gebhart/patrepeval huggingface dataset:
Peptide Targeting and Delivery across the Blood−Brain Barrier Utilizing Synthetic Triglyceride Esters:  Design, Synthesis, and Bioactivity (1997)

As an approach to the development of therapeutically useful peptide pharmaceuticals that can penetrate the blood-brain barrier, we have designed and demonstrated the application of a carrier-targeting system. We have developed a prodrug design strategy that is designed to utilize membrane-bound enzymes whereby release of a bioactive peptide from a highly lipophilic triglyceride peptide-carrier is achieved in situ, thus attaining high localized concentrations of the bioactive peptide. Following localization of such a system, normal peptidase and lipase action is utilized to release the active peptide (deltorphin II) intact and in high concentration. At present, the exact mechanisms are unclear, but the observed results in which analgesia is observed following peripheral administration suggest that the active peptide is able to cross the blood-brain barrier and sustain prolonged periods of analgesia as determined by antinociception tests by release of the bioactive peptide. In vitro tests of binding and bioactivity by the peptide conjugate show essentially no potency in either target or control analogues, but potent antinociceptive effects are observed following peripheral administration.
Store-Operated Calcium Entry Controls Innate and Adaptive Immune Cell Function in Inflammatory Bowel Disease (2021)

Abstract Objective Inflammatory bowel disease (IBD) is characterized by dysregulated intestinal immune responses and constitutes a major clinical challenge in need of new treatment modalities to improve patient care. Store-operated Ca 2+ entry (SOCE) is the predominant Ca 2+ influx pathway in T cells and other immune cells, regulating many of their functional properties. It is currently unknown whether the pharmacologic blockade of SOCE represents a suitable drug-target for IBD treatment. Design Using mass and flow cytometry the effects of SOCE inhibition on lamina propria (LP) immune cells of patients with ulcerative colitis (UC) and Crohn’s disease (CD) were investigated. Primary organoid cultures served to study the impact of SOCE inhibition on the function, differentiation and survival of intestinal epithelial cells (IEC). T cell transfer models of colitis were applied to examine how the genetic or pharmacologic ablation of SOCE affects the clinical course of IBD in mice. Results We observed that the LP of IBD patients is characterized by an enrichment of innate lymphoid cells (ILC), CD4 + and CD8 + effector- as well as T regulatory cells producing IL-17 and TNFα. The pharmacologic inhibition of SOCE attenuated the production of pathogenic cytokines including IL-2, IL-4, IL-6, IL-17, TNFα and IFNγ by human colonic T cells and ILC, reduced the production of IL-6 by B cells and the production of IFNγ by myeloid cells, without affecting the viability, differentiation and function of primary IEC. T cell-specific genetic deletion of the SOCE signaling components Orai1 , Stim1 or Stim2 revealed that the magnitude of SOCE correlates with the function of T cells and intestinal inflammation in mice. Moreover, the pharmacologic inhibition of SOCE alleviated the clinical course of colitic mice. Conclusion Our data suggest that SOCE inhibition may serve as a new pharmacologic strategy for treating IBD.
Metastatic cloacogenic carcinoma of the anus: sequential responses to adriamycin and cis-dichlorodiammineplatinum(II). (1978)

A case of cloacogenic carcinoma of the anus with pulmonary metastases successfully treated with adriamycin and subsequently with cis-dichlorodiammineplatinum(II) (CDP) is reviewed. Cloacogenic carcinoma of the anus is a very uncommon tumor, and this is the first report of a major response to chemotherapy alone. Adriamycin and/or CDP should be considered in the therapy of this tumor.
Abstract 3923: Molecular characterization of an animal model for neuroendocrine thyroid cancer (2014)

Abstract Neuroendocrine tumors are rare forms of cancers originating from hormone-producing cells that are scattered throughout the body. Medullary thyroid carcinoma (MTC) develops from calcitonin-secreting, C cells, in the thyroid gland. Surgical removal of the thyroid is the best treatment currently available for early stage cancer patients but advanced forms of MTC are often incurable and fatal. Thus, better therapies are needed. A lack of relevant animal models for this disease has slowed the development of new treatments. We have recently reported a novel conditional mouse model for MTC. In these mice, overexpression of the cyclin-dependent kinase 5 (Cdk 5), activator, p25 in C cells induces MTC tumors. Furthermore, interruption of p25 overexpression results in growth arrest of these tumors. Here we take advantage of our conditional mouse model to investigate the molecular pathways underlying MTC tumorigenesis. We used Illumina Mouse WG-6 v2.0 Expression BeadChip to compare the gene expression profile of proliferating versus arrested mouse MTC tumors. We found that a total of 920 genes encoding transcription factors, cell cycle proteins, motor proteins and angiogenesis factors were differentially regulated in growing versus arrested tumors. Particularly the genes encoding cell cycle proteins that are involved in the regulation of Rb pathway were significantly up-regulated in the proliferating tumors. Selected genes with higher degrees of change were evaluated by quantitative PCR and immunoblotting analyses. Taken together these findings suggests that the Rb signaling pathways is involved in MTC tumorigenesis and that Cdk5 may act as a critical regulator of the Rb signaling pathway in this cancer. Thus, targeting Cdk5 and/or the Rb pathway may be a valid strategy to stop the progression of neuroendocrine thyroid cancer. Citation Format: Karine Pozo, Antje Hillmann, Alexander Augustyn, Tanvir Singh, Florian Plattner, John Minna, Herbert Chen, Gilbert J. Cote, James A. Bibb, Fiemu E. Nwariaku. Molecular characterization of an animal model for neuroendocrine thyroid cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3923. doi:10.1158/1538-7445.AM2014-3923
Blood Transcriptional Biomarkers for Active Tuberculosis among Patients in the United States: a Case-Control Study with Systematic Cross-Classifier Evaluation (2015)

Blood transcriptional classifiers accurately detected active TB among U.S. adults. The accuracy of classifiers for active TB versus that of other diseases decreased when tested in new populations with different disease controls, suggesting additional studies are required to enhance generalizability. Classifiers that distinguish active TB from latent TB are accurate and generalizable across populations and can be explored as screening assays.
Structure-based drug design of new leads for phosphatase research. (2007)

Biological targets that are challenging to pursue for medicinal chemists, such as the protein phosphatases, require creative and innovative approaches for identifying and optimizing previously unknown classes of inhibitors. To achieve these lofty objectives, medicinal chemists must utilize the latest computational, structural biology, synthetic and analytical technologies in the drug development process. The iterative use of structure-based drug design often plays a key role, as illustrated by the independent discoveries of two research groups involving the identification and optimization of protein tyrosine phosphatase 1B inhibitors that have novel heterocyclic phosphotyrosine mimetics. The newly designed pharmacophore provides a promising chemical lead for phosphatase drug discovery and a valuable chemical tool for phosphatase research in general.
A Channel Subspace Post-Filtering Approach to Adaptive Least-Squares Estimation (2004)

A major challenge while communicating in dynamic channels, such as the underwater acoustic channel, is the large amount of time-varying inter-symbol interference (ISI) due to multipath. In many realistic channels, the fluctuations between different taps of the sampled channel impulse response are correlated. Traditional least-squares algorithms used for adapting channel equalizers do not exploit this correlation structure. A channel subspace post-filtering algorithm is presented that treats the least-squares channel estimate as a noisy time series and exploits the channel correlation structure to reduce the channel estimation error. The improvement in performance of the post-filtered channel estimator is predicted theoretically and demonstrated using both simulation and experimental data. Experimental data is also used to demonstrate the improvement in performance of a channel estimate-based decision feedback equalizer that uses this post-filtered channel estimate to determine the equalizer coefficients.
Characterization of MOS Transistors Using Dynamic Backside Reflectance Modulation Technique (2011)

Abstract The channel of metal-oxide-semiconductor (MOS) transistors at different modes of operation has been characterized using dynamic backside laser reflectance modulation technique for different NMOS and PMOS transistors with different channel lengths. The reflectance modulations contain a primary peak near the drain-end when the MOS transistor is in saturation mode. Comparison studies with a Pseudo-Two-Dimensional analytical model support the hypothesis that the observed peak corresponds to the pinch-off point.
Structure-based Virtual Screening Approaches in Kinase-directed Drug Discovery (2017)

Protein kinases are one of the most targeted protein families in current drug discovery pipelines. They are implicated in many oncological, inflammatory, CNS-related and other clinical indications. Virtual screening is a computational technique with a diverse set of available tools that has been shown many times to provide novel starting points for kinase-directed drug discovery. This review starts with a concise overview of the function, structural features and inhibitory mechanisms of protein kinases. In addition to briefly reviewing the practical aspects of structure-based virtual screenings, we discuss several case studies to illustrate the state of the art in the virtual screening for type I, type II, allosteric (type III-V) and covalent (type VI) kinase inhibitors. With this review, we strive to provide a summary of the latest advances in the structure-based discovery of novel kinase inhibitors, as well as a practical tool to anyone who wishes to embark on such an endeavor.
A Closed-Form Solution to Local Non-Rigid Structure-from-Motion (2020)

A recent trend in Non-Rigid Structure-from-Motion (NRSfM) is to express local, differential constraints between pairs of images, from which the surface normal at any point can be obtained by solving a system of polynomial equations. The systems of equations derived in previous work, however, are of high degree, having up to five real solutions, thus requiring a computationally expensive strategy to select a unique solution. Furthermore, they suffer from degeneracies that make the resulting estimates unreliable, without any mechanism to identify this situation. In this paper, we show that, under widely applicable assumptions, we can derive a new system of equation in terms of the surface normals whose two solutions can be obtained in closed-form and can easily be disambiguated locally. Our formalism further allows us to assess how reliable the estimated local normals are and, hence, to discard them if they are not. Our experiments show that our reconstructions, obtained from two or more views, are significantly more accurate than those of state-of-the-art methods, while also being faster.
Deuterium Mas Nmr Studies Of Dynamics On Multiple Timescales: Histidine And Oxalic Acid. (2014)

International audience ; Deuterium ((2) H) magic-angle spinning (MAS) nuclear magnetic resonance is applied to monitor the dynamics of the exchanging labile deuterons of polycrystalline L-histidine hydrochloride monohydrate-d7 and α-oxalic acid dihydrate-d6 . Direct experimental evidence of fast dynamics is obtained from T1Z and T1Q measurements. Further motional information is extracted from two-dimensional single-quantum (SQ) and double-quantum (DQ) MAS spectra. Differences between the SQ and DQ linewidths clearly indicate the presence of motions on intermediate timescales for the carboxylic moiety and the D2 O in α-oxalic acid dihydrate, and for the amine group and the D2 O in L-histidine hydrochloride monohydrate. Comparison of the relaxation rate constants of Zeeman and quadrupolar order with the relaxation rate constants of the DQ coherences suggests the co-existence of fast and slow motional processes.
Efficient MPEG-2 to H.264/AVC Transcoding of Intra-Coded Video (2007)

This paper presents an efficient transform-domain architecture and corresponding mode decision algorithms for transcoding intra-coded video from MPEG-2 to H.264/AVC. Low complexity is achieved in several ways. First, our architecture employs direct conversion of the transform coefficients, which eliminates the need for the inverse discrete cosine transform (DCT) and forward H.264/AVC transform. Then, within this transform-domain architecture, we perform macroblock-based mode decisions based on H.264/AVC transform coefficients, which is possible using a novel method of calculating distortion in the transform domain. The proposed method for distortion calculation could be used to make rate-distortion optimized mode decisions with lower complexity. Compared to the pixel-domain architecture with rate-distortion optimized mode decision, simulation results show that there is a negligible loss in quality incurred by the direct conversion of transform coefficients and the proposed transform-domain mode decision algorithms, while complexity is significantly reduced. To further reduce the complexity, we also propose two fast mode decision algorithms. The first algorithm ranks modes based on a simple cost function in the transform domain, then computes the rate-distortion optimal mode from a reduced set of ranked modes. The second algorithm exploits temporal correlations in the mode decision between temporally adjacent frames. Simulation results show that these algorithms provide additional computational savings over the proposed transform-domain architecture while maintaining virtually the same coding efficiency.
Total and Differential White Blood Cell Counts and Their Associations With Circulating Interleukin-6 Levels in Community-Dwelling Older Women (2005)

Positive in vivo associations of total WBC and its specific subpopulations were identified, including neutrophils, monocytes, and eosinophils, with circulating IL-6 levels in community-dwelling older women. These findings suggest significant contributions of WBC and its subpopulations to circulating IL-6 levels and potential effects from chronic elevation of IL-6 levels to the function of these circulating immune cells that warrant further investigation.
The Proprietorial Model (2015)

Mark Day puts the case for the proprietorial model of newspaper publishing, starting with a very simple proposition: that without Rupert Murdoch as an old-fashioned proprietor, we wouldn't have had The Australian 50 years ago and we wouldn't have it today.
Social networking site use by mothers of young children (2014)

In this paper, we present the first formal study of how mothers of young children (aged three and under) use social networking sites, particularly Facebook and Twitter, including mothers' perceptions of which SNSes are appropriate for sharing information about their children, changes in post style and frequency after birth, and the volume and nature of child-related content shared in these venues. Our findings have implications for improving the utility and usability of SNS tools for mothers of young children, as well as for creating and improving sociotechnical systems related to maternal and child health.
Sound Source Tracking by Drones with Microphone Arrays (2020)

This paper presents a method for sound source localization and tracking using drones with microphone arrays. Microphone array processing is an established technique for estimating the direction of a sound source. However, for search and rescue applications, mere sound source direction is insufficient since sound source location in terms of direction and distance is essential. Accordingly, we propose a novel method we call Multiple Triangulation and Gaussian Sum Filter Tracking (MT-GSFT). MT-GSFT obtains the sound source location by triangulation using microphone arrays attached to multiple drones. Since triangulation results differ among pairs of arrays, they are transformed into a probabilistic representation using a Gaussian mixture, then a Gaussian sum filter is applied to estimate the sound source trajectory. Numerical simulation demonstrated MT-GSFT is effective in removing outliers in sound source localization to track sound sources better than the Linear Intersection method.
Bromide and Hydroxide Conductivity–Morphology Relationships in Polymerized Ionic Liquid Block Copolymers (2015)

A polymerized ionic liquid (PIL) diblock copolymer, poly(MMA-b-MEBIm-Br), was synthesized at various compositions from an ionic liquid monomer, (1-[(2-methacryloyloxy)ethyl]-3-butylimidazolium bromide) (MEBIm-Br), and a nonionic monomer, methyl methacrylate (MMA), via the reverse addition–fragmentation chain transfer (RAFT) polymerization technique. A hydroxide-conducting PIL diblock copolymer, poly(MMA-b-MEBIm-OH), was also prepared via anion exchange metathesis of the bromide-conducting block copolymer. In a former study, the conductivity and morphology of the bromide- and hydroxide-conducting PIL diblock copolymer were examined at one fixed PIL composition: 17.3 mol %. In this study, additional PIL compositions of (6.6, 11.9, and 26.5 mol %) were explored to fully understand the previous unusual conductivity results. Both bromide and hydroxide conductivities were higher in the PIL block copolymer at PIL compositions of 11.9, 17.3, and 26.5 mol % compared to the PIL homopolymer under the same experimental conditions, even though the homopolymer possessed a higher water and ionic content compared to the block copolymers. These unusual results suggest that the confinement of the PIL microdomain within the block copolymer morphology enhances ion transport compared to its predicted value. Morphology factors (or normalized ionic conductivity, f) were as high as >3 at some conditions, which is much higher than the maximum theoretical limit for randomly oriented lamellar domains (f = 2/3). Application of percolation theory revealed a 3–4-fold enhancement of conductivity when comparing the inherent conductivity to the measured PIL homopolymer conductivity. Both morphology factor analysis and percolation theory corroborate with the absolute conductivity results and the hypothesis that PIL domain confinement in PIL block copolymers enhances conductivity over its bulk properties.
One‐ and Two‐Photon Photochemistry and Photophysics of Poly(arylenevinylene)s Containing a Biphenyl Moiety (2005)

Photochemical and photophysical properties were investigated for poly(arylenevinylene)s containing a flexible biphenyl "hinge" unit by applying one-photon (OP) and two-photon (TP) excitation to explore excited-state properties. The poly(arylenevinylene)s were poly[(2,5-dihexyloxy-p-phenylenevinylene)-alt-(4,4'-dihexyloxy-3,3'-biphenylenevinylene)] (1), poly[(2,5-dihexyloxy-p-phenylenevinylene)-alt-(2,2'-dihexyloxy-3,3'-biphenylenevinylene)] (2), and poly[(2,5-dihexyloxy-p-phenylenevinylene)-alt-(2,2'-biphenylenevinylene)] (3). Effective emission quantum yields and related photonic properties were evaluated on a realistic per-chromophore basis using effective conjugation lengths based on the Strickler-Berg relationship. Intramolecular photocyclization was deduced to occur in the one case where the biphenyl molecular connectivity permitted the reaction, based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), heteronuclear multiple-quantum coherence (HMQC)-NMR, and gel-permeation chromatography (GPC) results. The various photoprocesses could be induced by either OP or TP excitation, though the first excited singlet state is the photoactive state. The higher excitation energy of the TP excited state favors indirect population of the S, state by electronic coupling between the TP and OP excited states [lambda(max)TPE (nm): 726; delta (GM): 1=229, 2=215, 3= 109). Photochemical processes occurring from the lowest OP excited state (S1) could therefore also be indirectly induced by TP excitation.
Fièvre aphteuse et vaccination (2001)

Beaucoup d'interrogations sont actuellement soulevees par les choix strategiques en matiere de lutte contre la fievre aphteuse, a l'occasion de l'episode que connait actuellement le Royaume-Uni, et qui menace egalement le continent. En effet, voila une maladie extremement contagieuse, capable de diffuser a tres grande vitesse et a tres grande distance, y compris par voie aerienne (pour une synthese recente, voir [1]). Les caracteristiques de resistance de ce virus, son excretion a tres haut titre, en particulier par les porcs, son incubation tres courte, rendent la generation de foyers secondaires extremement efficace. Il existe des vaccins tres efficaces, qui ont ete utilises pendant une trentaine d'annees a large echelle en Europe, de maniere obligatoire dans la plupart des pays. Pourtant, l'usage de ces vaccins est devenu interdit en Europe (sauf derogation exceptionnelle) a partir du 31 decembre 1991. Certains pays comme le Royaume-Uni, proteges par leur situation insulaire ou leur position nord-europeenne, avaient largement anticipe cette interdiction. Quelles sont les raisons qui ont conduit a ces decisions ?
InAs nanowire GAA n-MOSFETs with 12–15 nm diameter (2016)

InAs nanowires (NW) grown by MOCVD with diameter d as small as 10 nm and gate-all-around (GAA) MOSFETs with d = 12-15 nm are demonstrated. I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on</sub> = 314 μA/μm, and S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sat</sub> =68 mV/dec was achieved at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dd</sub> = 0.5 V (I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">off</sub> = 0.1 μA/μm). Highest g <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> measured is 2693 μS/μm. Device performance is enabled by small diameter and optimized high-k/InAs gate stack process. Device performance tradeoffs between g <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> , R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">on</sub> , and I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">min</sub> are discussed.