Surface coil arrays brought in proximity of the human body enhance the performance of an MRI measurement both in speed and signal-to-noise ratio. However, size and cabling of such arrays can ...deteriorate the performance of the imaging, or put at risk the safety of the patient. An integrated CMOS direct conversion receiver is proposed, to be placed directly onto the receive coil and enhance the usability. The integrated design needs to preserve the high performance (both in silent noise figure and dynamic range) of discrete solutions, which benefit from dedicated technologies for every receiver sub-block. To exploit the full potential of a coil array, the receiver on each module must also minimize the coupling to nearby modules. The PCB carrying the ASIC will be fabricated with flexible substrate materials to further enhance the wearability and comfort for the patient. Such a modular approach together with the transmission of data over optical fibers results in a lightweight system that allows us to achieve fast development times.
Autoantibodies against amyloid beta (A beta) peptide found in patients with Alzheimer's disease (AD) also occur naturally in the general population independently of the cognitive status.
We compared ...serum A beta(1-42) autoantibody levels (A beta(1-42)-AL) of 96 AD patients and 30 healthy elderly control subjects (HC), assessing their diagnostic value for AD with a newly developed immunoprecipitation assay with radiolabeled A beta(1-42) peptide.
We found a highly significant decrease of A beta(1-42)-AL in AD patients (p = .001) independently of age, cognitive status, and apolipoprotein E epsilon4 carrier status. Amyloid beta(1-42) autoantibody levels were correlated with gender in AD, with a higher level occurring in women. When A beta(1-42) autoantibody sensitivity (specificity) was set >80%, specificity (sensitivity) was below 50% to correctly allocate patients and healthy control subjects.
Our data indicate a potentially pathophysiologic decrease of serum A beta(1-42) antibodies in AD. Amyloid beta(1-42) antibodies in the serum alone, however, seem not to be useful as a diagnostic marker of AD.
Hydrogenophaga intermedia strain S1 and Agrobacterium radiobacter strain S2 form a mixed bacterial culture which degrades sulfanilate (4-aminobenzenesulfonate) by a novel variation of the ...beta-ketoadipate pathway via 4-sulfocatechol and 3-sulfomuconate. It was previously proposed that the further metabolism of 3-sulfomuconate is catalysed by modified 3-carboxy-cis,cis-muconate-lactonizing enzymes (CMLEs) and that these 'type 2' enzymes were different from the conventional CMLEs ('type 1') from the protocatechuate pathway in their ability to convert 3-sulfomuconate in addition to 3-carboxy-cis,cis-muconate. In the present study the genes for two CMLEs (pcaB2S1 and pcaB2S2) were cloned from H. intermedia S1 and A. radiobacter S2, respectively. In both strains, these genes were located close to the previously identified genes encoding the 4-sulfocatechol-converting enzymes. The gene products of pcaB2S1 and pcaB2S2 were therefore tentatively identified as type 2 enzymes involved in the metabolism of 3-sulfomuconate. The genes were functionally expressed and the gene products were shown to convert 3-carboxy-cis,cis-muconate and 3-sulfomuconate. 4-Carboxymethylene-4-sulfo-but-2-en-olide (4-sulfomuconolactone) was identified by HPLC-MS as the product, which was enzymically formed from 3-sulfomuconate. His-tagged variants of both CMLEs were purified and compared with the CMLE from the protocatechuate pathway of Pseudomonas putida PRS2000 for the conversion of 3-carboxy-cis,cis-muconate and 3-sulfomuconate. The CMLEs from the 4-sulfocatechol pathway converted 3-sulfomuconate with considerably higher activities than 3-carboxy-cis,cis-muconate. Also the CMLE from P. putida converted 3-sulfomuconate, but this enzyme demonstrated a clear preference for 3-carboxy-cis,cis-muconate as substrate. Thus it was demonstrated that in the 4-sulfocatechol pathway, distinct CMLEs are formed, which are specifically adapted for the preferred conversion of sulfonated substrates.
The TERT gene encodes for the reverse transcriptase activity of the telomerase complex and mutations in TERT can lead to dysfunctional telomerase activity resulting in diseases such as dyskeratosis ...congenita (DKC). Here, we describe a novel TERT mutation at position T1129P leading to DKC with progressive bone marrow (BM) failure in homozygous members of a consanguineous family. BM hematopoietic stem cells (HSCs) of an affected family member were 300-fold reduced associated with a significantly impaired colony forming capacity in vitro and impaired repopulation activity in mouse xenografts. Recent data in yeast suggested improved cellular checkpoint controls by mTOR inhibition preventing cells with short telomeres or DNA damage from dividing. To evaluate a potential therapeutic option for the patient, we treated her primary skin fibroblasts and BM HSCs with the mTOR inhibitor rapamycin. This led to prolonged survival and decreased levels of senescence in T1129P mutant fibroblasts. In contrast, the impaired HSC function could not be improved by mTOR inhibition, as colony forming capacity and multilineage engraftment potential in xenotransplanted mice remained severely impaired. Thus, rapamycin treatment did not rescue the compromised stem cell function of TERTT1129P mutant patient HSCs and outlines limitations of a potential DKC therapy based on rapamycin.
Surface coil arrays brought in proximity of the human body enhance the performance of an MRI measurement both in speed and signal-to-noise ratio. However, size and cabling of such arrays can ...deteriorate the performance of the imaging, or put at risk the safety of the patient. An integrated CMOS direct conversion receiver is proposed, to be placed directly onto the receive coil and enhance the usability. The integrated design needs to preserve the high performance (both in silent noise figure and dynamic range) of discrete solutions, which benefit from dedicated technologies for every receiver sub-block. To exploit the full potential of a coil array, the receiver on each module must also minimize the coupling to nearby modules. The PCB carrying the ASIC will be fabricated with flexible substrate materials to further enhance the wearability and comfort for the patient. Such a modular approach together with the transmission of data over optical fibers results in a lightweight system that allows us to achieve fast development times.
Science Communication Leßmöllmann, Annette; Dascal, Marcelo; Gloning, Thomas
2019, Letnik:
17
eBook
This handbooks series aims to integrate knowledge of communication structures and processes. It is global in orientation, dedicated to cultural and epistemological diversity as well as different ...scholarly approaches. The series features volumes on 'messages, codes and channels', 'mode of address: communication situations and context', 'methodology in communication science' and 'application areas'. The latter features volumes devoted to a large range of specialist areas of communication science. The series as a whole aims at meeting the needs of undergraduates, postgraduates, academics and researchers across the area of communication studies.
Abstract 358▪▪This icon denotes an abstract that is clinically relevant.
During the induction of normal immune responses, activated B cells secrete the chemokines CCL3 and CCL4 for recruitment of ...regulatory T cells (Nat Immunol. 2:1126-32, 2001). This may represent a mechanism enabling cognate interactions between rare antigen-specific T and B cells. We previously reported that CCL3 and CCL4 RNA and protein are induced in CLL cells by co-culture with nurselike cells and after B cell antigen receptor (BCR) cross-linking (Blood 113:3050-8, 2009). We found higher levels of CCL3 and CCL4 in ZAP-70 positive cases, and CCL3 and CCL4 secretion was abrogated by the Syk inhibitor R406. These findings suggest that CCL3/CCL4 secretion by CLL cells correlates with the signaling capacity of the BCR. Also, we previously noticed higher plasma levels of CCL3 and CCL4 in CLL patients, when compared to healthy controls.
In this study, we measured CCL3 and CCL4 plasma levels by ELISA in 351 CLL patients, and correlated CCL3 and CCL4 levels with various prognostic markers, including RAI stage, immunoglobulin heavy chain variable region gene (IgVH) mutational status, ZAP-70, β2 microglobulin, CD38, white blood count (WBC), and cytogenetic subgroups. We found that the concentrations of CCL3 and CCL4 were significantly higher in plasma samples from CLL patients who had CLL cells that used unmutated IgVH genes or that expressed ZAP-70 or CD38, or who had an advanced stage of their disease (see Table 1). For example, the mean CCL3 plasma level was 56.4 ± 8.8 pg/ml in patients with CLL cells that used unmutated IgVH (mean ± SEM, n=123) versus 14.5 ± 2.4 in patients with CLL cells that used mutated IgVH (mean ± SEM, n=139, p<0.001). The mean CCL4 level was 171.4 ± 26.3 in patients that had CLL cells that used unmutated IgVH and 92.5 ± 17.5 in patients that had CLL that expressed mutated IgVH. On the other hand, the relative absolute white cell count or presence of chromosomal abnormalities did not correlate with high plasma levels of CCL3 or CCL4. Immunohistochemistry revealed that CCL4 was predominantly expressed in proliferation centers in approximately 50% of the cases. Currently, we are evaluating whether high plasma levels of CCL3 and/or CCL4 are associated with a relatively short time from diagnosis to requiring initial treatment by the IWCLL-working group criteria. Also, we are exploring whether high plasma levels of CCL3 or CCL4 are associated with high proportions of infiltrating T cells in proliferation centers.
Display omitted
These studies suggest that patients can be stratified by their relative plasma levels of CCL3 and/or CCL4 and that high plasma-levels of theses chemokines define a characteristic that may be associated with aggressive disease.
No relevant conflicts of interest to declare.
The new IEEE 11073 service-oriented device connectivity (SDC) standard proposals for networked point-of-care and surgical devices constitutes the basis for improved interoperability due to its ...independence of vendors. To accelerate the distribution of the standard a reference implementation is indispensable. However, the implementation of such a framework has to overcome several non-trivial challenges. First, the high level of complexity of the underlying standard must be reflected in the software design. An efficient implementation has to consider the limited resources of the underlying hardware. Moreover, the frameworks purpose of realizing a distributed system demands a high degree of reliability of the framework itself and its internal mechanisms. Additionally, a framework must provide an easy-to-use and fail-safe application programming interface (API). In this work, we address these challenges by discussing suitable software engineering principles and practical coding guidelines. A descriptive model is developed that identifies key strategies. General feasibility is shown by outlining environments in which our implementation has been utilized.
PDF
