gebhart/patrepeval huggingface dataset:
Adeno-Associated Virus-Based Gene Therapy for CNS Diseases (2016)

Gene therapy is at the cusp of a revolution for treating a large spectrum of CNS disorders by providing a durable therapeutic protein via a single administration. Adeno-associated virus (AAV)-mediated gene transfer is of particular interest as a therapeutic tool because of its safety profile and efficiency in transducing a wide range of cell types. The purpose of this review is to describe the most notable advancements in preclinical and clinical research on AAV-based CNS gene therapy and to discuss prospects for future development based on a new generation of vectors and delivery.
Lipid recognition propensities of amino acids in membrane proteins from atomic resolution data (2011)

We showed that the lipophilicity of amino acid residues determines the amino acid preferences for lipid tail groups in both membrane and water-soluble proteins, suggesting that tightly-bound lipid molecules and lipids in the annular shell interact with membrane proteins in a similar manner. In contrast, interactions between lipid head groups and amino acids showed a more variable pattern, apparently constrained by each protein's specific molecular function.
METABOLIC SYNDROME (2004)

RETURN TO ISSUEPREVNewsNEXTMETABOLIC SYNDROMEBecause of its complexity, this set of disorders teems with opportunities for drug development, but regulatory criteria for therapeutic outcomes are still lackingA. MAUREEN ROUHIView Author Information C&EN WASHINGTONCite this: Chem. Eng. News 2004, 82, 47, 83–102Publication Date (Print):November 22, 2004Publication History Published online14 November 2010Published inissue 22 November 2004https://doi.org/10.1021/cen-v082n047.p083Copyright © 2004 AMERICAN CHEMICAL SOCIETYArticle Views21Altmetric-Citations2LEARN 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 InReddit PDF (6 MB) SUBJECTS:Anatomy,Metabolic syndrome Get e-Alerts
Using powerful "turbo" codes for 14.4 kbit/s data service in GSM or PCS systems (2002)

The current maximum user data rate in GSM is 9.6 kbit/s per time slot. To increase the rate to 14.4 kbit/s by puncturing the code bits which are generated by the same convolutional coding scheme used for GSM 12.0 kbit/s, may result in a loss of about 2 dB and is not practicable in many situations. In this paper, a scheme based on "turbo" codes is introduced for the GSM 14.4 kbit/s data service. Our study indicates that the new approach can achieve almost the same performance as the GSM 12.0 kbit/s standard. Contrary to the common belief we have shown that the complexity increases less, if a new decoding algorithm for high code rates is used. Furthermore, this new coding scheme can be implemented in a currently available DSP for mobile communication.
The road not taken: A path to curing type 1 diabetes? (2009)

The past quarter century has seen a rapid increase in our knowledge about the natural history of autoimmune type 1 diabetes. However, we stand unable to achieve our ultimate goal of preventing or reversing this disease. This viewpoint discusses controversies in current management of type 1 diabetes, the challenges in translating promising studies from mouse models of the disease to humans, hurdles faced in designing optimal prevention and intervention studies, and potential strategies to overcome these obstacles.
Specificity of Gβγ Signaling to Kir3 Channels Depends on the Helical Domain of Pertussis Toxin-sensitive Gα Subunits (2007)

Acetylcholine signaling through muscarinic type 2 receptors activates atrial G protein-gated inwardly rectifying K(+) (Kir3) channels via the betagamma subunits of G proteins (Gbetagamma). Different combinations of recombinant Gbetagamma subunits have been shown to activate Kir3 channels in a similar manner. In native systems, however, only Gbetagamma subunits associated with the pertussis toxin-sensitive Galpha(i/o) subunits signal to K(+) channels. Additionally, in vitro binding experiments supported the notion that the C terminus of Kir3 channels interacts preferentially with Galpha(i) over Galpha(q). In this study we confirmed in two heterologous expression systems a preference of Galpha(i) over Galpha(q) in the activation of K(+) currents. To identify determinants of Gbetagamma signaling specificity, we first exchanged domains of Galpha(i) and Galpha(q) subunits responsible for receptor coupling selectivity and swapped their receptor coupling partners. Our results established that the G proteins, regardless of the receptor type to which they coupled, conferred specificity to Kir3 activation. We next tested signaling through chimeras between the Galpha(i) and Galpha(q) subunits in which the N terminus, the helical, or the GTPase domains of the Galpha subunits were exchanged. Our results revealed that the helical domain of Galpha(i) (residues 63-175) in the background of Galpha(q) could support Kir3 activation, whereas the reverse chimera could not. Moreover, the helical domain of the Galpha(i) subunit conferred "Galpha(i)-like" binding of the Kir3 C terminus to the Galpha(q) subunits that contained it. These results implicate the helical domain of Galpha(i) proteins as a critical determinant of Gbetagamma signaling specificity.
Three-dimensional scaling of the uniform color scales of the Optical Society of America (1989)

Three observers each judged differences between pairs of 25 colors in each of 12 intersecting oblique planes in the color space of the uniform color scales of the Optical Society of America (OSA). For each set of 25 colors, a three-dimensional configuration of points was determined for each observer, by use of the KYST algorithm. Equal judgments of differences between pairs of the colors are, as nearly as possible, represented in the configurations by equal distances between the points that represent the colors, and greater judgments by greater distances. The rms relative standard deviations of the judgments ranged from 0.061 to 0.214. The stress, as determined by the KYST algorithm, ranged from 0.048 to 0.151. In the configurations, the surfaces that correspond to the oblique planes in OSA color space are curved significantly.
Molecular Cloning, Characterization, and Potential Roles of Cytosolic and Mitochondrial Aldehyde Dehydrogenases in Ethanol Metabolism in Saccharomyces cerevisiae (1998)

The full-length DNAs for two Saccharomyces cerevisiae aldehyde dehydrogenase (ALDH) genes were cloned and expressed in Escherichia coli. A 2,744-bp DNA fragment contained an open reading frame encoding cytosolic ALDH1, with 500 amino acids, which was located on chromosome XVI. A 2,661-bp DNA fragment contained an open reading frame encoding mitochondrial ALDH5, with 519 amino acids, of which the N-terminal 23 amino acids were identified as the putative leader sequence. The ALDH5 gene was located on chromosome V. The commercial ALDH (designated ALDH2) was partially sequenced and appears to be a mitochondrial enzyme encoded by a gene located on chromosome XV. The recombinant ALDH1 enzyme was found to be essentially NADP dependent, while the ALDH5 enzyme could utilize either NADP or NAD as a cofactor. The activity of ALDH1 was stimulated two- to fourfold by divalent cations but was unaffected by K+ ions. In contrast, the activity of ALDH5 increased in the presence of K+ ions: 15-fold with NADP and 40-fold with NAD, respectively. Activity staining of isoelectric focusing gels showed that cytosolic ALDH1 contributed 30 to 70% of the overall activity, depending on the cofactor used, while mitochondrial ALDH2 contributed the rest. Neither ALDH5 nor the other ALDH-like proteins identified from the genomic sequence contributed to the in vitro oxidation of acetaldehyde. To evaluate the physiological roles of these three ALDH isoenzymes, the genes encoding cytosolic ALDH1 and mitochondrial ALDH2 and ALDH5 were disrupted in the genome of strain TWY397 separately or simultaneously. The growth of single-disruption delta ald1 and delta ald2 strains on ethanol was marginally slower than that of the parent strain. The delta ald1 delta ald2 double-disruption strain failed to grow on glucose alone, but growth was restored by the addition of acetate, indicating that both ALDHs might catalyze the oxidation of acetaldehyde produced during fermentation. The double-disruption strain grew very slowly on ethanol. The role of mitochondrial ALDH5 in acetaldehyde metabolism has not been defined but appears to be unimportant.
Long‐term safety from transmission of porcine endogenous retrovirus after pig‐to‐non‐human primate corneal transplantation (2017)

Within the limits of this study, there is no evidence to support any risk of PERV transmission from porcine corneal tissues to NHP recipients, despite the existence of PERV-expressing cells in porcine corneas.
Comparison of mapping algorithms used in high-throughput sequencing: application to Ion Torrent data (2014)

A benchmark procedure to compare HTS data mappers is introduced with a new definition for the mapping correctness as well as tools to generate simulated reads and evaluate mapping quality. The application of this procedure to Ion Torrent data from the whole genome sequencing of small genomes has allowed us to validate our benchmark procedure and demonstrate that it is helpful for selecting a mapper based on the intended application, questions to be addressed, and the technology used. This benchmark procedure can be used to evaluate existing or in-development mappers as well as to optimize parameters of a chosen mapper for any application and any sequencing platform.
Induction Speed Is Not a Determinant of Propofol Pharmacodynamics (2004)

: Population-based pharmacokinetics, combined with real-time electroencephalographic measures of drug effect, may provide a means to individualize pharmacodynamic modeling during target-controlled drug delivery. ARM seems useful as an automated measure of sedation and may provide the basis for automated monitoring and titration of sedation for a propofol delivery system.
Synthesis of Compound Libraries Based on 3,4-Diaminocyclopentanol Scaffolds (2000)

ADVERTISEMENT RETURN TO ISSUEReportNEXTSynthesis of Compound Libraries Based on 3,4-Diaminocyclopentanol ScaffoldsYousheng Guan, Mark A. Green, and Donald E. BergstromView Author Information Department of Medicinal Chemistry & Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907-1333, and Walther Cancer Institute, Indianapolis, Indiana 46208 Cite this: J. Comb. Chem. 2000, 2, 4, 297–300Publication Date (Web):June 20, 2000Publication History Received10 September 1999Published online20 June 2000Published inissue 1 July 2000https://pubs.acs.org/doi/10.1021/cc990053ghttps://doi.org/10.1021/cc990053gbrief-reportACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views388Altmetric-Citations19LEARN 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 optionsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Ammonia,Anions,Organic acids,Organic polymers,Scaffolds Get e-Alerts
Indium gallium nitride-based ultraviolet, blue, and green light-emitting diodes functionalized with shallow periodic hole patterns (2017)

In this study, we investigated the improvement in the light output power of indium gallium nitride (InGaN)-based ultraviolet (UV), blue, and green light-emitting diodes (LEDs) by fabricating shallow periodic hole patterns (PHPs) on the LED surface through laser interference lithography and inductively coupled plasma etching. Noticeably, different enhancements were observed in the light output powers of the UV, blue, and green LEDs with negligible changes in the electrical properties in the light output power versus current and current versus voltage curves. In addition, confocal scanning electroluminescence microscopy is employed to verify the correlation between the enhancement in the light output power of the LEDs with PHPs and carrier localization of InGaN/GaN multiple quantum wells. Light propagation through the PHPs on the UV, blue, and green LEDs is simulated using a three-dimensional finite-difference time-domain method to confirm the experimental results. Finally, we suggest optimal conditions of PHPs for improving the light output power of InGaN LEDs based on the experimental and theoretical results.
High power all-solid-state laser source for direct-write large screen laser projection displays (2003)

The system is based on a diode-pumped mode-locked Nd:YVO/sub 4/-laser, a synchronously pumped near infrared optical parametric oscillator (OPO) of KTiOAsO/sub 4/ (KTA), and second harmonic generation (SHG) and sum-frequency mixing (SFM) of the infrared OPO and laser radiation.
Image Denoising Via Sparse and Redundant Representations Over Learned Dictionaries (2006)

We address the image denoising problem, where zero-mean white and homogeneous Gaussian additive noise is to be removed from a given image. The approach taken is based on sparse and redundant representations over trained dictionaries. Using the K-SVD algorithm, we obtain a dictionary that describes the image content effectively. Two training options are considered: using the corrupted image itself, or training on a corpus of high-quality image database. Since the K-SVD is limited in handling small image patches, we extend its deployment to arbitrary image sizes by defining a global image prior that forces sparsity over patches in every location in the image. We show how such Bayesian treatment leads to a simple and effective denoising algorithm. This leads to a state-of-the-art denoising performance, equivalent and sometimes surpassing recently published leading alternative denoising methods.
Why Johnny can't encrypt: a usability evaluation of PGP 5.0 (1999)

User errors cause or contribute to most computer security failures, yet user interfaces for security still tend to be clumsy, confusing, or near-nonexistent. Is this simply due to a failure to apply standard user interface design techniques to security? We argue that, on the contrary, effective security requires a different usability standard, and that it will not be achieved through the user interface design techniques appropriate to other types of consumer software. To test this hypothesis, we performed a case study of a security program which does have a good user interface by general standards: PGP 5.0. Our case study used a cognitive walkthrough analysis together with a laboratory user test to evaluate whether PGP 5.0 can be successfully used by cryptography novices to achieve effective electronic mail security. The analysis found a number of user interface design flaws that may contribute to security failures, and the user test demonstrated that when our test participants were given 90 minutes in which to sign and encrypt a message using PGP 5.0, the majority of them were unable to do so successfully. We conclude that PGP 5.0 is not usable enough to provide effective security for most computer users, despite its attractive graphical user interface, supporting our hypothesis that user interface design for effective security remains an open problem. We close with a brief description of our continuing work on the development and application of user interface design principles and techniques for security.
Arsenic passivation of Si and Ge surfaces (1992)

Abstract This article reviews the passivating effect of arsenic monolayers on various silicon and germanium surfaces. It has been shown that such monolayers dramatically reduce the reactivity of the initial surfaces. The atomic structure and the nature of the bonding between the As layer and the various Si and Ge surfaces are described and the reasons for the passivation effects are discussed. Results of experimental and theoretical investigations of As-terminated Si and Ge surfaces are reviewed and compared with the same surfaces terminated with other atomic layers. Finally, the effect of As-termination on interface formation and heteroepitaxy is considered. In particular, the initial stage of GaAs growth on Si, which is dominated by the As-passivation of the Si substrate, is discussed.
IFN-γ-Inducible Protein 10 (CXCL10) Contributes to Airway Hyperreactivity and Airway Inflammation in a Mouse Model of Asthma (2002)

Allergic asthma is an inflammatory disease of the airways characterized by eosinophilic inflammation and airway hyper-reactivity. Cytokines and chemokines specific for Th2-type inflammation predominate in asthma and in animal models of this disease. The role of Th1-type inflammatory mediators in asthma remains controversial. IFN-gamma-inducible protein 10 (IP-10; CXCL10) is an IFN-gamma-inducible chemokine that preferentially attracts activated Th1 lymphocytes. IP-10 is up-regulated in the airways of asthmatics, but its function in asthma is unclear. To investigate the role of IP-10 in allergic airway disease, we examined the expression of IP-10 in a murine model of asthma and the effects of overexpression and deletion of IP-10 in this model using IP-10-transgenic and IP-10-deficient mice. Our experiments demonstrate that IP-10 is up-regulated in the lung after allergen challenge. Mice that overexpress IP-10 in the lung exhibited significantly increased airway hyperreactivity, eosinophilia, IL-4 levels, and CD8(+) lymphocyte recruitment compared with wild-type controls. In addition, there was an increase in the percentage of IL-4-secreting T lymphocytes in the lungs of IP-10-transgenic mice. In contrast, mice deficient in IP-10 demonstrated the opposite results compared with wild-type controls, with a significant reduction in these measures of Th2-type allergic airway inflammation. Our results demonstrate that IP-10, a Th1-type chemokine, is up-regulated in allergic pulmonary inflammation and that this contributes to the airway hyperreactivity and Th2-type inflammation seen in this model of asthma.
Inhibition of Microtubule Formation by Metabotropic Glutamate Receptors (2000)

Activation of glutamate receptors is known to alter the biophysical state of the cytoskeleton of neurons in the developing brain. In this study, we examined the ability of G protein-coupled metabotropic glutamate receptors (mGluRs) to inhibit the formation of processes induced by the expression of the microtubule-associated protein MAP2c. The infection of insect MG-1 cells with a recombinant baculovirus (BV) encoding MAP2c induced the formation of fine filamentous processes. The binding of MAPs to tubulin promotes tubulin polymerization and the formation of microtubules. Co-infection with BVs for the phosphoinositide (PI)-linked mGluR1a or mGluR1b receptor subtypes inhibited the formation of processes induced by MAP2c, whereas co-infection with BVs encoding the mGluR4a or mGluR4b subtypes that couple to adenylyl cyclase did not inhibit the formation of processes. The biochemical pathways responsible for producing the inhibitory effect of mGluR1 were investigated. Inhibitors of protein kinase C, calcium/calmodulin-dependent kinase, and protein tyrosine kinases did not block the inhibitory effect of mGluR1a. The calcium chelator BAPTA and the calcium depletor thapsigargin also did not affect the ability of mGluR1a to inhibit process formation. In contrast, inhibitors of phospholipase C reversed the effect of mGluR1 on process formation, suggesting that one or more metabolites in the PI pathway were responsible for the inhibitory effect. These findings indicate that PIs generated by activation of mGluRs inhibit the binding of MAPs to tubulin and reduce tubulin polymerization and microtubule stability.
A Human Blood-Brain Barrier Transcytosis Assay Reveals Antibody Transcytosis Influenced by pH-Dependent Receptor Binding (2014)

We have adapted an in vitro model of the human blood-brain barrier, the immortalized human cerebral microvascular endothelial cells (hCMEC/D3), to quantitatively measure protein transcytosis. After validating the receptor-mediated transport using transferrin, the system was used to measure transcytosis rates of antibodies directed against potential brain shuttle receptors. While an antibody to the insulin-like growth factor 1 receptor (IGF1R) was exclusively recycled to the apical compartment, the fate of antibodies to the transferrin receptor (TfR) was determined by their relative affinities at extracellular and endosomal pH. An antibody with reduced affinity at pH5.5 showed significant transcytosis, while pH-independent antibodies of comparable affinities at pH 7.4 remained associated with intracellular vesicular compartments and were finally targeted for degradation.
Chemical and Biological Characterization of Two FK506 Analogs Produced by Targeted Gene Disruption in Streptomyces sp. MA6548. (1997)

Two genetically engineered mutant strains of Streptomyces sp. MA6548 produced two FK506 analogs, 9-deoxo-31-O-demethylFK506 and 31-O-demethylFK506. The structures were determined by a combination of NMR and mass spectrometry. These compounds exhibited immunosuppressive and antifungal activities, albeit reduced, compared to FK506. Both compounds contain a free hydroxyl group at C-31 for the synthesis of novel FK506 derivatives.