Transport in the Trans-Pennine Corridor: Present Conditions and Future Options. Interregional Study Working Paper 3.

This paper reports on a desk study carried out by the Institute for Transport Studies as part of a wider study of opportunities for inter-regional working in the trans-Pennine corridor, considering economic, environmental and transport issues. It draws together available information on transport and movement flows in the trans-Pennine corridor. These patterns of movement are examined from a broad perspective which considers intra-regional, inter- regional and international movements within and across the study area. The report proposes a regional package approach to transport, based on demand management and modal transfer

High performance architecture design for large scale fibre-optic sensor arrays using distributed EDFAs and hybrid TDM/DWDM

A distributed amplified dense wavelength division multiplexing (DWDM) array architecture is presented for interferometric fibre optic sensor array systems. This architecture employs a distributed erbium doped fibre amplifier (EDFA) scheme to decrease the array insertion loss, and employs time division multiplexing (TDM) at each wavelength to increase the number of sensors that can be supported. The first experimental demonstration of this system is reported including results which show the potential for multiplexing and interrogating up to 4096 sensors using a single telemetry fibre pair with good system performance. The number can be increased to 8192 by using dual pump sources

The first metal complexes of 3,3'-bi-1,2,4-oxadiazole: A curiously ignored ligand

The crystal structure of 3,3'-bi-1,2,4-oxadiazole (1) reveals a planar centrosymmetric structure for this molecule in the solid state. It forms a mononuclear complex (3) with palladium(II) chloride, which is shown by X-ray crystallography to contain the ligand chelated through the two N4 nitrogens. The X-ray structure of the complex (5) with silver(I) nitrate shows a one-dimensional coordination polymer in which the ligand acts in a bridging mode, again with coordination through the N4 nitrogen atoms

The first metal complexes of 3,3'-bi-1,2,4-oxadiazole: A curiously ignored ligand

The crystal structure of 3,3'-bi-1,2,4-oxadiazole (1) reveals a planar centrosymmetric structure for this molecule in the solid state. It forms a mononuclear complex (3) with palladium(II) chloride, which is shown by X-ray crystallography to contain the ligand chelated through the two N4 nitrogens. The X-ray structure of the complex (5) with silver(I) nitrate shows a one-dimensional coordination polymer in which the ligand acts in a bridging mode, again with coordination through the N4 nitrogen atoms

933-93 The Regression of Left Ventricular Myofibrillary Proteins by ACE-inhibition (Lisinopril) is Associated with an Increase in Protein Synthetic Rates in Vivo

One of the most serious complications of systemic hypertension is myocardial tissue damage, including left ventricular hypertrophy, as a consequence of increased protein synthesis. However, the modulating role of translational events in the hypertrophy-regression transitionis poorly understood, especially where therapeutic regimes have been employed. These events were investigated in vivoin a genetic model of hypertension, namely in the spontaneously hypertensive rat (SHR); comparative responses were investigated in normotensive Wistar Kyoto rats (WKY). Rats were used at 4 months of age and treated with either the ACE-inhibitor lisinopril (5mg/kg/day) in tap water or plain tap water (controls). The groups were assigned as follows: WKY-CON, normotensive controls; WKY-LIS, normotensives plus lisinopril; SHR-CON, hypertensive controls; SHR-LIS, hypertensives plus lisinopril. Fractional rates of protein synthesis (ksdefined as the percentage of the myofibrillary protein pool renewed each day; %/day) were measured in vivowith the flooding dose technique using L-[4-3H]phenylalanine. Left ventricular myofibrillary proteins were extracted by differential solubility and high-speed centrifugation techniques; purity was assessed with SDS-PAGE. After 8 weeks treatment the myofibrillary protein contents (mg per region) in normotensive rats were as follows (all data as mean±SEMS, n=6–9): WKY-CON, 45±1 mg; WKY–LIS, 36±1 (p<0.001). In the hypertensive group regression of contractile protein content occurred; i.e., SHR-CON, 52±3mg; SHR-L1S, 38±1mg (p<0.001). Corresponding ksvalues were: WKY-CON, 8.3±0.2 %/d; WKY–LIS, 8.2±0.3 %/d (NS). In the SHR-group ksvalues were: SHR-CON, 8.2±0.3%/d; SHR-L1S, 9.2±0.3mg (p<0.025)ConclusionACE-induced regression of contractile protein composition in hypertension is associated with an increase in rates of translatio

Arabidopsis NAP1 regulates the formation of autophagosomes

The SCAR/WAVE complex is required for ARP2/3-mediated actin nucleation, and these complexes are highly conserved in plants and animals [1 and 2]. Proteins from the SCAR/WAVE complex have been found to be membrane associated in plants [3]. Using fluorescent protein fusions, we have found that NAP1 [4], a component of the SCAR/WAVE complex, locates to vesicles or puncta that appear upon applied pressure. These NAP1 vesicles can be endoplasmic reticulum (ER)-associated, can co-align with the cytoskeleton, and fuse to each other homotypically. More interestingly, the majority co-localizes with the autophagosome marker ATG8, and anti-NAP1 identifies autophagosomes in immuno-TEM. Macroautophagy (hereafter referred to as autophagy) is enhanced under certain stress conditions such as nitrogen starvation and salt stress. We show that fewer autophagosomes are generated in the NAP1 knockout mutant during starvation stress. The nap1 mutant (and KO mutants of other components of the SCAR/WAVE and ARP2/3 complexes) is more susceptible to nitrogen starvation and is less salt tolerant, indicating defective autophagy. In conclusion, our data show that NAP1 has another function in plant cells, and that is as a regulator of autophagy

Effect of Solar Wind Drag on the Determination of the Properties of Coronal Mass Ejections from Heliospheric Images

The Fixed-\Phi (F\Phi) and Harmonic Mean (HM) fitting methods are two methods to determine the average direction and velocity of coronal mass ejections (CMEs) from time-elongation tracks produced by Heliospheric Imagers (HIs), such as the HIs onboard the STEREO spacecraft. Both methods assume a constant velocity in their descriptions of the time-elongation profiles of CMEs, which are used to fit the observed time-elongation data. Here, we analyze the effect of aerodynamic drag on CMEs propagating through interplanetary space, and how this drag affects the result of the F\Phi and HM fitting methods. A simple drag model is used to analytically construct time-elongation profiles which are then fitted with the two methods. It is found that higher angles and velocities give rise to greater error in both methods, reaching errors in the direction of propagation of up to 15 deg and 30 deg for the F\Phi and HM fitting methods, respectively. This is due to the physical accelerations of the CMEs being interpreted as geometrical accelerations by the fitting methods. Because of the geometrical definition of the HM fitting method, it is affected by the acceleration more greatly than the F\Phi fitting method. Overall, we find that both techniques overestimate the initial (and final) velocity and direction for fast CMEs propagating beyond 90 deg from the Sun-spacecraft line, meaning that arrival times at 1 AU would be predicted early (by up to 12 hours). We also find that the direction and arrival time of a wide and decelerating CME can be better reproduced by the F\Phi due to the cancellation of two errors: neglecting the CME width and neglecting the CME deceleration. Overall, the inaccuracies of the two fitting methods are expected to play an important role in the prediction of CME hit and arrival times as we head towards solar maximum and the STEREO spacecraft further move behind the Sun.Comment: Solar Physics, Online First, 17 page

Janus kinase inhibitors are potential therapeutics for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a poorly treated multifactorial neurodegenerative disease associated with multiple cell types and subcellular organelles. As with other multifactorial diseases, it is likely that drugs will need to target multiple disease processes and cell types to be effective. We review here the role of Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signalling in ALS, confirm the association of this signalling with fundamental ALS disease processes using the BenevolentAI Knowledge Graph, and demonstrate that inhibitors of this pathway could reduce the ALS pathophysiology in neurons, glia, muscle fibres, and blood cells. Specifically, we suggest that inhibition of the JAK enzymes by approved inhibitors known as Jakinibs could reduce STAT3 activation and modify the progress of this disease. Analysis of the Jakinibs highlights baricitinib as a suitable candidate due to its ability to penetrate the central nervous system and exert beneficial effects on the immune system. Therefore, we recommend that this drug be tested in appropriately designed clinical trials for ALS

Collisionless hydrodynamics for 1D motion of inhomogeneous degenerate electron gases: equivalence of two recent descriptions

Recently I. Tokatly and O. Pankratov (''TP'', Phys. Rev. B 60, 15550 (1999)) used velocity moments of a semiclassical kinetic equation to derive a hydrodynamic description of electron motion in a degenerate electron gas. Independently, the present authors (Theochem 501-502, 327 (2000)) used considerations arising from the Harmonic Potential Theorem (Phys. Rev. Lett. 73, 2244 (1994)) to generate a new form of high-frequency hydrodynamics for inhomogeneous degenerate electron gases (HPT-N3 hydrodynamics). We show here that TP hydrodynamics yields HPT-N3 hydrodynamics when linearized about a Thomas-Fermi groundstate with one-dimensional spatial inhomnogeneity.Comment: 17p

Discrete molecular dynamics simulations of peptide aggregation

We study the aggregation of peptides using the discrete molecular dynamics simulations. At temperatures above the alpha-helix melting temperature of a single peptide, the model peptides aggregate into a multi-layer parallel beta-sheet structure. This structure has an inter-strand distance of 0.48 nm and an inter-sheet distance of 1.0 nm, which agree with experimental observations. In this model, the hydrogen bond interactions give rise to the inter-strand spacing in beta-sheets, while the Go interactions among side chains make beta-strands parallel to each other and allow beta-sheets to pack into layers. The aggregates also contain free edges which may allow for further aggregation of model peptides to form elongated fibrils.Comment: 15 pages, 8 figure