A different view on the AMOC and the timing of climate change

In dieser Dissertation analysiere ich übergreifend die wichtige Rolle des vertikalen Ekman Transports (Ekman pumping) und des Antarktischen Zirkumpolarstrom für die Ozeandynamik und Klimadynamik. Die Dissertation handelt von der Windsensitivität der Atlantischen Meridionalen Umwälzbewegung in Bezug auf die Ozeandynamik und von der zeitlichen Anpassung der Klimareaktion zu verändertem Klimaantrieb auf hundertjähriger Zeitskala in Bezug auf die Klimadynamik. Es zeigt sich, dass die Atlantische Meridionale Umwälzbewegung von lokalen Winden in der nördlichen Hemisphäre abhängt, neben nonlokalen Windeffekten die vom Südlichen Ozean ausgehen. Spezifischer, die Atlantische Meridionale Umwälzbewegung hängt von lokalen und nonlokalen vertikalen Ekman-Transport ab, der von der Rotation des Windvektors berechnet wird. Die windabhängigen Änderungen in der Umwälzbewegung spiegeln sich in der Tiefe der stärksten Umwälzbewegung wider. Die windgetriebene Ekmankompensation is baroklin and findet über der Tiefe der stärksten Umwälzbewegung statt. Die interne vertikale Scherung der Geschwindigkeit, die nicht von den Ekmanzellen beeinflusst wird, bleibt trotz veränderten Windantrieb konstant. Die zweite Publikation einleitend, der vertikale Ekman-Transport und der Antarktische Zirkumpolarstrom sowie die Atlantische Meridionale Umwälzbewegung forcieren die ozeanische Wärmeaufnahme und deren geographische Verteilung. Dementsprechend beeinflussen sie die Klimadynamik des Erdsystems. In dieser Verbindung hängt die Amplitude und zeitliche Anpassung der Oberflächenlufttemperatur des Erdsystems auf hundertjähriger Zeitskala vom Ozean ab. Ich hinterfrage ob der langzeitige Klimawandel durch eine einzelne e-folding Mode mit einer konstanten Zeitskala abhängt. Diese Zeitskala wird üblicher Weise als unabhängig von Temperatur und Zeit angesehen. Es zeigt sich, dass die Temperaturabhängigkeit der Klimarückkopplung sehr stark die neue Gleichgewichtstemperatur und die zeitliche Anpassung der langsamen Mode beeinflusst, die den langzeitigen Klimawandel beschreibt. Jedoch hängt die Zeitskala zusätzlich von der thermischen Trägheit des Ozeans ab, die inkonstant ist von einer globalen Perspektive. Es gibt eine geographische Zeitskalenverteilung, die von dynamischen Komponenten wie dem vertikalen Ekman-Transport und der Atlantischen Meridionalen Umwälzbewegung abhängt, und die Ozeanzirkulation kann sich mit der Zeit verändern.From an overarching perspective, in this thesis I analyze the particular rolof Ekman pumping and the Atlantic circumpolar current (ACC) for oceanand climate dynamics. It is about the wind sensitivity of the Atlantic Merid-ional Overturning Circulation (AMOC) considering ocean dynamics as wellas the temporal adjustment of the climate response to forcing on a centennialtimescale considering climate dynamics. I find that the AMOC depends onlocal northern hemisphere Ekman pumping besides nonlocal Southern hemi-sphere Ekman pumping. Ekman pumping is associated with the rotation ofthe surface wind stress vector. The changes in overturning are reflected bythe level of no motion which is the depth of maximum overturning. Wind-driven Ekman compensation is baroclinic and occurs above the level of nomotion, and the internal vertical velocity shear that is not influenced by theexternal Ekman cells stays approximately constant. Focusing on a secondpaper, Ekman pumping and the ACC as well as the AMOC force ocean heatuptake and its redistribution. That is, they influence the climate dynamicsof the Earth system. In this connection, the amplitude and timing of thesurface air temperature adjustment on a centennial timescale depends on theocean component. I question whether long-term climate change is describedby a single e-folding mode with a constant timescale which is commonly as-sumed to be independent of temperature or forcing and the evolution of time.I find that feedback temperature dependence strongly influences the equilib-rium temperature response and adjustment timescale of the slow mode whichdescribes long-term climate change. However, the timescale is additionallyinfluenced by the thermal inertia of the ocean in the sense that the latteris inconstant from a global perspective. There is timescale pattern that depends on dynamic components such as Ekman pumping and the AMOC, andthe ocean circulation can change over time.<br

Nonlocal and local wind forcing dependence of the Atlantic meridional overturning circulation and its depth scale

We use wind sensitivity experiments to understand the wind forcing dependencies of the level of no motion and the e-folding pycnocline scale as well as their relationship to northward transport of the mid-depth Atlantic meridional overturning circulation (AMOC) south and north of the equator. In contrast to previous studies, we investigate the interplay of nonlocal and local wind effects on a decadal timescale. We use 30-year simulations with a high-resolution ocean general circulation model (OGCM) which is an eddy-resolving version of the Max Planck Institute Ocean Model (MPIOM). Our findings deviate from the common perspective that the AMOC is a nonlocal phenomenon only, because northward transport in the inter-hemispheric cell can only be understood by analyzing nonlocal Southern Ocean wind effects and local wind effects in the northern hemisphere downwelling region where Ekman pumping takes place. Southern Ocean wind forcing predominantly determines the magnitude of the pycnocline scale throughout the basin, whereas northern hemisphere winds additionally influence the level of no motion locally. In that respect, the level of no motion is a better proxy for northward transport and mid-depth velocity profiles despite the Ekman return flow which is found to be baroclinic. We compare our results inferred from the wind experiments and a 100-year global warming experiment in which the atmospheric CO2 concentration is quadrupled, using MPIOM coupled to an atmospheric model. We find that the evolution of the level of no motion in response to global warming represents changes in vertical velocity profiles or northward transport, whereas the changes of the pycnocline scale are opposite to the changes of the level of no motion over time. Using the level of no motion as depth scale, the analysis of the wind experiments and the warming experiment suggests a hemisphere-dependent scaling of the strength of AMOC. Furthermore, we put forward the idea that the ability of numerical models to capture the spatial and temporal variations of the level of no motion is crucial to reproduce the mid-depth cell in an appropriate wa

Macular sensitivity and fixation patterns in normal eyes and eyes with uveitis with and without macular edema

PURPOSE: This study aims to investigate the relationship between macular sensitivity and thickness in eyes with uveitic macular edema (UME). DESIGN: This study is a prospective observational case series. METHODS: The setting for this study was clinical practice. The study included 59 (28 with UME, 31 without UME) eyes of 26 patients with uveitis and 19 eyes of 10 normal subjects. The procedure followed was fundus-related perimetry and retinal thickness map with an automated fundus perimetry/tomography system. Main outcome measures included quantification of macular sensitivity, fixation pattern, and relationship between macular sensitivity and thickness. RESULTS: Fixation stability revealed that 56 eyes (93.44%) had stable fixation (\u3e75% within the central 2° of point of fixation); three eyes (6.56%) were relatively unstable (75% located within 4°); and no eye had unstable fixation (50% of fixation point within 0.5 mm of foveal center); seven eyes (11.86%) had peri-central fixation location (25% \u3c 50% within 0.5 mm); and seven eyes (11.86%) had eccentric (280 μm. CONCLUSIONS: Perimetry quantification of macular sensitivity and retinal thickness, in association with other factors, may offer novel information regarding the impact of UME on retinal function

Protective effect of stromal Dickkopf-3 in prostate cancer: opposing roles for TGFBI and ECM-1

Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, is downregulated in prostate cancer and upregulated in the stroma in benign prostatic hyperplasia, but the function of stromal Dkk-3 is unclear. Here we show that DKK3 silencing in WPMY-1 prostate stromal cells increases TGF-β signaling activity and that stromal cellconditioned media inhibit prostate cancer cell invasion in a Dkk-3-dependent manner. DKK3 silencing increased the level of the cell-adhesion regulator TGF-β–induced protein (TGFBI) in stromal and epithelial cell-conditioned media, and recombinant TGFBI increased prostate cancer cell invasion. Reduced expression of Dkk-3 in patient tumors was associated with increased expression of TGFBI. DKK3 silencing reduced the level of extracellular matrix protein-1 (ECM-1) in prostate stromal cell-conditioned media but increased it in epithelial cell-conditioned media, and recombinant ECM-1 inhibited TGFBI-induced prostate cancer cell invasion. Increased ECM1 and DKK3 mRNA expression in prostate tumors was associated with increased relapse-free survival. These observations are consistent with a model in which the loss of Dkk-3 in prostate cancer leads to increased secretion of TGFBI and ECM-1, which have tumor-promoting and tumor-protective roles, respectively. Determining how the balance between the opposing roles of extracellular factors influences prostate carcinogenesis will be key to developing therapies that target the tumor microenvironment

Care of vision and ocular health in diabetic members of a national diabetes organization: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Regular examination and early treatment of diabetic retinopathy can prevent visual loss. The aim of the study was to describe the care of vision and ocular health in people with diabetes in Norway.</p> <p>Methods</p> <p>A cross-sectional questionnaire survey of a random sample (n = 1,887) of the Norwegian Diabetic Associations' (NDA) members was carried out in 2005. Questions were asked about care of vision and ocular health, history of ocular disease and visual symptoms, general medical history and diabetes management. The study was approved by the Regional Committee for Medical Research Ethics.</p> <p>Results</p> <p>The response rate was 74%. Forty-four questionnaires with incomplete data regarding gender, age or type of diabetes were excluded, leaving 1352 cases (52% females) for analysis. 451 (33%) had type 1 and 901 (67%) had type 2 diabetes, the mean duration of diabetes was respectively, 22 (sd ± 14) and 10 (sd ± 9) years. In all 1,052 (78%) had their eyes examined according to guidelines and 1,169 (87%) confirmed to have received information about regular eye examinations. One in two recalled to have received such information from their general practitioner. To have received information about the importance of eye examinations (PR 3.1, 95% CI 2.4 to 4.0), and diabetes duration > 10 years (PR 1.2, 95% CI 1.2 to 1.3), were independently associated with reporting regular eye examinations. A history of diabetic retinopathy was reported by 178 (13%) responders, of which 101 (57%) reported a history of laser treatment. Responders who had regular eye examinations reported more frequently a history of diabetic retinopathy (19% vs. 5%, p < 0.001). The frequency of retinopathy was significantly higher in responders with reported HbA1c values above treatment target (23% vs. 13%, p = 0.001). However, in responders who were not regularly examined, there was no difference in reported frequency of retinopathy with regard to HbA1c level.</p> <p>Conclusion</p> <p>Eight out of ten diabetic members of the NDA had their eyes examined according to current guidelines and the majority was well informed about the risk of vision loss due to diabetes. The results indicate that the reported history of diabetic retinopathy likely underestimates the prevalence of retinopathy.</p

Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus

Autosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been linked to two loci, MCDR1 (chromosome 6q16) and MCDR3 (chromosome 5p15-p13). Recently, non-coding variants upstream of PRDM13 (MCDR1) and a duplication including IRX1 (MCDR3) have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies on eighteen NCMD families, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. Three families carry the previously reported V2 variant (MCDR1), while five remain unsolved. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD and provide insights into the genetic pathways involved in human macular development

Comparing online campaigning: The evolution of interactive campaigning from Royal to Obama to Hollande

© 2016 Macmillan Publishers Ltd.Studies of election campaigning from a comparative perspective have a long history; this study approaches the topic through a most-similar regime perspective to explore the ebb and flow of innovations in digital campaigning between presidential campaigns in France and the United States. The hype surrounding the 2008 Obama campaign overshadowed innovations in France the previous year, while the 2011 contest gained little serious academic attention. Using a well-established content analysis methodology the research explains the strategic design of the digital dimension of the campaigns of the leading candidates (Sarkozy and Royal in 2007, Obama and McCain in 2008, Hollande and Sarkozy in 2011, and Obama and Romney in 2012). The research then assesses the strategic contribution of each feature using schematics for understanding the flow of communication, as well as the strategy employed by each candidate. The key findings are that the campaigns are becoming more interactive, with the citizens increasingly more able to enter into conversations with the campaign teams, however interactivity when it happens is carefully controlled. Largely, however, there is a strong similarity masked by the sophistication of US contests. Despite the advances in communication technology and the social trends they have instigated, campaign communication remains top-down and digital technologies are used to gather data and push supporters towards activism than creating an inclusive space for the co-creation that cyberoptimists argued would revitalise the structures of democracy

Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment

Introduction: The mammary primordium forms during embryogenesis as a result of inductive interactions between its constitutive tissues, the mesenchyme and epithelium, and represents the earliest evidence of commitment to the mammary lineage. Previous studies of embryonic mouse mammary epithelium indicated that, by mid-gestation, these cells are determined to a mammary cell fate and that a stem cell population has been delimited. Mammary mesenchyme can induce mammary development from simple epithelium even across species and classes, and can partially restore features of differentiated tissue to mouse mammary tumours in co-culture experiments. Despite these exciting properties, the molecular identity of embryonic mammary cells remains to be fully characterised. Methods: Here, we define the transcriptome of the mammary primordium and the two distinct cellular compartments that comprise it, the mammary primordial bud epithelium and mammary mesenchyme. Pathway and network analysis was performed and comparisons of embryonic mammary gene expression profiles to those of both postnatal mouse and human mammary epithelial cell sub-populations and stroma were made. Results: Several of the genes we have detected in our embryonic mammary cell signatures were previously shown to regulate mammary cell fate and development, but we also identified a large number of novel candidates. Additionally, we determined genes that were expressed by both embryonic and postnatal mammary cells, which represent candidate regulators of mammary cell fate, differentiation and progenitor cell function that could signal from mammary lineage inception during embryogenesis through postnatal development. Comparison of embryonic mammary cell signatures with those of human breast cells identified potential regulators of mammary progenitor cell functions conserved across species. Conclusions: These results provide new insights into genetic regulatory mechanisms of mammary development, particularly identification of novel potential regulators of mammary fate and mesenchymal-epithelial cross-talk. Since cancers may represent diseases of mesenchymal-epithelial communications, we anticipate these results will provide foundations for further studies into the fundamental links between developmental, stem cell and breast cancer biology

Combining Computational Prediction of Cis-Regulatory Elements with a New Enhancer Assay to Efficiently Label Neuronal Structures in the Medaka Fish

The developing vertebrate nervous system contains a remarkable array of neural cells organized into complex, evolutionarily conserved structures. The labeling of living cells in these structures is key for the understanding of brain development and function, yet the generation of stable lines expressing reporter genes in specific spatio-temporal patterns remains a limiting step. In this study we present a fast and reliable pipeline to efficiently generate a set of stable lines expressing a reporter gene in multiple neuronal structures in the developing nervous system in medaka. The pipeline combines both the accurate computational genome-wide prediction of neuronal specific cis-regulatory modules (CRMs) and a newly developed experimental setup to rapidly obtain transgenic lines in a cost-effective and highly reproducible manner. 95% of the CRMs tested in our experimental setup show enhancer activity in various and numerous neuronal structures belonging to all major brain subdivisions. This pipeline represents a significant step towards the dissection of embryonic neuronal development in vertebrates

Quantification of Optic Disc Edema during Exposure to High Altitude Shows No Correlation to Acute Mountain Sickness

BACKGROUND: The study aimed to quantify changes of the optic nerve head (ONH) during exposure to high altitude and to assess a correlation with acute mountain sickness (AMS). This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. METHODOLOGY/PRINCIPAL FINDINGS: A confocal scanning laser ophthalmoscope (cSLO, Heidelberg Retina Tomograph, HRT3®) was used to quantify changes at the ONH in 18 healthy participants before, during and after rapid ascent to high altitude (4559 m). Slitlamp biomicroscopy was used for clinical optic disc evaluation; AMS was assessed with Lake Louise (LL) and AMS-cerebral (AMS-c) scores; oxygen saturation (SpO₂) and heart rate (HR) were monitored. These parameters were used to correlate with changes at the ONH. After the first night spent at high altitude, incidence of AMS was 55% and presence of clinical optic disc edema (ODE) 79%. Key stereometric parameters of the HRT3® used to describe ODE (mean retinal nerve fiber layer [RNFL] thickness, RNFL cross sectional area, optic disc rim volume and maximum contour elevation) changed significantly at high altitude compared to baseline (p&lt;0.05) and were consistent with clinically described ODE. All changes were reversible in all participants after descent. There was no significant correlation between parameters of ODE and AMS, SpO₂ or HR. CONCLUSIONS/SIGNIFICANCE: Exposure to high altitude leads to reversible ODE in the majority of healthy subjects. However, these changes did not correlate with AMS or basic physiologic parameters such as SpO₂ and HR. For the first time, a quantitative approach has been used to assess these changes during acute, non-acclimatized high altitude exposure. In conclusion, ODE presents a reaction of the body to high altitude exposure unrelated to AMS