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- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 4. |
- Arthur, Edmund, et al.
(författare)
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Central Macular Thickness in Diabetic Patients : A Sex-based Analysis
- 2019
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Ingår i: Optometry and Vision Science. - : American Academy of Optometry. - 1040-5488 .- 1538-9235. ; 96:4, s. 266-275
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Tidskriftsartikel (refereegranskat)abstract
- SIGNIFICANCE The pathological changes in clinically significant diabetic macular edema lead to greater retinal thickening in men than in women. Therefore, male sex should be considered a potential risk factor for identifying individuals with the most severe pathological changes. Understanding this excessive retinal thickening in men may help preserve vision. PURPOSE The purpose of this study was to investigate the sex differences in retinal thickness in diabetic patients. We tested whether men with clinically significant macular edema had even greater central macular thickness than expected from sex differences without significant pathological changes. This study also aimed to determine which retinal layers contribute to abnormal retinal thickness. METHODS From 2047 underserved adult diabetic patients from Alameda County, CA, 142 patients with clinically significant macular edema were identified by EyePACS-certified graders using color fundus images (Canon CR6-45NM). First, central macular thickness from spectral domain optical coherence tomography (iVue; Optovue Inc.) was compared in 21 men versus 21 women without clinically significant macular edema. Then, a planned comparison contrasted the greater values of central macular thickness in men versus women with clinically significant macular edema as compared with those without. Mean retinal thickness and variability of central macular layers were compared in men versus women. RESULTS Men without clinically significant macular edema had a 12-μm greater central macular thickness than did women (245 ± 21.3 and 233 ± 13.4 μm, respectively; t40 = −2.18, P = .04). Men with clinically significant macular edema had a 67-μm greater central macular thickness than did women (383 ± 48.7 and 316 ± 60.4 μm, P < .001); that is, men had 55 μm or more than five times more (t20 = 2.35, P = .02). In men, the outer-nuclear-layer thickness was more variable, F10,10 = 9.34. CONCLUSIONS Underserved diabetic men had thicker retinas than did women, exacerbated by clinically significant macular edema.
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| 5. |
- Arthur, Edmund, et al.
(författare)
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Individual Retinal Layer Thickness in Diabetic Patients with Clinically Significant Macular Edema : A Gender Based Analysis
- 2016
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Konferensbidrag (refereegranskat)abstract
- Purpose: To compare segmented retinal layer thicknesses between male and female diabetics with clinically significant macular edema (CSME). This study expands our earlier analysis of central macular thickness (CMT) measurements in diabetic males vs. females. Methods: Diabetic retinopathy screening of 2080 diabetics from Alameda County, CA, indicated 142 patients with CSME, as judged by EyePACS certified graders using color fundus images (Canon CR6-45NM). Of the 2080 diabetics, 1784 were imaged with SD-OCT (Optovue iVue). From the 142 patients, we selected 11 males with good fixation, CMT > 300 µm, and no other ocular complications, along with 11 females with the greatest values of CMT while controlling for age, HbA1c and diabetes duration. Manual segmentation of retinal layers using custom software (Mathworks Matlab) of the SD-OCT images of these subjects was done. We analyzed thicknesses for regions 1 deg - 2 deg for nasal and temporal retina in a B-scan centered on the fovea. A 2 X 2 ANOVA probed the differences in thickness for gender, meridian, and their interaction. We also analyzed the central 1 mm of the outer retinal layers, and performed t-tests. Results: Males had significantly thicker nerve fiber layer (NFL) (13.30 ± 2.85 µm) than females (10.13 ± 6.13 µm) and ganglion cell layer-inner plexiform layer (GCL-IPL) (62.54 ± 21.18 µm) than females (48.07 ± 25.91 µm), p < 0.05. There was no effect of meridian and no interaction (p > 0.05). All other layers except the retinal pigment epithelium (RPE) were thicker for males than females even though these were not significant (p > 0.05). There were no significant differences for the layers of the outer retina, which were highly variable and distorted by cysts. Conclusion: Outside the fovea, NFL and GCL-IPL thicknesses were significantly higher in males than females.
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- Capano, B., et al.
(författare)
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ICT in the era of Open Innovation
- 2017
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Ingår i: Mondo Digitale. - : Associazione Italiana per l'Informatica e il Calcolo Automatico. - 1720-898X. ; 15:69, s. 221-240
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Tidskriftsartikel (refereegranskat)abstract
- Due to the increasingly fast technological advancement of the ICT world, 'hi-tech' industries feel a growing need to open to the external world of research and innovation. The usage of external innovation sources allows overcoming the limits of internal resources in terms of capacities, skills and creativity. With respect to the traditional concept of "Closed Innovation", that is the innovation constrained within the internal R&D departments, the "Open Innovation" paradigm leverages on tools that enable importing external resources, thus boosting the quality and quantity of innovative technological solutions. In this paper the basic concepts and the possible "Open Innovation" applications will be presented, starting from the introduction of the paradigm as invented by Henry William Chesbrough in 2003. Furthermore, methodologies and computer tools will be described that are widely adopted to apply the paradigm to industrial settings, as well as the possible barriers to its implementation. Lastly, given the importance of universities, research centers and other companies as external sources for Open Innovation, some pointers will be provided to the selection process of technology innovation partners.
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- Dorafshan Esfahani, Eshagh, 1980-
(författare)
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Methyltransferase Ash1, histone methylation and their impact on Polycomb repression
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antagonistic interactions between Polycomb Group (PcG) and Trithorax Group (TrxG) proteins orchestrate the expression of key developmental genes. Distinct maternally loaded repressors establish the silenced state of these genes in cells where they should not be expressed and later PcG proteins sense whether a target gene is inactive and maintain the repression throughout multiple cell divisions. PcG proteins are targeted to genes by DNA elements called Polycomb Response Elements (PREs). The proteins form two major classes of complexes, namely Polycomb Repressive Complex 1 (PRC1) and Polycomb Repressive Complex 2 (PRC2). Mechanistic details of Polycomb repression are not fully understood, however, tri-methylation of Lysine 27 of histone H3 (H3K27me3) is essential for this process. Using Drosophila cell lines deficient for either PRC1 or PRC2, I investigated the role of H3K27 methylation and the interdependence of PRC1 complexes for their recruitment to PREs. My results indicate that recruitment of PcG complexes to PREs proceed via multiple pathways and that H3K27 methylation is not needed for their targeting. However, the methylation is required to stabilize interactions of PRE-anchored PcG complexes with surrounding chromatin.TrxG proteins prevent erroneous repression of Polycomb target genes where these genes need to be expressed. Ash1 is a TrxG protein which binds Polycomb target genes when they are transcriptionally active. It contains a SET domain which methylates Lysine 36 of histone H3 (H3K36). In vitro, histone H3 methylated at K36 is a poor substrate for H3K27 methylation by PRC2. This prompted a model where Ash1 counteracts Polycomb repression through H3K36 methylation. However, this model was never tested in vivo and does not consider several experimental observations. First, in the ash1 mutant flies the bulk H3K36me2/H3K36me3 levels remain unchanged. Second, in Drosophila, there are two other H3K36-specific histone methyltransferases, NSD and Set2, which should be capable to inhibit PRC2. Third, Ash1 contains multiple evolutionary conserved domains whose roles have not been investigated. Therefore, I asked whether H3K36 methylation is critical for Ash1 to counteract Polycomb repression in vivo and whether NSD and Set2 proteins contribute to this process. I used flies lacking endogenous histone genes and complemented them with transgenic histone genes where Lysine 36 is replaced by Arginine. In these animals, I assayed erroneous repression of HOX genes as a readout for erroneous Polycomb repression. I used the same readout in the NSD or Set2 mutant flies. I also asked if other conserved domains of Ash1 are essential for its function. In addition to SET and domain, Ash1 contains three AT hook motifs as well as BAH and PHD domains. I genetically complemented ash1 loss of function animals with transgenic Ash1 variants, in each, one domain of Ash1 is deleted. I found that Ash1 is the only H3K36-specific histone methyltransferase which counteracts Polycomb repression in Drosophila. My findings suggest that the model, where Ash1 counteracts PcG repression by inhibiting PRC2 via methylation of H3K36, has to be revised. I also showed that, in vivo, Ash1 acts as a multimer and requires SET, BAH and PHD domains to counteract Polycomb repression.This work led to two main conclusions. First, trimethylation of H3K27 is not essential for targeting PcG proteins to PREs but acts afterwards to stabilize their interaction with the chromatin of the neighboring genes. Second, while SET domain is essential for Ash1 to oppose Polycomb repression, methylation of H3K36 does not play a central role in the process.
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| 9. |
- Hering, Bernhard J., et al.
(författare)
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Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia
- 2016
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:7, s. 1230-1240
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA(1c) <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant. RESULTS The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA(1c) level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.
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| 10. |
- Kampmann, Tobias Christoph, 1987-
(författare)
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Age, origin and tectonothermal modification of the Falun pyritic Zn-Pb-Cu-(Au-Ag) sulphide deposit, Bergslagen, Sweden
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Falun pyritic Zn-Pb-Cu-(Au-Ag) sulphide deposit, situated in the Palaeoproterozoic (1.9–1.8 Ga) Bergslagen lithotectonic unit in the south-western part of the Fennoscandian Shield, is one of the major base and precious metal sulphide deposits in Sweden. Felsic volcanic rocks and limestone hosting the deposit, as well as their hydrothermally altered equivalents and the mineralization, were affected by heterogeneous ductile strain and metamorphism under low-pressure, lower amphibolite-facies conditions during the Svecokarelian orogeny (2.0–1.8 Ga). These processes reworked the mineral assemblages of the original hydrothermal system and the mineralization, and also reshaped the structural geometry of the deposit.A three-dimensional modelling approach has been used in order to evaluate geometric relationships between lithologies at the deposit. The polyphase character (D1 and D2) of the strong ductile deformation at Falun is apparent. The main rock-forming minerals in the altered silicate-rich rocks are quartz, biotite and anthophyllite with porphyroblasts of cordierite and garnet, as well as retrogressive chlorite. Major static grain growth occurred between D1 and D2, inferred to represent the peak of metamorphism, as well as after D2 with growth (or recrystallization) of anthophyllite. A major shear zone with chlorite, talc and disseminated sulphides bounds the pyritic Zn-Pb-Cu-rich massive sulphide mineralization to the north, the latter being surrounded elsewhere by disseminated to semi-massive Cu-Au mineralization. F2 sheath folding along axes plunging steeply to the south-south-east is suggested as a key deformation mechanism, accounting for the cone-shaped mineralized bodies, which pinch out at depth, and explaining the similar character of intensely altered rocks on all sides of the massive sulphide mineralization. Immobile-element lithogeochemistry suggests that they share a common volcanic precursor. These relationships are consistent with a model in which the pyritic massive sulphide mineralization is located in the core of a sheath fold structure, surrounded by the same altered stratigraphic footwall rocks with Cu-Au mineralization.The geological evolution in the metavolcanic inlier that hosts the Falun deposit, constrained by secondary ion mass spectrometry (SIMS) U–Pb (zircon) geochronology, involved emplacement of a felsic volcanic and sub-volcanic rock suite at 1894±3 Ma, followed by hydrothermal alteration and mineralization. Subsequent burial and intrusion of late- to post-mineralization dykes occurred between 1896±3 Ma and 1891±3 Ma, followed by further burial and emplacement of plutons with variable composition during the time span 1894±3 Ma to 1893±3 Ma. The age determinations for all these magmatic suites overlap within their uncertainties, indicating a rapid sequence of continuous burial and different magmatic pulses. A metamorphic event, herein dated at 1831±8 Ma and 1822±5 Ma (SIMS U–Pb monazite), falls in the age range of a younger Svecokarelian metamorphic episode (M2). U-Th-Pb isotope systematics in monazite was completely reset during this event.During hydrothermal alteration and mineralization, a hot, reducing and acidic fluid carrying metals and sulphur together flowed upward along syn-volcanic faults, leading to intense chloritization, sericitization and silicification of calc-alkaline volcanic rocks in the stratigraphic footwall to the deposit. This resulted in proximal siliceous associations including Fe-rich chlorite, and dominant Mg-rich chlorite and sericite in more peripheral parts. Cu-Au stockwork mineralization formed in the siliceous core of the hydrothermal system as result of fluid cooling. Neutralization of the metal-bearing fluids upon carbonate interaction stratigraphically higher in the sub-seafloor regime led to formation of Zn-Pb-Cu-rich massive sulphide mineralization, the space for which was created by a combination of carbonate dissolution, primary porosity in the overlying volcanic rocks and secondary porosity produced during syn-volcanic faulting. A hybrid model for mineralization is suggested by alteration styles, metal zoning and textures indicating replacement of carbonate rock or highly porous pumice breccia by pyritic massive sulphide. Aspects of a sub-seafloor volcanogenic massive sulphide (VMS) system and carbonate replacement are both present. Partly Zn-Pb-(Ag) mineralized skarns comprise a separate and subordinate type of mineralization, probably formed after burial of the hydrothermal system to the contact-metasomatic regime.Textures and microstructures in the massive sulphide mineralization indicate that the ductile deformation and metamorphism resulted in internal mechanical and chemical remobilization of sulphide minerals. Laser ablation inductively coupled mass spectrometry (LA-ICP-MS) analysis of the main sulphide minerals suggests, for example, that trace elements (including Au) were liberated from pyrite during metamorphism. A system of auriferous quartz veins, affected by D2 ductile strain, occurs in intensely altered and mineralized rocks on the eastern side of the deposit. It is suggested that they formed after the peak of metamorphism and prior to the completion of the D2 tectonic event, as a result of fluid-assisted remobilization of sulphides and Au in the disseminated to semi-massive Cu-Au mineralization and possibly also the massive sulphide mineralization.
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