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- Saunders, N. R., et al.
(författare)
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Age-Dependent Transcriptome and Proteome Following Transection of Neonatal Spinal Cord of Monodelphis domestica (South American Grey Short-Tailed Opossum)
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- This study describes a combined transcriptome and proteome analysis of Monodelphis domestica response to spinal cord injury at two different postnatal ages. Previously we showed that complete transection at postnatal day 7 (P7) is followed by profuse axon growth across the lesion with near-normal locomotion and swimming when adult. In contrast, at P28 there is no axon growth across the lesion, the animals exhibit weight-bearing locomotion, but cannot use hind limbs when swimming. Here we examined changes in gene and protein expression in the segment of spinal cord rostral to the lesion at 24 h after transection at P7 and at P28. Following injury at P7 only forty genes changed (all increased expression); most were immune/inflammatory genes. Following injury at P28 many more genes changed their expression and the magnitude of change for some genes was strikingly greater. Again many were associated with the immune/inflammation response. In functional groups known to be inhibitory to regeneration in adult cords the expression changes were generally muted, in some cases opposite to that required to account for neurite inhibition. For example myelin basic protein expression was reduced following injury at P28 both at the gene and protein levels. Only four genes from families with extracellular matrix functions thought to influence neurite outgrowth in adult injured cords showed substantial changes in expression following injury at P28: Olfactomedin 4 (Olfm4, 480 fold compared to controls), matrix metallopeptidase (Mmp1, 104 fold), papilin (Papln, 152 fold) and integrin alpha 4 (Itga4, 57 fold). These data provide a resource for investigation of a priori hypotheses in future studies of mechanisms of spinal cord regeneration in immature animals compared to lack of regeneration at more mature stages.
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- Bentley, Michael J., et al.
(författare)
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A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum
- 2014
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse la. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community.
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- Jensen, S. B., et al.
(författare)
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A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact
- 2010
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Ingår i: SUPPORTIVE CARE IN CANCER. - 0941-4355. ; 18:8, s. 1061-1079
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Tidskriftsartikel (refereegranskat)abstract
- Purpose This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. Methods The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. Results Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Conclusions There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.
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- Bafadhel, Mona, et al.
(författare)
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Acute Exacerbations of Chronic Obstructive Pulmonary Disease : Identification of Biologic Clusters and Their Biomarkers
- 2011
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 184:6, s. 662-671
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology. Objectives: Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation. Methods: Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated. Measurements and Main Results: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed "pauciinflammatory." Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1 beta, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83-0.95); serum CXCL10, 0.83 (95% CI, 0.70-0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78-0.93), respectively. Conclusions: The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1 beta, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
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- Ek, C. Joakim, et al.
(författare)
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Barriers in the developing brain and Neurotoxicology
- 2012
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Ingår i: Neurotoxicology. - : Elsevier BV. - 0161-813X. ; 33:3, s. 586-604
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Tidskriftsartikel (refereegranskat)abstract
- The brain develops and grows within a well-controlled internal environment that is provided by cellular exchange mechanisms in the interfaces between blood, cerebrospinal fluid and brain. These are generally referred to by the term "brain barriers": blood-brain barrier across the cerebral endothelial cells and blood-CSF barrier across the choroid plexus epithelial cells. An essential component of barrier mechanisms is the presence of tight junctions between the endothelial and epithelial cells of these interfaces. This review outlines historical evidence for the presence of effective barrier mechanisms in the embryo and newborn and provides an up to date description of recent morphological, biochemical and molecular data for the functional effectiveness of these barriers. Intercellular tight junctions between cerebral endothelial cells and between choroid plexus epithelial cells are functionally effective as soon as they differentiate. Many of the influx and efflux mechanisms are not only present from early in development, but the genes for some are expressed at much higher levels in the embryo than in the adult and there is physiological evidence that these transport systems are functionally more active in the developing brain. This substantial body of evidence supporting the concept of well developed barrier mechanisms in the developing brain is contrasted with the widespread belief amongst neurotoxicologists that "the" blood-brain barrier is immature or even absent in the embryo and newborn. A proper understanding of the functional capacity of the barrier mechanisms to restrict the entry of harmful substances or administered therapeutics into the developing brain is critical. This knowledge would assist the clinical management of pregnant mothers and newborn infants and development of protocols for evaluation of risks of drugs used in pregnancy and the neonatal period prior to their introduction into clinical practice. (c) 2011 Elsevier Inc. All rights reserved.
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| 17. |
- Ek, C. Joakim, et al.
(författare)
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Pathological Changes in the White Matter after Spinal Contusion Injury in the Rat
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- It has been shown previously that after spinal cord injury, the loss of grey matter is relatively faster than loss of white matter suggesting interventions to save white matter tracts offer better therapeutic possibilities. Loss of white matter in and around the injury site is believed to be the main underlying cause for the subsequent loss of neurological functions. In this study we used a series of techniques, including estimations of the number of axons with pathology, immunohistochemistry and mapping of distribution of pathological axons, to better understand the temporal and spatial pathological events in white matter following contusion injury to the rat spinal cord. There was an initial rapid loss of axons with no detectable further loss beyond 1 week after injury. Immunoreactivity for CNPase indicated that changes to oligodendrocytes are rapid, extending to several millimetres away from injury site and preceding much of the axonal loss, giving early prediction of the final volume of white matter that survived. It seems that in juvenile rats the myelination of axons in white matter tracts continues for some time, which has an important bearing on interpretation of our, and previous, studies. The amount of myelin debris and axon pathology progressively decreased with time but could still be observed at 10 weeks after injury, especially at more distant rostral and caudal levels from the injury site. This study provides new methods to assess injuries to spinal cord and indicates that early interventions are needed for the successful sparing of white matter tracts following injury.
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| 18. |
- Liddelow, S. A., et al.
(författare)
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Mechanisms That Determine the Internal Environment of the Developing Brain: A Transcriptomic, Functional and Ultrastructural Approach
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- We provide comprehensive identification of embryonic (E15) and adult rat lateral ventricular choroid plexus transcriptome, with focus on junction-associated proteins, ionic influx transporters and channels. Additionally, these data are related to new structural and previously published permeability studies. Results reveal that most genes associated with intercellular junctions are expressed at similar levels at both ages. In total, 32 molecules known to be associated with brain barrier interfaces were identified. Nine claudins showed unaltered expression, while two claudins (6 and 8) were expressed at higher levels in the embryo. Expression levels for most cytoplasmic/regulatory adaptors (10 of 12) were similar at the two ages. A few junctional genes displayed lower expression in embryos, including 5 claudins, occludin and one junctional adhesion molecule. Three gap junction genes were enriched in the embryo. The functional effectiveness of these junctions was assessed using blood-delivered water-soluble tracers at both the light and electron microscopic level: embryo and adult junctions halted movement of both 286Da and 3kDa molecules into the cerebrospinal fluid (CSF). The molecular identities of many ion channel and transporter genes previously reported as important for CSF formation and secretion in the adult were demonstrated in the embryonic choroid plexus (and validated with immunohistochemistry of protein products), but with some major age-related differences in expression. In addition, a large number of previously unidentified ion channel and transporter genes were identified for the first time in plexus epithelium. These results, in addition to data obtained from electron microscopical and physiological permeability experiments in immature brains, indicate that exchange between blood and CSF is mainly transcellular, as well-formed tight junctions restrict movement of small water-soluble molecules from early in development. These data strongly indicate the brain develops within a well-protected internal environment and the exchange between the blood, brain and CSF is transcellular and not through incomplete barriers.
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- Nordin, J., et al.
(författare)
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Lensed Type Ia supernovae as probes of cluster mass models
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 440:3, s. 2742-2754
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Tidskriftsartikel (refereegranskat)abstract
- Using three magnified Type Ia supernovae (SNe Ia) detected behind CLASH (Cluster Lensing and Supernovae with Hubble) clusters, we perform a first pilot study to see whether standardizable candles can be used to calibrate cluster mass maps created from strong lensing observations. Such calibrations will be crucial when next-generation Hubble Space Telescope cluster surveys (e.g. Frontier) provide magnification maps that will, in turn, form the basis for the exploration of the high-redshift Universe. We classify SNe using combined photometric and spectroscopic observations, finding two of the three to be clearly of Type Ia and the third probable. The SNe exhibit significant amplification, up to a factor of 1.7 at similar to 5 Sigma significance (SN-L2). We conducted this as a blind study to avoid fine-tuning of parameters, finding a mean amplification difference between SNe and the cluster lensing models of 0.09 +/- 0.09(stat) +/- 0.05(sys) mag. This impressive agreement suggests no tension between cluster mass models and high-redshift-standardized SNe Ia. However, the measured statistical dispersion of Sigma(mu) = 0.21 mag appeared large compared to the dispersion expected based on statistical uncertainties (0.14). Further work with the SN and cluster lensing models, post-unblinding, reduced the measured dispersion to Sigma(mu) = 0.12. An explicit choice should thus be made as to whether SNe are used unblinded to improve the model, or blinded to test the model. As the lensed SN samples grow larger, this technique will allow improved constraints on assumptions regarding e.g. the structure of the dark matter halo.
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- Priyadarshi, S., et al.
(författare)
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Parallel Transient Simulation of Multiphysics Circuits Using Delay-Based Partitioning
- 2012
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Ingår i: IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems. - : Institute of Electrical and Electronics Engineers (IEEE). - 1937-4151 .- 0278-0070. ; 31:10, s. 1522-1535
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Tidskriftsartikel (refereegranskat)abstract
- A parallel transient simulation technique for multiphysics circuits is presented. The technique develops partitions utilizing the inherent delay present within a circuit and between physical domains. A state-variable-based circuit delay element is presented, which implements the coupling between two spatially or temporally isolated circuit partitions. A parallel delay-based iterative approach for interfacing delay-partitioned subcircuits is applied, which achieves the reasonable accuracy of nonparallel circuit simulation if both incorporate the same interblock delay. The partitioned subcircuits are distributed to different cores of a shared-memory multicore processor and solved in parallel. A multithreaded implementation of the methodology using OpenMP is presented. Examples showing superlinear speedup compared to unpartitioned single-core simulation using the direct method are presented. This paper also discusses the impact of load balancing and absolute delay on simulation speedup.
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| 24. |
- Rubin, D., et al.
(författare)
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Precision Measurement of The Most Distant Spectroscopically Confirmed Supernova Ia with the Hubble Space Telescope
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 763:1, s. 35-
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a redshift 1.71 supernova in the GOODS-North field. The Hubble Space Telescope (HST) ACS spectrum has almost negligible contamination from the host or neighboring galaxies. Although the rest-frame-sampled range is too blue to include any Si II line, a principal component analysis allows us to confirm it as a Type Ia supernova with 92% confidence. A recent serendipitous archival HST WFC3 grism spectrum contributed a key element of the confirmation by giving a host-galaxy redshift of 1.713 +/- 0.007. In addition to being the most distant SN Ia with spectroscopic confirmation, this is the most distant Ia with a precision color measurement. We present the ACS WFC and NICMOS 2 photometry and ACS and WFC3 spectroscopy. Our derived supernova distance is in agreement with the prediction of CDM.
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- Sale, Peter F., et al.
(författare)
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Transforming management of tropical coastal seas to cope with challenges of the 21st century
- 2014
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Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X .- 1879-3363. ; 85:1, s. 8-23
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Tidskriftsartikel (refereegranskat)abstract
- Over 1.3 billion people live on tropical coasts, primarily in developing countries. Many depend on adjacent coastal seas for food, and livelihoods. We show how trends in demography and in several local and global anthropogenic stressors are progressively degrading capacity of coastal waters to sustain these people. Far more effective approaches to environmental management are needed if the loss in provision of ecosystem goods and services is to be stemmed. We propose expanded use of marine spatial planning as a framework for more effective, pragmatic management based on ocean zones to accommodate conflicting uses. This would force the holistic, regional-scale reconciliation of food security, livelihoods, and conservation that is needed. Transforming how countries manage coastal resources will require major change in policy and politics, implemented with sufficient flexibility to accommodate societal variations. Achieving this change is a major challenge - one that affects the lives of one fifth of humanity.
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