Model Based Sensor System for Temperature Measurement in R744 Air Conditioning Systems

The goal is the development of a novel principle for the temperature acquisition of refrigerants in CO2 air conditioning systems. The new approach is based on measuring the temperature inside a pressure sensor, which is also needed in the system. On the basis of simulative investigations of different mounting conditions functional relations between measured and medium temperature will be derived.Comment: Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants

INTRODUCTION: There is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures. METHODS: We included 12,369 non-demented participants from eight population-based studies. Imputed genetic data and measured plasma Aβ1-40, Aβ1-42 levels and Aβ1-42/Aβ1-40 ratio were used to perform genome-wide association studies, and gene-based and pathway analyses. Significant variants and genes were followed up for their association with brain positron emission tomography Aβ deposition and AD risk. RESULTS: Single-variant analysis identified associations with apolipoprotein E (APOE) for Aβ1-42 and Aβ1-42/Aβ1-40 ratio, and BACE1 for Aβ1-40. Gene-based analysis of Aβ1-40 additionally identified associations for APP, PSEN2, CCK, and ZNF397. There was suggestive evidence for interaction between a BACE1 variant and APOE ε4 on brain Aβ deposition. DISCUSSION: Identification of variants near/in known major Aβ-processing genes strengthens the relevance of plasma-Aβ levels as an endophenotype of AD

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

3D-Simulation von Strukturen zur Modellgenerierung

Bei der 3D-Integration ergibt sich durch den geringen Abstand verschiedener Funktionsblöcke eine große Zahl möglicher physikalischer Wechselwirkungen innerhalb des 3D-Systems. Besonders der Einfluss von Integrations-, Packaging- und Verbindungstechnologien auf das Systemverhalten muss möglichst frühzeitig im Entwurfsprozess berücksichtigt werden. Um die Gesamtfunktionalität des Systems gewährleisten zu können, muss einerseits das Hochfrequenzverhalten der Verbindungsstrukturen in die Betrachtungen einbezogen werden, welches Signalintegrität, Übersprechverhalten und Verzögerungszeiten beeinflusst. Andererseits spielen thermische Interaktionen innerhalb der Stapelstruktur eine wichtige Rolle. Durch die hohe Packungsdichte können verlustleistungserzeugende und temperaturempfindliche Blöcke sehr eng beieinander liegen, ebenso können thermische Gradienten bzw. Temperaturwechsel im System durch die verschiedenen Ausdehnungskoeffizienten der eingesetzten Materialien einen großen Einfluss auf die mechanische Zuverlässigkeit haben. Durch die Vielfalt der zu berücksichtigenden physikalischen Effekte und der benötigten Entwurfswerkzeuge ist eine ebenenübergreifende Methodik für die multiphysikalische Modellierung und Simulation sowohl für Verbindungsstrukturen als auch für den kompletten Stack des 3D-Systems notwendig. Ein modularer Modellierungsansatz ermöglicht es, effizient und ebenenübergreifend - sowohl hinsichtlich der Modellabstraktionsebenen als auch der physikalischen Domänen - Effekte in 3D-Strukturen zu modellieren. Mit Hilfe von Feldsimulationen im HF-Bereich können parasitäre Schaltelementwerte für Widerstände, Kapazitäten und Induktivitäten der Verbindungsstrukturen ermittelt und später für die Schaltungs- und Systemsimulation bereitgestellt werden. Lösungsverfahren für partielle Differentialgleichungen werden ebenfalls für die Analyse der Wärmeausbreitung sowie als Basis für die Generierung von Verhaltensmodellen eingesetzt. Die genannten Verhaltensmodelle können mit Modellen für die elektrische Funktion kombiniert und somit für Gesamtsystemsimulationen genutzt werden

VHDL-AMS in MEMS design flow

Behavioral modeling languages can be used in different steps of top-down design and bottom-up verification of MEMS design. The available language facilities of VHDLAMS and the requirements of the applied methods in this process are confronted. Especially the application of Kirchhoffian networks to model 3D movements is taken into account. The decisions that should be done at the beginning of the modeling process are discussed. This is especially important if models from different sources shall be combined later on. Experiences using available simulation engines are presented. A micro mechanical accelerometer and an electrostatic beam actuator are investigated. Therefore a set of basic elements for MEMS simulation was created

A flow for parasitics extraction in 3D-systems

Due to high integration density in 3D-Systems parasitic effects, which are originally not taken into account during design-phase, has a growing influence on the behavior of the entire system. Therefore, the influences of these effects have to be minimized within the design process. In the following a hierarchical modeling based flow for parasitic extraction of capacitance in 3D-Systems is described. The flow contains layout data import, translation and export data to our own hierarchical XML-based description, and electromagnetic calculations for capacitance extraction

Electronic design automation for implementation of 3D integrated systems

The technology of vertical integration using Through Silicon Vias (TSVs) now is mature for commercial products with a smaller form factor, better performance, less power consumption and lower cost. This paper addresses two challenges faced with the design using vertical integration. First, methods for the characterization of the physical behavior of the new interconnect structures are described. Second, since issues of reliability and thermal management become more important and difficult and the design space is drastically larger, new early stage design tools are needed. A new floorplanning flow is introduced which supports the cost and performance optimized implementation of digital systems in a stack