Rapid relaxation NMR measurements to predict rate coefficients in ionic liquid mixtures. An examination of reaction outcome changes in a homologous series of ionic liquids

A series of ionic liquids based on the 1-alkyl-3-methylimidazolium cations were examined as components of the solvent mixture for a bimolecular substitution process. The effects on both the rate coefficient of the process and the NMR spin-spin relaxation of the solvent components of changing either the alkyl chain length or the amount of ionic liquid in the reaction mixture were determined. At a constant mole fraction, a shorter alkyl chain length resulted in a greater rate coefficient enhancement and a longer relaxation time, with the opposite effects for a longer alkyl chain length. For a given ionic liquid, increasing the proportion of salt in the reaction mixture resulted in a greater rate coefficient and a shorter relaxation time. The microscopic origins of the rate coefficient enhancement were determined and a step change found in the activation parameters on increasing the alkyl chain length from hexyl to octyl, suggesting notable structuring in solution. Across a range of ionic liquids and solvent compositions, the relaxation time from NMR measurements was shown to relate to the reaction rate coefficient. The approach of using fast and simple NMR relaxation measurements to predict reaction outcomes was exemplified using a morpholinium-based ionic liquid

The Accelerations of Stars Orbiting the Milky Way's Central Black Hole

Recent measurements, of the velocities of stars near the center of the Milky Way have provided the strongest evidence for the presence of a supermassive black hole in a galaxy, but the observational uncertainties poorly constrain many of the properties of the black hole. Determining the accelerations of stars in their orbits around the center provides much more precise information about the position and mass of the black hole. Here we report measurements of the accelerations for three stars located ~0.005 pc from the central radio source Sgr A*; these accelerations are comparable to those experienced by the Earth as it orbits the Sun. These data increase the inferred minimum mass density in the central region of the Galaxy by an order of magnitude relative to previous results and localized the dark mass to within 0.05 +- 0.04 arcsec of the nominal position of Sgr A*. In addition, the orbital period of one of the observed stars could be as short as 15 years, allowing us the opportunity in the near future to observe an entire period.Comment: To appear in September 21 2000 issue of Natur

Investigation of MicroRNA-134 as a Target against Seizures and SUDEP in a Mouse Model of Dravet Syndrome

Dravet syndrome (DS) is a catastrophic form of pediatric epilepsy mainly caused by noninherited mutations in the SCN1A gene. DS patients suffer severe and life-threatening focal and generalized seizures which are often refractory to available anti-seizure medication. Antisense oligonucleotides (ASOs) based approaches may offer treatment opportunities in DS. MicroRNAs are short noncoding RNAs that play a key role in brain structure and function by post-transcriptionally regulating gene expression, including ion channels. Inhibiting miRNA-134 (miR-134) using an antimiR ASO (Ant-134) has been shown to reduce evoked seizures in juvenile and adult mice and reduce epilepsy development in models of focal epilepsy. The present study investigated the levels of miR-134 and whether Ant-134 could protect against hyperthermia-induced seizures, spontaneous seizures and mortality (SUDEP) in F1.Scn1a(1/)tm1kea mice. At P17, animals were intracerebroventricular in-jected with 0.1–1 nmol of Ant-134 and subject to a hyperthermia challenge at postnatal day (P)18. A second cohort of P21 F1.Scn1a(1/)tm1kea mice received Ant-134 and were followed by video and EEG monitoring until P28 to track the incidence of spontaneous seizures and SUDEP. Hippocampal and cortical levels of miR-134 were similar between wild-type (WT) and F1.Scn1a(1/)tm1kea mice. Moreover, Ant-134 had no effect on hyperthermia-induced seizures, spontaneous seizures and SUDEP incidence were unchanged in Ant-134-treated DS mice. These findings suggest that targeting miR-134 does not have therapeutic applications in DS

From Rotating Atomic Rings to Quantum Hall States

Considerable efforts are currently devoted to the preparation of ultracold neutral atoms in the emblematic strongly correlated quantum Hall regime. The routes followed so far essentially rely on thermodynamics, i.e. imposing the proper Hamiltonian and cooling the system towards its ground state. In rapidly rotating 2D harmonic traps the role of the transverse magnetic field is played by the angular velocity. For particle numbers significantly larger than unity, the required angular momentum is very large and it can be obtained only for spinning frequencies extremely near to the deconfinement limit; consequently, the required control on experimental parameters turns out to be far too stringent. Here we propose to follow instead a dynamic path starting from the gas confined in a rotating ring. The large moment of inertia of the fluid facilitates the access to states with a large angular momentum, corresponding to a giant vortex. The initial ring-shaped trapping potential is then adiabatically transformed into a harmonic confinement, which brings the interacting atomic gas in the desired quantum Hall regime. We provide clear numerical evidence that for a relatively broad range of initial angular frequencies, the giant vortex state is adiabatically connected to the bosonic $\nu=1/2$ Laughlin state, and we discuss the scaling to many particles.Comment: 9 pages, 5 figure

Fish for the city: meta-analysis of archaeological cod remains and the growth of London's northern trade

The growth of medieval cities in Northern Europe placed new demands on food supply, and led to the import of fish from increasingly distant fishing grounds. Quantitative analysis of cod remains from London provides revealing insight into the changing patterns of supply that can be related to known historical events and circumstances. In particular it identifies a marked increase in imported cod from the thirteenth century AD. That trend continued into the fifteenth and sixteenth centuries, after a short downturn, perhaps attributable to the impact of the Black Death, in the mid fourteenth century. The detailed pattern of fluctuating abundance illustrates the potential of archaeological information that is now available from the high-quality urban excavations conducted in London and similar centres during recent decades

Decision support tools for agriculture: Towards effective design and delivery

Decision support tools, usually considered to be software-based, may be an important part of the quest for evidence-based decision-making in agriculture to improve productivity and environmental outputs. These tools can lead users through clear steps and suggest optimal decision paths or may act more as information sources to improve the evidence base for decisions. Yet, despite their availability in a wide range of formats, studies in several countries have shown uptake to be disappointingly low. This paper uses a mixed methods approach to investigate the factors affecting the uptake and use of decision support tools by farmers and advisers in the UK. Through a combination of qualitative interviews and quantitative surveys, we found that fifteen factors are influential in convincing farmers and advisers to use decision support tools, which include usability, cost-effectiveness, performance, relevance to user, and compatibility with compliance demands. This study finds a plethora of agricultural decision support tools in operation in the UK, yet, like other studies, shows that their uptake is low. A better understanding of the fifteen factors identified should lead to more effective design and delivery of tools in the future.This research was funded as part of Defra's Sustainable Intensification Platform (Project Code LM0201). In addition, WJS was funded by Arcadia, LVD was funded by the UK Natural Environment Research Council under the Biodiversity and Ecosystem Service Sustainability (BESS) programme, grant code NE/K015419/1. T.A. was supported by the European Commission's Marie Curie International Incoming Fellowship Programme (PIIF-GA-2011-303221) and the Isaac Newton Trust.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.agsy.2016.09.00

Cost-effectiveness of nurse-delivered cognitive behavioural therapy (CBT) compared to supportive listening (SL) for adjustment to multiple sclerosis

Background: Cognitive Behavioural Therapy (CBT) reduces distress in multiple sclerosis, and helps manage adjustment, but cost-effectiveness evidence is lacking. Methods: An economic evaluation was conducted within a multi-centre trial. 94 patients were randomised to either eight sessions of nurse-led CBT or supportive listening (SL). Costs were calculated from the health, social and indirect care perspectives, and combined with additional quality-adjusted life years (QALY) or improvement on the GHQ-12 score, to explore cost-effectiveness at 12 months. Results: CBT had higher mean health costs (£1610, 95% CI, −£187 to 3771) and slightly better QALYs (0.0053, 95% CI, −0.059 to 0.103) compared to SL but these differences were not statistically significant. This yielded £301,509 per QALY improvement, indicating that CBT is not cost-effective according to established UK NHS thresholds. The extra cost per patient improvement on the GHQ-12 scale was £821 from the same perspective. Using a £20,000, threshold, CBT in this format has a 9% probability of being cost effective. Although subgroup analysis of patients with clinical levels of distress at baseline showed an improvement in the position of CBT compared to SL, CBT was still not cost-effective. Conclusion: Nurse delivered CBT is more effective in reducing distress among MS patients compared to SL, but is highly unlikely to be cost-effective using a preference-based measure of health (EQ-5D). Results from a diseasespecif ic measure (GHQ-12) produced comparatively lower Incremental Cost-Effectiveness Ratios, but there is currently no acceptable willingness-to-pay threshold for this measure to guide decision-making

Antagomir-mediated suppression of microRNA-134 reduces kainic acid-induced seizures in immature mice

MicroRNAs are short non-coding RNAs that negatively regulate protein levels and perform important roles in establishing and maintaining neuronal network function. Previous studies in adult rodents have detected upregulation of microRNA-134 after prolonged seizures (status epilepticus) and demonstrated that silencing microRNA-134 using antisense oligonucleotides, termed antagomirs, has potent and long-lasting seizure-suppressive effects. Here we investigated whether targeting microRNA-134 can reduce or delay acute seizures in the immature brain. Status epilepticus was induced in 21 day-old (P21) male mice by systemic injection of 5 mg/kg kainic acid. This triggered prolonged electrographic seizures and select bilateral neuronal death within the CA3 subfield of the hippocampus. Expression of microRNA-134 and functional loading to Argonaute-2 was not significantly changed in the hippocampus after seizures in the model. Nevertheless, when levels of microRNA-134 were reduced by prior intracerebroventricular injection of an antagomir, kainic acid-induced seizures were delayed and less severe and mice displayed reduced neuronal death in the hippocampus. These studies demonstrate targeting microRNA-134 may have therapeutic applications for the treatment of seizures in children

Black Holes in Modified Gravity (MOG)

The field equations for Scalar-Tensor-Vector-Gravity (STVG) or modified gravity (MOG) have a static, spherically symmetric black hole solution determined by the mass $M$ with two horizons. The strength of the gravitational constant is $G=G_N(1+\alpha)$ where $\alpha$ is a parameter. A regular singularity-free MOG solution is derived using a nonlinear field dynamics for the repulsive gravitational field component and a reasonable physical energy-momentum tensor. The Kruskal-Szekeres completion of the MOG black hole solution is obtained. The Kerr-MOG black hole solution is determined by the mass $M$, the parameter $\alpha$ and the spin angular momentum $J=Ma$. The equations of motion and the stability condition of a test particle orbiting the MOG black hole are derived, and the radius of the black hole photosphere and the shadows cast by the Schwarzschild-MOG and Kerr-MOG black holes are calculated. A traversable wormhole solution is constructed with a throat stabilized by the repulsive component of the gravitational field.Comment: 14 pages, 3 figures. Upgraded version of paper to match published version in European Physics Journal

Spared CA1 pyramidal neuron function and hippocampal performance following antisense knockdown of microRNA-134

OBJECTIVE: Inhibition of microRNA-134 by an oligonucleotide antagomir (ant-134) has been shown to produce powerful antiseizure effects in multiple models of epilepsy. However, to successfully translate the treatment to the clinic, it is important to assess what potential adverse effects it may have on naive brain tissue. METHODS: To investigate this, adult male Sprague-Dawley rats were treated with either ant-134 or a scrambled control sequence. Animals were later assessed for spatial navigation, before ex vivo slices were taken to assess the effects of microRNA-134 knockdown on well-defined measures of intrinsic and synaptic properties. RESULTS: Hippocampal field potential recordings determined that silencing of microRNA-134 by ant-134 injection was associated with a reduction in epileptiform activity following application of 9 mmol/L K+ . Nevertheless, rats performed normally in the novel object location test. Action potential waveforms and miniature excitatory synaptic currents recorded in CA1 pyramidal neurons were unaffected by ant-134. SIGNIFICANCE: These results demonstrate that ant-134 confers a seizure-protective effect without obvious interference with hippocampal neuronal properties or network function. These findings support further development of this novel approach to epilepsy treatment