A low power clock generator with adaptive inter-phase charge balancing for variability compensation in 40-nm CMOS

Power dissipation besides chip area is still one main optimization issue in high performance CMOS design. Regarding high throughput building blocks for digital signal processing architectures which are optimized down to the physical level a complementary two-phase clocking scheme (CTPC) is often advantageous concerning ATE-efficiency. The clock system dissipates a significant part of overall power up to more than 50% in some applications. <br><br> One efficient power saving strategy for CTPC signal generation is the charge balancing technique. To achieve high efficiency with this approach a careful optimization of timing relations within the control is inevitable. <br><br> However, as in modern CMOS processes device variations increase, timing relations between sensitive control signals can be affected seriously. In order to compensate for the influence of global and local variations in this work, an adaptive control system for charge balancing in a CTPC generator is presented. An adjustment for the degree of charge recycling is performed in each clock cycle. In the case of insufficient recycling the delay elements which define duration and timing position of the recycling pulse are corrected by switchable timing units. <br><br> In a benchmark with the conventional clock generation system, a power reduction gain of up to 24.7% could be achieved. This means saving in power of more than 12% for a complete number-crunching building block

Precolonial centralisation, foreign aid and modern state capacity in Africa

In this paper, we empirically explore the determinants of bureaucratic capacity in contemporary Africa. We connect the aid-governance literature with the historical, political economy and anthropological literature on African state formation. Our Ordinary Least Squares (OLS) results show that there is a positive and statistically significant relationship between precolonial centralisation and bureaucratic quality in Africa from the mid-1990s onwards. Before the mid-1990s there is no such relationship. We also find that the often negative and statistically significant effect of aid dependence on bureaucratic capacity disappears, once we control for precolonial centralisation. The OLS results survive a set of robustness tests, including the addition of several control variables and instrumental variable estimation using a variety of instruments suggested in previous research. As the colonial period is slowly fading, the influence of precolonial political institutions on modern state capacity is reasserting itself. Our results provide further evidence for the importance of precolonial centralisation in our understanding of present day economic and political developments on the continent

Biphasic activation of complement and fibrinolysis during the human nasal allergic response

Complement, coagulation and fibrinolysis contribute to the pathology of many respiratory diseases. Here we detail the biphasic activation of these pathways following nasal allergen challenge. Understanding these mechanisms may lead to therapeutic insight in common respiratory diseases

Can we detect more ephemeral floods with higher density harmonized Landsat Sentinel 2 data compared to Landsat 8 alone?

Spatiotemporal quantification of surface water and flooding is essential given that floods are among the largest natural hazards. Effective disaster response management requires near real-time information on flood extent. Satellite remote sensing is the only way of monitoring these dynamics across vast areas and over time. Previous water and flood mapping efforts have relied on optical time series, despite cloud contamination. This reliance on optical data is due to the availability of systematically acquired and easily accessible optical data globally for over 40 years. Prior research used either MODIS or Landsat data, trading either high temporal density but lower spatial resolution or lower cadence but higher spatial resolution. Both MODIS and Landsat pose limitations as Landsat can miss ephemeral floods, whereas MODIS misses small floods and inaccurately delineates flood edges. Leveraging high temporal frequency of 3–4 days of the existing Landsat-8 (L8) and two Sentinel-2 (S2) satellites combined, in this research, we assessed whether the increased temporal frequency of the three sensors improves our ability to detect surface water and flooding extent compared to a single sensor (L8 alone). Our study area was Australia's Murray-Darling Basin, one of the world's largest dryland basins that experiences ephemeral floods. We applied machine learning to NASA's Harmonized Landsat Sentinel-2 (HLS) Surface Reflectance Product, which combines L8 and S2 observations, to map surface water and flooding dynamics. Our overall accuracy, estimated from a stratified random sample, was 99%. Our user's and producer's accuracy for the water class was 80% (±3.6%, standard error) and 76% (±5.8%). We focused on 2019, one of the most recent years when all three HLS sensors operated at full capacity. Our results show that water area (permanent and flooding) identified with the HLS was greater than that identified by L8, and some short-lived flooding events were detected only by the HLS. Comparison with high resolution (3 m) PlanetScope data identified extensive mixed pixels at the 30 m HLS resolution, highlighting the need for improved spatial resolution in future work. The HLS has been able to detect floods in cases when one sensor (L8) alone was not, despite 2019 being one of the driest years in the area, with few flooding events. The dense optical time-series offered by the HLS data is thus critical for capturing temporally dynamic phenomena (i.e., ephemeral floods in drylands), highlighting the importance of harmonized data such as the HLS

Natural Variation in an ABC Transporter Gene Associated with Seed Size Evolution in Tomato Species

Seed size is a key determinant of evolutionary fitness in plants and is a trait that often undergoes tremendous changes during crop domestication. Seed size is most often quantitatively inherited, and it has been shown that Sw4.1 is one of the most significant quantitative trait loci (QTLs) underlying the evolution of seed size in the genus Solanum—especially in species related to the cultivated tomato. Using a combination of genetic, developmental, molecular, and transgenic techniques, we have pinpointed the cause of the Sw4.1 QTL to a gene encoding an ABC transporter gene. This gene exerts its control on seed size, not through the maternal plant, but rather via gene expression in the developing zygote. Phenotypic effects of allelic variation at Sw4.1 are manifested early in seed development at stages corresponding to the rapid deposition of starch and lipids into the endospermic cells. Through synteny, we have identified the Arabidopsis Sw4.1 ortholog. Mutagenesis has revealed that this ortholog is associated with seed length variation and fatty acid deposition in seeds, raising the possibility that the ABC transporter may modulate seed size variation in other species. Transcription studies show that the ABC transporter gene is expressed not only in seeds, but also in other tissues (leaves and roots) and, thus, may perform functions in parts of the plants other than developing seeds. Cloning and characterization of the Sw4.1 QTL gives new insight into how plants change seed during evolution and may open future opportunities for modulating seed size in crop plants for human purposes

Advances in the therapy of Alzheimer's disease: Targeting amyloid beta and tau and perspectives for the future

Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD

Biomarker candidates of neurodegeneration in Parkinson’s disease for the evaluation of disease-modifying therapeutics

Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson’s disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies