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

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

Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic.

Biomarker discovery and development for clinical research, diagnostics and therapy monitoring in clinical trials have advanced rapidly in key areas of medicine - most notably, oncology and cardiovascular diseases - allowing rapid early detection and supporting the evolution of biomarker-guided, precision-medicine-based targeted therapies. In Alzheimer disease (AD), breakthroughs in biomarker identification and validation include cerebrospinal fluid and PET markers of amyloid-β and tau proteins, which are highly accurate in detecting the presence of AD-associated pathophysiological and neuropathological changes. However, the high cost, insufficient accessibility and/or invasiveness of these assays limit their use as viable first-line tools for detecting patterns of pathophysiology. Therefore, a multistage, tiered approach is needed, prioritizing development of an initial screen to exclude from these tests the high numbers of people with cognitive deficits who do not demonstrate evidence of underlying AD pathophysiology. This Review summarizes the efforts of an international working group that aimed to survey the current landscape of blood-based AD biomarkers and outlines operational steps for an effective academic-industry co-development pathway from identification and assay development to validation for clinical use.I recieved an honorarium from Roche Diagnostics for my participation in the advisory panel meeting leading to this pape