Extracellular nucleotides have been implicated as signaling molecules used by microglia to sense adverse physiological conditions, such as neuronal damage. They act through purinoceptors, especially the G-protein-coupled P2Y receptor P2Y 12 R. Emerging evidence has indicated that activated spinal microglia responding to nerve injury are key cellular intermediaries in the resulting highly debilitating chronic pain state, namely neuropathic pain. However, the role of microglial P2Y 12 Rs in neuropathic pain remains unknown. Here, we show that the level of P2Y 12 R mRNA expression was markedly increased in the spinal cord ipsilateral to the nerve injury and that this expression was highly restricted to ionized binding calcium adapter molecule 1-positive microglia. An increase in the immunofluorescence of P2Y 12 R protein in the ipsilateral spinal cord was also observed after nerve injury, and P2Y 12 R-positive cells were double labeled with the microglial marker OX-42. Blocking spinal P2Y 12 R by the intrathecal administration of its antagonist AR-C69931MX prevented the development of tactile allodynia (pain hypersensitivity to innocuous stimuli), a hallmark of neuropathic pain syndrome. Furthermore, mice lacking P2ry 12 (P2ry 12 ؊/؊ ) displayed impaired tactile allodynia after nerve injury without any change in basal mechanical sensitivity. Moreover, a single intrathecal administration of AR-C69931MX or oral administration of clopidogrel (a P2Y 12 R blocker clinically in use) to nerve-injured rats produced a striking alleviation of existing tactile allodynia. Together, our findings indicate that activation of P2Y 12 Rs in spinal microglia may be a critical event in the pathogenesis of neuropathic pain and suggest that blocking microglial P2Y 12 R might be a viable therapeutic strategy for treating neuropathic pain.
Residence time controlled reaction: The Swern oxidation of alcohols has been accomplished by using a microscale flow system, consisting of micromixers and microscale tube reactors (see schematic representation; DMSO=dimethylsulfoxide, TFAA=trifluoroacetic anhydride), at higher temperatures (−20 to 20 °C) than those for conventional macroscale batch systems (−50 °C or below).
Verweildauer‐gesteuerte Reaktion: Die Swern‐Oxidation von Alkoholen ließ sich bei höheren Temperaturen (−20–20 °C) als den für konventionelle makroskalige Batchsysteme üblichen (−50 °C und niedriger) durchführen, indem ein mikroskaliges Flusssystem genutzt wurde, das aus Mikromixern und mikroskaligen Röhrenreaktoren besteht (siehe Schema; DMSO=Dimethylsulfoxid, TFAA= Trifluoressigsäureanhydrid).
Enumeration of all combinatorial types of point configurations and polytopes is a fundamental problem in combinatorial geometry. Although many studies have been done, most of them are for 2-dimensional and non-degenerate cases.Finschi and Fukuda (2001) published the first database of oriented matroids including degenerate (i.e., non-uniform) ones and of higher ranks. In this paper, we investigate algorithmic ways to classify them in terms of realizability, although the underlying decision problem of realizability checking is NP-hard. As an application, we determine all possible combinatorial types (including degenerate ones) of 3-dimensional configurations of 8 points, 2-dimensional configurations of 9 points and 5dimensional configurations of 9 points. We could also determine all possible combinatorial types of 5-polytopes with 9 vertices.
Effects of interfaces such as metal/polymer interfaces and polymer/polymer interfaces on the space-charge distribution in multiply low-density polyethylene have been investigated using a pulsed electroacoustic method. It has been found that the heterocharge was dominant in an artificial interface existing in a polyethylene sample. The time dependence of the heterocharge distribution in the interface on applied voltages and polarity was studied. From these charge distributions, the modified electrical field was calculated based on Poisson’s equation. The calculated result indicated that the actual field was stronger than the applied uniform field at the artificial interface. A new data display method for a three- or two-dimensional plot is employed to display all measurement data on one plot in which the space charge becomes visible so that the results can be easily and conveniently understood.
Neighborly polytopes are those that maximize the number of faces in each dimension among all polytopes with the same number of vertices. Despite their extremal properties they form a surprisingly rich class of polytopes, which has been widely studied and is the subject of many open problems and conjectures.In this paper, we study the enumeration of neighborly polytopes beyond the cases that have been computed so far. To this end, we enumerate neighborly oriented matroids -a combinatorial abstraction of neighborly polytopes -of small rank and corank. In particular, if we denote by OM(n, r) the set of all oriented matroids of rank r and n elements, we determine all uniform neighborly oriented matroids in OM(5, ≤ 12), OM(6, ≤ 9), OM(7, ≤ 11) and OM(9, ≤ 12) and all possible face lattices of neighborly oriented matroids in OM(6, 10) and OM (8,11). Moreover, we classify all possible face lattices of uniform 2-neighborly oriented matroids in OM(7, 10) and OM (8,11). Based on the enumeration, we construct many interesting examples and test open conjectures. arXiv:1408.0688v2 [math.CO]
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