Composing control flow and formula rules for computing on grids

We define computation on grids as the composition, through pushout constructions, of control flows, carried across adjacency relations between grid cells, with formulas updating the value of some attribute. The approach is based on the identification of a subcategory of attributed typed graphs suitable to the definition of pushouts on grids, and is illustrated in the context of the Cyberfilm visual language

Impairment of cerebellar long‑term depression and GABAergic transmission in prion protein deficient mice ectopically expressing PrPLP/Dpl

Prion protein (PrPC) knockout mice, named as the “Ngsk” strain (Ngsk Prnp0/0 mice), show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Our previous study indicated that the mutant mice also exhibited alterations in cerebellum-dependent delay eyeblink conditioning, even at a young age (16 weeks of age) when neurological changes had not occurred. Thus, this electrophysiological study was designed to examine the synaptic function of the cerebellar cortex in juvenile Ngsk Prnp0/0 mice. We showed that Ngsk Prnp0/0 mice exhibited normal paired-pulse facilitation but impaired long-term depression of excitatory synaptic transmission at synapses between parallel fibres and PCs. GABAA-mediated inhibitory postsynaptic currents recorded from PCs were also weakened in Ngsk Prnp0/0 mice. Furthermore, we confirmed that Ngsk Prnp0/0 mice (7–8-week-old) exhibited abnormalities in delay eyeblink conditioning. Our findings suggest that these alterations in both excitatory and inhibitory synaptic transmission to PCs caused deficits in delay eyeblink conditioning of Ngsk Prnp0/0 mice. Therefore, the Ngsk Prnp0/0 mouse model can contribute to study underlying mechanisms for impairments of synaptic transmission and neural plasticity, and cognitive deficits in the central nervous system

The use of uniaxial accelerometry for the assessment of physical-activity-related energy expenditure: a validation study against whole-body indirect calorimetry

Assessing the total energy expenditure (TEE) and the levels of physical activity in free-living conditions with non-invasive techniques remains a challenge. The purpose of the present study was to investigate the accuracy of a new uniaxial accelerometer for assessing TEE and physical-activity-related energy expenditure (PAEE) over a 24 h period in a respiratory chamber, and to establish activity levels based on the accelerometry ranges corresponding to the operationally defined metabolic equivalent (MET) categories. In study 1, measurement of the 24 h energy expenditure of seventy-nine Japanese subjects (40 (SD 12) years old) was performed in a large respiratory chamber. During the measurements, the subjects wore a uniaxial accelerometer (Lifecorder; Suzuken Co. Ltd, Nagoya, Japan) on their belt. Two moderate walking exercises of 30 min each were performed on a horizontal treadmill. In study 2, ten male subjects walked at six different speeds and ran at three different speeds on a treadmill for 4 min, with the same accelerometer. O2 consumption was measured during the last minute of each stage and was expressed in MET. The measured TEE was 8447 (SD 1337) kJ/d. The accelerometer significantly underestimated TEE and PAEE (91·9 (SD 5·4) and 92·7 (SD 17·8) % chamber value respectively); however, there was a significant correlation between the two values (r 0·928 and 0·564 respectively; P<0·001). There was a strong correlation between the activity levels and the measured MET while walking (r2 0·93; P<0·001). Although TEE and PAEE were systematically underestimated during the 24 h period, the accelerometer assessed energy expenditure well during both the exercise period and the non-structured activities. Individual calibration factors may help to improve the accuracy of TEE estimation, but the average calibration factor for the group is probably sufficient for epidemiological research. This method is also important for assessing the diurnal profile of physical activit

Soluble Siglec-9 suppresses arthritis in a collagen-induced arthritis mouse model and inhibits M1 activation of RAW264.7 macrophages

Background: The aim of this study was to assess the effects of soluble sialic acid-binding immunoglobulin-type lectin (sSiglec)-9 on joint inflammation and destruction in a murine collagen-induced arthritis (CIA) model and in monolayer cultures of murine macrophages (RAW264.7 cells and peritoneal macrophages) and fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis. Methods: DBA/1J mice were immunized with type II collagen. Effects of sSiglec-9 were evaluated using a physiologic arthritis score, histological analysis, serum tumor necrosis factor (TNF)-α concentration, and the proportion of forkhead box P3 (Foxp3)-positive regulatory T (Treg) cells. In vivo biofluorescence imaging was used to assess the distribution of sSiglec-9. Levels of M1 (TNF-α, interleukin [IL]-6, and inducible nitric oxide synthase) and M2 (CD206, Arginase-1, and IL-10) macrophage markers and phosphorylation of intracellular signaling molecules were examined in macrophages, and levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were examined in FLS. Results: sSiglec-9 significantly suppressed the clinical and histological incidence and severity of arthritis. The proportion of Foxp3-positive Treg cells significantly improved and serum TNF-α concentration decreased in vivo. Although sSiglec-9 reduced the expression of M1 markers in macrophages, it did not affect the expression of M2 markers and MMPs in FLS. Nuclear factor (NF)-kB p65 phosphorylation was attenuated by sSiglec-9, and chemical blockade of the NF-kB pathway reduced M1 marker expression in RAW264.7 cells. Conclusions: In this study, we have demonstrated the therapeutic effects of sSiglec-9 in a murine CIA model. The mechanism underlying these effects involves the suppression of M1 proinflammatory macrophages by inhibiting the NF-kB pathway. sSiglec-9 may provide a novel therapeutic option for patients with rheumatoid arthritis refractory to currently available drugs

A Conversation Analysis Study of Speaking Rate Control by a Dysarthric Patient : A Case in which Dysarthria Improved in Conversation Continuity and Length of Utterances through Using a Pacing Board

ペーシングボードの使用により発話明瞭度が向上したdysarthria例に対して,会話分析の立場から「会話の伝達率」と「1発話の長さ」を検討し,主に以下の結果を得た.(1)ペーシングボード非使用時の会話伝達率は54.0%であったのに比し,使用時では98.1%と向上していた.(2)1発話の長さに関しては,モーラ数による比較ではペーシングボード非使用時の平均モーラ数は5.9,使用時は11.9であった.また平均文節数は非使用時1.4,使用時2.8と両指標とも約2倍に延長していた.以上の結果に基づいて,dysarthriaにおける発話速度調節訓練について会話分析から検討を加えた.Conversational transmissibility and length of utterances were studied in a　dysarthric patient who improved in intelligibility　because of use of a pacing board.The following results were obtained : (1)Conversational transmissibility was 54% when the pacing board was not used, whereas　transmissibility improved to 98.1 % when the board was used. (2) Comparison of the utterance length was made based on the number of mora, in which the average mora was 5.9 without use of the pacing board and 11.9 with use of the board. The number of average segments was 1.4 without　the board as opposed to 2.8 with the board. In both cases the indices increased by　nearly twofold when the pacing board was used. Based on these results, discussion　was held on the training of speaking rate control by the dysarthric speaker based on　conversation analysis

Daptomycin-related Musculoskeletal Adverse Events and Statin Use

Background. There is a growing concern about the association between the combined use of daptomycin (DAP) and statins and the occurrence of musculoskeletal adverse events (MAEs), but this remains controversial. This study aimed to clarify the association between statin use and DAP-related MAEs. Methods. We used a mixed approach that combines 2 methodologies. First, we conducted a meta-analysis to examine the effects of statin use on DAP-related MAEs. Second, we conducted a disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to further confirm the results of the meta-analysis and to examine the effect of each type of statin on DAP-related MAEs in a large population. Results. In the meta-analysis, statin use significantly increased the incidence of DAP-related rhabdomyolysis (odds ratio [OR]: 3.83; 95% confidence interval [CI]: 1.43–10.26) but not DAP-related myopathy (OR: 1.72; 95% CI: .95–3.12). In the disproportionality analysis using the FAERS, the use of statin significantly increased the reporting OR (ROR) for DAP-related myopathy (ROR: 5.69; 95% CI: 4.31–7.51) and rhabdomyolysis (ROR: 5.77; 95% CI: 4.33–7.68). Atorvastatin, rosuvastatin, and simvastatin all increased the incidence of DAP-related myopathy and rhabdomyolysis. Conclusion. The mixed approach combining a meta-analysis and disproportionality analysis showed that statin use was associated with the occurrence of DAP-related rhabdomyolysis. The appropriate use of statins and DAP should be performed with careful consideration of its safety

ナンカイ トウナンカイ ジシン ナドノ ダイキボ サイガイ ニ タイスル トクシマシ イシカイ ノ トリクミ : カコ 5ネンカン ニオケル 3ツ ノ カイゼン

Here is a report on activities of the Tokushima City Medical Association for the past５years for prevention and management of possible large-scaled natural disasters such as an earthquake in the Nankai and East Nankai regions. Paying attention to the fact that Tokushima is a city of good river network with unique topography, e.g. the towheads are connected by many bridges, and assuming a situation that all the bridges have collapsed,１６medical institutions were selected as a first aid station on the virtual map and obtained their approval for cooperation. However, after conducting simulation training, some members of the Tokushima City Medical Association claimed，“We can not do anything with no suitable equipment in a first aid station.”Thus, we requested some budget from the Tokushima Municipal Government, and then, a first aid medical kit JM１ was installed at all the １６ first aid stations in July 2００４. In previous years, disaster prevention training was held once a year at the riverbed of the Yoshino River, however, the first joint triage training of local residents and medical professionals was held at Kamona Elementary School on August ２６,２００７, in which actually local residents, fire fighters, physicians and nurses joined. Since then, the training has been held every３to４months in Shin-machi, Hachiman, Ronden, Tsuda and Sako areas in turn. The Tokushima City Medical Association believes that participating the disaster prevention training introduced here and continuing the practice should be the only way for good prevention and management of an unpredictable great disaster

Sustained delivery of sphingosine-1-phosphate using poly(lactic-co-glycolic acid)-based microparticles stimulates Akt/ERK-eNOS mediated angiogenesis and vascular maturation restoring blood flow in ischemic limbs of mice

金沢大学医薬保健研究域医学系Therapeutic angiogenesis is a promising strategy for treating ischemia. The lysophospholipid mediator sphingosine-1-phosphate (S1P) acts on vascular endothelial cells to stimulate migration and tube formation, and plays the critical role in developmental angiogenesis. We developed poly(lactic-co-glycolic-acid) (PLGA)-based S1P-containing microparticles (PLGA-S1P), which are biodegradable and continuously release S1P, and studied the effects of PLGA-S1P on neovascularization in murine ischemic hindlimbs. Intramuscular injections of PLGA-S1P stimulated blood flow in C57BL/6 mice dose-dependently, with repeated administrations at a 3-day interval, rather than a single bolus or 6-day interval, over 28. days conferring the optimal stimulating effect. In Balb/c mice that exhibit limb necrosis and dysfunction due to retarded blood flow recovery, injections of PLGA-S1P stimulated blood flow with alleviation of limb necrosis and dysfunction. PLGA-S1P alone did not induce edema in ischemic limbs, and rather blocked vascular endothelial growth factor-induced edema. PLGA-S1P not only increased the microvessel densities in ischemic muscle, but promoted coverage of vessels with smooth muscle cells and pericytes, thus stabilizing vessels. PLGA-S1P stimulated Akt and ERK with increased phosphorylation of endothelial nitric oxide synthase in ischemic muscle. The effects of the nitric oxide synthase inhibitor, Nω-nitro-l-arginine methylester, showed that PLGA-S1P-induced blood flow stimulation was partially dependent on nitric oxide. Injections of PLGA-S1P also increased the expression of angiogenic factors and the recruitment of CD45-, CD11b- and Gr-1-positive myeloid cells, which are implicated in post-ischemic angiogenesis, into ischemic muscle. These results indicate that PLGA-based, sustained local delivery of S1P is a potentially useful therapeutic modality for stimulating post-ischemic angiogenesis. © 2010 Elsevier B.V

Phospholipase Cbeta4 and protein kinase Calpha and/or protein kinase CbetaI are involved in the induction of long term depression in cerebellar Purkinje cells.

Activation of the type-1 metabotropic glutamate receptor (mGluR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depression (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKCgamma-deficient mice, thus, in the present study, we examined cerebellar LTD in PLCbeta4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLCbeta1 was expressed weakly and uniformly, PLCbeta2 was not detected, PLCbeta3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLCbeta4 was expressed uniformly throughout. In PLCbeta4-deficient mice, expression of total PLCbeta, the mGluR1-mediated Ca(2+) response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKCalpha, -betaI, -betaII, and -gamma in mouse cerebellar Purkinje cells during LTD induction. Both PKCalpha and PKCbetaI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLCbeta4 in rostral cerebellar Purkinje cells induced LTD via PKCalpha and/or PKCbetaI