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Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Archaeological fieldwork at Hjarnø Sund in Horsens Fjord (eastern Jutland, Denmark) has explored an eroding Mesolithic shell midden. Its stratigraphy is characterized by two layers, containing marine mollusk taxa typically collected by Mesolithic hunter-gatherers for food. In the field, the lower layer appeared to be dominated by oysters (Ostrea edulis), while the upper one by cockles (Cerastoderma edule), which was confirmed by our zooarchaeological study. Accelerator mass spectrometry radiocarbon (AMS 14C) dating on shells and paired charcoal samples from the two layers indicate that these are chronologically consecutive (separated by as little as 0–163 yr [95.4%]) and that the oyster-to-cockle shift dated between ~5500–5300 and ~5300–5200 cal BC (around or just after the Kongemose/Ertebølle transition). The shell midden at Hjarnø Sund is, thus, one of the oldest-known in Denmark, demonstrating that intensive shellfish exploitation was a hallmark of the Ertebølle culture from its inception. Oyster-to-cockle shifts, thus, also occurred at times other than the Mesolithic–Neolithic Transition and may have been ultimately caused by local shoreline displacements, resulting from changes in sedimentation, possibly induced by drops in relative sea level.
In 2005 an airborne survey was carried out from a Twin Otter aircraft at Pâkitsup Akuliarusersua (Paakitsoq) near Ilulissat in West Greenland. The survey aimed to measure ice thickness with a 60 MHz coherent radar and surface elevation with a scanning laser altimeter. Positioning information came from multiple on-board differential GPS units and an inertial navigation system. The region surveyed covers >80km along the ice margin and has a total area of ~2700km2 with varying density of measurements: the between-track distance was ~1 km near the margin, increasing to ~3km away from the margin. Regional high-resolution maps of basal topography under the Greenland ice sheet are useful for resolving important glaciological and hydrological questions and for enhancing related process studies, such as the influence of basal meltwater on ice dynamics. The ice-sheet margin in this region is also currently under consideration for hydropower development and has a long and continuing history of glaciological investigations, lately with emphasis on the connection between surface meltwater formation and surface velocity of the ice sheet. Here we present a new regional map of the surface and basal topography of the ice-sheet margin and discuss some of the implications for reported observations at Swiss Camp.
This article reports investigation of the effects of high-rate stochastic micro-mechanics on the produced particulate size distribution during ball milling of reactive bimetallic foils (nanoheaters), by experimental and computational modeling. In particular, Ni-Al foils are ball-milled at various load charges, revolution rates and process durations, and the resulting particulate geometries are characterized by micrograph statistical analysis. Numerical simulation of the evolving particulate structure is based on coalescence and fragmentation of flexible monometallic ellipsoidal primitives, impacted by milling balls and vial walls with kinetic theory-based kinematics. Particulates are constrained by discrete compliant and continuum media and undergo conceptual ideal elastic transformations modeled by strain energy methods, and recast into inelastic frictional and plasticity-driven welding and fracture events. Finally the theoretical model predictions of particulate size distribution are validated against laboratory microscopy observations.
The relationship between childhood adversity and bipolar affective
disorder remains unclear.
To understand the size and significance of this effect through a
statistical synthesis of reported research.
Search terms relating to childhood adversity and bipolar disorder were
entered into Medline, EMBASE, PsycINFO and Web of Science. Eligible
studies included a sample diagnosed with bipolar disorder, a comparison
sample and a quantitative measure of childhood adversity.
In 19 eligible studies childhood adversity was 2.63 times (95% CI
2.00–3.47) more likely to have occurred in bipolar disorder compared with
non-clinical controls. The effect of emotional abuse was particularly
robust (OR = 4.04, 95% CI 3.12–5.22), but rates of adversity were similar
to those in psychiatric controls.
Childhood adversity is associated with bipolar disorder, which has
implications for the treatment of this clinical group. Further
prospective research could clarify temporal causality and explanatory
The spatial pattern and morphometry of bedforms and their relationship to sediment thickness have been analysed in the Marguerite Bay Palaeo-ice stream Trough, western Antarctic Peninsula. Over 17 000 glacial landforms were measured from geophysical datasets, and sediment thickness maps were generated from acoustic sub-bottom profiler data. These analyses reveal a complex bedform pattern characterised by considerable spatial diversity, influenced heavily by the underlying substrate. The variability in length and density of mega-scale lineations indicates an evolving bedform signature, whereby landforms are preserved at different stages of maturity. Lineation generation and attenuation is associated with regions of thick, soft till where deformation was likely to be the greatest. The distribution of soft till and the localised extent of grounding-zone wedges (GZWs) indicate a dynamic sedimentary system characterised by considerable spatio-temporal variability in sediment erosion, transport and deposition. Formation of GZWs on the outer shelf of Marguerite Trough, within the error range of the radiocarbon dates, requires large sediment fluxes (upwards of 1000 m3 a−1 (m grounding line width)−1), and a >1 m thick mobile till layer, or rapid basal sliding velocities (upwards of 6 km a−1).
A considerable expansion of biogas production in Germany, paralleled by a strong increase in maize acreage, has caused growing concern that greenhouse gas (GHG) emissions during crop substrate production might counteract the GHG emission saving potential. Based on a 2-year field trial, a GHG balance was conducted to evaluate the mitigation potential of regionally adapted cropping systems (continuous maize, maize-wheat-Italian ryegrass, perennial ryegrass ley), depending on nitrogen (N) level and N type. Considering the whole production chain, all cropping systems investigated contributed to the mitigation of GHG emissions (6·7–13·3 t CO2 eq/ha), with continuous maize revealing a carbon dioxide (CO2) saving potential of 55–61% compared with a fossil energy mix reference system. The current sustainability thresholds in terms of CO2 savings set by the EU Renewable Energy Directive could be met by all cropping systems (48–76%). Emissions from crop production had the largest impact on the mitigation effect (⩾50%) unless the biogas residue storage was not covered. The comparison of N fertilizer types showed less pronounced differences in GHG mitigation potential, whereas considerable site effects were observed.
Blood lipid response to a given dietary intervention could be determined by the effect of diet, gene variants or gene–diet interactions. The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP–diet interaction effects on total cholesterol, LDL-cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect), and a 6-month ad libitum weight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP–dietary protein interaction effect on TAG was identified for lipin 1 (LPIN1) rs4315495, with a decrease in TAG of − 0·26 mmol/l per A-allele/protein unit (95 % CI − 0·38, − 0·14, P= 0·000043). In conclusion, we investigated SNP–diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism pathways, and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration.
The stress–vulnerability model of psychosis continues to be influential. The aim of this study was to compare emotional and symptomatic responses to stress in individuals at ultra-high risk (UHR) of developing psychosis, in age- and gender-matched healthy controls, and in patients with non-affective psychosis.
A total of 27 UHR, 27 psychotic and 27 healthy individuals completed the experience sampling method, an ambulant diary technique, where they were required to fill in self-assessment questions about their emotions, symptoms and perceived stress at semi-random times of the day for 6 days. Quesionnaire and interview assessments were also completed.
Multilevel regression analyses showed that individuals at UHR of developing psychosis reported greater negative emotions in response to stress than the healthy individuals. Against the initial hypotheses, the UHR individuals also experienced greater emotional reactivity to stress when compared with the patient group. No significant differences were observed between the patients and the non-clinical sample. Stress measures significantly predicted the intensity of psychotic symptoms in UHR individuals and patients, but the extent of this did not significantly differ between the groups.
Individuals at UHR of developing psychosis may be particularly sensitive to everyday stressors. This effect may diminish after transition to psychosis is made and in periods of stability. Subtle increases in psychotic phenomena occur in response to stressful events across the continuum of psychosis.
This Report asks whether American courts that decide constitutional cases, and ultimately the Justices of the U.S. Supreme Court, may be characterized as legislators, and in particular, as “positive” legislators. After defining the terms, the report reviews the Supreme Court's practice of constitutional lawmaking and considers academic and political reactions to that practice. The Report concludes with an account of challenges that the Court has encountered in crafting remedies fit to fulfill the promise of its constitutional rulings.
LEGISLATORS AND POSITIVE LEGISLATORS
The topic of this Report engages two analytically distinct ideas – legislation and “positive legislation.” By legislation, we mean any action that adds a rule to a given system of law. Historically, American jurisprudence has displayed an ambivalent attitude to the idea that judges legislate in this sense. Judicial lawmaking is, of course, an entirely familiar feature of common law adjudication, but until the latter part of the nineteenth century, this proposition was widely considered heretical. The orthodox view was that what might look like judicially created rules were, in fact, deductions from a preexisting body of common law principles. By the middle of the twentieth century, however, this idea had been fully debunked, and there was common agreement that “judges do and must legislate,” although they can “do so only interstitially; they are confined from molar to molecular motions.” Critically, moreover, such judge-made law was universally acknowledged to be subject to correction and revision by elected legislatures.
We conducted a Spitzer Space Telescope survey of 28 Luminous (11 < log (LIR/L⊙) < 12, LIRGs) and Ultra-Luminous Infrared Galaxies (log (LIR/L⊙) > 12, ULIRGs). Many of these galaxies are found in pairs or associations and are powered by either nuclear activity or star-formation (Sanders & Mirabel 1996). Our main goal is to understand the relative importance of starbursts and AGNs in interacting systems. Is the frequency of AGN and starbursts in these interacting galaxies related to their luminosities? What is the importance of the merger stage and the frequency of AGNs? We present our conclusions and diagnostic diagrams based in the observed near infrared lines and compare to studies based solely in optical data.
Somatic cell count (SCC) is generally regarded as an indicator of udder health. A cut-off value of 100×103 cells/ml is currently used in Germany to differentiate between normal and abnormal secretion of quarters. In addition to SCC, differential cell counts (DCC) can be applied for a more detailed analysis of the udder health status. The aim of this study was to differentiate somatic cells in foremilk samples of udder quarters classified as normal secreting by SCC <100×103 cells/ml. Twenty cows were selected and 72 normal secreting udder quarters were compared with a control group of six diseased quarters (SCC >100×103 cells/ml). In two severely diseased quarters of the control group (SCC of 967×103 cells/ml and 1824×103 cells/ml) Escherichia coli and Staphylococcus aureus were detected. DCC patterns of milk samples (n=25) with very low SCC values of ⩽6·25×103 cells/ml revealed high lymphocyte proportions of up to 92%. Milk cell populations in samples (n=41) with SCC values of (>6·25 to ⩽25)×103 cells/ml were also dominated by lymphocytes (mean value 47%), whereas DCC patterns of milk from udder quarters (n=6) with SCC values (>25 to ⩽100)×103 cells/ml changed. While in samples (n=3) with SCC values of (27–33)×103 cells/ml macrophages were predominant (35–40%), three milk samples with (43–45)×103 cells/ml indicated already inflammatory reactions based on the predominance of polymorphonuclear leucocytes (PMN) (54–63%). In milk samples of diseased quarters PMN were categorically found as dominant cell population with proportions of ⩾65%. Macrophages were the second predominant cell population in almost all samples tested in relationship to lymphocytes and PMN. To our knowledge, this is the first study evaluating cell populations in low SCC milk in detail. Udder quarters classified as normal secreting by SCC <100×103 cells/ml revealed already inflammatory processes based on DCC.
Biodegradable magnetic nanoparticles were synthesized using Poly(L-Lactic Acid) and magnetite nanoparticles (∼14 nm) at different dosages, and then these nanaoparticles (nanocomposites) and pure magnetic particles were targeted in external magnetic fields by changing the test parameters. The magnetic field test results showed that magnetic saturation, fluid speed, magnetic field distance and particle size were extremely effective for a magnetic guidance system that is needed for an effective drug delivery approach. Thus, it is assumed that such nanoparticles can carry drugs (chemotherapy) to be able to cure cancer tumors as well as many other diseases.
Photoemission spectra from HTSC materials ( primarily 123 -type ), cleaved and measured at 20K, reveal a rich DOS structure which compares favorably with a calculated band structure, except for a residual 0.5 eV shift which may reflect some correlation effects. Band dispersion is observed throughout the valence bands, with clear evidence for a 0.2 eV wide band dispersing through EF. The orbital character at EF is a mix of Cu-3d and O-2p. There is unambiguous evidence for a large BCS-like gap (2Δ≥ 4kTc).
A fiber optic phase and polarization modulator is presented in which a thin transparent piezoelectric polyvinylidene fluoride film with indium tin oxide electrode metallization is placed directly in the path of the output of a single mode fiber. Experimental characterization is presented in terms of the linearity of response, phase shifting coefficient, and frequency response for two arrangements differing in the boundary clamping conditions. Many applications to fiber optic switches, intensity modulators and demultiplexers are indicated.
A system to detect and locate impacts by foreign bodies on a surface was developed and tested. Fiber optic extrinsic Fabry-Perot interferometer (EFPI) strain sensors were attached to or embedded in the surface, so that stress waves emanating from an impact could be detected. By employing an artificial neural network to process the sensor outputs, the impact location could be inferred to centimeter range accuracy directly from the arrival time data. In particular, the network could be trained to determine impact location regardless of material anisotropy. Results demonstrate that a back-propagation network identifiesimpact location for an anisotropic graphite/bismaleimide plate with the same accuracy as that for an isotropic aluminum plate.
We have formed suspended bridges of carbon nanotubes between microcantilevers using electron beam dissociation of metal-organic vapours. By electron beam exposure of a surface in the presence of gold-carbon molecules emitted inside an environmental scanning electron microscope, we are able to form tips and other freestanding nanostructures of high metallic content. Suspended bridges made entirely of this material exhibit resistances less than 50 times that of pure gold, and consist of dense metallic cores surrounded by a crust of nanoparticles. We used standard microfabrication techniques to produce silicon chips with multiple microcantilevers extending over the edge. Individual multiwalled carbon nanotubes grown catalyticcally by chemical vapour deposition, were positioned across two cantilevers using in-situ nanomanipulation tools. Drawing a cross-shaped gold-carbon bond on each end of the carbon nanotube consistently resulted in electrical contact with resistances in the range 1-90 Ω and linear current-voltage characteristics. We found that soldering bonds having a line width down to 10-15 nm form connections and last for days in ambient conditions.
We report the synthesis and sol-gel polymerization of 4-nitro-N,N-bis[(3- triethoxysilyl)propyl]aniline 1. An efficient synthesis of the monomer was developed by the hydrosilylation of N, N-diallyl-4-nitroaniline. Optical quality thin films were synthesized by spin coating an n-butanol solution of 1 using formic acid as catalyst and source of water. We improved the temporal stability of the NLO signal from films prepared from 4-nitro-N,N-bis[(3-triethoxysilyl)propyl]aniline by increasing the intensity of the poling field and extending the heating period during the poling/curing stage. By Maker fringe analysis, a X(2) value of 9 × 10−8 esu was measured for these polysilsesquioxanes. If one assumes that the major component of the NLO effect is along the z-axis, the X(2) value corresponds to a d33 coefficient of 18.9 pm/V and a r33 value of 4.7 pm/V.