gebhart/patrepeval huggingface dataset:
Inhibition of Coronavirus Entry <i>In Vitro</i> and <i>Ex Vivo</i> by a Lipid-Conjugated Peptide Derived from the SARS-CoV-2 Spike Glycoprotein HRC Domain (2020)

The emergence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of the 2019 coronavirus disease (COVID-19), has erupted into a global pandemic that has led to tens of millions of infections and hundreds of thousands of deaths worldwide. The development of therapeutics to treat infection or as prophylactics to halt viral transmission and spread is urgently needed. SARS-CoV-2 relies on structural rearrangements within a spike (S) glycoprotein to mediate fusion of the viral and host cell membranes. Here, we describe the development of a lipopeptide that is derived from the C-terminal heptad repeat (HRC) domain of SARS-CoV-2 S that potently inhibits infection by SARS-CoV-2. The lipopeptide inhibits cell-cell fusion mediated by SARS-CoV-2 S and blocks infection by live SARS-CoV-2 in Vero E6 cell monolayers more effectively than previously described lipopeptides. The SARS-CoV-2 lipopeptide exhibits broad-spectrum activity by inhibiting cell-cell fusion mediated by SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV) and blocking infection by live MERS-CoV in cell monolayers. We also show that the SARS-CoV-2 HRC-derived lipopeptide potently blocks the spread of SARS-CoV-2 in human airway epithelial (HAE) cultures, an <i>ex vivo</i> model designed to mimic respiratory viral propagation in humans. While viral spread of SARS-CoV-2 infection was widespread in untreated airways, those treated with SARS-CoV-2 HRC lipopeptide showed no detectable evidence of viral spread. These data provide a framework for the development of peptide therapeutics for the treatment of or prophylaxis against SARS-CoV-2 as well as other coronaviruses.<b>IMPORTANCE</b> SARS-CoV-2, the causative agent of COVID-19, continues to spread globally, placing strain on health care systems and resulting in rapidly increasing numbers of cases and mortalities. Despite the growing need for medical intervention, no FDA-approved vaccines are yet available, and treatment has been limited to supportive therapy for the alleviation of symptoms. Entry inhibitors could fill the important role of preventing initial infection and preventing spread. Here, we describe the design, synthesis, and evaluation of a lipopeptide that is derived from the HRC domain of the SARS-CoV-2 S glycoprotein that potently inhibits fusion mediated by SARS-CoV-2 S glycoprotein and blocks infection by live SARS-CoV-2 in both cell monolayers (<i>in vitro</i>) and human airway tissues (<i>ex vivo</i>). Our results highlight the SARS-CoV-2 HRC-derived lipopeptide as a promising therapeutic candidate for SARS-CoV-2 infections.
The Panama Canal: Waterway for the Twenty-First Century (2001)

This paper describes what is happening in Panama with regard to the Canal's current operation and future plans. Beginning with a history of the Canal's recent ownership transfer from the United States back to Panama, the paper continues by describing changing trends in the use of the Canal. A brief discussion of laws in place that prevent interruption of Canal operation, such as provisions against strikes, is also included. Other interesting specifics, such as the fact that usage of the Canal is increasing and so are the sizes of the ships using the Canal, are incorporated throughout the discussion. Future renovations look promising, and there is no reason to fear for the future of the Canal and its increasingly important role in this ever-changing world.
I<scp>NHIBITION OF</scp> C<scp>ARCINOGENESIS BY</scp> D<scp>IETARY</scp> P<scp>OLYPHENOLIC</scp> C<scp>OMPOUNDS</scp> (2001)

Plants consumed by humans contain thousands of phenolic compounds. The effects of dietary polyphenols are of great current interest due to their antioxidative and possible anticarcinogenic activities. A popular belief is that dietary polyphenols are anticarcinogens because they are antioxidants, but direct evidence for this supposition is lacking. This chapter reviews the inhibition of tumorigenesis by phenolic acids and derivatives, tea and catechins, isoflavones and soy preparations, quercetin and other flavonoids, resveratrol, and lignans as well as the mechanisms involved based on studies in vivo and in vitro. Polyphenols may inhibit carcinogenesis by affecting the molecular events in the initiation, promotion, and progression stages. Isoflavones and lignans may influence tumor formation by affecting estrogen-related activities. The bioavailability of the dietary polyphenols is discussed extensively, because the tissue levels of the effective compounds determine the biological activity. Understanding the bioavailability and blood and tissue levels of polyphenols is also important in extrapolating results from studies in cell lines to animal models and humans. Epidemiological studies concerning polyphenol consumption and human cancer risk suggest the protective effects of certain food items and polyphenols, but more studies are needed for clear-cut conclusions. Perspectives on the application of dietary polyphenols for the prevention of human cancer and possible concerns on the consumption of excessive amounts of polyphenols are discussed.
<title>Parallel coordinates: survey of recent results</title> (1993)

A brief description of the parallel coordinate system is provided, followed by an application to exploratory data analysis of certain multivariate data. The calculation of minimum distance (L2) between trajectories (timed paths) is considered next and close bounds via L1 distance are obtained, a simplification of importance in Air Traffic Control. Line neighborhoods are defined as the totality of lines satisfying certain parameters. The point region defined by the set of points belonging to these sets of lines in general leads to ambiguities as to lines actually belonging to the line neighborhood. This is of importance in applications involving line detection. Eickemeyer's representation of p-flats in N-space is applied to the representation of polytopes. It is shown that this representation permits analysis and display of convexity or non-convexity of the polytope being represented. Finally the representation of surfaces in three dimensions is exhibited. In general such surfaces are represented by two regions, together with a point-by-point association of points in the two regions. For developable surfaces the regions are replaced by curves, the point-by-point association being of a simple nature.
CCD-based synchrotron x-ray detector for protein crystallograph-performance projected from an experiment (1987)

The intense x radiation from a synchrotron source could, with a suitable detector, provide a complete set of diffraction images from a protein crystal before the crystal is damaged by radiation (2-3 min). An area detector consisting of a 40 mm dia. x-ray fluorescing phosphor, coupled with an image intensifier and lens to a CCD image sensor, was developed to determine the effectiveness of such a detector in protein crystallography. The detector was used in an experiment with a rotating anode x-ray generator. Diffraction patterns from a lysozyme crystal obtained with this detector are compared to those obtained with film. The two images appear to be virtually identical. The flux of 10/ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> x-ray photons/s was observed on the detector at the rotating anode generator. At the 6-GeV synchrotron being designed at Argonne, the flux on an 80×80 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> detector is expected to be ≫ 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">9</sup> photons/s. The projected design of such a synchrotron detector shows that a diffraction-peak count ≫ 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> could be obtained in ˜0.5 s. With an additional ˜0.5 s readout time of a 512×512 pixel CCD, the data acquisition time per frame would be ˜1 s so that ninety 1 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">o</sup> diffraction images could be obtained, with approximately 1% precision, in less than 3 min.
Total Synthesis of (±)-Phomactin A. Lessons Learned from Respecting a Challenging Structural Topology (2011)

Our struggles and ultimate success in achieving a total synthesis of phomactin A are described. Our strategy features an intramolecular oxa-[3 + 3] annulation to construct its unique ABD-tricyclic manifold. Although the synthesis would constitute a distinctly new approach with the 12-membered D-ring of phomactin A being assembled simultaneously with the 1-oxadecalin at an early stage, the ABD-tricycle represents a unique structural topology that would pose a number of unprecedented challenges. One challenge concerned elaborating this tricycle to have oxygenation at the proper carbon atoms. To overcome this, we would utilize a Kornblum-DeLaMare ring-opening of a peroxide bridge as well as a challenging late-stage 1,3-allylic alcohol transposition. Further, the structural intricacies of the ABD-tricycle were uncovered by a conformational analysis that would be critical for the C5a-homologation.
Synthesis and Characterization of Porous Carbon Nanofibers with Hollow Cores Through the Thermal Treatment of Electrospun Copolymeric Nanofiber Webs (2006)

Porous, fibrous carbon nanofibers containing hollow cores (see image) are fabricated by electrospinning two immiscible polymer solutions followed by thermal treatment at 1000 °C in an inert atmosphere. This new type of carbon nanofibers has controlled porosity combined with a low density and expected high electrical and mechanical properties due to an interlinked fiber morphology, and may be utilized as an efficient electromagnetic shielding material.
Alternative difference analysis scheme combining <i>R</i>-space EXAFS fit with global optimization XANES fit for X-ray transient absorption spectroscopy (2017)

Time-resolved X-ray absorption spectroscopy (TR-XAS), based on the laser-pump/X-ray-probe method, is powerful in capturing the change of the geometrical and electronic structure of the absorbing atom upon excitation. TR-XAS data analysis is generally performed on the laser-on minus laser-off difference spectrum. Here, a new analysis scheme is presented for the TR-XAS difference fitting in both the extended X-ray absorption fine-structure (EXAFS) and the X-ray absorption near-edge structure (XANES) regions. R-space EXAFS difference fitting could quickly provide the main quantitative structure change of the first shell. The XANES fitting part introduces a global non-derivative optimization algorithm and optimizes the local structure change in a flexible way where both the core XAS calculation package and the search method in the fitting shell are changeable. The scheme was applied to the TR-XAS difference analysis of Fe(phen)<sub>3</sub> spin crossover complex and yielded reliable distance change and excitation population.
The Human Papillomavirus E7 Oncoprotein Functionally Interacts with the S4 Subunit of the 26 S Proteasome (1997)

Human papillomaviruses (HPV) have been etiologically linked to human cervical cancer. More than 90% of cervical cancer tissues express two HPV-encoded oncoproteins E6 and E7. Both E6 and E7 proteins possess transformation activity. and together they cooperate to transform primary human keratinocytes, fibroblasts. and epithelial cells. The transforming activity of E7 is associated with its ability to bind the retinoblastoma tumor suppressor protein (Rb). However, the carboxyl-terminal mutants of E7 are also defective for transformation, suggesting that other cellular targets for E7 might exist. We screened a human placenta cDNA library by yeast two-hybrid assay using HPV 16 E7 as a bait and identified the subunit 4 (S4) ATPase of the 26 S proteasome as a novel E7-binding protein. E7 binds to S4 through the carboxyl-terminal zinc binding motif, and the binding is independent of E7 sequences involved in binding to Rb. The interaction between S4 and E7 can be easily detected by in vitro protein binding assays. Moreover, we found that E7 increases the ATPase activity of S4. A recent study has shown that, in epithelial cells, E7 degrades Rb through the 26 S proteasome pathway. We hypothesize that E7 might target Rb for degradation by 26 S proteasome through its interaction with the subunit 4 of the proteasome.
消费“她”时代驾临 (2013)

女性已经成为消费市场的绝对主力，她们能赚会花。资料显示，中国女性年消费额是男性的7倍，美国斯坦福大学研究报告也表明，10个购物狂中有9个是女性。2013年1月，中信银行与零点研究咨询集团联合发布了《柔韧的力量——2012年中国都市女性平衡与选择白皮书》。白皮书围绕都市女性生活中的重要组成部分：婚恋、家庭、事业、经济、社交等方面展开，深度洞察女性日常生活所面临的种种压力和困惑，她们如何平衡不同角色，以及当代女性目前最需要的帮助和指导等。
A glycophospholipid membrane anchor acts as an apical targeting signal in polarized epithelial cells. (1989)

Glycosyl-phosphatidylinositol- (GPI) anchored proteins contain a large extracellular protein domain that is linked to the membrane via a glycosylated form of phosphatidylinositol. We recently reported the polarized apical distribution of all endogenous GPI-anchored proteins in the MDCK cell line (Lisanti, M. P., M. Sargiacomo, L. Graeve, A. R. Saltiel, and E. Rodriguez-Boulan. 1988. Proc. Natl. Acad. Sci. USA. 85:9557-9561). To study the role of this mechanism of membrane anchoring in targeting to the apical cell surface, we use here decay-accelerating factor (DAF) as a model GPI-anchored protein. Endogenous DAF was localized on the apical surface of two human intestinal cell lines (Caco-2 and SK-CO15). Recombinant DAF, expressed in MDCK cells, also assumed a polarized apical distribution. Transfer of the 37-amino acid DAF signal for GPI attachment to the ectodomain of herpes simplex glycoprotein D (a basolateral antigen) and to human growth hormone (a regulated secretory protein) by recombinant DNA methods resulted in delivery of the fusion proteins to the apical surface of transfected MDCK cells. These results are consistent with the notion that the GPI anchoring mechanism may convey apical targeting information.
ChemInform Abstract: Alkylation of 6‐Substituted Purines by α‐Bromo‐ω‐haloalkanes Under Interphase Catalysis Conditions. (1988)

Abstract The reaction specified in the title proceeds regiospecifically at the N‐9 position of the purines (I) to give the 9‐(ω‐haloalkyl)purines (III) and (VI).
A comprehensive framework for detecting and preventing VoIP fraud and misuse (2014)

The SUNSHINE framework presented in this paper aims at detecting and preventing VoIP fraud and misuse. The SUNSHINE architecture is modular, and considers both prevention and detection at the network as well as the application level. SUNSHINE offers a combination of firewalling and intrusion detection, a distributed sensing system, a CDR analysis based on statistical analysis and artificial intelligence, a component for correlating and aggregating alarms, and a DNS-based real-time blacklist for VoIP. The SUNSHINE framework has been implemented based on components contributed by the project partners and first insights from initial deployment are already available.
Description d’un appareil destiné à l’étude de la polarisation de la lumière de fluorescence (1965)

Dans ce mémoire est décrit un appareil conçu pour étudier l’état de polarisation de la lumière de fluorescence. Le montage proposé conserve une bonne précision dans le cas des faibles taux de polarisation car il permet de mesurer directement, avec la sensibilité maximale, la différence IV — IH des intensités correspondant aux positions verticale et horizontale de l’analyseur. La valeur d’un rapport de polarisation voisin de 0,1 peut ainsi être obtenue avec une erreur relative de 1 % environ.
Automatic optical soliton control using cascaded Er <sup>3+</sup> -doped fibre amplifiers (1990)

Automatic amplitude control in an optical soliton transmission system is demonstrated for the first time using Er3+-doped fibre amplifiers and repeaters. After 250 km transmission, soliton pulses with consistent intensity and pulse width are obtained for a change in input signal level of 6 dB about the optimum value.
<i>PIK3CA</i> Mutations in Colorectal Cancer Are Associated with Clinical Resistance to EGFR-Targeted Monoclonal Antibodies (2009)

The monoclonal antibodies (moAb) panitumumab and cetuximab target the epidermal growth factor receptor (EGFR) and have proven valuable for the treatment of metastatic colorectal cancer (mCRC). EGFR-mediated signaling involves two main intracellular cascades: on one side KRAS activates BRAF, which in turn triggers the mitogen-activated protein kinases. On the other, membrane localization of the lipid kinase PIK3CA counteracts PTEN and promotes AKT1 phosphorylation, thereby activating a parallel intracellular axis. Constitutive activation of KRAS bypasses the corresponding signaling cascade and, accordingly, patients with mCRC bearing KRAS mutations are clinically resistant to therapy with panitumumab or cetuximab. We hypothesized that mutations activating PIK3CA could also preclude responsiveness to EGFR-targeted moAbs through a similar mechanism. Here, we present the mutational analysis of PIK3CA and KRAS and evaluation of the PTEN protein status in a cohort of 110 patients with mCRC treated with anti-EGFR moAbs. We observed 15 (13.6%) PIK3CA and 32 (29.0%) KRAS mutations. PIK3CA mutations were significantly associated with clinical resistance to panitumumab or cetuximab; none of the mutated patients achieved objective response (P = 0.038). When only KRAS wild-type tumors were analyzed, the statistical correlation was stronger (P = 0.016). Patients with PIK3CA mutations displayed a worse clinical outcome also in terms of progression-free survival (P = 0.035). Our data indicate that PIK3CA mutations can independently hamper the therapeutic response to panitumumab or cetuximab in mCRC. When the molecular status of the PIK3CA/PTEN and KRAS pathways are concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to EGFR moAbs can be identified.
The express Web server (1999)

Article Free Access Share on The express Web server: a user interface for standards development Authors: David A. Sauder National Institute of Standards and Technology, 100 Bureau Dr., Stop 8260, Gaithersburg, MD National Institute of Standards and Technology, 100 Bureau Dr., Stop 8260, Gaithersburg, MDView Profile , Joshua Lubell National Institute of Standards and Technology, 100 Bureau Dr., Stop 8260, Gaithersburg, MD National Institute of Standards and Technology, 100 Bureau Dr., Stop 8260, Gaithersburg, MDView Profile Authors Info & Claims SAC '99: Proceedings of the 1999 ACM symposium on Applied computingFebruary 1999 Pages 610–615https://doi.org/10.1145/298151.298493Published:28 February 1999Publication History 1citation375DownloadsMetricsTotal Citations1Total Downloads375Last 12 Months11Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Modification of the Picryl Chloride-Induced Allergic Dermatitis Model in Mouse Ear Lobes by 12-<i>O</i>-Tetradecanoylphorbol 13-Acetate, and Analysis of the Role of Histamine in the Modified Model (2008)

Induction of the antigen-nonspecific inflammation by TPA enhanced the PiCl-induced allergic inflammation. Histamine plays significant roles in the early-phase swelling via H1 receptors, and the late-phase swelling via H3/H4 receptors in this TPA-modified allergic dermatitis model.
Closing the ISR-Navigation loop (2010)

Due to the lack of sufficiently accurate real-time information about the availability and quality of the data that is being collected to meet the ISR goals, opportunities to fill in coverage holes can hardly be detected during an on-going mission. The goal of the research presented in this paper is to provide the operator with so-called coverage awareness by providing the information needed to assess the availability of the collected data in reference to locations about which information is required. The concept relies on three elements. The main element is a so-called coverage database which is updated in real-time with information about the locations that have been surveyed, the sensors used and the time this occurred. The second element is a module that creates the content of the coverage database in realtime, using the vehicle and sensor state to compute the footprint covered by the surveillance sensor(s). The third element is the visualization module which is used to translate elements of the coverage database into a graphical overlay which can be conformally integrated with a conventional map. The first part of the paper discusses the rationale underlying the concept. Next, the coverage database, the real-time update process and the visualization concept are discussed in more detail. In the third part of the paper, the concept is illustrated using an example situation created in a simulation environment.
Tantalum oxide thin films as protective coatings for sensors (1999)

Reactively sputtered tantalum oxide thin-films have been investigated as protective coating for aggressive media exposed sensors. Tantalum oxide is shown to be chemically very robust. The etch rate in aqueous potassium hydroxide with pH 11 at 140/spl deg/C is lower than 0.008 /spl Aring//h. Etching in liquids with pH values in the range from pH 2-11 have generally given etch rates below 0.04 /spl Aring//h. On the other hand patterning is possible in hydrofluoric acid. Further, the passivation behaviour of amorphous tantalum oxide and polycrystalline Ta/sub 2/O/sub 5/ is different in buffered hydrofluoric acid. By ex-situ annealing in O/sub 2/ the residual thin-film stress can be altered from compressive to tensile and annealing at 450/spl deg/C for 30 minutes gives a stress-free film. The step coverage of the sputter deposited amorphous tantalum oxide is reasonable, but metallisation lines are hard to cover. Sputtered tantalum oxide exhibits high dielectric strength and the pinhole density for 0.5 /spl mu/m thick films is below 3 cm/sup -2/.