| 1. |
- A. Strumpfer, Johan, et al.
(författare)
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Stretching of Twitchin Kinase
- 2012
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Ingår i: Biophysical Journal. - St. Louis, MO, United States : Cell Press. - 0006-3495 .- 1542-0086. ; 102:3 Supplement 1, s. 361a-362a
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Tidskriftsartikel (refereegranskat)abstract
- The giant proteins from the titin family, that form cytoskeletal filaments, have emerged as key mechanotransducers in the sarcomere. These proteins contain a conserved kinase region, which is auto-inhibited by a C-terminal tail domain. The inhibitory tail domain occludes the active sites of the kinases, thus preventing ATP from binding. It was proposed that through application of a force, such as that arising during muscle contraction, the inhibitory tail becomes detached, lifting inhibition. The force-sensing ability of titin kinase was demonstrated in AFM experiments and simulations [Puchner, et al., 2008, PNAS:105, 13385], which showed indeed that mechanical forces can remove the autoinhibitory tail of titin kinase. We report here steered molecular dynamics simulations (SMD) of the very recently resolved crystal structure of twitchin kinase, containing the kinase region and flanking fibronectin and immuniglobulin domains, that show a variant mechanism. Despite the significant structural and sequence similarity to titin kinase, the autoinhibitory tail of twitchin kinase remains in place upon stretching, while the N-terminal lobe of the kinase unfolds. The SMD simulations also show that the detachment and stretching of the linker between fibronectin and kinase regions, and the partial extension of the autoinhibitory tail, are the primary force-response. We postulate that this stretched state, where all structural elements are still intact, may represent the physiologically active state.
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| 2. |
- Aagaard, Lise, et al.
(författare)
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Global Patterns of Adverse Drug Reactions Over a Decade Analyses of Spontaneous Reports to VigiBase (TM)
- 2012
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Ingår i: Drug Safety. - : Adis. - 0114-5916 .- 1179-1942. ; 35:12, s. 1171-1182
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although systems to collect information about suspected adverse drug reactions (ADRs) were established in many countries and by the WHO in the 1960s, few studies have examined reported ADRs related to national income. Objective: The aim of the study was to characterize ADRs reported to the WHO-ADR database, VigiBase (TM), and to relate data to national income. Methods: We analysed ADR reports submitted to VigiBase (TM) from 2000 to 2009 with respect to reporting rate, age and sex of patient, type, seriousness and medications. Reports were also analysed with respect to national income level, classified in accordance with the World Bank definition: low, lower-middle, upper-middle and high. Results: We analysed 1 359 067 ADR reports including 3 013 074 ADRs. Overall, 16% of reports were serious and 60% were reported for females. High-income countries had the highest ADR reporting rates (range 3-613 reports/million inhabitants/year) and low-income countries the lowest (range 0-21). Distribution of ADRs across income groups with respect to age group, seriousness and sex was non-significant. Overall, the majority of ADRs were reported for nervous system medications, followed by cardiovascular medicines. Low-income countries reported relatively more ADRs for antiinfectives for systemic use than high-income countries, and high-income countries reported more ADRs for antineoplastic and immunomodulating agents than lower-income groups. Conclusion: This study showed that high-income countries had the highest ADR reporting rates and low-income countries the lowest, with large variations across countries in each group. Significant differences in ADR reporting rates were only found for ADRs of the type skin and subcutaneous tissue disorders and for the therapeutic groups antiinfectives for systemic use and antineoplastic and immunomodulation agents. To strengthen ADR reporting rates, especially in low-income countries, more research is needed about the impact of organizational structures and economic resources of national pharmacovigilance centres and ADR reporting practices on the large variations in ADR reporting rates within income groups.
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| 3. |
- Aanaes, K, et al.
(författare)
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Extensive Endoscopic Image-Guided Sinus Surgery Decreases BPI-ANCA in Patients with Cystic Fibrosis
- 2012
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Ingår i: Scandinavian Journal of Immunology. - : Blackwell Publishing. - 0300-9475 .- 1365-3083. ; 76:6, s. 573-579
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Tidskriftsartikel (refereegranskat)abstract
- Antineutrophil cytoplasm autoantibodies (ANCA) directed against bactericidal/permeability-increasing protein (BPI) are common in patients with cystic fibrosis (CF), and serum levels are correlated with lung colonization by Pseudomonas aeruginosa and the severity of lung damage. The production of BPI-ANCA may be due to the costimulation of BPI when mounting an immune response against P. aeruginosa. The effect of surgery aiming to eradicate bacteria and infected tissue on BPI-ANCA levels is sparsely described. A cohort of patients with CF were included: 53 patients having extensive image-guided sinus surgery (EIGSS) with topical postoperative antibiotic treatment, 131 non-operated controls and 36 who had double lung transplantation (LTX). In all 219 patients, serum samples before and after surgery or at similar intervals were analysed for IgG and IgA BPI-ANCA. The EIGSS group showed a highly significant decrease in both IgA and IgG BPI-ANCA levels compared with their own preoperative values and control group values (P andlt; 0.0010.02). The LTX patients also showed a highly significant decrease in both IgA and IgG BPI-ANCA levels (P andlt; 0.001). EIGSS and LTX decrease IgA and IgG BPI-ANCA levels in patients with CF, indicating that extensive removal of infected tissue influences the pathogenic process of autoantibody production. The results shown herein are in favour of applying EIGSS in selected patients with CF and for using BPI-ANCA as a surrogate marker for guiding further therapeutic interventions.
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| 4. |
- Aartsen, Marja, et al.
(författare)
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Ageing in the light of crises : Economic crisis, demographic change, and the search for meaning
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Old age has many images, with the one of a crisis regaining momentum. While images of activity and opportunity gained ground during recent decades, this trend now seems to reverse. The current economic crisis drains the financial resources of older people, which increases old age poverty. Moreover, governments react to the double-pressure of economic crises and population ageing through budget cuts, which reduces support systems for older people. It, moreover, centers public discourses more strongly on social problems associated with old age. Both developments underline the needs associated with old age and draw our attention away from the potentials of old age. In other words, they bring discussions on old age back to the topic of crises. This working paper discusses how the economic crisis affects older people, how governments, labour markets, and families react to the double-pressure of population ageing and economic crisis, and how individuals perceive their old age. It concludes with reflections on the implications of growing crisis-centrism in discussions on old age. Such crisis-centrism can lead us to overlook social inequalities in old age and to neglect the subjective character of the perception of old age. The public image of old age might, thus, be stronger associated with the idea of crisis than what older people’s lived experience suggests.
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| 5. |
- Abate, Ebba, et al.
(författare)
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The Impact of Asymptomatic Helminth Co-Infection in Patients with Newly Diagnosed Tuberculosis in North-West Ethiopia
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls. less thanbrgreater than less thanbrgreater thanMethodology: Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment. less thanbrgreater than less thanbrgreater thanResults: Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV2/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well. less thanbrgreater than less thanbrgreater thanConclusion: One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV2/TB group.
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| 6. |
- Abbas, Muhammad
(författare)
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On the Implementation of Integer and Non-Integer Sampling Rate Conversion
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main focus in this thesis is on the aspects related to the implementation of integer and non-integer sampling rate conversion (SRC). SRC is used in many communication and signal processing applications where two signals or systems having different sampling rates need to be interconnected. There are two basic approaches to deal with this problem. The first is to convert the signal to analog and then re-sample it at the desired rate. In the second approach, digital signal processing techniques are utilized to compute values of the new samples from the existing ones. The former approach is hardly used since the latter one introduces less noise and distortion. However, the implementation complexity for the second approach varies for different types of conversion factors. In this work, the second approach for SRC is considered and its implementation details are explored. The conversion factor in general can be an integer, a ratio of two integers, or an irrational number. The SRC by an irrational numbers is impractical and is generally stated for the completeness. They are usually approximated by some rational factor.The performance of decimators and interpolators is mainly determined by the filters, which are there to suppress aliasing effects or removing unwanted images. There are many approaches for the implementation of decimation and interpolation filters, and cascaded integrator comb (CIC) filters are one of them. CIC filters are most commonly used in the case of integer sampling rate conversions and often preferred due to their simplicity, hardware efficiency, and relatively good anti-aliasing (anti-imaging) characteristics for the first (last) stage of a decimation (interpolation). The multiplierless nature, which generally yields to low power consumption, makes CIC filters well suited for performing conversion at higher rate. Since these filters operate at the maximum sampling frequency, therefore, are critical with respect to power consumption. It is therefore necessary to have an accurate and efficient ways and approaches that could be utilized to estimate the power consumption and the important factors that are contributing to it. Switching activity is one such factor. To have a high-level estimate of dynamic power consumption, switching activity equations in CIC filters are derived, which may then be used to have an estimate of the dynamic power consumption. The modeling of leakage power is also included, which is an important parameter to consider since the input sampling rate may differ several orders of magnitude. These power estimates at higher level can then be used as a feed-back while exploring multiple alternatives.Sampling rate conversion is a typical example where it is required to determine the values between existing samples. The computation of a value between existing samples can alternatively be regarded as delaying the underlying signal by a fractional sampling period. The fractional-delay filters are used in this context to provide a fractional-delay adjustable to any desired value and are therefore suitable for both integer and non-integer factors. The structure that is used in the efficient implementation of a fractional-delay filter is know as Farrow structure or its modifications. The main advantage of the Farrow structure lies in the fact that it consists of fixed finite-impulse response (FIR) filters and there is only one adjustable fractional-delay parameter, used to evaluate a polynomial with the filter outputs as coefficients. This characteristic of the Farrow structure makes it a very attractive structure for the implementation. In the considered fixed-point implementation of the Farrow structure, closed-form expressions for suitable word lengths are derived based on scaling and round-off noise. Since multipliers share major portion of the total power consumption, a matrix-vector multiple constant multiplication approach is proposed to improve the multiplierless implementation of FIR sub-filters.The implementation of the polynomial part of the Farrow structure is investigated by considering the computational complexity of different polynomial evaluation schemes. By considering the number of operations of different types, critical path, pipelining complexity, and latency after pipelining, high-level comparisons are obtained and used to short list the suitable candidates. Most of these evaluation schemes require the explicit computation of higher order power terms. In the parallel evaluation of powers, redundancy in computations is removed by exploiting any possible sharing at word level and also at bit level. As a part of this, since exponents are additive under multiplication, an ILP formulation for the minimum addition sequence problem is proposed.
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| 7. |
- Abbasi, Mazhar Ali, et al.
(författare)
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Anions effect on the low temperature growth of ZnO nanostructures
- 2012
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Ingår i: Vacuum. - : Elsevier. - 0042-207X .- 1879-2715. ; 86:12, s. 1998-2001
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Tidskriftsartikel (refereegranskat)abstract
- Seed mediated aqueous chemical growth (ACG) route was used for the growth of ZnO nanostructures on Si substrate in four different growth mediums. The growth medium has shown to affect the morphology and the size of the different nanostructures. We observed that the medium containing zinc nitrate anions yields the nanorods, in a medium containing zinc acetate anions nano-candles are obtained. While in a medium containing zinc chloride anions ZnO nano-discs were obtained and in a medium containing zinc sulfate anions nano-flakes are achieved. Growth in these different mediums has also shown effect on the optical emission characteristics of the different ZnO nanostructures.
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| 8. |
- Abbasi, Mazhar Ali, et al.
(författare)
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Potentiometric Zinc Ion Sensor Based on Honeycomb-Like NiO Nanostructures
- 2012
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Ingår i: Sensors. - : MDPI. - 1424-8220. ; 12:11, s. 15424-15437
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Tidskriftsartikel (refereegranskat)abstract
- In this study honeycomb-like NiO nanostructures were grown on nickel foam by a simple hydrothermal growth method. The NiO nanostructures were characterized by field emission electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD) techniques. The characterized NiO nanostructures were uniform, dense and polycrystalline in the crystal phase. In addition to this, the NiO nanostructures were used in the development of a zinc ion sensor electrode by functionalization with the highly selective zinc ion ionophore 12-crown-4. The developed zinc ion sensor electrode has shown a good linear potentiometric response for a wide range of zinc ion concentrations, ranging from 0.001 mM to 100 mM, with sensitivity of 36 mV/decade. The detection limit of the present zinc ion sensor was found to be 0.0005 mM and it also displays a fast response time of less than 10 s. The proposed zinc ion sensor electrode has also shown good reproducibility, repeatability, storage stability and selectivity. The zinc ion sensor based on the functionalized NiO nanostructures was also used as indicator electrode in potentiometric titrations and it has demonstrated an acceptable stoichiometric relationship for the determination of zinc ion in unknown samples. The NiO nanostructures-based zinc ion sensor has potential for analysing zinc ion in various industrial, clinical and other real samples.
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| 9. |
- AbdGawad, Mohamed, et al.
(författare)
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Decreased Neutrophil Apoptosis in Quiescent ANCA-Associated Systemic Vasculitis
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: ANCA-Associated Systemic Vasculitis (AASV) is characterized by leukocytoclasis, accumulation of unscavenged apoptotic and necrotic neutrophils in perivascular tissues. Dysregulation of neutrophil cell death may contribute directly to the pathogenesis of AASV. less thanbrgreater than less thanbrgreater thanMethods: Neutrophils from Healthy Blood Donors (HBD), patients with AASV most in complete remission, Polycythemia Vera (PV), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and renal transplant recipients (TP) were incubated in vitro, and the rate of spontaneous apoptosis was measured by FACS. Plasma levels of cytokines and sFAS were measured with cytometric bead array and ELISA. Expression of pro/anti-apoptotic factors, transcription factors C/EBP-alpha, C/EBP-beta and PU.1 and inhibitors of survival/JAK2-pathway were measured by real-time-PCR. less thanbrgreater than less thanbrgreater thanResults: AASV, PV and RA neutrophils had a significantly lower rate of apoptosis compared to HBD neutrophils (AASV 50 +/- 14% vs. HBD 64 +/- 11%, p andlt; 0.0001). In RA but not in AASV and PV, low apoptosis rate correlated with increased plasma levels of GM-CSF and high mRNA levels of anti-apoptotic factors Bcl-2A1 and Mcl-1. AASV patients had normal levels of G-CSF, GM-CSF and IL-3. Both C/EBP-alpha, C/EBP-beta were significantly higher in neutrophils from AASV patients than HBD. Levels of sFAS were significantly higher in AASV compared to HBD. less thanbrgreater than less thanbrgreater thanConclusion: Neutrophil apoptosis rates in vitro are decreased in AASV, RA and PV but mechanisms seem to differ. Increased mRNA levels of granulopoiesis-associated transcription factors and increased levels of sFAS in plasma were observed in AASV. Additional studies are required to define the mechanisms behind the decreased apoptosis rates, and possible connections with accumulation of dying neutrophils in regions of vascular lesions in AASV patients.
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| 10. |
- Abdulla, Parosh Aziz, et al.
(författare)
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Automatic fence insertion in integer programs via predicate abstraction
- 2012
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Ingår i: Static Analysis. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783642331244 - 9783642331251 ; , s. 164-180
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Konferensbidrag (refereegranskat)abstract
- We propose an automatic fence insertion and verification framework for concurrent programs running under relaxed memory. Unlike previous approaches to this problem, which allow only variables of finite domain, we target programs with (unbounded) integer variables. The problem is difficult because it has two different sources of infiniteness: unbounded store buffers and unbounded integer variables. Our framework consists of three main components: (1) a finite abstraction technique for the store buffers, (2) a finite abstraction technique for the integer variables, and (3) a counterexample guided abstraction refinement loop of the model obtained from the combination of the two abstraction techniques. We have implemented a prototype based on the framework and run it successfully on all standard benchmarks together with several challenging examples that are beyond the applicability of existing methods.
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