Empirical model for quasi direct current interruption with a convoluted arc

This contribution considers various aspects of a quasi direct current, convoluted arc produced by a magnetic field (B-field) connected in parallel with an RLC circuit that have not been considered in combination. These aspects are the arc current limitation due to the arc convolution, changes in arc resistance due to the B-field and material ablation, and the relative significance of the RLC circuit in producing an artificial current zero. As a result, it has been possible to produce an empirical equation for predicting the current interruption capability in terms of the B-field magnitude and RLC components

Overload robust IGBT design for SSCB application

This paper presents an optimised power semiconductor architecture based on the CIGBT approach to be used in solid-state circuit breaker (SSCB) applications where the conduction losses have to be as low as possible without compromising the forward voltage blocking capability. Indeed, a high overcurrent turn-off and short-circuit withstand capabilities have to be ensured. Starting from a standard NPT-IGBT design for switching applications, the results show that the proposed device, which is optimised by the application of the individual clustered concept, offers a reduction in conduction losses of 13%, without compromise on voltage blocking capability. An original design solution is implemented to further ensure short-circuit and overload turn-off capabilities at maximum ambient temperature and twice the nominal rated current

Telomerase inhibition by siRNA causes senescence and apoptosis in Barrett's adenocarcinoma cells: mechanism and therapeutic potential

BACKGROUND: In cancer cells, telomerase induction helps maintain telomere length and thereby bypasses senescence and provides enhanced replicative potential. Chemical inhibitors of telomerase have been shown to reactivate telomere shortening and cause replicative senescence and apoptotic cell death of tumor cells while having little or no effect on normal diploid cells. RESULTS: We designed siRNAs against two different regions of telomerase gene and evaluated their effect on telomere length, proliferative potential, and gene expression in Barrett's adenocarcinoma SEG-1 cells. The mixture of siRNAs in nanomolar concentrations caused a loss of telomerase activity that appeared as early as day 1 and was essentially complete at day 3. Inhibition of telomerase activity was associated with marked reduction in median telomere length and complete loss of detectable telomeres in more than 50% of the treated cells. Telomere loss caused senescence in 40% and apoptosis in 86% of the treated cells. These responses appeared to be associated with activation of DNA sensor HR23B and subsequent activation of p53 homolog p73 and p63 and E2F1. Changes in these gene regulators were probably the source of observed up-regulation of cell cycle inhibitors, p16 and GADD45. Elevated transcript levels of FasL, Fas and caspase 8 that activate death receptors and CARD 9 that interacts with Bcl10 and NFKB to enhance mitochondrial translocation and activation of caspase 9 were also observed. CONCLUSION: These studies show that telomerase siRNAs can cause effective suppression of telomerase and telomere shortening leading to both cell cycle arrest and apoptosis via mechanisms that include up-regulation of several genes involved in cell cycle arrest and apoptosis. Telomerase siRNAs may therefore be strong candidates for highly selective therapy for chemoprevention and treatment of Barrett's adenocarcinoma

A mechanistic model of tau amyloid aggregation based on direct observation of oligomers.

Protein aggregation plays a key role in neurodegenerative disease, giving rise to small oligomers that may become cytotoxic to cells. The fundamental microscopic reactions taking place during aggregation, and their rate constants, have been difficult to determine due to lack of suitable methods to identify and follow the low concentration of oligomers over time. Here we use single-molecule fluorescence to study the aggregation of the repeat domain of tau (K18), and two mutant forms linked with familial frontotemporal dementia, the deletion mutant ΔK280 and the point mutant P301L. Our kinetic analysis reveals that aggregation proceeds via monomeric assembly into small oligomers, and a subsequent slow structural conversion step before fibril formation. Using this approach, we have been able to quantitatively determine how these mutations alter the aggregation energy landscape.D.K. acknowledges funding from the Wellcome Trust (WT089703) and MRC. E.M. acknowledges funding from the Wellcome Trust (WT089703), DZNE and Max-Planck-Society. M.K. acknowledges fellowships from the Danish research council and the Lundbeck Foundation. N.S. and M.H.H acknowledge funding from the Augustus Newman foundation. G.A.G is funded by the Schiff Foundation. T.P.J.K acknowledges funding from the ERC, Augustus Newman Foundation and the BBSRC.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/ncomms802

Single left coronary artery with origin of right coronary artery from left circumflex: a case report

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: A 40-years-old female presented with intermittent chest pain and dyspnea on exertion. Case Presentation: Electrocardiography showed sinus rhythm with ST-depression in inferior and lateral leads. Subsequent exercise treadmill testing revealed significant ST-depression in V4–V5 and V6 leads. Coronary angiography later showed a single left coronary artery with right coronary artery arising from left circumflex artery, a rare anomaly of coronary arteries. No atheromatous lesion was seen during angiography. Conclusion: The dignosis of this anomaly is importsnt because the symptoms cannot be differentiated from atherosclerotic coronary artery disease. Case presentation A 40-years-old female was admitted to the hospital with intermittent substernal chest pain and dyspnea. She visited our outpatient clinic because of exacerbation o

Home-based system for physical activity monitoring in patients with multiple sclerosis (Pilot study)

Background Limitations in physical activity are considered as a key problem in patients with multiple sclerosis (PwMS). Contemporary methods to assess the level of physical activity in PwMS are regular clinical observation. However, these methods either rely on high recall and accurate reporting from the patients (e.g. self-report questionnaires), or they are conducted during a particular clinical assessment with predefined activities. Therefore, the main aim of this pilot study was to develop an objective method to gather information about the real type and intensity of daily activities performed by PwMS in every-day living situations using an accelerometer. Furthermore, the accelerometer-derived measures are investigated regarding their potential for discriminating between different MS groups. Methods Eleven PwMS that were able to walk independently (EDSS&#8201;&#8804;&#8201;5) were divided into two groups: mild disability (EDSS 1&#8211;2.5; n&#8201;=&#8201;6) and moderate disability (EDSS 3 &#8211;5; n&#8201;=&#8201;5). Participants made use of an activity monitor device attached to their waist during their normal daily activities over 4 measurements. Activity parameters were assessed and compared for the time of each participant&#8217;s first measurement and follow-up measurement. Furthermore, differences between both subgroups, and the correlation of activity parameters with the clinical neurological variable (EDSS) were investigated. Results Participants showed significant decline in step count (p&#8201;=&#8201;0.008), maximum walking speed (p&#8201;=&#8201;0.02) and physical activity intensity (p&#8201;=&#8201;0.03) throughout the study period. Compared to the mild subgroup, moderate affected participant accumulated less number of steps (G1: 9214.33&#8201;±&#8201;2439.11, G2: 5018.13&#8201;±&#8201;2416.96; p&#8201;<&#8201;0.005) and were slower (G1: 1.48&#8201;±&#8201;0.19, G2: 1.12&#8201;±&#8201;0.44; p&#8201;=&#8201;0.03). Additionally, the EDSS correlated negatively with mean walking speed (r&#8201;=&#8201;- 0.71, p&#8201;=&#8201;0.01) and steps count (r&#8201;=&#8201;- 0.54, p&#8201;=&#8201;0.08). Conclusions In this study, we used a portable activity monitoring sensor to gather information about everyday physical activity in PwMS at home. We showed that objective measurements using simple 3D accelerometers can track daily physical activity fluctuation. Furthermore, they track disability changes better than clinical measures. Thus, they can help to develop activity based treatments for PwMS