gebhart/patrepeval huggingface dataset:
RNA-based vaccine demonstrates prophylactic efficacy against Mycobacterium tuberculosis challenge in a mouse model (2022)

Abstract Mycobacterium tuberculosis (Mtb) is an opportunistic bacterial pathogen that causes tuberculosis disease (TB) and exerts an extensive burden on global health. The complex intra- and extracellular nature of this bacterium, coupled with different disease stages have made mechanistic studies evaluating the contributions of innate and adaptive host immunity challenging. In this work we leveraged two delivery platforms as prophylactic vaccines to assess immunity and subsequent efficacy against low dose and ultra-low dose aerosol challenge with Mtb H37Rv in C57BL/6 mice. Our proof-of-concept TB vaccine candidate ID91 was produced as a fusion protein formulated with a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant in a stable emulsion) or as a replicating-RNA (repRNA) formulated in a nanostructured lipid carrier (NLC). Results from this work demonstrate that protein subunit- and RNA-based vaccines preferentially elicit cellular immune responses to different ID91 epitopes. In a single prophylactic immunization screen, both platforms reduced pulmonary bacterial burden compared to controls. Excitingly, in prime-boost strategies, groups that received heterologous RNA-prime, protein-boost or combination (simultaneous in different sites) immunizations demonstrated the greatest reduction in bacterial burden and a unique humoral and cellular immune response profile. These data are the first to report that repRNA platforms are a viable system for TB vaccines and should be pursued with high priority Mtb antigens containing CD4+ and CD8+ T cell epitopes.
Circadian pattern to arrhythmias in a genetic mouse model of heart failure (2009)

Arrhythmias and sudden cardiac death have a circadian pattern of occurrence in humans. We hypothesized that a circadian pattern of arrhythmias is also present in transgenic mice with cardiac-specific overexpression of tumor necrosis factor alpha, which develop a dilated cardiomyopathy, arrhythmias and heart failure. To test this hypothesis, telemetry monitors were implanted and 24hr, ambulatory ECG was recorded ≥ 5 days later. Animals were maintained on a 12hr light/dark cycle. The incidence of ventricular arrhythmias increased between 3pm and 12am, whereas atrial arrhythmias surged between 4am and 12pm. This circadian pattern of arrhythmias is in excellent agreement with human data (taking into account a 12-hour shift between activity periods in diurnal humans and nocturnal rodents). The molecular mechanisms underlying such circadian patterns of arrhythmias were examined using gene expression analysis and mathematical modeling.
Analysis of Electromagnetic Response of 3-D Dielectric Fractals of Menger Sponge Type (2007)

Experimental studies and finite-difference time-domain simulations of electromagnetic (EM) response of the second-stage Menger sponge dielectric structures have been performed with different types of excitation in order to gain deeper insight into the phenomenon of EM wave localization in these fractals. Analysis of simulated amplitude distributionExperimental studies and finite-difference time-domain simulations of electromagnetic (EM) response of the second-stage Menger sponge dielectric structures have been performed with different types of excitation in order to gain deeper insight into the phenomenon of EM wave localization in these fractals. Analysis of simulated amplitude distributions of electric field oscillations in the Menger sponges has revealed bandgap-like effects caused by resonances in the front part of the structures, as well as formation of the full-wave resonance mode in the central cavity at the localization frequency. It is demonstrated that penetration of the waves inside the structure at the localization frequency leads to equalizing of the EM response from different parts of the 3D fractal, however, no high- <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> eigenmode is formed in the second-stage Menger sponge. Simulations of the modified fractal structures have been used to show the potential of formation of a bandgap with defect-related localized photon states by 3D fractals.s of electric field oscillations in the Menger sponges has revealed bandgap-like effects caused by resonances in the front part of the structures, as well as formation of the full-wave resonance mode in the central cavity at the localization frequency. It is demonstrated that penetration of the waves inside the structure at the localization frequency leads to equalizing of the EM response from different parts of the 3D fractal, however, no high- <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> eigenmode is formed in the second-stage Menger sponge. Simulations of the modified fractal structures have been used to show the potential of formation of a bandgap with defect-related localized photon states by 3D fractals.
COMPUTERIZED ANALYSIS OF BONE STRUCTURE FOR ASSESSMENT OF OSTEOPOROSIS (1992)

Caliguiri, P. M.D.; Giger, M. L. Ph.D.; Favus, M. M.D.; Jia, H. M.Sc.; Doi, K. Ph.D.; Carrascal, F. M.Sc.; L. Dixon, A. Takigawa. M.D. Author Information
T helper cell cytokines modulate intestinal stem cell renewal and differentiation (2018)

Raw data of immunofluorescence assays and FACS plots
Conclusion (2020)

This book explores ecologies design, from holistic, multiple perspective notion of how Life works. To embrace the threshold, the shifting, the ecotone, permeability, and other aspects of how ecosystems work and function were all thought to be key in engaging with ecologies design. The need for interdisciplinarity and genuine exploration of multiple perspectives, needs, and drivers for design has been highlighted by Graves, and Reed and Haggard. The difference of time spent in field by designers, even more immersive ones, and ethnographers is significant. The advocacy for place based ecological communities of elements within design, and openness to accommodating connections and living fluctuations are key design tactics, with the designers acting as ‘aligned others’, and giving voice to ecological contexts. Design projects need to have a wider contextual responsibility than an immediate site, extending to a project’s material, energy, and water origins and uses, both as part of built environment assemblage, and over time as wider environment changes.
Heterogeneity in a Complex Turbiditic Reservoir: Stochastic Modelling of Facies and Petrophysical Variability (1990)

ABSTRACT The paper presents an application of recently developped geostatistical conditional simulation techniques to the modelling of heterogeneity in a complex turbiditic reservoir. Heterogeneity is mainly controlled by the distribution of sandstones embedded in laminated facies. Channels and lobes account for most of the production. Their frequencies and geometries are critical factors that affect reservoir connectivity, hence oil recovery. The combined used of flexible stochastic techniques allows generating realistic 3D models of this complex architecture. The modelling strategy is multi-steps, with first a geologically constrained generation of facies distributions, and second, simulations of permeability variations within the previously generated facies distributions.
ChemInform Abstract: MILD CONVERSION OF CARBOXAMIDES AND CARBOXYLIC ACID HYDRAZIDES TO ACIDS AND ESTERS (1982)

Abstract Die Amide (Ia) bzw. Hydrazide (Ib) werden in Gegenwart von sauren Ionenaustauscherharzen mit Wasser bzw. Alkoholen in die Carbonsäuren bzw. Ester (II) übergeführt.
Individualized and generalized learner models for predicting missed hepatic metastases (2022)

The diagnostic performance of radiologist readers exhibits substantial variation that cannot be explained by CT acquisition protocol differences. Studying reader detectability from CT images may help identify why certain types of lesions are missed by multiple or specific readers. Ten subspecialized abdominal radiologists marked all suspected metastases in a multi-reader-multi-case study of 102 deidentified contrast-enhanced CT liver scans at multiple radiation dose levels. A reference reader marked ground truth metastatic and benign lesions with the aid of histopathology or tumor progression on later scans. Multi-slice image patches and 3D radiomic features were extracted from the CT images. We trained deep convolutional neural networks (CNN) to predict whether an average (generalized) or individual radiologist reader would detect or miss a specific metastasis from an image patch containing it. The individualized CNN showed higher performance with an area under the receiver operating characteristic curve (AUC) of 0.82 compared to a generalized one (AUC = 0.78) in predicting reader-specific detectability. Random forests were used to build the respective versions from radiomic features. Both the individualized (AUC = 0.64) and generalized (AUC = 0.59) predictors from radiomic features showed limited ability to differentiate detected from missed lesions. This shows that CNN can identify and learn automated features that are better predictors of reader detectability of lesions than radiomic features. Individualized prediction of difficult lesions may allow targeted training of idiosyncratic weaknesses but requires substantial training data for each reader.
Crystal Structures of Human Adenosine Kinase Inhibitor Complexes Reveal Two Distinct Binding Modes (2006)

Adenosine kinase (AK) is an enzyme responsible for converting endogenous adenosine (ADO) to adenosine monophosphate (AMP) in an adenosine triphosphate- (ATP-) dependent manner. The structure of AK consists of two domains, the first a large alpha/beta Rossmann-like nucleotide binding domain that forms the ATP binding site, and a smaller mixed alpha/beta domain, which, in combination with the larger domain, forms the ADO binding site and the site of phosphoryl transfer. AK inhibitors have been under investigation as antinociceptive, antiinflammatory, and anticonvulsant as well as antiinfective agents. In this work, we report the structures of AK in complex with two classes of inhibitors: the first, ADO-like, and the second, a novel alkynylpyrimidine series. The two classes of structures, which contain structurally similar substituents, reveal distinct binding modes in which the AK structure accommodates the inhibitor classes by a 30 degrees rotation of the small domain relative to the large domain. This change in binding mode stabilizes an open and a closed intermediate structural state and provide structural insight into the transition required for catalysis. This results in a significant rearrangement of both the protein active site and the orientation of the alkynylpyrimidine ligand when compared to the observed orientation of nucleosidic inhibitors or substrates.
Recent Advances in the Discovery of Competitive Protein Tyrosine Phosphatase 1B Inhibitors for the Treatment of Diabetes, Obesity, and Cancer (2009)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTRecent Advances in the Discovery of Competitive Protein Tyrosine Phosphatase 1B Inhibitors for the Treatment of Diabetes, Obesity, and CancerAndrew P. Combs†View Author Information Incyte Corporation, Experimental Station, E336/131A, Route 141 and Henry Clay Road, Wilmington, Delaware 19880†Contact information. Phone: 1-302-498-6832. Fax: 1-302-425-2750. E-mail: [email protected]Cite this: J. Med. Chem. 2010, 53, 6, 2333–2344Publication Date (Web):December 10, 2009Publication History Received22 July 2009Published online10 December 2009Published inissue 25 March 2010https://pubs.acs.org/doi/10.1021/jm901090bhttps://doi.org/10.1021/jm901090breview-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views6833Altmetric-Citations270LEARN 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 SUBJECTS:Drug discovery,Inhibitors,Peptides and proteins,Permeability,Pharmaceuticals Get e-Alerts
Distributed consensus algorithms for collaborative temperature control in smart buildings (2015)

Buildings with shared spaces such as corporate office buildings, university dorms, etc. involve multiple occupants who are likely to have different temperature preferences. The building temperature control system needs to balance the desire of all users, as well as take the building energy cost into account. Centralized temperature management is challenging as the use comfort function is held privately and not centrally known. This paper proposes a distributed temperature control algorithm which ensures that a consensus is attained among all occupants, irrespective of their temperature preferences. Occupants are only assumed to be rational, in that they choose their own temperature set-points to minimize a combination of their individual energy cost and discomfort. We establish the convergence of the proposed algorithm to the optimal temperature set-point that minimizes the sum of the energy cost and the aggregate discomfort of all occupants. Simulations with realistic parameter settings illustrate the performance of the algorithm and provide insights on the dynamics of the system with a mobile user population.
Structures of HIV-1 Neutralizing Antibody 10E8 Delineate the Mechanistic Basis of Its Multi-Peak Behavior on Size-Exclusion Chromatography (2021)

Antibody 10E8 is capable of effectively neutralizing HIV through its recognition of the membrane-proximal external region (MPER), and a suitably optimized version of 10E8 might have utility in HIV therapy and prophylaxis. However, 10E8 displays a three-peak profile on size-exclusion chromatography (SEC), complicating its manufacture. Here we show cis-trans conformational isomerization of the Tyr-Pro-Pro (YPP) motif in the heavy chain 3rd complementarity-determining region (CDR H3) of antibody 10E8 to be the mechanistic basis of its multipeak behavior. We observed 10E8 to undergo slow conformational isomerization and delineate a mechanistic explanation for effective comodifiers that were able to resolve its SEC heterogeneity and to allow an evaluation of the critical quality attribute of aggregation. We determined crystal structures of single and double alanine mutants of a key di-proline motif and of a light chain variant, revealing alternative conformations of the CDR H3. We also replicated both multi-peak and delayed SEC behavior with MPER-antibodies 4E10 and VRC42, by introducing a Tyr-Pro (YP) motif into their CDR H3s. Our results show how a conformationally dynamic CDR H3 can provide the requisite structural plasticity needed for a highly hydrophobic paratope to recognize its membrane-proximal epitope.
Quantitative PET of the apoptosis tracer 18F-C-SNAT following tumor therapy (2014)

165 Objectives To obtain quantitative in vivo pharmacokinetic measurements of the apoptosis / caspase-3 activated nano-aggregation tracer 18F-C-SNAT in a clinically relevant mouse model of tumor therapy. Methods HeLa tumor xenografts were implanted on the shoulder of nude mice, and were allowed to grow to a minimum of 5x5 mm before treatment with a series of chemotherapeutic drug injection. All mice (control n=6, treated n=5) were anesthetized with isoflurane and placed in a microPET/CT. A 15-min CT scan was performed followed by injection of 18F-C-SNAT (184 ± 54 µCi) and a 120-min dynamic PET scan. Tracer uptake over time was measured in regions of interest in the PET image by using the CT as an anatomical guide. The whole tumor region was subjected to a threshold algorithm selecting the top25% intensity pixels, generating a second region associated with the treatment response. Tracer pharmacokinetics was calculated using a 2-tissue compartmental model while using the tracer concentration in the left ventricle as an estimated input function. Results Uptake of 18F-C-SNAT was found to be 2.3 times higher in the treated tumors over the whole scan when comparing the area under curve — maximum uptake of 6.1 (± 1.1 sem) %ID/g in treated tumors compared with 2.5 (± 0.4 sem) %ID/g in controls — and 2.5 times higher tumor/muscle ratio in treated tumors (9.0 ± 1.7 sem) compared with controls (3.6 ± 0.6 sem) at the end of scan. The pharmacokinetics of 18F-C-SNAT in treated mice was found to be different from controls, the flow in and out (K1 and k2) of the treated tumor was higher but the net delivery (K1/k2) similar, the accumulation rate of 18F-C-SNAT (k3) was 1.85 times higher — whereas the washout rate (k4) was similar. Conclusions 18F-C-SNAT show significant increases in uptake, tumor/muscle ratios and accumulation rate in a clinically relevant model of tumor therapy. These findings support our theory that chemotherapeutic induced tumor apoptosis leads to higher accumulation of 18F-C-SNAT and thus enable the use of 18F-C-SNAT as a PET tracer for imaging tumor therapy. Research Support Mikael Palner is supported with a post doctoral fellowship from the Danish Cancer Society.
Local repair procedure for carbon‐fiber‐reinforced plastics by refilling with a thermoset matrix (2015)

ABSTRACT Textile‐reinforced composites have given rise to an increasingly important key technology for lightweight construction in aerospace, automotive, civil engineering, and many other industries. Because there exists no suitable repair procedure for carbon‐fiber‐reinforced plastics (CFRPs), damaged parts have to be replaced completely; this is extremely disadvantageous both ecologically and economically. With fiber‐reinforced composites used being more and more often, fast and efficient methods for the local repair of damaged CFRPs are essential. In this article, a novel repair procedure for CFRP is presented. The thermal activation by IR radiation of oxide semiconductors was used to locally degrade the thermoset matrix of the damaged CFRP through the maintenance of its structural stability and properties. The matrix‐free textile structure was then refilled with a thermoset epoxy matrix. Carbon fibers from the treated area were characterized with scanning electron microscopy, IR spectroscopy, thermogravimetric analysis, and subsequently, tensile strength for single fibers to verify the effectiveness of the procedure. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133 , 42964.
Extension of the Criegee Rearrangement: Synthesis of Enol Ethers from Secondary Allylic Hydroperoxides (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExtension of the Criegee Rearrangement: Synthesis of Enol Ethers from Secondary Allylic HydroperoxidesRichard M. Goodman and Yoshito KishiCite this: J. Org. Chem. 1994, 59, 18, 5125–5127Publication Date (Print):September 1, 1994Publication History Published online1 May 2002Published inissue 1 September 1994https://pubs.acs.org/doi/10.1021/jo00097a006https://doi.org/10.1021/jo00097a006research-articleACS PublicationsRequest reuse permissionsArticle Views757Altmetric-Citations20LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
Longitudinal distribution of ozone absorption in the lung: comparison of nasal and oral quiet breathing (1994)

Employing a bolus inhalation system, we noninvasively measured the fraction of inhaled ozone (O3) that is absorbed during a single breath (lambda) as a function of bolus penetration volume into the respiratory tract (Vp). During nasal breathing at a constant respiratory flow of 250 ml/s, lambda increased smoothly as Vp increased with 80% of the inhaled O3 absorbed in the upper airways and 90% absorbed at the distal end of the trachea. Oral breathing caused a distal shift of the lambda-Vp distribution to the extent that absorption in the upper airways was reduced to 50% and inhaled O3 was 90% absorbed only after a bolus reached the 13th bronchial generation. Therefore, an exercise-induced change from nasal to oral breathing can render the distal lung more susceptible to O3 damage because of an elevation in O3 dose. We also found that changing the peak inhaled bolus concentration over a 10-fold range of 0.4-4 ppm O3 did not affect the lambda-Vp distribution. This finding implies that the diffusion and chemical reaction dynamics that dictate O3 absorption are linear processes.
Illumination Level Independence in Relation to Emitter Profiles on Industrial High Efficiency Local Al-BSF Cells (2011)

We observe a relationship between bias dependence and the process flow applied to produce passivated emitter rear contacted (PERC) cells. The first process flow utilizes a deposited silicon oxide layer, for both diffusion mask and passivation purposes. The second process flow uses the same silicon oxide diffusion mask, but it is removed after diffusion and a freshly deposited silicon oxide layer is used for passivation purposes. Cells that have been passivated with fresh silicon oxide result in a large bias dependence at ultra low bias levels below 10-1 sun, but saturate performance beyond 10-1 sun. Cells that have been passivated with the silicon oxide diffusion mask, an increase bias increases performance. For this process, we also observe a relationship between illumination level dependence and the diffusion recipe which densifies the oxide. With a 90 ohm/sq emitter there is an increase in collection in the UV wavelength range compared to a 60ohm/sq emitter. What is unexpected is that, in the case of the 90 ohm/sq device, there is also an increase in collection of wavelengths above 700nm under no bias compared to the 60ohm/sq device. The cells studied in this paper are fabricated using 148.25 cm2, 160μm p-type Cz-Si wafers with screen printed Ag front contacts and are rear-side passivated with a deposited rear silicon oxide/silicon nitride stack and area locally contacted with Al. The highest efficiency of the cells studied is 19.2 % with a Voc of 637mV, Jsc of 38.2 mA/cm2 and a fill factor of 79.1%