Antinociceptive effects of lacosamide on spinal neuronal and behavioural measures of pain in a rat model of osteoarthritis.

Alterations in voltage-gated sodium channel (VGSC) function have been linked to chronic pain and are good targets for analgesics. Lacosamide (LCM) is a novel anticonvulsant that enhances the slow inactivation state of VGSCs. This conformational state can be induced by repeated neuronal firing and/or under conditions of sustained membrane depolarisation, as is expected for hyperexcitable neurones in pathological conditions such as epilepsy and neuropathy, and probably osteoarthritis (OA). In this study, therefore, we examined the antinociceptive effect of LCM on spinal neuronal and behavioural measures of pain, in vivo, in a rat OA model

QED effects in molecules: test on rotational quantum states of H2_2

Quantum electrodynamic effects have been systematically tested in the progression of rotational quantum states in the $X ^{1}\Sigma_{g}^{+}, v=0$ vibronic ground state of molecular hydrogen. High-precision Doppler-free spectroscopy of the $EF ^{1}\Sigma_{g}^{+} - X ^{1}\Sigma_{g}^{+}$ (0,0) band was performed with 0.005 cm$^{-1}$ accuracy on rotationally-hot H$_2$ (with rotational quantum states J up to 16). QED and relativistic contributions to rotational level energies as high as 0.13 cm$^{-1}$ are extracted, and are in perfect agreement with recent calculations of QED and high-order relativistic effects for the H$_2$ ground state.Comment: 4 pages, 3 figures, to be published in Physical Review Letter

Electrophysiological evidence for voltage-gated calcium channel 2 (Cav2) modulation of mechano- and thermosensitive spinal neuronal responses in a rat model of osteoarthritis.

Osteoarthritis (OA) remains one of the greatest healthcare burdens in western society, with chronic debilitating pain-dominating clinical presentation yet therapeutic strategies are inadequate in many patients. Development of better analgesics is contingent on improved understanding of the molecular mechanisms mediating OA pain. Voltage-gated calcium channels 2.2 (Cav2.2) play a critical role in spinal nociceptive transmission, therefore blocking Cav2.2 activity represents an attractive opportunity for OA pain treatment, but the only available licensed Cav2.2 antagonist ziconitide (PrilatTM) is of limited use. TROX-1 is an orally available, use dependent and state-selective Cav2 antagonist, exerting its analgesic effect primarily via Cav2.2 blockade, with an improved therapeutic window compared with ziconitide. Using a rat model of monosodium iodoacetate (MIA), 2mg, induced OA we used in vivo electrophysiology to assess the effects of spinal or systemic administration of TROX-1 on the evoked activity of wide dynamic range spinal dorsal horn neurons in response to electrical, natural mechanical (dynamic brush and von Frey 2, 8, 26 and 6g) and thermal (40, 45 and 45°C) stimuli applied to the peripheral receptive field. MIA injection into the knee joint resulted in mechanical hypersensitivity of the ipsilateral hind paw and weight-bearing asymmetry. Spinal administration of TROX-1 (0.1 and 1μg/50μl) produced a significant dose-related inhibition of dynamic brush, mechanical (von Frey filament (vF) 8, 26 and 60g) and noxious thermal-(45 and 48°C) evoked neuronal responses in MIA rats only. Systemic administration of TROX-1 produced a significant inhibition of the mechanical-(vF 8, 26 and 60g) evoked neuronal responses in MIA rats. TROX-1 did not produce any significant effect on any neuronal measure in Sham controls. Our in vivo electrophysiological results demonstrate a pathological state-dependent effect of TROX-1, which suggests an increased functional role of Cav2, likely Cav2.2, channels in mediating OA pain

Glen E. Dickenson and M. W. Husband to Governor Ross Barnett, 28 September 1962

Senders discuss the attempted invasions of both Cuba and Mississippi.https://egrove.olemiss.edu/west_union_gov/1057/thumbnail.jp

The lady vanishes: what's missing from the stem cell debate

Most opponents of somatic cell nuclear transfer and embryonic stem cell technologies base their arguments on the twin assertions that the embryo is either a human being or a potential human being, and that it is wrong to destroy a human being or potential human being in order to produce stem cell lines. Proponents’ justifications of stem cell research are more varied, but not enough to escape the charge of obsession with the status of the embryo. What unites the two warring sides in ‘the stem cell wars’ is that women are equally invisible to both: ‘the lady vanishes’. Yet the only legitimate property in the body is that which women possess in their reproductive tissue and the products of their reproductive labour. By drawing on the accepted characterisation in law of property as a bundle of rights, and on a Hegelian model of contract as mutual recognition, we can lessen the impact of the tendency to regard women and their eggs as merely receptacles and women’s reproductive labour as unimportant

A feasibility study of hand kinematics for EVA analysis using magnetic resonance imaging

A new method of analyzing the kinematics of joint motion is developed. Magnetic Resonance Imaging (MRI) offers several distinct advantages. Past methods of studying anatomic joint motion have usually centered on four approaches. These methods are x-ray projection, goniometric linkage analysis, sonic digitization, and landmark measurement of photogrammetry. Of these four, only x-ray is applicable for in vivo studies. The remaining three methods utilize other types of projections of inter-joint measurements, which can cause various types of error. MRI offers accuracy in measurement due to its tomographic nature (as opposed to projection) without the problems associated with x-ray dosage. Once the data acquisition of MR images was complete, the images were processed using a 3D volume rendering workstation. The metacarpalphalangeal (MCP) joint of the left index finger was selected and reconstructed into a three-dimensional graphic display. From the reconstructed volumetric images, measurements of the angles of movement of the applicable bones were obtained and processed by analyzing the screw motion of the MCP joint. Landmark positions were chosen at distinctive locations of the joint at fixed image threshold intensity levels to ensure repeatability. The primarily two dimensional planar motion of this joint was then studied using a method of constructing coordinate systems using three (or more) points. A transformation matrix based on a world coordinate system described the location and orientation of a local target coordinate system. Future research involving volume rendering of MRI data focusing on the internal kinematics of the hand's individual ligaments, cartilage, tendons, etc. will follow. Its findings will show the applicability of MRI to joint kinematics for gaining further knowledge of the hand-glove (power assisted) design for extravehicular activity (EVA)

The impact of Norwegian folk music on Norwegian jazz, 1945-1995

My research explores the interrelationship between Norwegian folk music and Norwegian jazz from 1945 to 1995 (with updates to 2002) and assesses the extent to which the results can now be considered as constituting an indigenous art form. A short historical overview of Norwegian geography and history contextualises the development of Norwegian folk music and, in particular, its musical characteristics. It is argued that the geographical remoteness of many Norwegian communities isolated the local culture from the rest of the land's population, a situation which continued until collectors such as Lindeman and Sandvik began their tours of the landlying districts from about 1830 and 1900 respectively, collecting material and comparing it with what was discovered elsewhere. The end of World War II heralded the start of an important phase of development in Swedish jazz, which began to cultivate a Scandinavian style of performance and a Scandinavian repertoire. In Norway, some years later, jazz musicians were influenced by indigenous folk music and the principal folk music types that provided inspiration are scrutinised. I then concentrate on defining a Scandinavian jazz style and a recognisable Norwegian variant. The importance of the Lydian mode in Norwegian music is discussed, and the theories of Geirr Tveitt and George Russell receive critical evaluation in relation to Norwegian jazz. Jan Garbarek's composition Molde Canticle is analysed, as is one of its successors, the album Uncharted Land. The contributions of ECM and Manfred Eicher are evaluated, and I conclude with a survey of the contributions of other central figures in the combined field of Norwegian folk music and jazz.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Achieving diffraction-limited performance on the Berkeley MET5

The Berkeley MET5, funded by EUREKA, is a 0.5-NA EUV projection lithography tool located at the Advanced Light Source at Berkeley National Lab. Wavefront measurements of the MET5 optic have been performed using a custom in-situ lateral shearing interferometer suitable for high-NA interferometry. In this paper, we report on the most recent characterization of the MET5 optic demonstrating an RMS wavefront 0.31 nm, and discuss the specialized mask patterns, gratings, and illumination geometries that were employed to accommodate the many challenges associated with high-NA EUV interferometry