The roan antelope (Hippotragus equinus) is the second largest African antelope, distributed throughout the continent in sub‐Saharan savannah habitat. Mitochondrial DNA (mtDNA) control region ...sequencing (401 bp, n = 137) and microsatellite genotyping (eight loci, n = 137) were used to quantify the genetic variability within and among 18 populations of this species. The within‐population diversity was low to moderate with an average mtDNA nucleotide diversity of 1.9% and average expected heterozygosity with the microsatellites of 46%, but significant differences were found among populations with both the mtDNA and microsatellite data. Different levels of genetic resolution were found using the two marker sets, but both lent strong support for the separation of West African populations (samples from Benin, Senegal and Ghana) from the remainder of the populations studied across the African continent. Mismatch distribution analyses revealed possible past refugia for roan in the west and east of Africa. The West African populations could be recognized together as an evolutionarily significant unit (ESU), referable to the subspecies H. e. koba. Samples from the rest of the continent constituted a geographically more diverse assemblage with genetic associations not strictly corresponding to the other recognized subspecies.
The Food and Drug Administration (FDA) Critical Path Initiative1 as well as the European Medicines Agency Road Map to 2010 (ref. 2) call for opportunities for more efficient drug development. One of ...the initiatives that has emerged in this context is the elaboration through guidance of exploratory investigational new drugs (INDs)/clinical trial applications (CTAs). This article reviews the history of these emerging guidances as well as the experience to date in their use by the industry.
Clinical Pharmacology & Therapeutics (2008) doi:10.1038/sj.clpt.6100461
Nanocomposite materials hold the power to revitalize and revolutionize the field of composite materials. Nanoscaled, even common materials can exhibit strikingly different material properties from ...the bulk counterparts. If these properties can be accessed at the bulk scale, not only can materials be better tailored to suit various applications, but the possibility of designing multi-functional materials expands exponentially. In this study, the Generalized Method of Cells (GMC) micromechanics model is used to model 3D nanoscale composite architecture, including an interfacial region between the included and matrix phases, and predict the effective viscoelastic properties of a gold nanorod, polymer matrix, nanocomposite. Scale is introduced by referencing the dimensions of the interface to those of the nanorods. Comparisons are made of micromechanical response based on volume fraction and number density, highlighting the scale effects resulting from the high surface area to volume ratio of nanoparticles. Effective composite viscoelastic properties were developed, for static creep, for varying interfacial elastic stiffnesses. These experiments suggest that an elastically stiff interface greatly increases the stiffness of the polymer in response to an ‘instantaneous’ step load, reduces the rapid creep response, and results in a rapid leveling off of the time-dependent strain curves. The response of the composite to increasing stiffness of the interface region eventually reaches a plateau or threshold value, where further increases in the stiffness of the interface produces negligible increases in stiffness, or further reduction in creep response.
Repeated treatment with psychostimulant drugs produces changes in brain and behaviour that far outlast their initial neuropharmacological actions. The nature of persistent drug‐induced ...neurobehavioural adaptations is of interest because they are thought to contribute to the development of dependence and addiction, and other forms of psychopathology, e.g. amphetamine psychosis. There are many reports that psychostimulants produce biochemical adaptations in brain monoamine systems, especially dopamine systems. The purpose of the present study was to determine if they might also alter the morphology of neurons in brain regions that receive monoaminergic innervation. Rats were given repeated injections of either amphetamine or cocaine, or, to control for general motor activity, allowed access to a running wheel. They were then left undisturbed for 24–25 days before their brains were processed for Golgi–Cox staining. Treatment with either amphetamine or cocaine (but not wheel running experience) increased the number of dendritic branches and the density of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens, and on apical dendrites of layer V pyramidal cells in the prefrontal cortex. Cocaine also increased dendritic branching and spine density on the basilar dendrites of pyramidal cells. In addition, both drugs doubled the incidence of branched spines on medium spiny neurons. It is suggested that some of the persistent neurobehavioural consequences of repeated exposure to psychostimulant drugs may be due to their ability to reorganize patterns of synaptic connectivity in the nucleus accumbens and prefrontal cortex.
Distributed measurements of agricultural erosion at the farm-scale are needed to evaluate both the on and off-site impacts of sediment redistribution. While best management practices have been shown ...to reduce surface erosion rates and improve water quality, their farm-scale effects can be difficult to quantify. In this study we use imagery from an unmanned aerial vehicle (UAV) and structure-from-motion multi-view stereo (SfM-MVS) to quantify erosion rates and their effects on crop yield across a 15.9-ha agricultural field. Our results highlight that the installation of catch basins were able to stop 159.52 t of sediment and associated nutrients from entering the waterway adjacent to the study site over the course of one year, corresponding to an erosion rate of 18.83 t ha−1 yr−1 across six study basins. Poor soil structure resulting from downslope tillage reduced crop yields on topographic shoulders of the study site, while accelerated water erosion processes were responsible for large areas of washout that caused highly variable crop growth in footslopes. The highest crop yields were associated with backslopes and topographically flat regions of the field which experienced minimal erosion. Change-detection results showed that UAV imagery was able to reliably quantify depositional plumes and was comparable to that of a terrestrial laser scanner (TLS) using a ± 0.04 m confidence interval.
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•UAV imagery and SfM-MVS was used to quantify agricultural erosion,•The average erosion rate of six steep tile-drained basins was 18.83 t ha−1 yr−1•57% of annual erosion was associated with spring storms after planting•Catch basins prevented 159.52 t of sediment from entering waterways•Erosion rates, soil texture, and landform elements were compared to crop yield
The Convective Transport of Active Species in the Tropics (CONTRAST) experiment was conducted from Guam (13.5°N, 144.8°E) during January–February 2014. Using the NSF/NCAR Gulfstream V research ...aircraft, the experiment investigated the photochemical environment over the tropical western Pacific (TWP) warm pool, a region of massive deep convection and the major pathway for air to enter the stratosphere during Northern Hemisphere (NH) winter. The new observations provide a wealth of information for quantifying the influence of convection on the vertical distributions of active species. The airborne in situ measurements up to 15-km altitude fill a significant gap by characterizing the abundance and altitude variation of a wide suite of trace gases. These measurements, together with observations of dynamical and microphysical parameters, provide significant new data for constraining and evaluating global chemistry–climate models. Measurements include precursor and product gas species of reactive halogen compounds that impact ozone in the upper troposphere/lower stratosphere. High-accuracy, in situ measurements of ozone obtained during CONTRAST quantify ozone concentration profiles in the upper troposphere, where previous observations from balloonborne ozonesondes were often near or below the limit of detection. CONTRAST was one of the three coordinated experiments to observe the TWP during January–February 2014. Together, CONTRAST, Airborne Tropical Tropopause Experiment (ATTREX), and Coordinated Airborne Studies in the Tropics (CAST), using complementary capabilities of the three aircraft platforms as well as ground-based instrumentation, provide a comprehensive quantification of the regional distribution and vertical structure of natural and pollutant trace gases in the TWP during NH winter, from the oceanic boundary to the lower stratosphere.
We report a novel and easily accessible method to chemically reduce graphene fluoride （GF） sheets with nanoscopic precision using high electrostatic fields generated between an atomic force ...microscope （AFM） tip and the GF substrate. Reduction of fluorine by the electric field produces graphene nanoribbons （GNR） with a width of 105-1,800 nm with sheet resistivity drastically decreased from 〉1 TΩ.sq.^-1 （GF） down to 46 kΩ.sq.^-1 （GNR）. Fluorine reduction also changes the topography, friction, and work function of the GF. Kelvin probe force microscopy measurements indicate that the work function of GF is 180-280 meV greater than that of graphene. The reduction process was optimized by varying the AFM probe velocity between 1.2 μm.s^-1 and 12 μm.s^-1 and the bias voltage applied to the sample between -8 and -12 V. The electrostatic field required to remove fluorine from carbon is -1.6 V.nm-1. Reduction of the fluorine may be due to the softening of the C-F bond in this intense field or to the accumulation and hydrolysis of adventitious water into a meniscus.
Hypertension and dementia commonly co-exist in older people, yet guidance is lacking on how to manage these co-existing conditions. The aim of this systematic review was to assess the evidence for ...the treatment of hypertension in older people with dementia. Medline, EMBASE, Cochrane Library and the national research register archives were searched. Inclusion criteria were: randomised controlled trial of hypertension treatment, included participants aged 65+ years, participants had a diagnosis of dementia (global cognitive decline for at least 6 months affecting daily function), and the study assessed cognitive outcomes using validated tools. Dementia prevention studies and poor quality studies were excluded. The initial search revealed 1178 papers of potential interest, of which 24 were selected for review and six met the full inclusion criteria. Trials included people with mild-to-moderate but not severe dementia; exclusion criteria for the trials were extensive. Four trials were placebo-controlled RCTs; the remaining two compared different antihypertensives. All trials reported MMSE scores at baseline and follow-up; four reported blood pressure changes at follow-up; and only three reported cardiovascular morbidity or mortality at follow-up. Only one of four placebo-controlled studies showed evidence of blood pressure reduction, but no clear evidence for benefit (or harm) from antihypertensives on cognition, physical function or other cardiovascular outcomes. We found no evidence to confirm or refute the hypothesis that treatment of hypertension in people with dementia leads to overall health benefit.
A major challenge for miniature bioelectronics is wireless power delivery deep inside the body. Electromagnetic or ultrasound waves suffer from absorption and impedance mismatches at biological ...interfaces. On the other hand, magnetic fields do not suffer these losses, which has led to magnetically powered bioelectronic implants based on induction or magnetothermal effects. However, these approaches have yet to produce a miniature stimulator that operates at clinically relevant high frequencies. Here, we show that an alternative wireless power method based on magnetoelectric (ME) materials enables miniature magnetically powered neural stimulators that operate up to clinically relevant frequencies in excess of 100 Hz. We demonstrate that wireless ME stimulators provide therapeutic deep brain stimulation in a freely moving rodent model for Parkinson's disease and that these devices can be miniaturized to millimeter-scale and fully implanted. These results suggest that ME materials are an excellent candidate to enable miniature bioelectronics for clinical and research applications.
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•Magnetoelectric materials enable millimeter-sized wireless stimulators•Wireless neural stimulators reach therapeutic frequencies in freely moving rodents•Miniature bioelectronic devices treat Parkinson's disease in a rat model
Magnetoelectric (ME) materials enable tiny remotely powered neural stimulators. Singer et al. demonstrate that alternating magnetic fields can power millimeter-sized ME stimulators in freely moving rodents. The extreme miniaturization made possible by this technology lays the foundation for a new class of minimally invasive bioelectronics.
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