Run-Time Reconfiguration for HyperTransport coupled FPGAs using ACCFS

In this paper we present a solution where only one FPGA is needed in a host coupled system, in which the FPGA can be reconfigured by a user application during run-time without loosing the host link connection. A hardware infrastructure on the FPGA and the software framework ACCFS (ACCelerator File System) on the host system is provided to the user which allow easy handling of reconfiguration and communication between the host and the FPGA. Such a system can be used for offloading compute kernels on the FPGA in high performance computing or exchanging functionality in highly available systems during run-time without loosing the host link during reconfiguration. The implementation was done for a HyperTransport coupled FPGA. The design of a HyperTransport cave was extended in such a way that it provides an infrastructure for run-time reconfigurable (RTR) modules

Ulcerating Lichen Planopilaris – Successful Treatment by Surgery

Lichen planus is a T-cell mediated autoimmune disorder affecting the skin and mucous membranes. Ulcerating lichen planus is uncommon mostly on oral and genital mucosa but not skin. Lichen planopilaris, however, is a subtype of lichen planus affection hair follicles and leading to permanent scarring alopecia. We report a case of lichen planopilaris of the scalp with multiple alopecic patches ulceration – a hitherto unreported clinical feature. The patient was treated surgically, and the defect could be closed by combined tissue advancement and extension

Fine Mapping of the 1p36 Deletion Syndrome Identifies Mutation of PRDM16 as a Cause of Cardiomyopathy

Deletion 1p36 syndrome is recognized as the most common terminal deletion syndrome. Here, we describe the loss of a gene within the deletion that is responsible for the cardiomyopathy associated with monosomy 1p36, and we confirm its role in nonsyndromic left ventricular noncompaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM). With our own data and publically available data from array comparative genomic hybridization (aCGH), we identified a minimal deletion for the cardiomyopathy associated with 1p36del syndrome that included only the terminal 14 exons of the transcription factor PRDM16 (PR domain containing 16), a gene that had previously been shown to direct brown fat determination and differentiation. Resequencing of PRDM16 in a cohort of 75 nonsyndromic individuals with LVNC detected three mutations, including one truncation mutant, one frameshift null mutation, and a single missense mutant. In addition, in a series of cardiac biopsies from 131 individuals with DCM, we found 5 individuals with 4 previously unreported nonsynonymous variants in the coding region of PRDM16. None of the PRDM16 mutations identified were observed in more than 6,400 controls. PRDM16 has not previously been associated with cardiac disease but is localized in the nuclei of cardiomyocytes throughout murine and human development and in the adult heart. Modeling of PRDM16 haploinsufficiency and a human truncation mutant in zebrafish resulted in both contractile dysfunction and partial uncoupling of cardiomyocytes and also revealed evidence of impaired cardiomyocyte proliferative capacity. In conclusion, mutation of PRDM16 causes the cardiomyopathy in 1p36 deletion syndrome as well as a proportion of nonsyndromic LVNC and DCM

Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1

Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure. Loss of Cadm1 protected mice from obesity, and tract-tracing analysis revealed Cadm1-positive innervation of POMC neurons via afferent projections originating from beyond the arcuate nucleus. Reducing Cadm1 expression in the hypothalamus and hippocampus promoted a negative energy balance and weight loss. These data identify essential roles for Cadm1-mediated neuronal input in weight regulation and provide insight into the central pathways contributing to human obesity.</p

Reliability and validity of needle biopsy evaluation of breast-abnormalities using the B-categorization – design and objectives of the Diagnosis Optimisation Study (DIOS)

<p>Abstract</p> <p>Background</p> <p>The planned nationwide implementation of mammography screening 2007 in Germany will increase the occurrence of mammographically detected breast abnormalities. These abnormalities are normally evaluated by minimal invasive core biopsy. To minimize false positive and false negative histological findings, quality assurance of the pathological evaluation of the biopsies is essential. Various guidelines for quality assurance in breast cancer diagnosis recommend applying the B-classification for histopathological categorization. However, to date there are only few studies that reported results about reliability and validity of B-classification. Therefore, objectives of our study are to determine the inter- and intraobserver variability (reliability study) and construct and predictive validity (validity study) of core biopsy evaluation of breast abnormalities. This paper describes the design and objectives of the DIOS Study.</p> <p>Methods/Design</p> <p>All consecutive asymptomatic and symptomatic women with breast imaging abnormalities who are referred to the University Hospital of Halle for core breast biopsy over a period of 24 months are eligible. According to the sample size calculation we need 800 women for the study. All patients in the study population underwent clinical and radiological examination. Core biopsy is performed by stereotactic-, ultrasound- or magnetic resonance (MR) guided automated gun method or vacuum assisted method. The histopathologic agreement (intra- and interobserver) of pathologists and the histopathologic validity will be evaluated. Two reference standards are implemented, a reference pathologist and in case of suspicious or malignant findings the histopathologic result of excision biopsy. Furthermore, a self administrated questionnaire which contains questions about potential risk factors of breast cancer, is sent to the participants approximately two weeks after core biopsy. This enables us to run a case-control-analysis (woman with breast cancer histological verified after excision are defined as cases, woman without malignant breast lesions are defined as controls) to investigate the predictive values of various risk factors on breast cancer risk.</p> <p>Conclusion</p> <p>The analysis of reliability and validity of the histopathological evaluation of core biopsy specimens of breast abnormalities is intended to provide important information needed for a high quality in breast cancer diagnostic and for planning of treatment strategies.</p

NMR Structure of Lipoprotein YxeF from Bacillus subtilis Reveals a Calycin Fold and Distant Homology with the Lipocalin Blc from Escherichia coli

The soluble monomeric domain of lipoprotein YxeF from the Gram positive bacterium B. subtilis was selected by the Northeast Structural Genomics Consortium (NESG) as a target of a biomedical theme project focusing on the structure determination of the soluble domains of bacterial lipoproteins. The solution NMR structure of YxeF reveals a calycin fold and distant homology with the lipocalin Blc from the Gram-negative bacterium E.coli. In particular, the characteristic β-barrel, which is open to the solvent at one end, is extremely well conserved in YxeF with respect to Blc. The identification of YxeF as the first lipocalin homologue occurring in a Gram-positive bacterium suggests that lipocalins emerged before the evolutionary divergence of Gram positive and Gram negative bacteria. Since YxeF is devoid of the α-helix that packs in all lipocalins with known structure against the β-barrel to form a second hydrophobic core, we propose to introduce a new lipocalin sub-family named ‘slim lipocalins’, with YxeF and the other members of Pfam family PF11631 to which YxeF belongs constituting the first representatives. The results presented here exemplify the impact of structural genomics to enhance our understanding of biology and to generate new biological hypotheses

Integrating Genome-Wide Genetic Variations and Monocyte Expression Data Reveals Trans-Regulated Gene Modules in Humans

One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs) have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns—independent component analysis—to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify major trans-acting regulators. We detected three genomic regions significantly associated with co-regulated gene modules. Association of these loci with multiple expression traits was replicated in Cardiogenics, an independent study in which expression profiles of monocytes were available in 758 subjects. The locus 12q13 (lead SNP rs11171739), previously identified as a type 1 diabetes locus, was associated with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of which (MADCAM1) is a potential candidate for mediating T1D susceptibility. The locus 12q24 (lead SNP rs653178), which has demonstrated extensive disease pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was associated to a pattern strongly correlating to blood pressure level. The strongest trans eQTL in this pattern was CRIP1, a known marker of cellular proliferation in cancer. The locus 12q15 (lead SNP rs11177644) was associated with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans eQTLs, several of them tumor-related genes. This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the mechanisms linking genome-wide association loci to disease

Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis

Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE

Execution of SPE code in an Opteron-Cell/B.E. hybrid system

It is a great research interest to integrate the Cell/B.E. processor into an AMD Opteron system. The result is a system benefiting from the advantages of both processors: the high computational power of the Cell/B.E. and the high I/O throughput of the Opteron. The task of this diploma thesis is to accomplish, that Cell-SPU code initially residing on the Opteron could be executed on the Cell under the GNU/Linux operating system. However, the SPUFS (Synergistic Processing Unit File System), provided from STI (Sony, Toshiba, IBM), does exactly the same thing on the Cell. The Cell is a combination of a PowerPC core and Synergistic Processing elements (SPE). The main work is to analyze the SPUFS and migrate it to the Opteron System. The result of the migration is a project called RSPUFS (Remote Synergistic Processing Unit File System), which provides nearly the same interface as SPUFS on the Cell side. The differences are caused by the TCP/IP link between Opteron and Cell, where no Remote Direct Memory Access (RDMA) is available. So it is not possible to write synchronously to the local store of the SPEs. The synchronization occurs implicitly before executing the Cell-SPU code. But not only semantics have changed: to access the XDR memory RSPUFS extends SPUFS with a special XDR interface, where the application can map the XDR into the local address space. The application must be aware of synchronization with an explicit call of the provided ''xdr\_sync'' routine. Another difference is, that RSPUFS does not support the gang principle of SPUFS, which is necessary to set the affinity between the SPEs. This thesis deals not only with the operating system part, but also with a library called ''libspe''. Libspe provides a wrapper around the SPUFS system calls. It is essential to port this library to the Opteron, because most of the Cell applications use it. Libspe is not only a wrapper, it saves a lot of work for the developer as well, like loading the Cell-SPU code or managing the context and system calls initiated by the SPE. Thus it has to be ported, too. The result of the work is, that an application can link against the modified libspe on the Opteron gaining direct access to the Synergistic Processor Elements

Design of on-chip RFID transponder antennas

Manufacturing the transponder antenna directly on top of the silicon substrate of the transponder integrated circuit has the advantage of a cheap and miniaturized transponder tag. No additional mounting and joining processes is necessary. For passive transponder tags the complete system can be fabricated using the standard CMOS process. The size of the antenna depends on the wavelength of the transmission frequency. In the presented project a frequency of 61 GHz was chosen. This makes it possible to design a chip of about one square millimeter. In modern silicon technologies, there is more than enough space behind the area of the antenna for the necessary electronic circuit. Regarding the high frequency and the small antenna diameter, only a very small amount of energy is expected to be available for powering the electronic circuit. Therefore, only identification and authentication with embedded cryptographic functions are planned for applications with a reading range of about five millimeters in the first steps. More energy-critical functions like passive sensor measurements will be addressed in the future. In general the design process of the transponder antenna is an iterative process based on high frequency electromagnetic field simulations. The process is similar to the design of customized UHF antennas. The antenna type is a slot antenna, consisting of the antenna slot itself and a surrounding frame. The conductive substrate material results in unavoidable losses. However, an antenna gain of 1.5 dB is achieved. The antenna gain can be boosted up to 5.6 dB with a metallic backplane on the chip with the right thickness. Additional losses, originating from the metallic filling structures in the circuit are already included in these numbers. The filling structures are necessary for technological reasons in the manufacturing process: the metallic covering has to be between a minimum and a maximum value. The filling area behind the frame does not reduce the antenna quality. In this area also the electronic circuit is placed. The filling directly below the antenna structure itself should be at the minimum allowed value. A critical point is the influence of the filling to the antenna impedance parameters. These parameters have to be fitted to the input parameters of the electronic circuit for an optimal match. Unfortunately the filling structures are restricted by the technology rules and are too complex to be simulated in the field simulations. On the other hand, the antenna and the electronic parts are manufactured in the same steps. A post-process matching is impossible. Therefore, a first antenna on silicon substrate is manufactured and verified to find differences between simulation and real measurement. This will help to find a simplified model of the filling structures in the simulation and to allow a spot landing of the antenna impedance to the complex conjugated circuit impedance after manufacturing