947 resultados para N-LINKED GLYCOSYLATIONS


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Electric vehicles (EVs) and hybrid electric vehicles (HEVs) can reduce greenhouse gas emissions while switched reluctance motor (SRM) is one of the promising motor for such applications. This paper presents a novel SRM fault-diagnosis and fault-tolerance operation solution. Based on the traditional asymmetric half-bridge topology for the SRM driving, the central tapped winding of the SRM in modular half-bridge configuration are introduced to provide fault-diagnosis and fault-tolerance functions, which are set idle in normal conditions. The fault diagnosis can be achieved by detecting the characteristic of the excitation and demagnetization currents. An SRM fault-tolerance operation strategy is also realized by the proposed topology, which compensates for the missing phase torque under the open-circuit fault, and reduces the unbalanced phase current under the short-circuit fault due to the uncontrolled faulty phase. Furthermore, the current sensor placement strategy is also discussed to give two placement methods for low cost or modular structure. Simulation results in MATLAB/Simulink and experiments on a 750-W SRM validate the effectiveness of the proposed strategy, which may have significant implications and improve the reliability of EVs/HEVs.

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The northern Everglades Water Conservation Areas have experienced recent ecological shifts in primary producer community structure involving marl periphyton mats and dense Typha-dominated macrophyte stands. Multiple investigations have identified phosphorus (P) as a driver of primary producer community structure, but effects of water impoundment beginning in the 1950s and changes in water hardness [e.g., (CaCO3)] have also been identified as a concern. In an effort to understand pre-1950, primary producer community structure and identify community shifts since 1950, we measured pigment proxies on three sediment cores collected in Water Conservation Area-2A (WCA-2A) along a phosphorus enrichment gradient. Photosynthetic pigments, sediment total phosphorus content (TP), organic matter, total organic carbon and nitrogen were used to infer historic primary producer communities and changes in water quality and hydrology regulating those communities. Excess 210Pb was used to establish historic dates for the sediment cores. Results indicate the northern area of WCA-2A increased marl deposition and increased algal abundance ca. 1920. This increase in (presumably) calcareous periphyton before intensive agriculture and impoundment suggest canal-derived calcium inputs and to some extent early drainage effects played a role in initiating this community shift. The northern area community then shifted to Typha dominance around 1965. The areas to the south in WCA-2A experienced increased marl deposition and algal abundance around or just prior to 1950s impoundment, the precise timing limited by core age resolution. Continued increases in algal abundance were evident after 1950, coinciding with impoundment and deepening of canals draining into WCA-2A, both likely increasing water mineral and nutrient concentrations. The intermediate site developed a Typha-dominated community ca. 1995 while the southern-most core site WCA-2A has yet to develop Typha dominance. Numerous studies link sediment TP >650 mg P/kg to marsh habitat degradation into Typha-dominance. The northern and intermediate cores where Typha is currently support this previous research by showing a distinct shift in the sediment record to Typha dominance corresponding to sediment TP between 600 and 700 mg P/kg. These temporal and spatial differences are consistent with modern evidence showing water-column gradients in mineral inputs (including Ca, carbonates, and phosphorus) altering primary producer community structure in WCA-2A, but also suggest hydroperiod has an effect on the mechanisms regulating periphyton development and Typha dominance.

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The objective of this study is to design and development of an enzyme-linked biosensor for detection and quantification of phosphate species. Various concentrations of phosphate species were tested and completed for this study. Phosphate is one of the vital nutrients for all living organisms. Phosphate compounds can be found in nature (e.g., water sediments), and they often exist in aninorganic form. The amount of phosphates in the environment strongly influences the operations of living organisms. Excess amount of phosphate in the environment causes eutrophication which in turn causes oxygen deficit for the other living organisms. Fish die and degradation of habitat in the water occurs as a result of eutrophication. In contrast, low phosphate concentration causes death of vegetation since plants utilize the inorganic phosphate for photosynthesis, respiration, and regulation of enzymes. Therefore, the phosphate quantity in lakes and rivers must be monitored. Result demonstrated that phosphate species could be detected in various organisms via enzyme-linked biosensor in this research.

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La tesi ha lo scopo di introdurre Investiga, un'applicazione per l'estrazione automatica di informazioni da articoli scientifici in formato PDF e pubblicazione di queste informazioni secondo i principi e i formati Linked Open Data, creata per la tesi. Questa applicazione è basata sul Task 2 della SemPub 2016, una challenge che ha come scopo principale quello di migliorare l'estrazione di informazioni da articoli scientifici in formato PDF. Investiga estrae i capitoli di primo livello, le didascalie delle figure e delle tabelle da un dato articolo e crea un grafo delle informazioni così estratte collegate adeguatamente tra loro. La tesi inoltre analizza gli strumenti esistenti per l'estrazione automatica di informazioni da documenti PDF e dei loro limiti.

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Underwater photo-transect surveys were conducted on September 23-27, 2007 at different sections of the reef flat, reef crest and reef slope in Heron Reef. This survey was done by swimming along pre-defined transect sites and taking a picture of the bottom substrate parallel to the bottom at constant vertical distance (30cm) every two to three metres. A total of 3,586 benthic photos were taken. A floating GPS setup connected to the swimmer/diver by a line enabled recording of coordinates of transect surveys. Approximation of the coordinates for each benthic photo was based on the photo timestamp and GPS coordinate time stamp, using GPS Photo Link Software. Coordinates of each photo were interpolated by finding the the gps coordinates that were logged at a set time before and after the photo was captured. The output of this process was an ArcMap point shapefile, a Google Earth KML file and a thumbnail of each benthic photo taken. The data in the ArcMap shapefile and in the Google Earth KML file consisted of the approximated coordinate of each benthic photo taken during the survey. Using the GPS Photo Link extension within the ArcMap environment, opening the ArcMap shapefile will enable thumbnail to be displayed on the associated benthic cover photo whenever hovering with the mouse over a point on the transect. By downloading the GPSPhotoLink software from the www.geospatialexperts.com, and installing it as a trial version the ArcMap exstension will be installed in the ArcMap environment.

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© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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Postprint

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Inflammatory breast cancer (IBC) is an extremely rare but highly aggressive form of breast cancer characterized by the rapid development of therapeutic resistance leading to particularly poor survival. Our previous work focused on the elucidation of factors that mediate therapeutic resistance in IBC and identified increased expression of the anti-apoptotic protein, X-linked inhibitor of apoptosis protein (XIAP), to correlate with the development of resistance to chemotherapeutics. Although XIAP is classically thought of as an inhibitor of caspase activation, multiple studies have revealed that XIAP can also function as a signaling intermediate in numerous pathways. Based on preliminary evidence revealing high expression of XIAP in pre-treatment IBC cells rather than only subsequent to the development of resistance, we hypothesized that XIAP could play an important signaling role in IBC pathobiology outside of its heavily published apoptotic inhibition function. Further, based on our discovery of inhibition of chemotherapeutic efficacy, we postulated that XIAP overexpression might also play a role in resistance to other forms of therapy, such as immunotherapy. Finally, we posited that targeting of specific redox adaptive mechanisms, which are observed to be a significant barrier to successful treatment of IBC, could overcome therapeutic resistance and enhance the efficacy of chemo-, radio-, and immuno- therapies. To address these hypotheses our objectives were: 1. to determine a role for XIAP in IBC pathobiology and to elucidate the upstream regulators and downstream effectors of XIAP; 2. to evaluate and describe a role for XIAP in the inhibition of immunotherapy; and 3. to develop and characterize novel redox modulatory strategies that target identified mechanisms to prevent or reverse therapeutic resistance.

Using various genomic and proteomic approaches, combined with analysis of cellular viability, proliferation, and growth parameters both in vitro and in vivo, we demonstrate that XIAP plays a central role in both IBC pathobiology in a manner mostly independent of its role as a caspase-binding protein. Modulation of XIAP expression in cells derived from patients prior to any therapeutic intervention significantly altered key aspects IBC biology including, but not limited to: IBC-specific gene signatures; the tumorigenic capacity of tumor cells; and the metastatic phenotype of IBC, all of which are revealed to functionally hinge on XIAP-mediated NFκB activation, a robust molecular determinant of IBC. Identification of the mechanism of XIAP-mediated NFκB activation led to the characterization of novel peptide-based antagonist which was further used to identify that increased NFκB activation was responsible for redox adaptation previously observed in therapy-resistant IBC cells. Lastly, we describe the targeting of this XIAP-NFκB-ROS axis using a novel redox modulatory strategy both in vitro and in vivo. Together, the data presented here characterize a novel and crucial role for XIAP both in therapeutic resistance and the pathobiology of IBC; these results confirm our previous work in acquired therapeutic resistance and establish the feasibility of targeting XIAP-NFκB and the redox adaptive phenotype of IBC as a means to enhance survival of patients.

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Secure Access For Everyone (SAFE), is an integrated system for managing trust

using a logic-based declarative language. Logical trust systems authorize each

request by constructing a proof from a context---a set of authenticated logic

statements representing credentials and policies issued by various principals

in a networked system. A key barrier to practical use of logical trust systems

is the problem of managing proof contexts: identifying, validating, and

assembling the credentials and policies that are relevant to each trust

decision.

SAFE addresses this challenge by (i) proposing a distributed authenticated data

repository for storing the credentials and policies; (ii) introducing a

programmable credential discovery and assembly layer that generates the

appropriate tailored context for a given request. The authenticated data

repository is built upon a scalable key-value store with its contents named by

secure identifiers and certified by the issuing principal. The SAFE language

provides scripting primitives to generate and organize logic sets representing

credentials and policies, materialize the logic sets as certificates, and link

them to reflect delegation patterns in the application. The authorizer fetches

the logic sets on demand, then validates and caches them locally for further

use. Upon each request, the authorizer constructs the tailored proof context

and provides it to the SAFE inference for certified validation.

Delegation-driven credential linking with certified data distribution provides

flexible and dynamic policy control enabling security and trust infrastructure

to be agile, while addressing the perennial problems related to today's

certificate infrastructure: automated credential discovery, scalable

revocation, and issuing credentials without relying on centralized authority.

We envision SAFE as a new foundation for building secure network systems. We

used SAFE to build secure services based on case studies drawn from practice:

(i) a secure name service resolver similar to DNS that resolves a name across

multi-domain federated systems; (ii) a secure proxy shim to delegate access

control decisions in a key-value store; (iii) an authorization module for a

networked infrastructure-as-a-service system with a federated trust structure

(NSF GENI initiative); and (iv) a secure cooperative data analytics service

that adheres to individual secrecy constraints while disclosing the data. We

present empirical evaluation based on these case studies and demonstrate that

SAFE supports a wide range of applications with low overhead.

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Inflammatory breast cancer (IBC) is the deadliest, distinct subtype of breast cancer. High expression of epidermal growth factor receptors [EGFR or human epidermal growth factor receptor 2 (HER2)] in IBC tumors has prompted trials of anti-EGFR/HER2 monoclonal antibodies to inhibit oncogenic signaling; however, de novo and acquired therapeutic resistance is common. Another critical function of these antibodies is to mediate antibody-dependent cellular cytotoxicity (ADCC), which enables immune effector cells to engage tumors and deliver granzymes, activating executioner caspases. We hypothesized that high expression of anti-apoptotic molecules in tumors would render them resistant to ADCC. Herein, we demonstrate that the most potent caspase inhibitor, X-linked inhibitor of apoptosis protein (XIAP), overexpressed in IBC, drives resistance to ADCC mediated by cetuximab (anti-EGFR) and trastuzumab (anti-HER2). Overexpression of XIAP in parental IBC cell lines enhances resistance to ADCC; conversely, targeted downregulation of XIAP in ADCC-resistant IBC cells renders them sensitive. As hypothesized, this ADCC resistance is in part a result of the ability of XIAP to inhibit caspase activity; however, we also unexpectedly found that resistance was dependent on XIAP-mediated, caspase-independent suppression of reactive oxygen species (ROS) accumulation, which otherwise occurs during ADCC. Transcriptome analysis supported these observations by revealing modulation of genes involved in immunosuppression and oxidative stress response in XIAP-overexpressing, ADCC-resistant cells. We conclude that XIAP is a critical modulator of ADCC responsiveness, operating through both caspase-dependent and -independent mechanisms. These results suggest that strategies targeting the effects of XIAP on caspase activation and ROS suppression have the potential to enhance the activity of monoclonal antibody-based immunotherapy.

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Pressurised slurries of fine-grained sediment expelled from the base of the active layer have been observed in recent years in the High Arctic. Such mud ejections, however, are poorly understood in terms of how exactly climate and landscape factors determine when and where they occur. Mud ejections at the Cape Bounty Arctic Watershed Observatory, Melville Island, Nunavut, were systematically mapped in 2012 and 2013, and this was combined with observations of mud ejection activity and climatic measurements carried out since 2003. The mud ejections occur late in the melt season during warm years and closely following major rainfall events. High-resolution satellite imagery demonstrates that mud ejections are associated with polar semi-desert vegetative settings, flat or low-sloping terrain and south-facing slopes. The localised occurrence of mud ejections appears to be related to differential soil moisture retention.

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Background: There are a lack of reliable data on the epidemiology and associated burden and costs of asthma. We sought to provide the first UK-wide estimates of the epidemiology, healthcare utilisation and costs of asthma. 

Methods: We obtained and analysed asthma-relevant data from 27 datasets: these comprised national health surveys for 2010-11, and routine administrative, health and social care datasets for 2011-12; 2011-12 costs were estimated in pounds sterling using economic modelling. 

Results: The prevalence of asthma depended on the definition and data source used. The UK lifetime prevalence of patient-reported symptoms suggestive of asthma was 29.5 % (95 % CI, 27.7-31.3; n = 18.5 million (m) people) and 15.6 % (14.3-16.9, n = 9.8 m) for patient-reported clinician-diagnosed asthma. The annual prevalence of patient-reported clinician-diagnosed-and-treated asthma was 9.6 % (8.9-10.3, n = 6.0 m) and of clinician-reported, diagnosed-and-treated asthma 5.7 % (5.7-5.7; n = 3.6 m). Asthma resulted in at least 6.3 m primary care consultations, 93,000 hospital in-patient episodes, 1800 intensive-care unit episodes and 36,800 disability living allowance claims. The costs of asthma were estimated at least £1.1 billion: 74 % of these costs were for provision of primary care services (60 % prescribing, 14 % consultations), 13 % for disability claims, and 12 % for hospital care. There were 1160 asthma deaths. 

Conclusions: Asthma is very common and is responsible for considerable morbidity, healthcare utilisation and financial costs to the UK public sector. Greater policy focus on primary care provision is needed to reduce the risk of asthma exacerbations, hospitalisations and deaths, and reduce costs.

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Research has consistently found sex differences in mental rotation. Twin research has suggested that females with male co-twins perform better than females with female co-twins on mental rotation. Because twins share both pre-natal and post-natal environments, it is not possible to test whether this advantage is due to in-uterine transmission of testosterone from males to females or due to socialisation processes. The present study explored whether the advantage of females with brothers can be observed in non-twin siblings. Participants (N = 1799) were assessed on mental rotation. The observed group differences were overall small: males performed significantly better than females; females with sisters performed similarly to females with brothers; importantly, males with brothers performed significantly better than both female groups. The results suggest that sex differences in mental rotation are driven by the group of males with brothers.