, some appear specialized for certain functions, such as interface formation, metal coordination, or even water binding. Structural biology has benefited greatly from previously observed degeneracies in structure. The decomposition of the known structural universe into a finite set of compact TERMs offers exciting opportunities toward better understanding, design, and prediction of protein structure.
A Susceptibility Gene Set for Early Onset Colorectal Cancer That Integrates Diverse Signaling Pathways: Implication for Tumorigenesis (2007)

The data suggest that the patient's mucosa is primed for tumorigenesis when cellular homeostasis is disrupted, and that the seven overexpressed genes could potentially predict early onset CRC.
The enhancement of gate-induced-drain-leakage (GIDL) current in short-channel SOI MOSFET and its application in measuring lateral bipolar current gain beta (1992)

An off-state leakage current unique for short-channel SOI MOSFETs is reported. This off-state leakage is the amplification of gate-induced-drain-leakage current by the lateral bipolar transistor in an SOI device due to the floating body. The leakage current can be enhanced by as much as 100 times for 1/4 mu m SOI devices. This can pose severe constraints in future 0.1 mu m SOI device design. A novel technique was developed based on this mechanism to measure the lateral bipolar transistor current gain beta of SOI devices without using a body contact.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Decision support and disease management: a logic engineering approach (1998)

This paper describes the development and application of PROforma, a unified technology for clinical decision support and disease management. Work leading to the implementation of PROforma has been carried out in a series of projects funded by European agencies over the past 13 years. The work has been based on logic engineering, a distinct design and development methodology that combines concepts from knowledge engineering, logic programming, and software engineering. Several of the projects have used the approach to demonstrate a wide range of applications in primary and specialist care and clinical research. Concurrent academic research projects have provided a sound theoretical basis for the safety-critical elements of the methodology. The principal technical results of the work are the PROforma logic language for defining clinical processes and an associated suite of software tools for delivering applications, such as decision support and disease management procedures. The language supports four standard objects (decisions, plans, actions, and enquiries), each of which has an intuitive meaning with well-understood logical semantics. The development toolset includes a powerful visual programming environment for composing applications from these standard components, for verifying consistency and completeness of the resulting specification and for delivering stand-alone or embeddable applications. Tools and applications that have resulted from the work are described and illustrated, with examples from specialist cancer care and primary care. The results of a number of evaluation activities are included to illustrate the utility of the technology.
MRI Detection of Thrombin with Aptamer Functionalized Superparamagnetic Iron Oxide Nanoparticles (2008)

Design of smart MRI contrast agent based on superparamagnetic iron oxide nanoparticles and aptamers has been described for the detection of human alpha-thrombin protein. The contrast agent is based on the assembly of the aptamer functionalized nanoparticles in the presence of thrombin. A detectable change in MRI signal is observed with 25 nM thrombin in human serum. Changes were neither observed with control analytes, streptavidin, or bovine serum albumin, nor with inactive aptamer functionalized nanoparticles.
Electrochemical polymerization of amino-, pyrrole-, and hydroxy-substituted tetraphenylporphyrins (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrochemical polymerization of amino-, pyrrole-, and hydroxy-substituted tetraphenylporphyrinsA. Bettelheim, B. A. White, S. A. Raybuck, and Royce W. MurrayCite this: Inorg. Chem. 1987, 26, 7, 1009–1017Publication Date (Print):April 1, 1987Publication History Published online1 May 2002Published inissue 1 April 1987https://pubs.acs.org/doi/10.1021/ic00254a011https://doi.org/10.1021/ic00254a011research-articleACS PublicationsRequest reuse permissionsArticle Views5027Altmetric-Citations348LEARN 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
Hemostatic Markers in Acute Ischemic Stroke (1996)

Elevated hemostatic markers after acute ischemic stroke identify patients with increased risk for mortality. This association appears to be independent of stroke severity or stroke type.
Factors influencing the stability of freeze-dried stress-resilient and stress-sensitive strains of bifidobacteria (2013)

Freeze-drying is a common method for preservation of probiotics, including bifidobacteria, for further industrial applications. However, the stability of freeze-dried bifidobacteria varies depending on the freeze-drying method and subsequent storage conditions. The primary goals of this study were to develop an optimized freeze-drying procedure and to determine the effects of temperature, water activity, and atmosphere on survival of freeze-dried bifidobacteria. To address these goals, a commercially used bifidobacteria strain that is resilient to stress, Bifidobacterium animalis ssp. lactis Bb-12, and a characterized intestinal strain that is more sensitive to stress conditions, Bifidobacterium longum DJO10A, were used. A freeze-drying protocol was developed using trehalose as the cryoprotectant, which resulted in almost no loss of viability during freeze-drying. Resuscitation medium, temperature, and time did not significantly influence recovery rates when this cryoprotectant was used. The effects of temperature (-80 to 45°C), water activity (0.02 to 0.92), and atmosphere (air, vacuum, and nitrogen) were evaluated for the stability of the freeze-dried powders during storage. Freeze-dried B. animalis ssp. lactis Bb-12 was found to survive under all conditions tested, with optimum survival at temperatures up to 21°C, water activities up to 0.44, and all 3 atmospheres tested. The intestinal-adapted strain B. longum DJO10A was much more sensitive to the different storage conditions, but could be adequately maintained using optimum conditions. These optimum storage conditions included frozen storage, replacement of oxygen with nitrogen, and water activities between 0.11 and 0.22. These results indicated that an optimized storage environment is required to maintain viability of stress-sensitive bifidobacteria strains, whereas stress-resilient bifidobacteria strains can maintain viability over a wide range of storage conditions, which is practical in countries where controlled cold storage conditions may not be readily available.
Stereochemical Control of the DNA Binding Affinity, Sequence Specificity, and Orientation Preference of Chiral Hairpin Polyamides in the Minor Groove (1998)

Three-ring polyamides containing pyrrole (Py) and imidazole (Im) amino acids covalently coupled by γ-aminobutyric acid (γ) form six-ring hairpins that recognize five-base-pair sequences in the minor groove of DNA. Selective chiral substitution of the “γ-turn” enhances the properties of polyamide hairpins with regard to DNA affinity and sequence specificity. Polyamides of core sequence composition ImPyPy-γ-PyPyPy which differ by selective stereochemical substitution of the prochiral α-position in the γ-turn were prepared. The DNA binding properties of two enantiomeric polyamides were analyzed by footprinting and affinity cleavage on a DNA fragment containing two match sites (5‘-TGTTA-3‘ and 5‘-ACATT-3‘) and one 5‘-TGTCA-3‘ mismatch site. Quantitative footprint titrations demonstrate that replacement of γ-aminobutyric acid by (R)-2,4-diaminobutyric acid enhances DNA binding affinity for the 5‘-TGTTA-3‘ match site 13-fold (Ka = 3.8 × 109 M-1). The enhanced affinity is achieved without a compromise in sequence selectivity, which in fact increases and is found to be 100-fold higher relative to binding at a single base pair mismatch sequence, 5‘-TGTCA-3‘. An (S)-2,4-diaminobutyric acid linked hairpin binds with 170-fold reduced affinity relative to the R-enantiomer and only 5-fold sequence specificity versus a 5‘-ACATT-3‘ reversed orientation site. These effects are modulated by acetylation of the chiral amine substituents. This study identifies structural elements which should facilitate the design of new hairpin polyamides with improved DNA binding affinity, sequence specificity, and orientational selectivity.
Cellular Activation of the Self-Quenched Fluorescent Reporter Probe in Tumor Microenvironment (2002)

The effect of intralysosomal proteolysis of near-infrared fluorescent (NIRF) self-quenched macromolecular probe (PGC-Cy5.5) has been previously reported and used for tumor imaging. Here we demonstrate that proteolysis can be detected noninvasively in vivo at the cellular level. A codetection of GFP fluorescence (using two-photon excitation) and NIRF was performed in tumor-bearing animals injected with PGC-Cy5.5. In vivo microscopy of tumor cells in subdermal tissue layers (up to 160 microm) showed a strong Cy5.5 dequenching effect in GFP-negative cells. This observation was corroborated by flow cytometry, sorting, and reverse transcription polymerase chain reaction analysis of tumor-isolated cells. Both GFP-positive (81% total) and GFP-negative (19% total) populations contained Cy5.5-positive cells. The GFP-negative cells were confirmed to be host mouse cells by the absence of rat cathepsin mRNA signal. The subfraction of GFP-negative cells (2.5-3.0%) had seven times higher NIRF intensity than the majority of GFP-positive or GFP-negative cells (372 and 55 AU, respectively). Highly NIRF-positive, FP-negative cells were CD45- and MAC3-positive. Our results indicate that: 1) intracellular proteolysis can be imaged in vivo at the cellular level using cathepsin-sensitive probes; 2) tumor-recruited cells of hematopoetic origin participate most actively in uptake and degradation of long-circulating macromolecular probes.
Sample Filtration, Concentration, and Separation Integrated on Microfluidic Devices (2003)

Microfabricated devices integrating sample filtration, solid-phase extraction, and chromatographic separation with solvent programming were demonstrated. Filtering of the sample was accomplished at the sample inlet with an array of seven channels each 1 microm deep and 18 microm wide. Sample concentration and separation were performed on channels 5 microm deep and 25 microm wide coated with a C18 phase, and elution was achieved under isocratic, step, or linear gradient conditions. For the solid-phase extraction, signal enhancement factors of 400 over a standard injection of 1.0 s were observed for a 320-s injection. Four polycyclic aromatic compounds were resolved by open channel electrochromatography in under 50 s. Chip operation was unaffected by the presence of the 5-microm silica particles at the filter entrance.
Cellular expression of green fluorescent protein, coupled with high-resolution in vivo videomicroscopy, to monitor steps in tumor metastasis (1999)

High resolution intravital videomicroscopy has provided a powerful tool for directly observing steps in the metastatic process, and for clarifying molecular mechanisms of metastasis and modes of action of anti-metastasis therapeutics. Cells previously have been identified in vivo using exogenously added fluorescent labels, limiting observations to a few cell divisions, or by natural markers (e.g. melanin) expressed only by specific cell types. Here we tested the utility of stable green fluorescent protein (GFP)-transfected cells for monitoring and quantifying sequential steps in the metastatic process. Using CHO-K1 cells that stably express GFP, we document the visualization and quantification by intravital videomicroscopy of sequential steps in metastasis within mouse liver, from initial arrest of cells in the microvasculature to the growth and angiogenesis of metastases. Individual, non-dividing cells, as well as micro- and macrometastases could clearly be detected and quantified, as could fine cellular details such as pseudopodial projections, even after extended periods of in vivo growth. We quantified the size distribution of micrometastases and their locations relative to the liver surface using 50 micrometer thick formalin-fixed tissue sections. The data suggest preferential growth and survival of micrometastases near the liver surface. Furthermore, we observed a small population of single cells that persisted over the 11 day observation period, which may represent dormant cells with potential for subsequent proliferation. This study demonstrates the advantages of GFP-expressing cells, coupled with real-time high resolution videomicroscopy, for long-term in vivo studies to visualize and quantify sequential steps of the metastatic process.
The mu opioid receptor: A new target for cancer therapy? (2015)

Mu opioids are among the most widely used drugs for patients with cancer with both acute and chronic pain as well as in the perioperative period. Several retrospective studies have suggested that opioid use might promote tumor progression and as a result negatively impact survival in patients with advanced cancer; however, in the absence of appropriate prospective validation, any changes in recommendations for opioid use are not warranted. In this review, the authors present preclinical and clinical data that support their hypothesis that the mu opioid receptor is a potential target for cancer therapy because of its plausible role in tumor progression. The authors also propose the hypothesis that peripheral opioid antagonists such as methylnaltrexone, which reverses the peripheral effects of mu opioids but maintains centrally mediated analgesia and is approved by the US Food and Drug Administration for the treatment of opioid-induced constipation, can be used to target the mu opioid receptor.
598. Dialkylaminoalkylquinolines (1957)

E. P. Adams, F. P. Doyle and J. H. C. Nayler, J. Chem. Soc., 1957, 3066 DOI: 10.1039/JR9570003066
COCCIDIOIDOMYCOSIS AND OTHER SYSTEMIC MYCOSES OF MARINE MAMMALS STRANDING ALONG THE CENTRAL CALIFORNIA, USA COAST: 1998–2012 (2015)

A wide range of systemic mycoses have been reported from captive and wild marine mammals from North America. Examples include regionally endemic pathogens such as Coccidioides and Blastomyces spp., and novel pathogens like Cryptococcus gattii, which appear may have been introduced to North America by humans. Stranding and necropsy data were analyzed from three marine mammal stranding and response facilities on the central California coast to assess the prevalence, host demographics, and lesion distribution of systemic mycoses affecting locally endemic marine mammals. Between 1 January 1998 and 30 June 2012, >7,000 stranded marine mammals were necropsied at the three facilities. Necropsy and histopathology records were reviewed to identify cases of locally invasive or systemic mycoses and determine the nature and distribution of fungal lesions. Forty-one animals (0.6%) exhibited cytological, culture- or histologically confirmed locally invasive or systemic mycoses: 36 had coccidioidomycosis, two had zygomycosis, two had cryptococcosis, and one was systemically infected with Scedosporium apiospermum (an Ascomycota). Infected animals included 18 California sea lions (Zalophus californianus), 20 southern sea otters (Enhydra lutris nereis), two Pacific harbor seals (Phoca vitulina richardsi), one Dall's porpoise (Phocoenoides dalli), and one northern elephant seal (Mirounga angustirostris). Coccidioidomycosis was reported from 15 sea lions, 20 sea otters, and one harbor seal, confirming that Coccidioides spp. is the most common pathogen causing systemic mycosis in marine mammals stranding along the central California coast. We also report the first confirmation of C. gattii infection in a wild marine mammal from California and the first report of coccidioidomycosis in a wild harbor seal. Awareness of these pathogenic fungi during clinical care and postmortem examination is an important part of marine mammal population health surveillance and human health protection. Temporal-spatial overlap may be observed for pathogenic mycoses infecting coastal marine mammals and adjacent human populations.
Compact Superconducting Diplexer Design With Conductor-Backed Coplanar Waveguide Structures (2015)

This paper presents a compact superconducting diplexer with conductor-backed coplanar waveguide (CBCPW) structures. The couplings of the CBCPW structure resonators are significantly weaker than those of traditional microstrip resonators. High isolations between two channels are therefore achieved by using the CBCPW structures because of their highly suppressed unwanted cross couplings. The CBCPW diplexer consists of two four-pole channel bandpass filters. The couplings in the CBCPW structures, in which the air layer below the substrate varies in height, are simulated and compared with the coupling simulations of microstrip structures. The comparison shows that the coupling intensities of the CBCPW structures are nearly one order of magnitude lower than those of the traditional microstrip structures. The fabricated diplexer exhibits high performance with a compact core size of only <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$20\ \mbox{mm}\times 14\ \mbox{mm} $</tex-math></inline-formula> , and its measurements agree well with the simulations. The measured insertion losses of both channels are less than 0.19 dB, and the isolations are over 53 dB.
The Feasibility of Applying the Active TvTime System to Automatic Vehicle Location (1974)

The National Bureau of Standards Boulder Laboratory has studied the use of television as a carrier for accurate time and frequency signals. The usefulness of the TvTime System applied to locating cars and other vehicles automatically is examined. Such a need exists in transit, police, taxi, utility and many commercial fleets. Past approaches to the problem are outlined. The NBS TvTime System and experimental results will be discussed. Two models of a car locating system are outlined, each having three parts: (1) a TV decoder in the car, (2) a radio link such as a mobile channel between car and central dispatch, and (3) a computer which determines the car's position. Results show that this system is capable of achieving a location accuracy of better than 60 m with 95 percent confidence. Some advantages and limitations of the system will be discussed and cost estimates for the equipment given.