1,875 research outputs found
Predictors of Visual Acuity After Treatment of Neovascular Age-Related Macular Degeneration â Current Perspectives
Drop Traffic in Microfluidic Ladder Networks with Fore-Aft Structural Asymmetry
We investigate the dynamics of pairs of drops in microfluidic ladder networks
with slanted bypasses, which break the fore-aft structural symmetry. Our
analytical results indicate that unlike symmetric ladder networks, structural
asymmetry introduced by a single slanted bypass can be used to modulate the
relative drop spacing, enabling them to contract, synchronize, expand, or even
flip at the ladder exit. Our experiments confirm all these behaviors predicted
by theory. Numerical analysis further shows that while ladder networks
containing several identical bypasses are limited to nearly linear
transformation of input delay between drops, mixed combination of bypasses can
cause significant non-linear transformation enabling coding and decoding of
input delays.Comment: 4 pages, 5 figure
Extraction of bodily features for gait recognition and gait attractiveness evaluation
This is the author's accepted manuscript. The final publication is available at Springer via
http://dx.doi.org/10.1007/s11042-012-1319-2. Copyright @ 2012 Springer.Although there has been much previous research on which bodily features are most important in gait analysis, the questions of which features should be extracted from gait, and why these features in particular should be extracted, have not been convincingly answered. The primary goal of the study reported here was to take an analytical approach to answering these questions, in the context of identifying the features that are most important for gait recognition and gait attractiveness evaluation. Using precise 3D gait motion data obtained from motion capture, we analyzed the relative motions from different body segments to a root marker (located on the lower back) of 30 males by the fixed root method, and compared them with the original motions without fixing root. Some particular features were obtained by principal component analysis (PCA). The left lower arm, lower legs and hips were identified as important features for gait recognition. For gait attractiveness evaluation, the lower legs were recognized as important features.Dorothy Hodgkin Postgraduate Award and HEFCE
Problematic mukbang watching and its relationship to disordered eating and internet addiction: a pilot study among emerging adult mukbang watchers
Internet technology has facilitated the use of a wide variety of different activities and applications in online contexts. One such activity is watching mukbang (i.e., watching videos of âeating broadcastsâ where someone eats a large amount of food while interacting with viewers). In the present study, the relationship of problematic mukbang watching with disordered eating and internet addiction was examined. Participants were 140 emerging adults who watched mukbang at least once in the past 30 days (66% female; Mageâ=â21.66, SDâ=â1.88, rangeâ=â19â29 years). Structural equation modeling indicated that problematic mukbang watching was positively associated with both disordered eating and internet addiction. The present study is the first to explore the predictive role of problematic mukbang watching on adverse consequences, and suggests that mukbang watching may be problematic for a minority of emerging adults and that problematic mukbang watching warrants further examination of its impact on mental health and wellbeing
Clinical decision support of therapeutic drug monitoring of phenytoin: measured versus adjusted phenytoin plasma concentrations
<p>Abstract</p> <p>Background</p> <p>Therapeutic drug monitoring of phenytoin by measurement of plasma concentrations is often employed to optimize clinical efficacy while avoiding adverse effects. This is most commonly accomplished by measurement of total phenytoin plasma concentrations. However, total phenytoin levels can be misleading in patients with factors such as low plasma albumin that alter the free (unbound) concentrations of phenytoin. Direct measurement of free phenytoin concentrations in plasma is more costly and time-consuming than determination of total phenytoin concentrations. An alternative to direct measurement of free phenytoin concentrations is use of the Sheiner-Tozer equation to calculate an adjusted phenytoin that corrects for the plasma albumin concentration. Innovative medical informatics tools to identify patients who would benefit from adjusted phenytoin calculations or from laboratory measurement of free phenytoin are needed to improve safety and efficacy of phenytoin pharmacotherapy. The electronic medical record for an academic medical center was searched for the time period from August 1, 1996 to November 30, 2010 for patients who had total phenytoin and free phenytoin determined on the same blood draw, and also a plasma albumin measurement within 7 days of the phenytoin measurements. The measured free phenytoin plasma concentration was used as the gold standard.</p> <p>Results</p> <p>In this study, the standard Sheiner-Tozer formula for calculating an estimated (adjusted) phenytoin level more frequently underestimates than overestimates the measured free phenytoin relative to the respective therapeutic ranges. Adjusted phenytoin concentrations provided superior classification of patients than total phenytoin measurements, particularly at low albumin concentrations. Albumin plasma concentrations up to 7 days prior to total phenytoin measurements can be used for adjusted phenytoin concentrations.</p> <p>Conclusions</p> <p>The results suggest that a measured free phenytoin should be obtained where possible to guide phenytoin dosing. If this is not feasible, then an adjusted phenytoin can supplement a total phenytoin concentration, particularly for patients with low plasma albumin.</p
Silicon particles as trojan horses for potential cancer therapy
[EN] Background: Porous silicon particles (PSiPs) have been used extensively as drug delivery systems, loaded with chemical species for disease treatment. It is well known from silicon producers that silicon is characterized by a low reduction potential, which in the case of PSiPs promotes explosive oxidation reactions with energy yields exceeding that of trinitrotoluene (TNT). The functionalization of the silica layer with sugars prevents its solubilization, while further functionalization with an appropriate antibody enables increased bioaccumulation inside selected cells. Results: We present here an immunotherapy approach for potential cancer treatment. Our platform comprises the use of engineered silicon particles conjugated with a selective antibody. The conceptual advantage of our system is that after reaction, the particles are degraded into soluble and excretable biocomponents. Conclusions: In our study, we demonstrate in particular, specific targeting and destruction of cancer cells in vitro. The fact that the LD50 value of PSiPs-HER-2 for tumor cells was 15-fold lower than the LD50 value for control cells demonstrates very high in vitro specificity. This is the first important step on a long road towards the design and development of novel chemotherapeutic agents against cancer in general, and breast cancer in particular.The authors acknowledge financial support from the following projects FIS2009-07812, MAT2012-35040, PROMETEO/2010/043, CTQ2011-23167, CrossSERS, FP7 MC-IEF 329131, and HSFP (project RGP0052/2012) and Medcom Tech SA. Xiang Yu acknowledges support by the Chinese government (CSC, Nr. 2010691036).Fenollosa Esteve, R.; Garcia-Rico, E.; Alvarez, S.; Alvarez, R.; Yu, X.; Rodriguez, I.; Carregal-Romero, S.... (2014). Silicon particles as trojan horses for potential cancer therapy. 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Addressing Reported Pro-Apoptotic Functions of NF-ÎșB: Targeted Inhibition of Canonical NF-ÎșB Enhances the Apoptotic Effects of Doxorubicin
The ability of the transcription factor NF-ÎșB to upregulate anti-apoptotic proteins has been linked to the chemoresistance of solid tumors to standard chemotherapy. In contrast, recent studies have proposed that, in response to doxorubicin, NF-ÎșB can be pro-apoptotic through repression of anti-apoptotic target genes. However, there is little evidence analyzing the outcome of NF-ÎșB inhibition on the cytotoxicity of doxorubicin in studies describing pro-apoptotic NF-ÎșB activity. In this study, we further characterize the activation of NF-ÎșB in response to doxorubicin and evaluate its role in chemotherapy-induced cell death in sarcoma cells where NF-ÎșB is reported to be pro-apoptotic. Doxorubicin treatment in U2OS cells induced canonical NF-ÎșB activity as evidenced by increased nuclear accumulation of phosphorylated p65 at serine 536 and increased DNAâbinding activity. Co-treatment with a small molecule IKKÎČ inhibitor, Compound A, abrogated this response. RTâPCR evaluation of anti-apoptotic gene expression revealed that doxorubicin-induced transcription of cIAP2 was inhibited by Compound A, while doxorubicin-induced repression of other anti-apoptotic genes was unaffected by Compound A or siRNA to p65. Furthermore, the combination of doxorubicin and canonical NF-ÎșB inhibition with Compound A or siRNA to p65 resulted in decreased cell viability measured by trypan blue staining and MTS assay and increased apoptosis measured by cleaved poly (ADP-ribose) polymerase and cleaved caspase 3 when compared to doxorubicin alone. Our results demonstrate that doxorubicin-induced canonical NF-ÎșB activity associated with phosphorylated p65 is anti-apoptotic in its function and that doxorubicin-induced repression of anti-apoptotic genes occurs independent of p65. Therefore, combination therapies incorporating NF-ÎșB inhibitors together with standard chemotherapies remains a viable method to improve the clinical outcomes in patients with advanced stage malignancies
A Generic Platform for Cellular Screening Against Ubiquitin Ligases
Ubiquitin signalling regulates most aspects of cellular life, thus deregulation of ubiquitylation has been linked with a number of diseases. E3 ubiquitin ligases provide substrate selectivity in ubiquitylation cascades and are therefore considered to be attractive targets for developing therapeutic molecules. In contrast to established drug target classes, such as protein kinases, GPCRs, hormone receptors and ion channels, ubiquitin drug discovery is in its early stages. This is, in part, due to the complexity of the ubiquitylation pathways and the lack of robust quantitative technologies that allow high-throughput screening of inhibitors. Here we report the development of a Ubiquitin Ligase Profiling system, which is a novel and generic cellular technology designed to facilitate identification of selective inhibitors against RING type E3 ubiquitin ligases. Utilization of this system requires a single co-transfection of cells with assay vectors, thereby enabling readout of E3 ubiquitin ligase catalytic activity within the cellular environment. Therefore, our robust high-throughput screening platform offers novel opportunities for the development of inhibitors against this difficult-to-target E3 ligase enzyme class
A novel mechanism of immunity controls the onset of cinnamycin biosynthesis in Streptomyces cinnamoneus DSM 40646
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