Structural Features of Layered Iron Pnictide Oxides (Fe2As2)(Sr4M2O6)

Structural features of newly found perovskite-based iron pnictide oxide system have been systematically studied. Compared to REFePnO system, perovskite-based system tend to have lower Pn-Fe-Pn angle and higher pnictogen height owing to low electronegativity of alkaline earth metal and small repulsive force between pnictogen and oxygen atoms. As-Fe-As angles of (Fe2As2)(Sr4Cr2O6), (Fe2As2)(Sr4V2O6) and (Fe2Pn2)(Sr4MgTiO6) are close to ideal tetrahedron and those pnictogen heights of about 1.40 A are close to NdFeAsO with optimized carrier concentration. These structural features of this system may leads to realization of high Tc superconductivity.Comment: 3pages, 2figures, 1table, proceedings of M2S 200

MITSuME--Multicolor Imaging Telescopes for Survey and Monstrous Explosions

Development of MITSuME is reported. Two 50-cm optical telescopes have been built at Akeno in Yamanashi prefecture and at Okayama Astrophysical Observatory (OAO) in Okayama prefecture. Three CCD cameras for simultaneous g'RcIc photometry are to be mounted on each focal plane, covering a wide FOV of about 30" x 30". The limiting magnitude at V is fainter than 18. In addition to these two optical telescopes, a 91-cm IR telescope with a 1 deg x 1 deg field of view is being built at OAO, which performs photometry in YJHK bands. These robotic telescopes can start the observation of counterparts of a GRB within a minute from an alert. We aim to obtain photometric redshifts exceeding 10 with these telescopes. The performance and the current construction status of the telescopes are presented.Comment: 4 pages, 3 figures, 4th Workshop on Gamma-Ray Burst in the Afterglow Era, Roma, October 18-22, 200

Cultural trauma, counter-narratives, and dialogical intellectuals: the works of Murakami Haruki and Mori Tatsuya in the context of the Aum affair

In this article, we offer a new conceptualization of intellectuals as carriers of cultural trauma through a case study of the Aum Affair, a series of crimes and terrorist attacks committed by the Japanese new religious movement Aum Shinrikyō. In understanding the performative roles intellectuals play in trauma construction, we offer a new dichotomy between “authoritative intellectuals,” who draw on their privileged parcours and status to impose a distinct trauma narrative, and “dialogical intellectuals,” who engage with local actors dialogically to produce polyphonic and open-ended trauma narratives. We identify three dimensions of dialogical intellectual action: firstly, the intellectuals may be involved in dialogue with local participants; secondly, the intellectual products themselves may be dialogical in content; and thirdly, there might be a concerted effort on the part of the intellectuals to record and to disseminate dialogue between local participants. In the context of the Aum Affair, we analyze the works of Murakami Haruki and Mori Tatsuya as dialogical intellectuals while they sought, with the help of local actors’ experiences, to challenge and to alter the orthodox trauma narrative of Aum Shinrikyō as exclusively a social evil external to Japanese society and an enemy to be excluded from it. Towards the end of the article, we discuss the broader significance of this case study and suggest that in light of recent societal and technological developments, the role and scope of dialogical intellectuals as carriers of trauma are changing and possibly expanding

The utility of pathway selective estrogen receptor ligands that inhibit nuclear factor-κB transcriptional activity in models of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease that produces synovial proliferation and joint erosions. The pathologic lesions of RA are driven through the production of inflammatory mediators in the synovium mediated, in part, by the transcription factor NF-κB. We have identified a non-steroidal estrogen receptor ligand, WAY-169916, that selectively inhibits NF-κB transcriptional activity but is devoid of conventional estrogenic activity. The activity of WAY-169916 was monitored in two models of arthritis, the HLA-B27 transgenic rat and the Lewis rat adjuvant-induced model, after daily oral administration. In both models, a near complete reversal in hindpaw scores was observed as well as marked improvements in the histological scores. In the Lewis rat adjuvant model, WAY-169916 markedly suppresses the adjuvant induction of three serum acute phase proteins: haptoglobin, α1-acid glycoprotein (α1-AGP), and C-reactive protein (CRP). Gene expression experiments also demonstrate a global suppression of adjuvant-induced gene expression in the spleen, liver, and popliteal lymph nodes. Finally, WAY-169916 was effective in suppressing tumor necrosis factor-α-mediated inflammatory gene expression in fibroblast-like synoviocytes isolated from patients with RA. Together, these data suggest the utility of WAY-169916, and other compounds in its class, in treating RA through global suppression of inflammation via selective blockade of NF-κB transcriptional activity

Oestrogen is important for maintenance of cartilage and subchondral bone in a murine model of knee osteoarthritis

Introduction: Oestrogen depletion may influence onset and/or progression of osteoarthritis. We investigated in an ovariectomized mouse model the impact of oestrogen loss and oestrogen supplementation on articular cartilage and subchondral bone in tibia and patella, and assessed bone changes in osteoarthritis development.Methods: C3H/HeJ mice were divided into four groups: sham-operated, oestrogen depletion by ovariectomy (OVX), OVX with estradiol supplementation (OVX+E) and OVX with bisphosphonate (OVX+BP). Each mouse had one knee injected with low-dose iodoacetate (IA), and the contralateral knee was injected with saline. Cartilage was analysed histologically 12 weeks postsurgery; bone changes were monitored over time using in vivo micro-computed tomography.Results: In tibiae, OVX alone failed to induce cartilage damage, but OVX and IA combination significantly induced cartilage damage. In patellae, OVX alone induced significant cartilage damage, whic

Nano-motion Dynamics are Determined by Surface-Tethered Selectin Mechanokinetics and Bond Formation

The interaction of proteins at cellular interfaces is critical for many biological processes, from intercellular signaling to cell adhesion. For example, the selectin family of adhesion receptors plays a critical role in trafficking during inflammation and immunosurveillance. Quantitative measurements of binding rates between surface-constrained proteins elicit insight into how molecular structural details and post-translational modifications contribute to function. However, nano-scale transport effects can obfuscate measurements in experimental assays. We constructed a biophysical simulation of the motion of a rigid microsphere coated with biomolecular adhesion receptors in shearing flow undergoing thermal motion. The simulation enabled in silico investigation of the effects of kinetic force dependence, molecular deformation, grouping adhesion receptors into clusters, surface-constrained bond formation, and nano-scale vertical transport on outputs that directly map to observable motions. Simulations recreated the jerky, discrete stop-and-go motions observed in P-selectin/PSGL-1 microbead assays with physiologic ligand densities. Motion statistics tied detailed simulated motion data to experimentally reported quantities. New deductions about biomolecular function for P-selectin/PSGL-1 interactions were made. Distributing adhesive forces among P-selectin/PSGL-1 molecules closely grouped in clusters was necessary to achieve bond lifetimes observed in microbead assays. Initial, capturing bond formation effectively occurred across the entire molecular contour length. However, subsequent rebinding events were enhanced by the reduced separation distance following the initial capture. The result demonstrates that vertical transport can contribute to an enhancement in the apparent bond formation rate. A detailed analysis of in silico motions prompted the proposition of wobble autocorrelation as an indicator of two-dimensional function. Insight into two-dimensional bond formation gained from flow cell assays might therefore be important to understand processes involving extended cellular interactions, such as immunological synapse formation. A biologically informative in silico system was created with minimal, high-confidence inputs. Incorporating random effects in surface separation through thermal motion enabled new deductions of the effects of surface-constrained biomolecular function. Important molecular information is embedded in the patterns and statistics of motion

Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery—a pilot study

The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally administered etoricoxib and to compare it with effect data, i.e., COX-2-inhibition in patients after hip surgery. The study was performed in a blinded, randomized, parallel group design. A total of 12 adult patients were included who received 120 mg etoricoxib (n = 8) or placebo (n = 4) on day 1 post-surgery. Samples from plasma, CSF, and tissue exudates were collected over a period of 24 h post-dosing and analyzed for etoricoxib and prostaglandin E2 (PGE2) using liquid chromatography-tandem mass spectrometry and immuno-assay techniques. CSF area under the curve (AUC) [AUCs(O–24h)] for etoricoxib amounted to about 5% of the total AUC in plasma (range: 2–7%). Individual CSF lag times with respect to (50%) peak plasma concentration were ≤2 h in all but one case (median: 1 h). PGE2 production in tissue was significantly blocked by the COX-2 inhibitor starting with the appearance of etoricoxib in tissue and lasting for the whole observation period of 24 h (P < 0.01). In conclusion, etoricoxib reaches the CSF and site of surgery at effective concentrations and reduces PGE2 production at the presumed site of action

Targeting Bone Alleviates Osteoarthritis in Osteopenic Mice and Modulates Cartilage Catabolism

Subchondral bone modifications occur early in the development of osteoarthritis (OA). The level of bone resorption might impact cartilage remodeling. We therefore assessed the in vivo and in vitro effects of targeting bone resorption in OA and cartilage metabolism.OA was induced by meniscectomy (MNX) in ovariectomized osteopenic mice (OP) treated with estradiol (E2), pamidronate (PAM), or phosphate buffered saline (PBS) for 6 weeks. We assessed the subchondral bone and cartilage structure and the expression of cartilage matrix proteases. To assess the involvement of bone soluble factors in cartilage metabolism, supernatant of human bone explants pre-treated with E2 or PAM were transferred to cartilage explants to assess proteoglycan release and aggrecan cleavage. OPG/RANKL mRNA expression was assessed in bone explants by real-time quantitative PCR. The role of osteoprotegerin (OPG) in the bone-cartilage crosstalk was tested using an OPG neutralizing antibody.Bone mineral density of OP mice and osteoclast number were restored by E2 and PAM (p<0.05). In OP mice, E2 and PAM decreased ADAMTS-4 and -5 expression, while only PAM markedly reduced OA compared to PBS (2.0±0.63 vs 5.2±0.95; p<0.05). OPG/RANKL mRNA was increased in human bone explants treated with both drugs (2.2-3.7-fold). Moreover, supernatants from bone explants cultured with E2 or PAM reduced aggrecan cleavage and cartilage proteoglycan release (73±8.0% and 80±22% of control, respectively, p<0.05). This effect was reversed with osteoprotegerin blockade.The inhibition of bone resorption by pamidronate in osteopenic mice alleviates the histological OA score with a reduction in the expression of aggrecanases. Bone soluble factors, such as osteoprotegerin, impact the cartilage response to catabolic factors. This study further highlights the importance of subchondral bone in the regulation of joint cartilage damage in OA

The effect of salient stimuli on neural oscillations, isometric force, and their coupling.

Survival in a suddenly-changing environment requires animals not only to detect salient stimuli, but also to promptly respond to them by initiating or revising ongoing motor processes. We recently discovered that the large vertex brain potentials elicited by sudden supramodal stimuli are strongly coupled with a multiphasic modulation of isometric force, a phenomenon that we named cortico-muscular resonance (CMR). Here, we extend our investigation of the CMR to the time-frequency domain. We show that (i) both somatosensory and auditory stimuli evoke a number of phase-locked and non-phase-locked modulations of EEG spectral power. Remarkably, (ii) some of these phase-locked and non-phase-locked modulations are also present in the Force spectral power. Finally, (iii) EEG and Force time-frequency responses are correlated in two distinct regions of the power spectrum. An early, low-frequency region (∼4 Hz) reflects the previously-described coupling between the phase-locked EEG vertex potential and force modulations. A late, higher-frequency region (beta-band, ∼20 Hz) reflects a second coupling between the non-phase-locked increase of power observed in both EEG and Force. In both time-frequency regions, coupling was maximal over the sensorimotor cortex contralateral to the hand exerting the force, suggesting an effect of the stimuli on the tonic corticospinal drive. Thus, stimulus-induced CMR occurs across at least two different types of cortical activities, whose functional significance in relation to the motor system should be investigated further. We propose that these different types of corticomuscular coupling are important to alter motor behaviour in response to salient environmental events