gebhart/patrepeval huggingface dataset:
Highlights on the Development of A<sub>2A</sub> Adenosine Receptor Agonists and Antagonists (2006)

Although significant progress has been made in the past few decades demonstrating that adenosine modulates a variety of physiological and pathophysiological processes through the interaction with four subtypes of a family of cell-surface G-protein-coupled receptors, clinical evaluation of some adenosine receptor ligands has been discontinued. Major problems include side effects due to the wide distribution of adenosine receptors, low brain penetration (which is important for the targeting of CNS diseases), short half-life of compounds, or a lack of effects, in some cases perhaps due to receptor desensitization or to low receptor density in the targeted tissue. Currently, three A(2A) adenosine receptor agonists have begun phase III studies. Two of them are therapeutically evaluated as pharmacologic stress agents and the third proved to be effective in the treatment of acute spinal cord injury (SCI), while avoiding the adverse effects of steroid agents. On the other hand, the great interest in the field of A(2A) adenosine receptor antagonists is related to their application in neurodegenerative disorders, in particular, Parkinson's disease, and some of them are currently in various stages of evaluation. This review presents an update of medicinal chemistry and molecular recognition of A(2A) adenosine receptor agonists and antagonists, and stresses the strong need for more selective ligands at the A(2A) human subtype.
A novel peptide to induce production of antibodies for detection of equine CC10 (2013)

Recurrent airway obstruction (RAO) in horses is a type‐1 immediate hypersensitivity allergic response involving reaginic antibodies mainly IgE and some IgG subclasses. Antigen antibody reaction leads to degranulation of mast cells, resulting in release of inflammatory mediators. The overall goal of the study was to establish a direct function correlation between Clara Cell proteins (CC10) and RAO in horses. The specific aims were: 1) to develop a rabbit polyclonal antibody to the “C” terminal 21 amino acid peptide of equine CC10 protein, 2) to validate this antibody in an antibody capture endpoint ELISA with peptide as the capture antigen and peroxidase conjugated goat anti‐rabbit IgG as detection antibody, 3) to detect the peptide using a competitive ELISA, 4) to determine CC10 specific IgG titer in clinically healthy and RAO‐affected horses using the competitive ELISA system. The results showed that the newly developed peptide with 21 amino acids produced polyclonal antibodies in rabbits. An antibody titer of >;100,000 was detected at a dilution between 1000 and 10000. A concentration‐dependent inhibition of antibody binding to peptide‐coated plate by the peptide was observed in competitive inhibition assay. Clinically healthy horses had significantly higher IgG titer suggesting the peptide's homology to common environmental antigens. The peptide has potential to induce antibody production against allergens. Supported by Equine Health Studies Program, LSU School of Veterinary Medicine.
Endoxifen: A new, protein kinase C inhibitor to treat acute and mixed mania associated with bipolar I disorder (2020)

Endoxifen at a low daily dose of 8 mg was as efficacious and safe in patients with BPD I acute manic episodes with/without mixed features.
High‐speed frequency‐switching synthesizer using fractional N phase‐locked loop (1994)

Abstract A fractional N phase‐locked loop frequency synthe sizer has been developed for small‐size and low‐power applications. It has fast frequency switching and low‐phase noise. the fractional N‐frequency synthesizer realizes fast switching by the high‐frequency reference signal and by widening the loop bandwidth. However, when the bandwidth was widened, deterioration of phase noise is observed. Then the loop bandwidth which is necessary for fast frequency switching and which gives low‐phase noise performance is determined. Based on these conditions, loop filter switching was studied which realized fast switching by widening the loop bandwidth and the low‐phase noise performance by making the loop bandwidth narrow after the frequency switching. In the conventional filter switching, VCO control voltage fluctuates at the time of switching and the frequency switching time becomes longer. A new method is proposed which gives small switching fluctuation and which can shorten the frequency switching time. Finally, the synthesizer circuit in the 900‐MHz band was fabricated and the lock‐up time of 1.3 ms, the phase noise of ‐120 dBc/Hz at 50 kHz offset from carrier and spurious level of ‐83 dBc were obtained.
Classification of retinal diseases based on OCT Images (2017)

Optical Coherence Topography (OCT) is an emerging biomedical imaging technology that offers non-invasive real-time, high-resolution imaging of highly scattering tissues. It is widely used in ophthalmology to perform diagnostic imaging on the structure of the anterior eye and the retina. Clinical studies are carried out to assess the application of OCT for some retinal diseases. OCT can provide means for early detection for various types of diseases because morphological changes often occur before the physical symptoms of these diseases. In addition, follow-up imaging can assess treatment effectiveness and recurrence of a disease. A review in this area is needed to identify the results and the findings from OCT images in the field of retinal diseases and how to use these findings to help in clinical applications. This paper overviews the current techniques that are developed to determine the ability of OCT images for early detection/diagnosis of retinal diseases. Also, the paper remarks several challenges that face the researchers in the analysis of the OCT retinal images.
Newborn screening for lysosomal storage disorders. (1999)

Lysosomal storage disorders (LSD) represent a group of over 40 distinct genetic diseases with a total incidence of approximately 1:7,000 births. Bone marrow transplantation and enzyme replacement therapy are currently in use for the treatment of some disorders and new forms of enzyme and gene replacement therapy are actively being researched. The effectiveness of these therapies, particularly for the LSD involving the central nervous system and bone pathology, will rely heavily upon the early diagnosis and treatment of the disorder, before the onset of irreversible pathology. In the absence of a family history the only practical way to detect these disorders will be by a newborn screening program. One common feature of these disorders is an increase in the number and size of lysosomes within the cell from approximately 1% to as much as 50% of total cellular volume. Associated with this, is a corresponding increase in some lysosomal proteins. We propose that the measurement of one or more of these proteins in blood spots taken from Guthrie cards, will form the basis of a newborn screening program, for the detection of all LSD. We have identified a number of lysosomal proteins as potential markers for LSD. The level of these proteins has been determined in blood spots taken from Guthrie cards and in plasma samples from over 300 LSD affected individuals representing 25 disorders. Based on these results we have proposed a strategy for a newborn screening program involving a two tier system, utilizing time resolved fluorescence immunoquantification of the protein markers in the first tier, followed by tandem mass spectrometry for the determination of stored substrates in the second tier assays.
Strategy of Metal–Polymer Composite Stent To Accelerate Biodegradation of Iron-Based Biomaterials (2017)

The new principle and technique to tune biodegradation rates of biomaterials is one of the keys to the development of regenerative medicine and next-generation biomaterials. Biodegradable stents are new-generation medical devices applied in percutaneous coronary intervention, etc. Recently, both corrodible metals and degradable polymers have drawn much attention in biodegradable stents or scaffolds. It is, however, a dilemma to achieve good mechanical properties and appropriate degradation profiles. Herein, we put forward a metal-polymer composite strategy to achieve both. Iron stents exhibit excellent mechanical properties but low corrosion rate in vivo. We hypothesized that coating of biodegradable aliphatic polyester could accelerate iron corrosion due to the acidic degradation products, etc. To demonstrate the feasibility of this composite material technique, we first conducted in vitro experiments to affirm that iron sheet corroded faster when covered by polylactide (PLA) coating. Then, we fabricated three-dimensional metal-polymer stents (MPS) and implanted the novel stents in the abdominal aorta of New Zealand white rabbits, setting metal-based stents (MBS) as a control. A series of in vivo experiments were performed, including measurements of residual mass and radial strength of the stents, histological analysis, micro-computed tomography, and optical coherence tomography imaging at the implantation site. The results showed that MPS could totally corrode in some cases, whereas iron struts of MBS in all cases remained several months after implantation. Corrosion rates of MPS could be easily regulated by adjusting the composition of PLA coatings.
An Efficient Synthesis of 1,2,9,9a-Tetrahydrocyclopropa[c]benz[e]indol-4-one CBI: An Enhanced and Simplified Analog of the CC-1065 and Duocarmycin Alkylation Subunits (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn Efficient Synthesis of 1,2,9,9a-Tetrahydrocyclopropa[c]benz[e]indol-4-one CBI: An Enhanced and Simplified Analog of the CC-1065 and Duocarmycin Alkylation SubunitsDale L. Boger and Jeffrey A. McKieCite this: J. Org. Chem. 1995, 60, 5, 1271–1275Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/jo00110a034https://doi.org/10.1021/jo00110a034research-articleACS PublicationsRequest reuse permissionsArticle Views1880Altmetric-Citations140LEARN 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 (2)»Supporting Information Supporting Information Get e-Alerts
Optical Interferometers with Reduced Sensitivity to Thermal Noise (2008)

A fundamental limit to the sensitivity of optical interferometry is thermal noise that drives fluctuations in the positions of the surfaces of the interferometer's mirrors, and thereby in the phase of the intracavity field. Schemes for reducing this thermally driven phase noise are presented that rely upon the coherent character of the underlying displacements and strains. Although the position of the physical surface fluctuates, the optical phase upon reflection can have reduced sensitivity to this motion. While practical implementation of such schemes for coherent compensation face certain challenges, we hope to stimulate further work on this important thermal noise problem.
Redox-Responsive Magnetic Nanoparticle for Targeted Convection-Enhanced Delivery of<i>O</i><sup>6</sup>-Benzylguanine to Brain Tumors (2014)

Resistance to temozolomide (TMZ) based chemotherapy in glioblastoma multiforme (GBM) has been attributed to the upregulation of the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT). Inhibition of MGMT using O(6)-benzylguanine (BG) has shown promise in these patients, but its clinical use is hindered by poor pharmacokinetics that leads to unacceptable toxicity. To improve BG biodistribution and efficacy, we developed superparamagnetic iron oxide nanoparticles (NP) for targeted convection-enhanced delivery (CED) of BG to GBM. The nanoparticles (NPCP-BG-CTX) consist of a magnetic core coated with a redox-responsive, cross-linked, biocompatible chitosan-PEG copolymer surface coating (NPCP). NPCP was modified through covalent attachment of BG and tumor targeting peptide chlorotoxin (CTX). Controlled, localized BG release was achieved under reductive intracellular conditions and NPCP-BG-CTX demonstrated proper trafficking of BG in human GBM cells in vitro. NPCP-BG-CTX treated cells showed a significant reduction in MGMT activity and the potentiation of TMZ toxicity. In vivo, CED of NPCP-BG-CTX produced an excellent volume of distribution (Vd) within the brain of mice bearing orthotopic human primary GBM xenografts. Significantly, concurrent treatment with NPCP-BG-CTX and TMZ showed a 3-fold increase in median overall survival in comparison to NPCP-CTX/TMZ treated and untreated animals. Furthermore, NPCP-BG-CTX mitigated the myelosuppression observed with free BG in wild-type mice when administered concurrently with TMZ. The combination of favorable physicochemical properties, tumor cell specific BG delivery, controlled BG release, and improved in vivo efficacy demonstrates the great potential of these NPs as a treatment option that could lead to improved clinical outcomes.
Abstract 2802: Fine-tuning T cell receptors for adoptive T cell therapy (2014)

Abstract Adoptive T cell therapy (ACT) with gene-modified T cells is emerging as a highly promising strategy for the treatment of many types of cancer. Therapies associated with the induction of anti-tumor immunity, such as the administration of vaccines or the ex-vivo expansion of patient-derived TILs, have historically had limited success. This lack of efficacy is almost certainly brought about as a consequence of thymic selection, leading to a paucity of T cells, and T cell receptors, in the circulating repertoire, with a sufficient degree of sensitivity towards tumor-associated antigens. An alternative approach, which has generated promising results, relies on the adoptive transfer of patient-derived T cells that have been first modified to express a chimeric antigen receptor (CAR). Nevertheless, a lack of tumor-specific antibody targets limits the wider applicability of CAR T cells. To overcome these issues we have developed a strategy that involves the transfer of T cells expressing engineered TCRs with optimised affinity for a defined tumor antigen. Since TCRs recognize peptide antigens presented on the cell surface in complex with human leukocyte antigen (HLA), they give access to the large pool of intracellular proteins. Furthermore, the use of TCRs means that the natural interaction between a T cell and the corresponding antigen presenting cell is preserved. Importantly, for any given antigen, engineered TCRs require individual optimization, to ensure the appropriate balance between potency and specificity. Recent and emerging clinical data using engineered TCRs for ACT are beginning to corroborate promising pre-clinical findings, with evidence of both potent and durable responses in vivo. However, experiences have also highlighted the dangers of this approach. The main risks associated with TCR adoptive therapy are target presentation on healthy tissue and TCR cross-reactivity to a look-alike peptide. Understanding these risks and ensuring comprehensive and robust safety testing mechanisms are in place is pivotal to mitigate these risks. Citation Format: Bent Jakobsen. Fine-tuning T cell receptors for adoptive T cell therapy. [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 2802. doi:10.1158/1538-7445.AM2014-2802
Development of quantum well thermoelectric device (2003)

The electronic and thermal properties of bulk materials are altered when they are incorporated into quantum wells. Two-dimensional quantum wells have been synthesized by alternating layers of B/sub 4/C and B/sub 9/C in one system and alternating layers of Si and Si/sub 0.8/G/sub 0.2/ in another system. Such nanostructures are being investigated as candidate thermoelectric materials for high figures of merit (Z). The predicted enhancement is attributed to the confined motion of charge carriers and phonons in the two dimensions and separating them from the ion scattering centers. Molecular beam epitaxy (MBE) and sputtering techniques have been used to prepare these multilayer films. Films have been deposited on single-crystal silicon substrates. The /spl alpha/ and /spl rho/ properties of these films have been determined over a broad range of temperatures from 4.2 K to 1200 K and were previously reported. The /spl alpha//sup 2///spl rho/ values for these P type B-C and N type SiGe films were more than a factor of 10 to 30 times higher than bulk P type B-C and N type SiGe. Several one and two couple devices were fabricated with P-type B/sub 4/C/B/sub 9/C QW films and N-type bulk Bi/sub 2/Te/sub 3/. One of these couples produced 0.182 milliwatt at a /spl Delta/T of a 50/spl deg/C. This device produced ten times more power than the bulk Bi/sub 2/Te/sub 3/ commercial material of the same dimensions and /spl Delta/T. Hi-Z is also producing thicker B/sub 4/C/B/sub 9/C films (>10 /spl mu/m) on thinner Si substrates (<1 /spl mu/m) to minimize thermal bypass heat losses. Successful scale up of these films for the P-leg is expected to yield a 1 cm square device that will produce /spl sim/5 Watts at a /spl Delta/T of 200/spl deg/C. With a minimum assumption for thermal losses the device efficiency should approach 20%.
A monolithic or hybrid broadband compensated balun (2002)

A compact microstrip balun structure, capable of multioctave performance, has been devised for monolithic or hybrid circuit applications. The structure requires no suspended substrate techniques and can be designed to occupy only a small amount of circuit area, thus allowing it to be easily integrated with a variety of monolithic circuit designs such as mixers, multipliers, and class B push-pull amplifiers. If a matching network is incorporated with the balun structure, a 10:1 operational bandwidth can be achieved.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Revisiting the Design of Data Stream Processing Systems on Multi-Core Processors (2017)

Driven by the rapidly increasing demand for handling real-time data streams, many data stream processing (DSP) systems have been proposed. Regardless of the different architectures of those DSP systems, they are mostly aiming at scaling out using a cluster of commodity machines and built around a number of key design aspects: a) pipelined processing with message passing, b) on-demand data parallelism, and c) JVM based implementation. However, there lacks a study on those key design aspects on modern scale-up architectures, where more CPU cores are being put on the same die, and the onchip cache hierarchies are getting larger, deeper, and complex. Multiple sockets bring non-uniform memory access (NUMA) effort. In this paper, we revisit the aforementioned design aspects on a modern scale-up server. Specifically, we use a series of applications as micro benchmark to conduct detailed profiling studies on Apache Storm and Flink. From the profiling results, we observe two major performance issues: a) the massively parallel execution model causes serious front-end stalls, which are a major performance bottleneck issue on a single CPU socket, b) the lack of NUMA-aware mechanism causes major drawback on the scalability of DSP systems on multi-socket architectures. Addressing these issues should allow DSP systems to exploit modern scale-up architectures, which also benefits scaling out environments. We present our initial efforts on resolving the above-mentioned performance issues, which have shown up to 3.2x and 3.1x improvement on the performance of Storm and Flink, respectively.
Comparison of reconstruction accuracy and efficiency among autocalibrating data‐driven parallel imaging methods (2008)

The class of autocalibrating "data-driven" parallel imaging (PI) methods has gained attention in recent years due to its ability to achieve high quality reconstructions even under challenging imaging conditions. The aim of this work was to perform a formal comparative study of various data-driven reconstruction techniques to evaluate their relative merits for certain imaging applications. A total of five different reconstruction methods are presented within a consistent theoretical framework and experimentally compared in terms of the specific measures of reconstruction accuracy and efficiency using one-dimensional (1D)-accelerated Cartesian datasets. It is shown that by treating the reconstruction process as two discrete phases, a calibration phase and a synthesis phase, the reconstruction pathway can be tailored to exploit the computational advantages available in certain data domains. A new "split-domain" reconstruction method is presented that performs the calibration phase in k-space (k(x), k(y)) and the synthesis phase in a hybrid (x, k(y)) space, enabling highly accurate 2D neighborhood reconstructions to be performed more efficiently than previously possible with conventional techniques. This analysis may help guide the selection of PI methods for a given imaging task to achieve high reconstruction accuracy at minimal computational expense.
Bayesian background modeling for foreground detection (2005)

We propose a Bayesian learning method to capture the background statistics of a dynamic scene. We model each pixel as a set of layered normal distributions that compete with each other. Using a recursive Bayesian learning mechanism, we estimate not only the mean and variance but also the probability distribution of the mean and covariance of each model. This learning algorithm preserves the multimodality of the background process and is capable of estimating the number of required layers to represent each pixel.
Sagnac interferometer amplitude modulator (1996)

Summary form only given. We have demonstrated broadband amplitude modulation using a travelling wave phase modulator in a Sagnac interferometer. The inherent bias stability when using a regular phase modulator makes this scheme advantageous over the Mach-Zehnder configuration in situations where low frequency response is not essential, such as subcarrier multiplexed analog communications and fiberfed radar applications.