284 research outputs found

    Adaptive RF front-ends : providing resilience to changing environments

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    Design considerations for RF power amplifiers demonstrated through a GSM/EDGE power amplifier module

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    This paper describes the design considerations for RF power amplifiers in general, including trends in systems, linearity and efficiency, the PA environment, implementation is sues and technology. As an example a triple-band (900/1800/1900MHz) dual mode (GSMIEdge) power amplifier module is described in this article. The RF transistors and biasing circuitry are implemented in silicon bipolar technology. A multi-layer LTCC substrate is used as carrier

    Sclerostin: Current Knowledge and Future Perspectives

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    In recent years study of rare human bone disorders has led to the identification of important signaling pathways that regulate bone formation. Such diseases include the bone sclerosing dysplasias sclerosteosis and van Buchem disease, which are due to deficiency of sclerostin, a protein secreted by osteocytes that inhibits bone formation by osteoblasts. The restricted expression pattern of sclerostin in the skeleton and the exclusive bone phenotype of good quality of patients with sclerosteosis and van Buchem disease provide the basis for the design of therapeutics that stimulate bone formation. We review here current knowledge of the regulation of the expression and formation of sclerostin, its mechanism of action, and its potential as a bone-building treatment for patients with osteoporosis

    Optimizing adalimumab treatment in psoriasis with concomitant methotrexate (OPTIMAP): study protocol for a pragmatic, single-blinded, investigator-initiated randomized controlled trial

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    markdownabstract__Background:__ The introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases. __Methods:__ This is an investigator-initiated, multicenter randomized controlled trial (RCT) designed to compare the combination treatment of adalimumab and methotrexate with adalimumab monotherapy in patients with psoriasis. The primary outcome is adalimumab drug survival at week 49. Other outcomes include improvement in disease severity and quality of life, tolerability, and safety. Moreover, anti-adalimumab antibodies and adalimumab serum concentrations will be measured and correlations between genotypes and clinical outcomes will be assessed. Patient recruitment started in March 2014. Up to now, 36 patients have been randomized. Many more patients have been (pre)screened. A total of 93 patients is desired to meet an adequate sample size. In our experience, the main limitation for recruitment is prior adalimumab therapy and intolerability or toxicity for methotrexate in the past. __Discussion:__ OPTIMAP is the first RCT to examine combination therapy with adalimumab and methotrexate in a psoriasis population. With data derived from this study we expect to provide valuable clinical data on long-term treatment outcomes. These data will be supported by assessment of the impact of concomitant methotrexate on adalimumab pharmacokinetics. Furthermore, the influence of several single nucleotide polymorphisms on adalimumab response will be analyzed in order to support the development of a more personalized approach for this targeted therapy. Trial registration:NTR4499. Registered on 7 April 2014

    Recognizing Emotions in a Foreign Language

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    Expressions of basic emotions (joy, sadness, anger, fear, disgust) can be recognized pan-culturally from the face and it is assumed that these emotions can be recognized from a speaker's voice, regardless of an individual's culture or linguistic ability. Here, we compared how monolingual speakers of Argentine Spanish recognize basic emotions from pseudo-utterances ("nonsense speech") produced in their native language and in three foreign languages (English, German, Arabic). Results indicated that vocal expressions of basic emotions could be decoded in each language condition at accuracy levels exceeding chance, although Spanish listeners performed significantly better overall in their native language ("in-group advantage"). Our findings argue that the ability to understand vocally-expressed emotions in speech is partly independent of linguistic ability and involves universal principles, although this ability is also shaped by linguistic and cultural variables

    Myeloma cells suppress osteoblasts through sclerostin secretion

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    Wingless-type (Wnt) signaling through the secretion of Wnt inhibitors Dickkopf1, soluble frizzled-related protein-2 and -3 has a key role in the decreased osteoblast (OB) activity associated with multiple myeloma (MM) bone disease. We provide evidence that another Wnt antagonist, sclerostin, an osteocyte-expressed negative regulator of bone formation, is expressed by myeloma cells, that is, human myeloma cell lines (HMCLs) and plasma cells (CD138+ cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. We demonstrated that BM stromal cells (BMSCs), differentiated into OBs and co-cultured with HMCLs showed, compared with BMSCs alone, reduced expression of major osteoblastic-specific proteins, decreased mineralized nodule formation and attenuated the expression of members of the activator protein 1 transcription factor family (Fra-1, Fra-2 and Jun-D). Moreover, in the same co-culture system, the addition of neutralizing anti-sclerostin antibodies restored OB functions by inducing nuclear accumulation of β-catenin. We further demonstrated that the upregulation of receptor activator of nuclear factor κ-B ligand and the downregulation of osteoprotegerin in OBs were also sclerostin mediated. Our data indicated that sclerostin secretion by myeloma cells contribute to the suppression of bone formation in the osteolytic bone disease associated to MM

    The Interface Region Imaging Spectrograph (IRIS)

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    The Interface Region Imaging Spectrograph (IRIS) small explorer spacecraft provides simultaneous spectra and images of the photosphere, chromosphere, transition region, and corona with 0.33-0.4 arcsec spatial resolution, 2 s temporal resolution and 1 km/s velocity resolution over a field-of-view of up to 175 arcsec x 175 arcsec. IRIS was launched into a Sun-synchronous orbit on 27 June 2013 using a Pegasus-XL rocket and consists of a 19-cm UV telescope that feeds a slit-based dual-bandpass imaging spectrograph. IRIS obtains spectra in passbands from 1332-1358, 1389-1407 and 2783-2834 Angstrom including bright spectral lines formed in the chromosphere (Mg II h 2803 Angstrom and Mg II k 2796 Angstrom) and transition region (C II 1334/1335 Angstrom and Si IV 1394/1403 Angstrom). Slit-jaw images in four different passbands (C II 1330, Si IV 1400, Mg II k 2796 and Mg II wing 2830 Angstrom) can be taken simultaneously with spectral rasters that sample regions up to 130 arcsec x 175 arcsec at a variety of spatial samplings (from 0.33 arcsec and up). IRIS is sensitive to emission from plasma at temperatures between 5000 K and 10 MK and will advance our understanding of the flow of mass and energy through an interface region, formed by the chromosphere and transition region, between the photosphere and corona. This highly structured and dynamic region not only acts as the conduit of all mass and energy feeding into the corona and solar wind, it also requires an order of magnitude more energy to heat than the corona and solar wind combined. The IRIS investigation includes a strong numerical modeling component based on advanced radiative-MHD codes to facilitate interpretation of observations of this complex region. Approximately eight Gbytes of data (after compression) are acquired by IRIS each day and made available for unrestricted use within a few days of the observation.Comment: 53 pages, 15 figure

    Extracorporeal shock waves down-regulate the expression of interleukin-10 and tumor necrosis factor-alpha in osteoarthritic chondrocytes

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    <p>Abstract</p> <p>Background</p> <p>The purpose of this study was to investigate the effects of extra corporeal shock waves (ESW) therapy on the metabolism of healthy and osteoarthritic human chondrocytes, and particularly on the expression of IL-10, TNF-alpha and beta1 integrin.</p> <p>Methods</p> <p>Human adult articular cartilage was obtained from 9 patients (6 male and 3 females), with primary knee osteoarthritis (OA), undergoing total joint replacement and from 3 young healthy donors (HD) (2 males, 1 female) with joint traumatic fracture. After isolation, chondrocytes underwent ESW treatment (electromagnetic generator system, MINILITH SL1, STORZ MEDICAL) at different parameters of impulses, energy levels and energy flux density. After that, chondrocytes were cultured in 24-well plate in DMEM supplemented with 10% FCS for 48 hours and then beta<sub>1 </sub>integrin surface expression and intracellular IL-10 and TNF-alpha levels were evaluated by flow-cytometry.</p> <p>Results</p> <p>At baseline, osteoarthritic chondrocytes expressed significantly lower levels of beta1 integrin and higher levels and IL-10 and TNF-alpha levels. Following ESW application, while beta1 integrin expression remain unchanged, a significant decrease of IL-10 and TNF-alpha intracellular levels was observed both in osteoarthritic and healthy chondrocytes. IL-10 levels decreased at any impulses and energy levels, while a significant reduction of TNF-alpha was mainly found at middle energies.</p> <p>Conclusion</p> <p>Our study confirmed that osteoarthritic chondrocytes express low beta<sub>1 </sub>integrin and high TNF-alpha and IL-10 levels. Nonetheless, ESW treatment application down-regulate the intracellular levels of TNF-alpha and IL-10 by chondrocytes, suggesting that ESW might restore TNF-alpha and IL-10 production by osteoarthritic chondrocytes at normal levels. However, further in vivo and in vitro studies are necessary to establish if ESW can represent a viable option in the treatment of OA.</p

    Talking Less during Social Interactions Predicts Enjoyment: A Mobile Sensing Pilot Study

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    Can we predict which conversations are enjoyable without hearing the words that are spoken? A total of 36 participants used a mobile app, My Social Ties, which collected data about 473 conversations that the participants engaged in as they went about their daily lives. We tested whether conversational properties (conversation length, rate of turn taking, proportion of speaking time) and acoustical properties (volume, pitch) could predict enjoyment of a conversation. Surprisingly, people enjoyed their conversations more when they spoke a smaller proportion of the time. This pilot study demonstrates how conversational properties of social interactions can predict psychologically meaningful outcomes, such as how much a person enjoys the conversation. It also illustrates how mobile phones can provide a window into everyday social experiences and well-being

    Wnt signaling and orthopedics, an overview

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    Wnt signaling is a ubiquitous system for intercellular communication, with multiple functions during development and in homeostasis of the body. It comprises several ligands, receptors, and inhibitors. Some molecules, such as sclerostin, appear to have bone-specific functions, and can be targeted by potential drugs. Now, ongoing clinical trials are testing these drugs as treatments for osteoporosis. Animal studies have also suggested that these drugs can accelerate fracture healing and implant fixation. This brief overview focuses on currently available information on the effects of manipulations of Wnt signaling on bone healing
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