2,219 research outputs found

    Co-regularised support vector regression

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    We consider a semi-supervised learning scenario for regression, where only few labelled examples, many unlabelled instances and different data representations (multiple views) are available. For this setting, we extend support vector regression with a co-regularisation term and obtain co-regularised support vector regression (CoSVR). In addition to labelled data, co-regularisation includes information from unlabelled examples by ensuring that models trained on different views make similar predictions. Ligand affinity prediction is an important real-world problem that fits into this scenario. The characterisation of the strength of protein-ligand bonds is a crucial step in the process of drug discovery and design. We introduce variants of the base CoSVR algorithm and discuss their theoretical and computational properties. For the CoSVR function class we provide a theoretical bound on the Rademacher complexity. Finally, we demonstrate the usefulness of CoSVR for the affinity prediction task and evaluate its performance empirically on different protein-ligand datasets. We show that CoSVR outperforms co-regularised least squares regression as well as existing state-of-the-art approaches for affinity prediction

    Accelerated Wound Healing Using a Novel Far-Infrared Ceramic Blanket.

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    INTRODUCTION: Wounds are associated with ranges of simple to complex disruption or damage to anatomical structure and function. They are also associated with enormous economic and social costs, increasing yearly, resulting in a severe impact on the wellbeing of individuals and society. Technology that might accelerate wound healing is associated with many benefits to injured people. METHODS: BALBc mice underwent symmetrical excisional wounds through the panniculus carnosus. They were divided into a treatment group placed on an autonomous ceramic far-field infrared blanket (cIFRB) and a control group maintained under standard conditions. We also expanded and cultured adipose tissue-derived mesenchymal stem cells (MSCs) on cIFRB and compared them to standard conditions subjected to a scratch injury to compare survival, proliferation, and wound healing. RESULTS: The wound healing of the cIRFB treatment group was significantly faster than the control group of mice. The wound-healing effect of mesenchymal stem cells on cIRFB was also increased and associated with significant migration to the wound area. CONCLUSIONS: Wound healing is improved in a mouse model exposed to cFIRB. The ceramic blanket also promotes survival, proliferation, increased migration, and wound healing of MSCs without affecting their survival and proliferation. The utilization of cFIRB in cellular biology and medical applications may be promising in many situations currently explored in animal and human models. This technology needs no direct or battery power source and is entirely autonomous and noninvasive, making its application possible in any environment

    Contribution of the nucleon-hyperon reaction channels to K^- production in proton-nucleus collisions

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    The cross sections for producing K^- mesons in nucleon-hyperon elementary processes are estimated assuming one-pion exchange and using the experimentally known pion-hyperon cross sections. The results are implemented in a transport model which is applied to calculation of proton-nucleus collisions. In significant difference to earlier estimates for heavy-ion collisions the inclusion of the nucleon-hyperon cross section roughly doubles the K^- production in near-threshold proton-nucleus collisions

    Effects of abscisic acid treatment and night temperatures on anthocyanin composition in Pinot noir grapes

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    Potted Pinot noir grapevines were grown under continuous high temperature (30 °C) or low night (15 °C) and high day (30 °C) temperatures after veraison. Half of the total number of clusters of each vine was sprayed with 250 ppm abscisic acid (ABA) at veraison. Anthocyanin accumulation in berry skins grown under high night temperatures was lower than that in berries grown under low night temperatures. HPLC analysis showed that the ratios of delphinidin-3-glucoside, cyanidin-3-glucoside and petunidin-3-glucoside to the total anthocyanin content were greatly reduced under high night temperatures. ABA treatment enhanced anthocyanin accumulation under high night temperatures to almost the same level as under low night temperatures; the ratio of each anthocyanin to the total anthocyanin, however, was not affected by ABA treatment.

    Fibronectin as an adjuvant in the diagnosis of oral inflammatory myofibroblastic tumor

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    Inflammatory myofibroblastic tumor is a distinctive lesion composed of myofibroblastic spindle shaped cells accompanied by inflammatory infiltrate that may arise in various organs. It is believed to be a noneoplastic inflammatory condition, although this is still controversial. The recognition of inflammatory myofibroblastic tumor as an entity is important especially to avoid unnecessary surgery. A few cases have been reported in the oral cavity. This report primarily presents a case of inflammatory myofibroblastic tumor that arose in the floor of mouth of a 23-year-old woman. The proliferating spindle cells were immunoreactive for vimentin, smooth muscle actin, and muscle specific actin and negative for desmin, AE1/AE3, S-100, CD68, MyoD1 and caldesmon. In an attempt to assess the potential neoplastic nature of this lesion, immunohistochemical expression of ALK protein was performed, although no immunoreactivity was detected. Also, the presence of well differentiated myofibroblasts identified by fibronectin is discussed, as well as the importance in establishing an immunoprofile to better consolidate the diagnosis. We conclude that the study of fibronectin in case series may aid the diagnosis as well as the prediction of the tumor course

    Preclinical PET imaging of bispecific antibody ERY974 targeting CD3 and glypican 3 reveals that tumor uptake correlates to T cell infiltrate

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    BACKGROUND: Bispecific antibodies redirecting T cells to the tumor obtain increasing interest as potential cancer immunotherapy. ERY974, a full-length bispecific antibody targeting CD3ε on T cells and glypican 3 (GPC3) on tumors, has been in clinical development However, information on the influence of T cells on biodistribution of bispecific antibodies, like ERY974, is scarce. Here, we report the biodistribution and tumor targeting of zirconium-89 (89Zr) labeled ERY974 in mouse models using immuno-positron emission tomography (PET) imaging. METHODS: To study both the role of GPC3 and CD3 on the biodistribution of [89Zr]Zr-N-suc-Df-ERY974, 89Zr-labeled control antibodies targeting CD3 and non-mammalian protein keyhole limpet hemocyanin (KLH) or KLH only were used. GPC3 dependent tumor targeting of [89Zr]Zr-N-suc-Df-ERY974 was tested in xenograft models with different levels of GPC3 expression. In addition, CD3 influence on biodistribution of [89Zr]Zr-N-suc-Df-ERY974 was evaluated by comparing biodistribution between tumor-bearing immunodeficient mice and mice reconstituted with human immune cells using microPET imaging and ex vivo biodistribution. Ex vivo autoradiography was used to study deep tissue distribution. RESULTS: In tumor-bearing immunodeficient mice, [89Zr]Zr-N-suc-Df-ERY974 tumor uptake was GPC3 dependent and specific over [89Zr]Zr-N-suc-Df-KLH/CD3 and [89Zr]Zr-N-suc-Df-KLH/KLH. In mice engrafted with human immune cells, [89Zr]Zr-N-suc-Df-ERY974 specific tumor uptake was higher than in immunodeficient mice. Ex vivo autoradiography demonstrated a preferential distribution of [89Zr]Zr-N-suc-Df-ERY974 to T cell rich tumor tissue. Next to tumor, highest specific [89Zr]Zr-N-suc-Df-ERY974 uptake was observed in spleen and lymph nodes. CONCLUSION: [89Zr]Zr-N-suc-Df-ERY974 can potentially be used to study ERY974 biodistribution in patients to support drug development

    Photoproduction of Lambda(1405) and Sigma^{0}(1385) on the proton at E_\gamma = 1.5-2.4 GeV

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    Differential cross sections for γpK+Λ(1405)\gamma p \to K^+\Lambda(1405) and γpK+Σ0(1385)\gamma p \to K^+\Sigma^0(1385) reactions have been measured in the photon energy range from 1.5 to 2.4 GeV and the angular range of 0.8<cos(Θ)<1.00.8<\cos(\Theta)<1.0 for the K+K^+ scattering angle in the center-of-mass system. This data is the first measurement of the Λ(1405)\Lambda(1405) photoproduction cross section. The lineshapes of \LamS measured in Σ+π\Sigma^+\pi^- and Σπ+\Sigma^-\pi^+ decay modes were different with each other, indicating a strong interference of the isospin 0 and 1 terms of the Σπ\Sigma\pi scattering amplitudes. The ratios of \LamS production to \SigS production were measured in two photon energy ranges: near the production threshold (1.5<Eγ<2.01.5<E_\gamma<2.0 GeV) and far from it (2.0<Eγ<2.42.0 <E_\gamma<2.4 GeV). The observed ratio decreased in the higher photon energy region, which may suggest different production mechanisms and internal structures for these hyperon resonances

    Identification of a novel biomarker candidate, a 4.8-kDa peptide fragment from a neurosecretory protein VGF precursor, by proteomic analysis of cerebrospinal fluid from children with acute encephalopathy using SELDI-TOF-MS

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    <p>Abstract</p> <p>Background</p> <p>Acute encephalopathy includes rapid deterioration and has a poor prognosis. Early intervention is essential to prevent progression of the disease and subsequent neurologic complications. However, in the acute period, true encephalopathy cannot easily be differentiated from febrile seizures, especially febrile seizures of the complex type. Thus, an early diagnostic marker has been sought in order to enable early intervention. The purpose of this study was to identify a novel marker candidate protein differentially expressed in the cerebrospinal fluid (CSF) of children with encephalopathy using proteomic analysis.</p> <p>Methods</p> <p>For detection of biomarkers, CSF samples were obtained from 13 children with acute encephalopathy and 42 children with febrile seizure. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology, which is currently applied in many fields of biological and medical sciences. Diagnosis was made by at least two pediatric neurologists based on the clinical findings and routine examinations. All specimens were collected for diagnostic tests and the remaining portion of the specimens were used for the SELDI-TOF MS investigations.</p> <p>Results</p> <p>In experiment 1, CSF from patients with febrile seizures (n = 28), patients with encephalopathy (n = 8) (including influenza encephalopathy (n = 3), encephalopathy due to rotavirus (n = 1), human herpes virus 6 (n = 1)) were used for the SELDI analysis. In experiment 2, SELDI analysis was performed on CSF from a second set of febrile seizure patients (n = 14) and encephalopathy patients (n = 5). We found that the peak with an m/z of 4810 contributed the most to the separation of the two groups. After purification and identification of the 4.8-kDa protein, a 4.8-kDa proteolytic peptide fragment from the neurosecretory protein VGF precursor (VGF4.8) was identified as a novel biomarker for encephalopathy.</p> <p>Conclusions</p> <p>Expression of VGF4.8 has been reported to be decreased in pathologically degenerative changes such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, and encephalopathy. Thus, the VGF4.8 peptide might be a novel marker for degenerative brain conditions.</p

    Target mass number dependence of subthreshold antiproton production in proton-, deuteron- and alpha-particle-induced reactions

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    Data from KEK on subthreshold \bar{\mrm{p}} as well as on π±\pi^\pm and \mrm{K}^\pm production in proton-, deuteron- and α\alpha-induced reactions at energies between 2.0 and 12.0 A GeV for C, Cu and Pb targets are described within a unified approach. We use a model which considers a nuclear reaction as an incoherent sum over collisions of varying numbers of projectile and target nucleons. It samples complete events and thus allows for the simultaneous consideration of all final particles including the decay products of the nuclear residues. The enormous enhancement of the \bar{\mrm{p}} cross section, as well as the moderate increase of meson production in deuteron and α\alpha induced compared to proton-induced reactions, is well reproduced for all target nuclei. In our approach, the observed enhancement near the production threshold is mainly due to the contributions from the interactions of few-nucleon clusters by simultaneously considering fragmentation processes of the nuclear residues. The ability of the model to reproduce the target mass dependence may be considered as a further proof of the validity of the cluster concept.Comment: 9 pages, 4 figure

    First Dark Matter Limits from a Large-Mass, Low-Background Superheated Droplet Detector

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    We report on the fabrication aspects and calibration of the first large active mass (15\sim15 g) modules of SIMPLE, a search for particle dark matter using Superheated Droplet Detectors (SDDs). While still limited by the statistical uncertainty of the small data sample on hand, the first weeks of operation in the new underground laboratory of Rustrel-Pays d'Apt already provide a sensitivity to axially-coupled Weakly Interacting Massive Particles (WIMPs) competitive with leading experiments, confirming SDDs as a convenient, low-cost alternative for WIMP detection.Comment: Final version, Phys. Rev. Lett. (in press
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