gebhart/patrepeval huggingface dataset:
A mechanistically novel peptide agonist of the IL-7 receptor that addresses limitations of IL-7 cytokine therapy (2023)

Abstract Interleukin (IL)-7 is broadly active on T-cell populations, and modified versions have been clinically evaluated for a variety of therapeutic applications, including cancer, lymphopenia and infectious diseases; and found to be relatively well-tolerated and biologically active. Here we describe novel IL-7R agonists that are unrelated in structure to IL-7, bind to the receptor subunits differently from IL-7, but closely emulate IL-7 biology. The small size, low structural complexity, and the natural amino acid composition of the pharmacologically active peptide MDK1472 allows facile incorporation into protein structures, such as the IgG2-Fc fusion MDK-703. This molecule possesses properties potentially better suited to therapeutic applications than native IL-7 or its derivatives. We compared these compounds with IL-7 for immune cell selectivity, induction of IL-7R signaling, receptor-mediated internalization, proliferation, and generation of immune cell phenotypes in human and non-human primate (NHP) peripheral blood cells in vitro; and found them to be similar in biological activity to IL-7. In cynomolgus macaques, MDK-703 exhibits a circulating half-life of 46 hr, and produces sustained T-cell expansion characteristic of IL-7 treatment. In the huCD34 + -engrafted NSG mouse model of the human immune system, MDK-703 induces an immune cell profile very similar to that generated by IL-7-derived compounds; including the pronounced expansion of memory T-cells, particularly the population of stem-like memory T-cells (Tscm), which may be important for anti-tumor activities reported with IL-7 treatment. Clinical administration of IL-7 and modified variants has been reported to induce anti-drug antibodies (ADAs), including IL-7 neutralizing antibodies. The novel peptide agonist reported here scores very low in predicted immunogenicity, and because the peptide lacks sequence similarity with IL-7, the problematic immunogenic neutralization of endogenous cytokine should not occur.
Molecular profiling of Adolescent Idiopathic Scoliosis: toward a comprehensive understanding of ais aetiology (2010)

The adolescent idiopathic scoliosis (AIS) is the most common deformity arising during childhood. Although its aetiology remains unknown, we have demonstrated a differential dysfunction of melatonin signalling through Gi proteins in osteoblasts isolated from AIS patients, leading to their stratification into three functional subgroups. Herein we examine the molecular profiles of these AIS groups using the functional classification developed by Moreau et al.
Increasing Protein Stability through Control of the Nanoscale Environment (2006)

We have discovered a novel property of single-walled carbon nanotubes (SWNTs)-their ability to stabilize proteins at elevated temperatures and in organic solvents to a greater extent than conventional flat supports. Experimental results and theoretical analysis reveal that the stabilization results from the curvature of SWNTs, which suppresses unfavorable protein-protein lateral interactions. Our results also indicate that the phenomenon is not unique to SWNTs but could be extended to other nanomaterials. The protein-nanotube conjugates represent a new generation of active and stable catalytic materials with potential use in biosensors, diagnostics, and bioactive films and other hybrid materials that integrate biotic and abiotic components.
Systematic Investigation of Controlled Nanostructuring of Mn<sub>12</sub> Single-Molecule Magnets Templated by Metal–Organic Frameworks (2017)

This is the first systematic study exploring metal-organic frameworks (MOFs) as platforms for the controlled nanostructuring of molecular magnets. We report the incorporation of seven single-molecule magnets (SMMs) of general composition [Mn<sub>12</sub>O<sub>12</sub>(O<sub>2</sub>CR)<sub>16</sub>(OH<sub>2</sub>)<sub>4</sub>], with R = CF<sub>3</sub> (1), (CH<sub>3</sub>)CCH<sub>2</sub> (2), CH<sub>2</sub>Cl (3), CH<sub>2</sub>Br (4), CHCl<sub>2</sub> (5), CH<sub>2</sub>Bu<sup>t</sup> (6), and C<sub>6</sub>H<sub>5</sub> (7), into the hexagonal channel pores of a mesoporous MOF host. The resulting nanostructured composites combine the key SMM properties with the functional properties of the MOF. Synchrotron-based powder diffraction with difference envelope density analysis, physisorption analysis (surface area and pore size distribution), and thermal analyses reveal that the well-ordered hexagonal structure of the host framework is preserved, and magnetic measurements indicate that slow relaxation of the magnetization, characteristic of the corresponding Mn<sub>12</sub> derivative guests, occurs inside the MOF pores. Structural host-guest correlations including the bulkiness and polarity of peripheral SMM ligands are discussed as fundamental parameters influencing the global SMM@MOF loading capacities. These results demonstrate that employing MOFs as platforms for the nanostructuration of SMMs is not limited to a particular host-guest system but potentially applicable to a multitude of other molecular magnets. Such fundamental findings will assist in paving the way for the development of novel advanced spintronic devices.
A 1.25 Gb/s high sensitive peak detector in optical burst-mode receiver using a 0.18 μm CMOS technology (2004)

This paper introduces a novel peak detection in the burst-mode receiver considering the extinction ratio (6dB) of the received burst packet cells. The peak detector is designed using a 0.18 /spl mu/m CMOS technology and can be applied to the optical burst-mode receiver in an Ethernet PON system. By adopting this method, we can get the -29 dBm sensitivity and -8 dBm overload at 1.25 Gb/s.
Link-coloring based scheme for multicast and unicast protection (2013)

We propose a computationally efficient link-coloring based scheme that facilitates end-to-end protection for dynamic multicast and unicast connections. For a given source node, links are colored as red or blue such that, for any destination node, the red and blue paths are guaranteed to be node disjoint. Red and blue trees, constructed using only the red and blue links, respectively, always form redundant trees (RTs) independent of the used tree selection method. RTs connect the source of a multicast connection to all its destinations in such a way that in the event of a single link or node failure in the network, every destination is still connected to the source in at least one of the two trees. In network topologies where such RTs cannot be constructed due to lack of required path diversity, our scheme constructs two multicast trees such that the red and blue paths to any destination node only share cut links or nodes. To our knowledge, our scheme is the first that can construct such RTs. Although finding the optimal RTs is known to be NP-complete, extensive simulations show that our scheme calculates near optimal RTs and substantially outperforms other solutions.
Strategies for Biopolymer Engineering of PHB-Like Materials (1991)

Abstract : The overall objective of this proposal is to study the genetics and enzymology of polyhydroxybutyrate (PHB) biosynthesis at the molecular level in order to provide strategies for the development of new PHB-like biopolymers. Specific aims are to (1) control the chain length of the PHB polymers produced in fermentation processes through genetic manipulation; (2) incorporate different monomers into PHB producing co-polymers with different physical properties, and (3) examine the physical/rheological properties of these new biopolymers in order to develop criteria at the molecular level.
Hold-up time extension Circuit with integrated magnetics (2006)

A circuit that substantially extends the hold-up time of ac-dc power supplies is introduced. By using integrated magnetics, the power density of this hold-up time extension circuit is maximized. The performance of the proposed approach was evaluated on a universal line range 1-kW power supply.
Detecting malicious clients in ISP networks using HTTP connectivity graph and flow information (2014)

This paper considers an approach to identify previously undetected malicious clients in Internet Service Provider (ISP) networks by combining flow classification with a graph-based score propagation method. Our approach represents all HTTP communications between clients and servers as a weighted, near-bipartite graph, where the nodes correspond to the IP addresses of clients and servers while the links are their interconnections, weighted according to the output of a flow-based classifier. We employ a two-phase alternating score propagation algorithm on the graph to identify suspicious clients in a monitored network. Using a symmetrized weighted adjacency matrix as its input, we show that our score propagation algorithm is less vulnerable towards inflating the malicious scores of popular Web servers with high in-degrees compared to the normalization used in PageRank, a widely used graph-based method. Experimental results on a 4-hour network trace collected by a large Internet service provider showed that incorporating flow information into score propagation significantly improves the precision of the algorithm.
Synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO) and its analogs based on KDO aldolase-catalyzed reactions (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO) and its analogs based on KDO aldolase-catalyzed reactionsTakeshi Sugai, Gwo Jenn Shen, Yoshitaka Ichikawa, and Chi Huey WongCite this: J. Am. Chem. Soc. 1993, 115, 2, 413–421Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://pubs.acs.org/doi/10.1021/ja00055a008https://doi.org/10.1021/ja00055a008research-articleACS PublicationsRequest reuse permissionsArticle Views930Altmetric-Citations93LEARN 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 Get e-Alerts
Functional analysis of a NAC‐type transcription factor OsNAC6 involved in abiotic and biotic stress‐responsive gene expression in rice (2007)

The OsNAC6 gene is a member of the NAC transcription factor gene family in rice. Expression of OsNAC6 is induced by abiotic stresses, including cold, drought and high salinity. OsNAC6 gene expression is also induced by wounding and blast disease. A transactivation assay using a yeast system demonstrated that OsNAC6 functions as a transcriptional activator, and transient localization studies with OsNAC6-sGFP fusion protein revealed its nuclear localization. Transgenic rice plants over-expressing OsNAC6 constitutively exhibited growth retardation and low reproductive yields. These transgenic rice plants showed an improved tolerance to dehydration and high-salt stresses, and also exhibited increased tolerance to blast disease. By utilizing stress-inducible promoters, such as the OsNAC6 promoter, it is hoped that stress-inducible over-expression of OsNAC6 in rice can improve stress tolerance by suppressing the negative effects of OsNAC6 on growth under normal growth conditions. The results of microarray analysis revealed that many genes that are inducible by abiotic and biotic stresses were upregulated in rice plants over-expressing OsNAC6. A transient transactivation assay showed that OsNAC6 activates the expression of at least two genes, including a gene encoding peroxidase. Collectively, these results indicate that OsNAC6 functions as a transcriptional activator in response to abiotic and biotic stresses in plants. We conclude that OsNAC6 may serve as a useful biotechnological tool for the improvement of stress tolerance in various kinds of plants.
Quaternary structure regulates hemin dissociation from human hemoglobin. (1997)

Chiancone and co-workers (1) published studies of hemin loss from immobilized αβ dimers and isolated α and β subunits of human hemoglobin that we failed to read and to take into account. Their conclusions were the same as ours but were reported 1 year earlier: “... in human hemoglobin the heme-globin linkage in the α chains is stabilized by interactions between unlike chains at the α1β1 interface, whereas heme binding to the β chains is stabilized by interactions at the α1β2interface” (1). As they noted, the rate constants for hemin dissociation from proteins attached to Sepharose 4B are 3 to 10 times greater than those for hemin loss in solution.
Steadiface: Real-Time Face-Centric Stabilization on Mobile Phones (2019)

We present Steadiface, a new real-time face-centric video stabilization method that simultaneously removes hand shake and keeps subject's head stable. We use a CNN to estimate the face landmarks and use them to optimize a stabilized head center. We then formulate an optimization problem to find a virtual camera pose that locates the face to the stabilized head center while retains smooth rotation and translation transitions across frames. We test the proposed method on fieldtest videos and show it stabilizes both the head motion and background. It is robust to large head pose, occlusion, facial appearance variations, and different kinds of camera motions. We show our method advances the state of art in selfie video stabilization by comparing against alternative methods. The whole process runs very efficiently on a modern mobile phone (8.1 ms/frame).
<title>Efficient reconstruction algorithm for CT fluoroscopy</title> (2001)

In interventional procedures, computed tomography (CT) has demonstrated its effectiveness in guiding operators through otherwise difficult tasks. By providing near real time feedback, CT fluoroscopy (CTF) enables the operator to dynamically adjust the location and orientation of the biopsy instrument. The most important performance parameter of CTF is the system temporal response. In this paper, we present a mathematical framework that accurately characterizes the system response of a needle type instrument. Based on the model, a modified halfscan reconstruction algorithm is presented. The algorithm makes use of the redundant nature of CTF data processing and enables efficient generation of CT images. The effectiveness of the algorithm is demonstrated by theoretical analysis and phantom experiments.
Mesoporous zirconium oxide nanomaterials effectively enrich phosphopeptides for mass spectrometry-based phosphoproteomics (2009)

This work represents the first use of mesoporous zirconium oxide nanomaterials for highly effective and selective enrichment of phosphorylated peptides.
Diffuse polarization spectroscopy on tissue phantoms and biological cell suspensions (1996)

We present experimental results that show the spatial variations of the diffuse-backscattered intensity, when linearly polarized light is incident on highly scattering media. Experiments on polystyrene-sphere suspensions demonstrate that the radial and azimuthal variations of the observed pattern depend on the concentration and size of the particles constituting the scattering medium. Measurements performed on rodent-cell suspensions show the potential of this method for biological-cell characterization, especially the distinction between normal and cancerous cells.
Comparison techniques for VSB fractured vs. unfractured data (2013)

There are known VSB (Variable shape beam) mask writers in production today that require mask data with all angle edges to be approximated by staircases (stacked slits) in either a horizontal or vertical direction. The approximation uses 0, 45 or 90 degree edges, depending on the fracture setup and the angle of the edges in the original data. In order to gauge the effectiveness of the algorithm that fractures the original design to the VSB format, several methods can be employed to analyze the differences between the fractured data in the VSB format output and the original data before fracture. This is commonly referred to as skew error. This paper explores various methods and approaches that can be used, and examines each in detail. The goal is to highlight the differences and the effectiveness of each method in order to provide mask makers with the necessary information to make decisions best suited for their MDP-to-Lithography process flow. The first method explored is an XOR operation, followed by a double geometric biasing, aka Underover Sizing. The second method explored is an XOR operation, followed by a cut out of the differences starting from the unfractured polygon edges, aka Path Implode. The third method analyzed is an XOR operation, followed by measurement of the differences in the direction orthogonal to the unfractured edges, aka Difference Measurement. The fourth and last method analyzed is a mix of the last two, and employs an XOR operation, followed by measurement of the differences in the direction orthogonal to the unfractured edges, followed by a cut out of the measurement results, aka Measurement Implode.
Inhibition of mitochondrial fragmentation diminishes Huntington’s disease–associated neurodegeneration (2013)

Huntington's disease (HD) is the result of expression of a mutated Huntingtin protein (mtHtt), and is associated with a variety of cellular dysfunctions including excessive mitochondrial fission. Here, we tested whether inhibition of excessive mitochondrial fission prevents mtHtt-induced pathology. We developed a selective inhibitor (P110-TAT) of the mitochondrial fission protein dynamin-related protein 1 (DRP1). We found that P110-TAT inhibited mtHtt-induced excessive mitochondrial fragmentation, improved mitochondrial function, and increased cell viability in HD cell culture models. P110-TAT treatment of fibroblasts from patients with HD and patients with HD with iPS cell-derived neurons reduced mitochondrial fragmentation and corrected mitochondrial dysfunction. P110-TAT treatment also reduced the extent of neurite shortening and cell death in iPS cell-derived neurons in patients with HD. Moreover, treatment of HD transgenic mice with P110-TAT reduced mitochondrial dysfunction, motor deficits, neuropathology, and mortality. We found that p53, a stress gene involved in HD pathogenesis, binds to DRP1 and mediates DRP1-induced mitochondrial and neuronal damage. Furthermore, P110-TAT treatment suppressed mtHtt-induced association of p53 with mitochondria in multiple HD models. These data indicate that inhibition of DRP1-dependent excessive mitochondrial fission with a P110-TAT-like inhibitor may prevent or slow the progression of HD.
Production of Potato Cyst Nematode Hatching Stimulus by Hairy Root Cultures of Tomato. (1991)

Hairy root clones of tomato (Lycopersicon esculentum) were obtained by inoculation of the stems of sterile plants with Agrobacterium rhizogenes. The transformed root cultures produced a potato cyst nematode hatching stimulus, which was detected both in the extract of the cultured roots and in th culture medium.The hatching stimulus was also produced by non-transformed tomato root cultures. Large portions of the hatching stimuli synthesized in the hairy and non-transformed roots were found to be released into the medium.Five independent clones of the tomato hairy root cultures displayed considerable variation in the production of stimulus.
(<i>S</i>)-4-(Difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530), a Potent, Orally Bioavailable, and Brain-Penetrable Dual Inhibitor of Class I PI3K and mTOR Kinase (2019)

The phosphoinositide 3-kinase (PI3K)/mechanistic target of rapamycin (mTOR) pathway is frequently overactivated in cancer, and drives cell growth, proliferation, survival, and metastasis. Here, we report a structure–activity relationship study, which led to the discovery of a drug-like adenosine 5′-triphosphate-site PI3K/mTOR kinase inhibitor: (S)-4-(difluoromethyl)-5-(4-(3-methylmorpholino)-6-morpholino-1,3,5-triazin-2-yl)pyridin-2-amine (PQR530, compound 6), which qualifies as a clinical candidate due to its potency and specificity for PI3K and mTOR kinases, and its pharmacokinetic properties, including brain penetration. Compound 6 showed excellent selectivity over a wide panel of kinases and an excellent selectivity against unrelated receptor enzymes and ion channels. Moreover, compound 6 prevented cell growth in a cancer cell line panel. The preclinical in vivo characterization of compound 6 in an OVCAR-3 xenograft model demonstrated good oral bioavailability, excellent brain penetration, and efficacy. Initial toxicity studies in rats and dogs qualify 6 for further development as a therapeutic agent in oncology.
Block Co-polymeric Magnetic Resonance Contrast Agents (1994)

Shen D, Fritz T, Wu GL, Kulik B, Palestrant D, Unger E. Block co-polymeric magnetic resonance contrast agents. Invest Kadiol 1994;29:S217–S219.
Automatic Selection of Scanner Color Profiles (2011)

We propose an automatic procedure for color scanner profile selection, which greatly improves the color quality of the final scanned images, and also the user experience. By just analyzing a small number of initial rows of the scanned image, our algorithm is capable of distinguishing among the available color profiles, and then it uses the one that better fits with the substrate of the original. The selection can be done “on the fly” with no time penalty for the user, and the color results obtained are improved when compared to a scanner workflow where no color profiles are used
Laser operation with two controlled transverse modes (2005)

Summary form only given. In a laser resonator operating with many transverse modes, the emerging output beam quality is relatively poor. Improvement of the beam quality is typically obtained by inserting an aperture inside the resonator so as to reduce the effective radius of the gain medium, until only the optimal fundamental mode of Gaussian shape exists. Unfortunately, this results in a significant reduction of the output power. It is possible to operate a laser with a single high-order transverse mode by applying intra-cavity elements, such as apertures or phase elements. Such high-order modes exploit a relatively large volume of the gain medium, so the output power is relatively high. However, the intensity distribution of a single high-order mode usually consists of some low-intensity regions, resulting in inefficient utilization of the gain medium, with respect to the multi-mode operation. We demonstrate a novel resonator configuration in which it is possible to select two different transverse modes, each of which has a specific polarization, and can be manipulated separately. The intensity distributions of these modes can be chosen to be complementary, i.e. the peaks of the first mode would fall on the valleys of the second mode. Thus, the gain medium can be exploited more efficiently. This results in an increase in the total output power, yet with better beam quality than with the multi-mode operation.