5,588 research outputs found

    Calcium channel α2δ1 proteins mediate trigeminal neuropathic pain states associated with aberrant excitatory synaptogenesis.

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    To investigate a potential mechanism underlying trigeminal nerve injury-induced orofacial hypersensitivity, we used a rat model of chronic constriction injury to the infraorbital nerve (CCI-ION) to study whether CCI-ION caused calcium channel α2δ1 (Cavα2δ1) protein dysregulation in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 cervical dorsal spinal cord (Vc/C2). Furthermore, we studied whether this neuroplasticity contributed to spinal neuron sensitization and neuropathic pain states. CCI-ION caused orofacial hypersensitivity that correlated with Cavα2δ1 up-regulation in trigeminal ganglion neurons and Vc/C2. Blocking Cavα2δ1 with gabapentin, a ligand for the Cavα2δ1 proteins, or Cavα2δ1 antisense oligodeoxynucleotides led to a reversal of orofacial hypersensitivity, supporting an important role of Cavα2δ1 in orofacial pain processing. Importantly, increased Cavα2δ1 in Vc/C2 superficial dorsal horn was associated with increased excitatory synaptogenesis and increased frequency, but not the amplitude, of miniature excitatory postsynaptic currents in dorsal horn neurons that could be blocked by gabapentin. Thus, CCI-ION-induced Cavα2δ1 up-regulation may contribute to orofacial neuropathic pain states through abnormal excitatory synapse formation and enhanced presynaptic excitatory neurotransmitter release in Vc/C2

    Analysis of electromagnetic interference from power system processing and transmission components for Space Station Freedom

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    The goal of this research project was to analyze the potential effects of electromagnetic interference (EMI) originating from power system processing and transmission components for Space Station Freedom. The approach consists of four steps: (1) developing analytical tools (models and computer programs); (2) conducting parameterization (what if?) studies; (3) predicting the global space station EMI environment; and (4) providing a basis for modification of EMI standards

    Bone loss and aggravated autoimmune arthritis in HLA-DRβ1-bearing humanized mice following oral challenge with Porphyromonas gingivalis

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    BACKGROUND: The linkage between periodontal disease and rheumatoid arthritis is well established. Commonalities among the two are that both are chronic inflammatory diseases characterized by bone loss, an association with the shared epitope susceptibility allele, and anti-citrullinated protein antibodies. METHODS: To explore immune mechanisms that may connect the two seemingly disparate disorders, we measured host immune responses including T-cell phenotype and anti-citrullinated protein antibody production in human leukocyte antigen (HLA)-DR1 humanized C57BL/6 mice following exposure to the Gram-negative anaerobic periodontal disease pathogen Porphyromonas gingivalis. We measured autoimmune arthritis disease expression in mice exposed to P. gingivalis, and also in arthritis-resistant mice by flow cytometry and multiplex cytokine-linked and enzyme-linked immunosorbent assays. We also measured femoral bone density by microcomputed tomography and systemic cytokine production. RESULTS: Exposure of the gingiva of DR1 mice to P. gingivalis results in a transient increase in the percentage of Th17 cells, both in peripheral blood and cervical lymph nodes, a burst of systemic cytokine activity, a loss in femoral bone density, and the generation of anti-citrullinated protein antibodies. Importantly, these antibodies are not produced in response to P. gingivalis treatment of wild-type C57BL/6 mice, and P. gingivalis exposure triggered expression of arthritis in arthritis-resistant mice. CONCLUSIONS: Exposure of gingival tissues to P. gingivalis has systemic effects that can result in disease pathology in tissues that are spatially removed from the initial site of infection, providing evidence for systemic effects of this periodontal pathogen. The elicitation of anti-citrullinated protein antibodies in an HLA-DR1-restricted fashion by mice exposed to P. gingivalis provides support for the role of the shared epitope in both periodontal disease and rheumatoid arthritis. The ability of P. gingivalis to induce disease expression in arthritis-resistant mice provides support for the idea that periodontal infection may be able to trigger autoimmunity if other disease-eliciting factors are already present

    Table-like magnetocaloric effect in Gd56Ni15Al27Zr2 alloy and its field independence feature

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    In order to obtain “table-like” magnetocaloric effect (MCE), multiple-phase Gd56Ni15Al27Zr2 alloy was prepared by arc-melting followed by suck-casting method. Powder x-ray diffraction and calorimetric measurements reveal that the sample contains both glassy and crystalline phases. The fraction of the glassy phase is about 62%, estimated from the heat enthalpy of the crystallization. The crystalline phases, Gd2Al and GdNiAl further broadened the relatively wider magnetic entropy change (−ΔSM) peak of the amorphous phase, which resulted in the table-like MCE over a maximum temperature range of 52.5 K to 77.5 K. The plateau feature of the MCE was found to be nearly independent of the applied magnetic field from 3 T to 5 T. The maximum −ΔSMvalue of the MCE platforms is 6.0 J/kg K under applied magnetic field change of 5 T. Below 3 T, the field independence of the table-like feature disappears. The relatively large constant values of −ΔSM for the respective applied magnetic fields have promising applications in magnetic refrigeration using regenerative Ericsson cycle

    MHV-Vertices for Gravity Amplitudes

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    We obtain a CSW-style formalism for calculating graviton scattering amplitudes and prove its validity through the use of a special type of BCFW-like parameter shift. The procedure is illustrated with explicit examples.Comment: 21 pages, minor typos corrected, proof added in section

    An Activity Index for Raw Accelerometry Data and Its Comparison with Other Activity Metrics

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    Accelerometers have been widely deployed in public health studies in recent years. While they collect high-resolution acceleration signals (e.g., 10–100 Hz), research has mainly focused on summarized metrics provided by accelerometers manufactures, such as the activity count (AC) by ActiGraph or Actical. Such measures do not have a publicly available formula, lack a straightforward interpretation, and can vary by software implementation or hardware type. To address these problems, we propose the physical activity index (AI), a new metric for summarizing raw tri-axial accelerometry data. We compared this metric with the AC and another recently proposed metric for raw data, Euclidean Norm Minus One (ENMO), against energy expenditure. The comparison was conducted using data from the Objective Physical Activity and Cardiovascular Health Study, in which 194 women 60–91 years performed 9 lifestyle activities in the laboratory, wearing a tri-axial accelerometer (ActiGraph GT3X+) on the hip set to 30 Hz and an Oxycon portable calorimeter, to record both tri-axial acceleration time series (converted into AI, AC, and ENMO) and oxygen uptake during each activity (converted into metabolic equivalents (METs)) at the same time. Receiver operating characteristic analyses indicated that both AI and ENMO were more sensitive to moderate and vigorous physical activities than AC, while AI was more sensitive to sedentary and light activities than ENMO. AI had the highest coefficients of determination for METs (0.72) and was a better classifier of physical activity intensity than both AC (for all intensity levels) and ENMO (for sedentary and light intensity). The proposed AI provides a novel and transparent way to summarize densely sampled raw accelerometry data, and may serve as an alternative to AC. The AI’s largely improved sensitivity on sedentary and light activities over AC and ENMO further demonstrate its advantage in studies with older adults

    Impaired pain sensation in mice lacking prokineticin 2

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    Prokineticins (PKs), consisting of PK1 and PK2, are a pair of newly identified regulatory peptides. Two closely related G-protein coupled receptors, PKR1 and PKR2, mediate the signaling of PKs. PKs/PKRs participate in the regulation of diverse biological processes, ranging from development to adult physiology. A number of studies have indicated the involvement of PKs/PKRs in nociception. Here we show that PK2 is a sensitizer for nociception. Intraplantar injection of recombinant PK2 resulted in a strong and localized hyperalgesia with reduced thresholds to nociceptive stimuli. PK2 mobilizes calcium in dissociated dorsal root ganglion (DRG) neurons. Mice lacking the PK2 gene displayed strong reduction in nociception induced by thermal and chemical stimuli, including capsaicin. However, PK2 mutant mice showed no difference in inflammatory response to capsaicin. As the majority of PK2-responsive DRG neurons also expressed transient receptor potential vanilloid (TRPV1) and exhibited sensitivity to capsaicin, TRPV1 is likely a significant downstream molecule of PK2 signaling. Taken together, these results reveal that PK2 sensitize nociception without affecting inflammation

    Recursive Calculation of One-Loop QCD Integral Coefficients

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    We present a new procedure using on-shell recursion to determine coefficients of integral functions appearing in one-loop scattering amplitudes of gauge theories, including QCD. With this procedure, coefficients of integrals, including bubbles and triangles, can be determined without resorting to integration. We give criteria for avoiding spurious singularities and boundary terms that would invalidate the recursion. As an example where the criteria are satisfied, we obtain all cut-constructible contributions to the one-loop n-gluon scattering amplitude, A_n^{oneloop}(...--+++...), with split-helicity from an N=1 chiral multiplet and from a complex scalar. Using the supersymmetric decomposition, these are ingredients in the construction of QCD amplitudes with the same helicities. This method requires prior knowledge of amplitudes with sufficiently large numbers of legs as input. In many cases, these are already known in compact forms from the unitarity method.Comment: 36 pages; v2 clarification added and typos fixed, v3 typos fixe

    Variations of the Argentine Gyre Observed in the GRACE Time‐Variable Gravity and Ocean Altimetry Measurements

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    We investigate the nonseasonal and high‐frequency variations of the Argentine Gyre in the south Atlantic Ocean by analyzing the time‐variable gravity (TVG) measurements from the Gravity Recovery and Climate Experiment (GRACE) satellite mission in conjunction with the satellite ocean altimetry and two ocean general circulation model outputs (GLORYS2V4 and ECCO V4R3). We solve the empirical orthogonal functions (EOF) and complex EOF and find good agreement between TVG and altimetry observations, confirming the barotropic structure of the Argentine Gyre. In particular, the leading EOF modes of the overall up‐and‐down undulation in TVG and altimetry variations are found to be in pace temporally with the Antarctic Oscillation Index with correlation as high as 0.69 at zero time shift. Furthermore, the leading complex EOF mode signifies a counterclockwise dipole pattern of ~25‐day periodicity within the overall gyre with multiscale amplitude modulation. The fact that GRACE does observe these signals, while the de‐aliasing background ocean model fails to, ascertains that GRACE data have adequate sensitivity to allow the detection of TVG signals at spatial and temporal resolutions higher than practiced hitherto. The ~25‐day oscillation is well recovered in the GLORYS2V4 ocean general circulation model, but not in ECCO V4R3. Our study demonstrates that satellite‐observed TVG fields can be useful in studying oceanographic gyres, particularly the polar gyres, that are not well observed by altimetry and in situ data.This work is supported by Taiwan Ministry of Science and Technology grants 105-2811-M-001-031 and 106-2116-M-001-013 and by National Nature Science Foundation of China grants 41474019, 41504014, and 41704012
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