| 1. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Abramowski, A., et al.
(författare)
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Constraints on the gamma-ray emission from the cluster-scale AGN outburst in the Hydra A galaxy cluster
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. A103-
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Tidskriftsartikel (refereegranskat)abstract
- Context. In some galaxy clusters, powerful active galactic nuclei (AGN) have blown bubbles with cluster scale extent into the ambient medium. The main pressure support of these bubbles is not known to date, but cosmic rays are a viable possibility. For such a scenario copious gamma-ray emission is expected as a tracer of cosmic rays from these systems. Aims. Hydra A, the closest galaxy cluster hosting a cluster scale AGN outburst, located at a redshift of 0.0538, is investigated for being a gamma-ray emitter with the High Energy Stereoscopic System (H.E.S.S.) array and the Fermi Large Area Telescope (Fermi-LAT). Methods. Data obtained in 20.2 h of dedicated H. E. S. S. observations and 38 months of Fermi-LAT data, gathered by its usual all-sky scanning mode, have been analyzed to search for a gamma-ray signal. Results. No signal has been found in either data set. Upper limits on the gamma-ray flux are derived and are compared to models. These are the first limits on gamma-ray emission ever presented for galaxy clusters hosting cluster scale AGN outbursts. Conclusions. The non-detection of Hydra A in gamma-rays has important implications on the particle populations and physical conditions inside the bubbles in this system. For the case of bubbles mainly supported by hadronic cosmic rays, the most favorable scenario, which involves full mixing between cosmic rays and embedding medium, can be excluded. However, hadronic cosmic rays still remain a viable pressure support agent to sustain the bubbles against the thermal pressure of the ambient medium. The largest population of highly-energetic electrons, which are relevant for inverse-Compton gamma-ray production is found in the youngest inner lobes of Hydra A. The limit on the inverse-Compton gamma-ray flux excludes a magnetic field below half of the equipartition value of 16 mu G in the inner lobes.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Horikoshi, Momoko, et al.
(författare)
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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| 8. |
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| 9. |
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| 10. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 11. |
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| 12. |
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| 13. |
- Gorelov, D., et al.
(författare)
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Isomeric Yield Ratios of Fission Products Measured with the Jyfltrap
- 2014
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Ingår i: Acta Physica Polonica B. - 0587-4254 .- 1509-5770. ; 45:2, s. 211-216
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Tidskriftsartikel (refereegranskat)abstract
- Experimental methods to determine isomeric yield ratios usually apply gamma-spectroscopic techniques. In such methods, ground and isomeric states are distinguished by their decays. In the present work, several isomeric yield ratios of fission products have been measured by utilizing capabilities of the double Penning-trap mass spectrometer JYFLTRAP, where isomeric and ground state were separated by their masses. To verify the new experimental technique, the results were compared to those from gamma-spectroscopy measurements.
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| 14. |
- Jamil, S., et al.
(författare)
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Neuroblastoma cells injected into experimental mature teratoma reveal a tropism for embryonic loose mesenchyme
- 2013
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 43:3, s. 831-838
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Tidskriftsartikel (refereegranskat)abstract
- Embryonic neural tumors are responsible for a disproportionate number of cancer deaths in children. Although dramatic improvements in survival for pediatric malignancy has been achieved in previous years advancements seem to be slowing down. For the development of new enhanced therapy and an increased understanding of the disease, pre-clinical models better capturing the neoplastic niche are essential. Tumors of early childhood present in this respect a particular challenge. Here, we explore how components of the embryonic process in stem-cell induced mature teratoma can function as an experimental in vivo microenvironment instigating the growth of injected childhood neuroblastoma (NB) cell lines. Three human NB cell lines, IMR-32, Kelly and SK-N-BE(2), were injected into mature pluripotent stem cell-induced teratoma (PSCT) and compared to xenografts of the same cell lines. Proliferative NB cells from all lines were readily detected in both models with a typical histology of a poorly differentiated NB tumor with a variable amount of fibrovascular stroma. Uniquely in the PSCT microenvironment, NB cells were found integrated in a non-random fashion. Neuroblastoma cells were never observed in areas with well-differentiated somatic tissue i.e. bone, muscle, gut or areas of other easily identifiable tissue types. Instead, the three cell lines all showed initial growth exclusively occurring in the embryonic loose mesenchymal stroma, resulting in a histology recapitulating NB native presentation in vivo. Whether this reflects the 'open' nature of loose mesenchyme more easily giving space to new cells compared to other more dense tissues, the rigidity of matrix providing physical cues modulating NB characteristics, or if embryonic loose mesenchyme may supply developmental cues that attracted or promoted the integration of NB, remains to be tested. We tentatively hypothesize that mature PSCT provide an embryonic niche well suited for in vivo studies on NB.
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| 15. |
- Kashif, M., et al.
(författare)
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Morphological, optical, and Raman characteristics of ZnO nanoflakes prepared via a sol-gel method
- 2012
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Ingår i: PHYSICA STATUS SOLIDI A-APPLICATIONS AND MATERIALS SCIENCE. - : Wiley-VCH Verlag Berlin. - 1862-6300. ; 209:1, s. 143-147
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Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional (2D) ZnO nanoflakes were grown on thin aluminum layer, deposited on silicon substrate, using a sol-gel method. The surface morphologies of ZnO nanoflakes at different precursor concentrations were studied using scanning electron microscopy (SEM). Combined studies of SEM, photoluminescence (PL), and Raman spectroscopy suggested that nanorods started to grow along with nanoflakes at a precursor concentration of 0.05 M and the density of the nanorods significantly increased when the concentration was raised to 0.075 M. Both the UV-luminescence and Raman spectra were intensified and redshifted with the increment of precursor concentration. Spectral intensification suggests improvement in crystal qualities and better optical properties of the fabricated ZnO nanostructures. The structural defects at lower levels of precursor were probably due to the hypoxic environment, whereas, the redshift of PL and Raman spectra was due to the local heating of ZnO nanocrystals.
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| 16. |
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| 17. |
- Mousis, O., et al.
(författare)
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Scientific rationale for Saturn's in situ exploration
- 2014
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Ingår i: Planetary and Space Science. - : Elsevier BV. - 0032-0633 .- 1873-5088. ; 104, s. 29-47
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Tidskriftsartikel (refereegranskat)abstract
- Remote sensing observations meet some limitations when used to study the bulk atmospheric composition of the giant planets of our solar system. A remarkable example of the superiority of in situ probe measurements is illustrated by the exploration of Jupiter, where key measurements such as the determination of the noble gases' abundances and the precise measurement of the helium mixing ratio have only been made available through in situ measurements by the Galileo probe. This paper describes the main scientific goals to be addressed by the future in situ exploration of Saturn placing the Galileo probe exploration of Jupiter in a broader context and before the future probe exploration of the more remote ice giants. In situ exploration of Saturn's atmosphere addresses two broad themes that are discussed throughout this paper: first, the formation history of our solar system and second, the processes at play in planetary atmospheres. In this context, we detail the reasons why measurements of Saturn's bulk elemental and isotopic composition would place important constraints on the volatile reservoirs in the protosolar nebula. We also show that the in situ measurement of CO (or any other disequilibrium species that is depleted by reaction with water) in Saturn's upper troposphere may help constraining its bulk O/H ratio. We compare predictions of Jupiter and Saturn's bulk compositions from different formation scenarios, and highlight the key measurements required to distinguish competing theories to shed light on giant planet formation as a common process in planetary systems with potential applications to most extrasolar systems. In situ measurements of Saturn's stratospheric and tropospheric dynamics, chemistry and cloud-forming processes will provide access to phenomena unreachable to remote sensing studies. Different mission architectures are envisaged, which would benefit from strong international collaborations, all based on an entry probe that would descend through Saturn's stratosphere and troposphere under parachute down to a minimum of 10 bar of atmospheric pressure. We finally discuss the science payload required on a Saturn probe to match the measurement requirements.
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| 18. |
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| 19. |
- Qi, Qibin, et al.
(författare)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
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Tidskriftsartikel (refereegranskat)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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| 20. |
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| 21. |
- Aboul-Ata, Aboul-Ata E, et al.
(författare)
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Plant-based vaccines: novel and low-cost possible route for mediterranean innovative vaccination strategies.
- 2014
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Ingår i: Advances in Virus Research. - : Elsevier. - 1557-8399. ; 89, s. 1-37, s. 1-37
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Forskningsöversikt (refereegranskat)abstract
- A plant bioreactor has enormous capability as a system that supports many biological activities, that is, production of plant bodies, virus-like particles (VLPs), and vaccines. Foreign gene expression is an efficient mechanism for getting protein vaccines against different human viral and nonviral diseases. Plants make it easy to deal with safe, inexpensive, and provide trouble-free storage. The broad spectrum of safe gene promoters is being used to avoid risk assessments. Engineered virus-based vectors have no side effect. The process can be manipulated as follows: (a) retrieve and select gene encoding, use an antigenic protein from GenBank and/or from a viral-genome sequence, (b) design and construct hybrid-virus vectors (viral vector with a gene of interest) eventually flanked by plant-specific genetic regulatory elements for constitutive expression for obtaining chimeric virus, (c) gene transformation and/or transfection, for transient expression, into a plant-host model, that is, tobacco, to get protocols processed positively, and then moving into edible host plants, (d) confirmation of protein expression by bioassay, PCR-associated tests (RT-PCR), Northern and Western blotting analysis, and serological assay (ELISA), (e) expression for adjuvant recombinant protein seeking better antigenicity, (f) extraction and purification of expressed protein for identification and dosing, (g) antigenicity capability evaluated using parental or oral delivery in animal models (mice and/or rabbit immunization), and (h) growing of construct-treated edible crops in protective green houses. Some successful cases of heterologous gene-expressed protein, as edible vaccine, are being discussed, that is, hepatitis C virus (HCV). R9 mimotope, also named hypervariable region 1 (HVR1), was derived from the HVR1 of HCV. It was used as a potential neutralizing epitope of HCV. The mimotope was expressed using cucumber mosaic virus coat protein (CP), alfalfa mosaic virus CP P3/RNA3, and tobacco mosaic virus (TMV) CP-tobacco mild green mosaic virus (TMGMV) CP as expression vectors into tobacco plants. Expressed recombinant protein has not only been confirmed as a therapeutic but also as a diagnostic tool. Herpes simplex virus 2 (HSV-2), HSV-2 gD, and HSV-2 VP16 subunits were transfected into tobacco plants, using TMV CP-TMGMV CP expression vectors.
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| 22. |
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| 23. |
- Ahmad, Shafqat, et al.
(författare)
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Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. : combined analysis of 111,421 individuals of European ancestry
- 2013
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 9:7, s. 1003607-1003607
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Tidskriftsartikel (refereegranskat)abstract
- Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
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| 24. |
- Ahmad, Shafqat, et al.
(författare)
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Gene x physical activity interactions in obesity : combined analysis of 111,421 individuals of European ancestry
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 9:7, s. e1003607-
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Tidskriftsartikel (refereegranskat)abstract
- Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
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| 25. |
- Al-Refai, Mohammed, et al.
(författare)
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Monotone iterative sequences for non-local elliptic problems
- 2011
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Ingår i: European journal of applied mathematics (Print). - : Cambridge University Press. - 0956-7925 .- 1469-4425. ; 22:6, s. 533-552
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we establish an existence and uniqueness result for a class of non-local elliptic differential equations with the Dirichlet boundary conditions, which, in general, do not accept a maximum principle. We introduce one monotone sequence of lower-upper pairs of solutions and prove uniform convergence of that sequence to the actual solution of the problem, which is the unique solution for some range of γ(the parameter of the problem). The convergence of the iterative sequence is tested through examples with an order of convergence greater than
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| 26. |
- Ali, Abdulemir, et al.
(författare)
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Dissatisfied patients after total knee arthroplasty
- 2014
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 85:3, s. 229-233
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - In 2003, an enquiry by the Swedish Knee Arthroplasty Register (SKAR) 2-7 years after total knee arthroplasty (TKA) revealed patients who were dissatisfied with the outcome of their surgery but who had not been revised. 6 years later, we examined the dissatisfied patients in one Swedish county and a matched group of very satisfied patients. Patients and methods - 118 TKAs in 114 patients, all of whom had had their surgery between 1996 and 2001, were examined in 2009-2010. 55 patients (with 58 TKAs) had stated in 2003 that they were dissatisfied with their knees and 59 (with 60 TKAs) had stated that they were very satisfied with their knees. The patients were examined clinically and radiographically, and performed functional tests consisting of the 6-minute walk and chair-stand test. All the patients filled out a visual analog scale (VAS, 0-100 mm) regarding knee pain and also the Hospital and Anxiety and Depression scale (HAD). Results - Mean VAS score for knee pain differed by 30 mm in favor of the very satisfied group (p < 0.001). 23 of the 55 patients in the dissatisfied group and 6 of 59 patients in the very satisfied group suffered from anxiety and/or depression (p = 0.001). Mean range of motion was 11 degrees better in the very satisfied group (p < 0.001). The groups were similar with regard to clinical examination, physical performance testing, and radiography. Interpretation - The patients who reported poor response after TKA continued to be unhappy after 8-13 years, as demonstrated by VAS pain and HAD, despite the absence of a discernible objective reason for revision.
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| 27. |
- Ali, Imran, et al.
(författare)
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Cadmium-induced effects on cellular signaling pathways in the liver of transgenic estrogen reporter mice.
- 2012
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 127:1, s. 66-75
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen-like effects of cadmium (Cd) have been reported in several animal studies, and recent epidemiological findings suggest increased risk of hormone-dependent cancers after Cd exposure. The mechanisms underlying these effects are still under investigation. Our aim was to study the effects of Cd on cellular signaling pathways in vivo with special focus on estrogen signaling and to perform benchmark dose analysis on the effects. Transgenic adult ERE-luciferase male mice were exposed subcutaneously to 0.5-500 μg CdCl(2) per kg body weight (bw) or 17α-ethinylestradiol (EE2) for 3 days. These doses had no effects on organ and bw or testicular histology, indicating subtoxic exposure levels. The transgene luciferase, reporting genomic estrogen response, was significantly increased by EE2 but not by Cd. However, Cd significantly affected kinase phosphorylation and endogenous gene expression. Interestingly, gene expression changes displayed a traditional dose-response relationship, with benchmark dose levels for the expression of Mt1, Mt2, p53, c-fos, and Mdm2 being 92.9, 19.9, 7.6, 259, and 25.9 μg/kg bw, respectively, but changes in kinase phosphorylation were only detected at low exposure levels. Phosphorylation of Erk1/2 was significantly increased even in the lowest dose group, 0.5 μg/kg bw, rendering pErk1/2 a more sensitive sensor of exposure than changes in gene expression. Collectively, our data suggest that the effects triggered by Cd in vivo are markedly concentration dependent. Furthermore, we conclude that the estrogen-like effects of Cd are likely to result from a mechanism different from steroidal estrogens.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Ali, Imran, et al.
(författare)
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Estrogen-like effects of cadmium in vivo do not appear to be mediated via the classical estrogen receptor transcriptional pathway.
- 2010
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 118:10, s. 1389-94
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cadmium (Cd), a ubiquitous food contaminant, has been proposed to be an endocrine disruptor by inducing estrogenic responses in vivo. Several in vitro studies suggested that these effects are mediated via estrogen receptors (ERs). OBJECTIVE: We performed this study to clarify whether Cd-induced effects in vivo are mediated via classical ER signaling through estrogen responsive element (ERE)-regulated genes or if other signaling pathways are involved. METHODS: We investigated the estrogenic effects of cadmium chloride (CdCl2) exposure in vivo by applying the Organisation for Economic Co-operation and Development (OECD) rodent uterotrophic bioassay to transgenic ERE-luciferase reporter mice. Immature female mice were injected subcutaneously with CdCl2 (5, 50, or 500 µg/kg body weight) or with 17α-ethinylestradiol (EE2) on 3 consecutive days. We examined uterine weight and histology, vaginal opening, body and organ weights, Cd tissue retention, activation of mitogen-activated protein kinase (MAPK) pathways, and ERE-dependent luciferase expression. RESULTS: CdCl2 increased the height of the uterine luminal epithelium in a dose-dependent manner without increasing the uterine wet weight, altering the timing of vaginal opening, or affecting the luciferase activity in reproductive or nonreproductive organs. However, we observed changes in the phosphorylation of mouse double minute 2 oncoprotein (Mdm2) and extracellular signal-regulated kinase (Erk1/2) in the liver after CdCl2 exposure. As we expected, EE2 advanced vaginal opening and increased uterine epithelial height, uterine wet weight, and luciferase activity in various tissues. CONCLUSION: Our data suggest that Cd exposure induces a limited spectrum of estrogenic responses in vivo and that, in certain targets, effects of Cd might not be mediated via classical ER signaling through ERE-regulated genes.
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| 32. |
- Ali, T. S., et al.
(författare)
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Violence permeating daily life: a qualitative study investigating perspectives on violence among women in Karachi, Pakistan
- 2012
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Ingår i: International journal of women's health. - : Informa UK Limited. - 1179-1411 .- 1179-1411. ; 4, s. 577-85
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study explored how married women perceive situations which create family conflicts and lead to different forms of violence in urban Pakistan. In addition, it examines perceptions of consequences of violence, their adverse health effects, and how women resist violence within marital life. METHODS: Five focus group discussions were conducted with 28 women in Karachi. Purposive sampling, aiming for variety in age, employment status, education, and socioeconomic status, was employed. The focus group discussions were conducted in Urdu and translated into English. Manifest and latent content analysis were applied. RESULTS: One major theme emerged during the analysis, ie, family violence through the eyes of females. This theme was subdivided into three main categories. The first category, ie, situations provoking violence and their manifestations, elaborates on circumstances that provoke violence and situations that sustain violence. The second category, ie, actions and reactions to exposure to violence, describes consequences of ongoing violence within the family, including those that result in suicidal thoughts and actions. The final category, ie, resisting violence, describes how violence is avoided through women's awareness and actions. CONCLUSION: The current study highlights how female victims of abuse are trapped in a society where violence from a partner and family members is viewed as acceptable, where divorce is unavailable to the majority, and where societal support of women is limited. There is an urgent need to raise the subject of violence against women and tackle this human rights problem at all levels of society by targeting the individual, family, community, and societal levels concurrently.
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| 33. |
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| 34. |
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| 35. |
- Ananthanarayanan, G., et al.
(författare)
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PACMan : Coordinated memory caching for parallel jobs
- 2012
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Ingår i: Proceedings of NSDI 2012. - : USENIX Association. ; , s. 267-280
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Konferensbidrag (refereegranskat)abstract
- Data-intensive analytics on large clusters is important for modern Internet services. As machines in these clusters have large memories, in-memory caching of inputs is an effective way to speed up these analytics jobs. The key challenge, however, is that these jobs run multiple tasks in parallel and a job is sped up only when inputs of all such parallel tasks are cached. Indeed, a single task whose input is not cached can slow down the entire job. To meet this "all-or-nothing" property, we have built PACMan, a caching service that coordinates access to the distributed caches. This coordination is essential to improve job completion times and cluster efficiency. To this end, we have implemented two cache replacement policies on top of PACMan's coordinated infrastructure fb-LIFE that minimizes average completion time by evicting large incomplete inputs, and LFU-F that maximizes cluster efficiency by evicting less frequently accessed inputs. Evaluations on production workloads from Facebook and Microsoft Bing show that PACMan reduces average completion time of jobs by 56% and 51% (small interactive jobs improve by 77%), and improves efficiency of the cluster by 47% and 54%, respectively.
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| 36. |
- Bailis, P., et al.
(författare)
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Bolt-on causal consistency
- 2013
-
Ingår i: SIGMOD '13 Proceedings of the 2013 ACM SIGMOD International Conference on Management of Data. - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450320375 ; , s. 761-772
-
Konferensbidrag (refereegranskat)abstract
- We consider the problem of separating consistency-related safety properties from availability and durability in distributed data stores via the application of a "bolt-on" shim layer that upgrades the safety of an underlying general-purpose data store. This shim provides the same consistency guarantees atop a wide range of widely deployed but often inflexible stores. As causal consistency is one of the strongest consistency models that remain available during system partitions, we develop a shim layer that upgrades eventually consistent stores to provide convergent causal consistency. Accordingly, we leverage widely deployed eventually consistent infrastructure as a common substrate for providing causal guarantees. We describe algorithms and shim implementations that are suitable for a large class of application-level causality relationships and evaluate our techniques using an existing, production-ready data store and with real-world explicit causality relationships.
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| 37. |
- Bailis, P., et al.
(författare)
-
HAT, not CAP : Towards highly available transactions
- 2013
-
Ingår i: 14th Workshop on Hot Topics in Operating Systems, HotOS 2013. - : USENIX Association.
-
Konferensbidrag (refereegranskat)abstract
- While the CAP Theorem is often interpreted to preclude the availability of transactions in a partition-prone environment, we show that highly available systems can provide useful transactional semantics, often matching those of today's ACID databases. We propose Highly Available Transactions (HATs) that are available in the presence of partitions. HATs support many desirable ACID guarantees for arbitrary transactional sequences of read and write operations and permit low-latency operation.
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| 38. |
- Bailis, P., et al.
(författare)
-
The potential dangers of causal consistency and an explicit solution
- 2012
-
Ingår i: Proceedings of the 3rd ACM Symposium on Cloud Computing, SoCC 2012. - New York, NY, USA : ACM. - 9781450317610
-
Konferensbidrag (refereegranskat)abstract
- Causal consistency is the strongest consistency model that is available in the presence of partitions and provides useful semantics for human-facing distributed services. Here, we expose its serious and inherent scalability limitations due to write propagation requirements and traditional dependency tracking mechanisms. As an alternative to classic potential causality, we advocate the use of explicit causality, or application-defined happens-before relations. Explicit causality, a subset of potential causality, tracks only relevant dependencies and reduces several of the potential dangers of causal consistency.
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| 39. |
- Biglarnia, Ali-Reza, et al.
(författare)
-
Transplantation av pankreas botande alternativ vid typ 1-diabetes : [Transplantation of pancreas, a curative option for type 1 diabetes]
- 2012
-
Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 109:39-40, s. 1754-1757
-
Tidskriftsartikel (refereegranskat)abstract
- In the past decade, pancreas transplantation (PTx) has become increasingly attractive as a curative treatment in patients with labile diabetes and secondary complications. In the United Kingdom, the percentage of deceased-donors utilized for PTx increased 5-fold between 2003 and 2007. The trend towards a higher number of annual pancreas transplantations is also observed in Sweden. The increasing activity and the excellent outcome are consequences of meticulous surgery, effective immunsuppression and adequate follow-up. The present report descibes the current status of PTx and shows the short- and long-term results during the last decade in Sweden.
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| 40. |
- Carter, Richard I., et al.
(författare)
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The fibrinogen cleavage product A alpha-Val(360), a specific marker of neutrophil elastase activity in vivo
- 2011
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Ingår i: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 66:8, s. 686-691
-
Tidskriftsartikel (refereegranskat)abstract
- Background Alpha-1-antitrypsin (A1AT) deficiency is the only recognised genetic risk factor for chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Since A1AT is the major inhibitor of neutrophil elastase (NE), this enzyme has become widely implicated in the pathogenesis of COPD in general; however, there is currently no specific biomarker for its pre-inhibition activity. Such a biomarker should be a measure of elastase-specific COPD disease activity with the potential to assess early targeted therapeutic intervention, in contrast to traditional and non-specific disease severity markers such as forced expiratory volume in 1 s. Methods In pilot studies, plasma A alpha-Val(360) and markers of neutrophil activation were measured in 95 subjects with a range of A1AT concentrations. A alpha-Val(360) and sputum elastase activity were also measured in a further seven PiZ A1AT-deficient subjects over the course of an acute exacerbation. Finally, A alpha-Val(360) was measured in plasma from subjects randomised to receive A1AT replacement or placebo in the EXACTLE trial. Results The plasma concentrations of A alpha-Val(360) and A1AT related exponentially, consistent with previous theoretical and in vitro experimental data. L-233 (an intracellular NE inhibitor) blocked generation of A alpha-Val(360) and subsequent A1AT/NE complex formation. A alpha-Val(360) was related to the spirometric severity of lung disease in A1AT deficiency, to sputum elastase activity in acute exacerbations and was decreased in subjects receiving A1AT replacement therapy (while remaining constant in those receiving placebo). Conclusions A alpha-Val(360) represents the first specific footprint of pre-inhibition NE activity and is a potential biomarker of disease activity and progression in subjects with elastase-dependent COPD.
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| 41. |
- Chylarecka, D., et al.
(författare)
-
Indirect Magnetic Coupling of Manganese Porphyrin to a Ferromagnetic Cobalt Substrate
- 2011
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:4, s. 1295-1301
-
Tidskriftsartikel (refereegranskat)abstract
- The coupling mechanism of magnetic molecules to ferromagnetic surfaces is of scientific interest to design and tune molecular spintronic interfaces utilizing their molecular and surface architecture. Indirect magnetic coupling has been proposed earlier on the basis of density functional theory +U (DFT+U) calculations, for the magnetic coupling of manganese(II) porphyrin (MnP) molecules to thin Co films. Here we provide an experimental X-ray magnetic circular dichroism (XMCD) spectroscopy and scanning tunneling microscopy (STM) study of manganese(III) tetraphenylporphyrin chloride (MnTPPCl) on rough (exhibiting a high density of monatomic steps) and smooth (exhibiting a low density of monatomic steps) thin Co films grown on a Cu(001) single crystal toward the assessment of the magnetic coupling mechanism. After deposition onto the surface, MnTPPCl molecules were found to couple ferromagnetically to both rough and smooth Co substrates. For high molecular coverage, we observed higher XMCD signals at the Mn L-edges on the smooth Co substrate than on the rough Co substrate, as expected for the proposed indirect magnetic coupling mechanism on the basis of its predominance on the flat surface areas. In particular, DFT+U calculations predict a weak ferromagnetic molecule-substrate coupling only if the chloride ion of the MnTPPCl molecule orients away (Co-Mn-Cl) from the Co surface.
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| 42. |
- El-Essawi, A, et al.
(författare)
-
Minimized perfusion circuits: an alternative in the surgical treatment of Jehovah's Witnesses
- 2013
-
Ingår i: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 28:1, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- Jehovah’s Witnesses present a challenge to cardiac surgeons, as quality of care is not only defined by mortality and morbidity, but also by the avoidance of blood transfusions. Over the last years, minimized perfusion circuits (MPC) have contributed substantially to the achievement of this goal in our clinic. Presented is a retrospective analysis of our experience. Methods: Twenty-nine Jehovah’s Witnesses, aged 69 ± 10 years, have undergone cardiac surgery with a MPC in our institution since 2005. The ROCsafe (Reservoir Optional Circuit) MPC was used in most of these patients (n=27) as it offers the unique possibility of a speedy integration of a reservoir in the event of a major air leak, thereby, negligating any safety concerns. Results: There was no in-hospital or 30-day postoperative mortality. Mean ICU stay was 1.6 ± 2 days with a mean intubation time of 11.3 ± 9.1 hrs. Postoperative complications included one myocardial infarction with accompanying low cardiac output, one stroke, one transient delirium, one idiopathic thrombocytopenia and three re-operations (one sternal infection, one postoperative bleeding and one delayed tamponade). The mean postoperative hospital stay was 9.9 ± 2.3 days. Mean decrease in hemoglobin was 2.1 ± 1.3 g/dl during cardiopulmonary bypass and 3.4 ±1.4 g/dl at discharge. The lowest postoperative hemoglobin level was 9.3 ±1.8 (Range 6-12.9). Conclusions: These encouraging results emphasize the role MPCs can play in optimizing the quality of patient care. We hope that this report can serve as a stimulus for similar experiences.
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| 43. |
- Fulati, Alimujiang, 1981-, et al.
(författare)
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An intracellular glucose biosensor based on nanoflake ZnO
- 2010
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 150:2, s. 673-680
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this study, an improved potentiometric intracellular glucose biosensor was fabricated with immobilization of glucose oxidase on a ZnO nanoporous material. The ZnO nanoporous material with a wall thickness around 200 nm was grown on the tip of a borosilicate glass capillary and used as a selective intracellular glucose sensor for the measurement of glucose concentrations in human adipocytes and frog oocytes. The results showed a fast response within 4 s and a linear glucosedependent electrochemical response over a wide range of glucose concentration (500 nM-10 mM). The measurements of intracellular glucose concentrations with our biosensor were consistent with the values of intracellular glucose concentrations reported in the literature. The sensor also demonstrated its capability by detecting an increase in the intracellular glucose concentration induced by insulin. We found that the ZnO nanoporous material provides sensitivity as high as 1.8 times higher than that obtained using ZnO nanorods under the same conditions. Moreover, the fabrication method in our experiment is simple and the excellent performance of the developed nanosensor in sensitivity, stability, selectivity, reproducibility and anti-interference was achieved. All these advantageous features of this intracellular glucose biosensor based on functionalised ZnO nanoporous material compared to ZnO nanorods demonstrate a promising way of enhancing glucose biosensor performance to measure reliable intracellular glucose concentrations within single living cells.
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| 44. |
- Ghodsi, Ali, et al.
(författare)
-
Multi-resource fair queueing for packet processing
- 2012
-
Ingår i: SIGCOMM'12 - Proceedings of the ACM SIGCOMM 2012 Conference Applications, Technologies, Architectures, and Protocols for Computer Communication. - New York, NY, USA : ACM. - 9781450314190 ; , s. 1-12
-
Konferensbidrag (refereegranskat)abstract
- Middleboxes are ubiquitous in today's networks and perform a variety of important functions, including IDS, VPN, firewalling, and WAN optimization. These functions differ vastly in their requirements for hardware resources (e.g., CPU cycles and memory bandwidth). Thus, depending on the functions they go through, different flows can consume different amounts of a middlebox's resources. While there is much literature on weighted fair sharing of link bandwidth to isolate flows, it is unclear how to schedule multiple resources in a middlebox to achieve similar guarantees. In this paper, we analyze several natural packet scheduling algorithms for multiple resources and show that they have undesirable properties. We propose a new algorithm, Dominant Resource Fair Queuing (DRFQ), that retains the attractive properties that fair sharing provides for one resource. In doing so, we generalize the concept of virtual time in classical fair queuing to multi-resource settings. The resulting algorithm is also applicable in other contexts where several resources need to be multiplexed in the time domain.
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| 45. |
- Hood, Michael E, et al.
(författare)
-
Distribution of the anther-smut pathogen Microbotryum on species of the Caryophyllaceae.
- 2010
-
Ingår i: The New phytologist. - : Wiley. - 1469-8137 .- 0028-646X. ; 187:1, s. 217-29
-
Tidskriftsartikel (refereegranskat)abstract
- *Understanding disease distributions is of fundamental and applied importance, yet few studies benefit from integrating broad sampling with ecological and phylogenetic data. Here, anther-smut disease, caused by the fungus Microbotryum, was assessed using herbarium specimens of Silene and allied genera of the Caryophyllaceae. *A total of 42,000 herbarium specimens were examined, and plant geographical distributions and morphological and life history characteristics were tested as correlates of disease occurrence. Phylogenetic comparative methods were used to determine the association between disease and plant life-span. *Disease was found on 391 herbarium specimens from 114 species and all continents with native Silene. Anther smut occurred exclusively on perennial plants, consistent with the pathogen requiring living hosts to overwinter. The disease was estimated to occur in 80% of perennial species of Silene and allied genera. The correlation between plant life-span and disease was highly significant while controlling for the plant phylogeny, but the disease was not correlated with differences in floral morphology. *Using resources available in natural history collections, this study illustrates how disease distribution can be determined, not by restriction to a clade of susceptible hosts or to a limited geographical region, but by association with host life-span, a trait that has undergone frequent evolutionary transitions.
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| 46. |
- Isikman, Arif Onder, 1988, et al.
(författare)
-
Joint phase noise estimation and data detection in coded multi-input-multi-output systems
- 2014
-
Ingår i: IET Communications. - : Institution of Engineering and Technology (IET). - 1751-8628 .- 1751-8636. ; 8:7, s. 981-989
-
Tidskriftsartikel (refereegranskat)abstract
- The problem of joint oscillator phase noise (PHN) estimation and data detection for multi-input multi-output (MIMO) systems using bit-interleaved-coded modulation is analysed. A new MIMO receiver that iterates between the estimator and the detector, based on the expectation-maximisation (EM) framework, is proposed. It is shown that at high signal-to-noise ratios, a maximum a posteriori (MAP) estimator can be used to carry out the maximisation step of the EM algorithm. Moreover, to reduce the computational complexity of the proposed EM algorithm, a soft decision-directed extended Kalman filter-smoother (EKFS) is applied instead of the MAP estimator to track the PHN parameters. The numerical results show that by combining the proposed EKFS-based approach with an iterative detector that employs low-density parity check codes, PHN can be accurately tracked. The simulations also demonstrate that compared to the existing algorithms, the proposed iterative receiver can significantly enhance the performance of MIMO systems in the presence of PHN.
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| 47. |
- Kazemi Seresht, Ali, 1980, et al.
(författare)
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The Challenge of Improved Secretory Production of Active Pharmaceutical Ingredients in Saccharomyces cerevisiae: A Case Study on Human Insulin Analogs
- 2013
-
Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 110:10, s. 2764-2774
-
Tidskriftsartikel (refereegranskat)abstract
- The yeast Saccharomyces cerevisiae has widely been used as a host for the production of heterologous proteins. Great attention has been put on improved secretory production of active pharmaceutical ingredients, and the secretory pathway of this eukaryotic host has been the playground of diverse strain engineering studies, aiming at enhanced cellular capacities for folding and trafficking of the target proteins. However, the cellular quality assessment for secretory proteins remains mostly unpredictable, and different target proteins often do not picture similar secretion yields, underlining the dependency of efficient secretion on the physicochemical properties of the protein of interest. In this study, two human insulin analog precursors (IAPs) with minor differences in their amino acid sequences were used as model secretory proteins. No differences between cells expressing these two proteins were found in the IAP transcript levels, gene copy numbers, or intra-cellularly accumulated proteins, yet a more than sevenfold difference in their secretion yields was found. Physiological characterization of cells expressing these proteins in batch processes revealed no significant difference in their specific growth rate, but an altered overflow metabolism. Global transcriptome analysis carried out in chemostat experiments pinpointed distinct steps during the protein maturation pathway to be differentially regulated and indicated an increased degradation of the IAP with the low secretion yield. In silico protein structure modeling of the IAPs suggested a difference in conformational stability, induced by the amino acid substitution, which most likely resulted in disparity in trafficking through the secretory pathway and thus a large difference in secretion yields.
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| 48. |
- Khattab, Ibrahim A., et al.
(författare)
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Photocatalytic degradation of azo dye Reactive Red 15 over synthesized titanium and zinc oxides photocatalysts : a comparative study
- 2012
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Ingår i: Desalination and Water Treatment. - : Informa UK Limited. - 1944-3994 .- 1944-3986. ; 48:1-3, s. 120-129
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticle TiO2 and ZnO were prepared by facile method. The XRD pattern study shows that there is no obvious difference in crystal composition of various shapes of TiO2 and ZnO. The photocatalytic degradation of Reactive Red 15, commonly used as a textile dye, using synthesized titanium and zinc oxides was investigated. The effects of influential parameters such as initial pH, catalyst loading, initial dye concentration and addition of hydrogen peroxide were studied. The degradation efficiency was expressed by the removal of color and chemical oxygen demand (COD). The study reveals that: (1) Both catalysts, under corresponding optimal conditions, can be employed as an effective photocatalyst for the elimination of color and COD from dye wastewater. Also, ZnO is more efficient catalyst than TiO2; (2) Addition of proper amount of hydrogen peroxide improves both the decolorization and the degradation of the dye; (3) The photocatalytic degradation of Reactive Red 15, in the presence of both photocatalysts, obeyed pseudo-first order kinetics. The biodegradability ratio BOD5/COD increases from original zero up to 0.52 and 0.6 within 90 minutes irradiation time using 1 and 0.75 g/L TiO2 and ZnO, respectively.
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| 49. |
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| 50. |
- Morris, Ulrika, et al.
(författare)
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Rapid diagnostic tests for molecular surveillance of Plasmodium falciparum malaria -assessment of DNA extraction methods and field applicability.
- 2013
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Ingår i: Malaria journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- The need for new malaria surveillance tools and strategies is critical, given improved global malaria control and regional elimination efforts. High quality Plasmodium falciparum DNA can reliably be extracted from malaria rapid diagnostic tests (RDTs). Together with highly sensitive molecular assays, wide scale collection of used RDTs may serve as a modern tool for improved malaria case detection and drug resistance surveillance. However, comparative studies of DNA extraction efficiency from RDTs and the field applicability are lacking. The aim of this study was to compare and evaluate different methods of DNA extraction from RDTs and to test the field applicability for the purpose of molecular epidemiological investigations.
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