ΔNp63 REGULATES A COMPLEX NETWORK OF TARGET GENES IN LIMB AND EPIDERMAL DEVELOPMENT

The skin is composed of two major compartments, the dermis and epidermis. The epidermis forms a barrier to protect the body. The stratified epithelium has self-renewing capacity throughout life, and continuous turnover is mediated by stem cells in the basal layer. p63 is structurally and functionally related to p53. In spite of their structural similarities, p63 is critical for the development and maintenance of stratified epithelial tissues, unlike p53. p63 is highly expressed in the epidermis and previously has been shown to play a critical role in the development and maintenance of the epidermis. The study of p63 has been complicated due to the existence of multiple isoforms: those with a transactivation domain (TAp63) and those lacking this domain (ΔNp63). Mice lacking p63 cannot form skin, have craniofacial and skeletal defects and die within hours after birth. These defects are due to the ability of p63 to regulate multiple processes in skin development including epithelial stem cell proliferation, differentiation, and adherence programs. To determine the roles of these isoforms in skin development and maintenance, isoform specific p63 conditional knock out mice were generated by our lab. TAp63-/- mice age prematurely, develop blisters, and display wound-healing defects that result from hyperproliferation of dermal stem cells. That results in premature depletion of these cells, which are necessary for wound repair, that indicates TAp63 plays a role in dermal/epidermal maintenance. To study the role of ΔNp63, I generated a ΔNp63-/- mouse and analyzed the skin by performing immunofluorescence for markers of epithelial differentiation. The ΔNp63-/- mice developed a thin, disorganized epithelium but differentiation markers were expressed. Interestingly, the epidermis from ΔNp63-/- mice co-expressed K14 and K10 in the same cell suggesting defects in epidermal differentiation and stratification. This phenotype is reminiscent of the DGCR8fl/fl;K14Cre and Dicerfl/fl;K14Cre mice skin. Importantly, DGCR8-/- embryonic stem cells (ESCs) display a hyperproliferation defect by failure to silence pluripotency genes. Furthermore, I have observed that epidermal cells lacking ΔNp63 display a phenotype reminiscent of embryonic stem cells instead of keratinocytes. Thus, I hypothesize that genes involved in maintaining pluripotency, like Oct4, may be upregulated in the absence of ΔNp63. To test this, q-RT PCR was performed for Oct4 mRNA with wild type and ΔNp63-/- 18.5dpc embryo skin. I found that the level of Oct4 was dramatically increased in the absence of ΔNp63-/-. Based on these results, I hypothesized that ΔNp63 induces differentiation by silencing pluripotency regulators, Oct4, Sox2 and Nanog directly through the regulation of DGCR8. I found that DGCR8 restoration resulted in repression of Oct4, Sox2 and Nanog in ΔNp63-/- epidermal cells and rescue differentiation defects. Loss of ΔNp63 resulted in pluripotency that caused defect in proper differentiation and stem cell like phenotype. This led me to culture the ΔNp63-/- epidermal cells in neuronal cell culture media in order to address whether restoration of DGCR8 can transform epidermal cells to neuronal cells. I found that DGCR8 restoration resulted in a change in cell fate. I also found that miR470 and miR145 play a role in the induction of pluripotency by repressing Oct4, Sox2 and Nanog. This indicates that ΔNp63 induces terminal differentiation through the regulation of DGCR8.

Development of nuclear emulsions with 1 μm spatial resolution for the AEgIS experiment

The main goal of the AEgIS experiment at CERN is to test the weak equivalence principle for antimatter. We will measure the Earth ' s gravitational acceleration g with antihydrogen atoms being launched in a horizontal vacuum tube and traversing a moiré de fl ectometer. We intend to use a position sensitive device made of nuclear emulsions (combined with a time-of- fl ight detector such as silicon μ strips) to measure precisely their annihilation points at the end of the tube. The goal is to determine g with a 1% relative accuracy. In 2012 we tested emulsion fi lms in vacuum and at room temperature with low energy antiprotons from the CERN antiproton decelerator. First results on the expected performance for AEgIS are presented

In Situ Monitoring of Free-Phase Gas Accumulation and Release in Peatlands Using Ground Penetrating Radar (GPR)

We tested a set of surface common mid-point (CMP) ground penetrating radar (GPR) surveys combined with elevation rods ( to monitor surface deformation) and gas flux measurements to investigate in-situ biogenic gas dynamics and ebullition events in a northern peatland ( raised bog). The main findings are: ( 1) changes in the two-way travel time from the surface to prominent reflectors allow estimation of average gas contents and evolution of free-phase gas (FPG); ( 2) peat surface deformation and gas flux measurements are strongly consistent with GPR estimated changes in FPG content over time; ( 3) rapid decreases in atmospheric pressure are associated with increased gas flux; and ( 4) single ebullition events can induce releases of methane much larger ( up to 192 g/m(2)) than fluxes reported by others. These results indicate that GPR is a useful tool for assessing the spatial distribution, temporal variation, and volume of biogenic gas deposits in peatlands.

Investigating Peatland Stratigraphy and Hydrogeology Using Integrated Electrical Geophysics

Hydrology has been suggested as the mechanism controlling vegetation and related surficial pore-water chemistry in large peatlands. Peatland hydrology influences the carbon dynamics within these large carbon reservoirs and will influence their response to global warming. A geophysical survey was completed in Caribou Bog, a large peatland in Maine, to evaluate peatland stratigraphy and hydrology. Geophysical measurements were integrated with direct measurements of peat stratigraphy from probing, fluid chemistry, and vegetation patterns in the peatland. Consistent with previous field studies, ground-penetrating radar (GPR) was an excellent method for delineating peatland stratigraphy. Prominent reflectors from the peat-lake sediment and lake sediment-mineral soil contacts were precisely recorded up to 8 m deep. Two-dimensional resistivity and induced polarization imaging were used to investigate stratigraphy beneath the mineral soil, beyond the range of GPR. We observe that the peat is chargeable, and that IP imaging is an alternative method for defining peat thickness. The chargeability of peat is attributed to the high surface-charge density on partially decomposed organic matter. The electrical conductivity imaging resolved glaciomarine sediment thickness (a confining layer) and its variability across the basin. Comparison of the bulk conductivity images with peatland vegetation revealed a correlation between confining layer thickness and dominant vegetation type, suggesting that stratigraphy exerts a control on hydrogeology and vegetation distribution within this peatland. Terrain conductivity measured with a Geonics EM31 meter correlated with confining glaciomarine sediment thickness and was an effective method for estimating variability in glaciomarine sediment thickness over approximately 18 km(2). Our understanding of the hydrogeology, stratigraphy, and controls on vegetation growth in this peatland was much enhanced from the geophysical study.

Seasonal Geophysical Monitoring of Biogenic Gases in a Northern Peatland: Implications for Temporal and Spatial Variability in Free Phase Gas Production Rates

A set of high resolution surface ground penetrating radar (GPR) surveys, combined with elevation rod ( to monitor surface deformation) and gas flux measurements, were used to investigate in situ biogenic gas dynamics within a northern peatland (Caribou Bog, Maine). Gas production rates were directly estimated from the time series of GPR measurements. Spatial variability in gas production was also investigated by comparing two sites with different geological and ecological attributes, showing differences and/or similarities depending on season. One site characterized by thick highly humified peat deposits (5-6 m), wooded heath vegetation and open pools showed large ebullition events during the summer season, with estimated emissions (based on an assumed range of CH(4) concentration) between 100 and 172 g CH(4) m(-2) during a single event. The other site characterized by thinner less humified peat deposits (2-3 m) and shrub vegetation showed much smaller ebullition events during the same season (between 13 and 23 g CH(4) m(-2)). A consistent period of free-phase gas (FPG) accumulation during the fall and winter, enhanced by the frozen surficial peat acting as a confining layer, was followed by a decrease in FPG after the snow/ice melt that released estimated fluxes between 100 and 200 g CH(4) m(-2) from both sites. Estimated FPG production rates during periods of biogenic gas accumulation ranged between 0.22 and 2.00 g CH(4) m(3) d(-1) and reflected strong seasonal and spatial variability associated with differences in temperature, peat soil properties, and/or depositional attributes (e. g., stratigraphy). Periods of decreased atmospheric pressure coincided with short-period increases in biogenic gas flux, including a very rapid decrease in FPG content associated with an ebullition event that released an estimated 39 and 67 g CH(4) m(-2) in less than 3.5 hours. These results provide insights into the spatial and seasonal variability in production and emission of biogenic gases from northern peatlands.

Surface Deformations as Indicators of Deep Ebullition Fluxes in a Large Northern Peatland

Peatlands deform elastically during precipitation cycles by small (+/- 3 cm) oscillations in surface elevation. In contrast, we used a Global Positioning System network to measure larger oscillations that exceeded 20 cm over periods of 4 - 12 hours during two seasonal droughts at a bog and fen site in northern Minnesota. The second summer drought also triggered 19 depressuring cycles in an overpressured stratum under the bog site. The synchronicity between the largest surface deformations and the depressuring cycles indicates that both phenomena are produced by the episodic release of large volumes of gas from deep semi-elastic compartments confined by dense wood layers. We calculate that the three largest surface deformations were associated with the release of 136 g CH4 m(-2), which exceeds by an order of magnitude the annual average chamber fluxes measured at this site. Ebullition of gas from the deep peat may therefore be a large and previously unrecognized source of radiocarbon depleted methane emissions from northern peatlands.

Seasonal Distribution and Movements of Shortnose Sturgeon and Atlantic Sturgeon in the Penobscot River Estuary, Maine

Relatively little is known about the distribution and seasonal movement patterns of shortnose sturgeon Acipenser brevirostrum and Atlantic sturgeon Acipenser oxyrinchus oxyrinchus occupying rivers in the northern part of their range. During 2006 and 2007, 40 shortnose sturgeon (66-113.4 cm fork length [FL]) and 8 Atlantic sturgeon (76.2-166.2 cm FL) were captured in the Penobscot River, Maine, implanted with acoustic transmitters, and monitored using an array of acoustic receivers in the Penobscot River estuary and Penobscot Bay. Shortnose sturgeon were present year round in the estuary and overwintered from fall (mid-October) to spring (mid-April) in the upper estuary. In early spring, all individuals moved downstream to the middle estuary. Over the course of the summer, many individuals moved upstream to approximately 2 km of the downstream-most dam (46 river kilometers [rkm] from the Penobscot River mouth [rkm 0]) by August. Most aggregated into an overwintering site (rkm 36.5) in mid-to late fall. As many as 50% of the tagged shortnose sturgeon moved into and out of the Penobscot River system during 2007, and 83% were subsequently detected by an acoustic array in the Kennebec River, located 150 km from the Penobscot River estuary. Atlantic sturgeon moved into the estuary from the ocean in the summer and concentrated into a 1.5-km reach. All Atlantic sturgeon moved to the ocean by fall, and two of these were detected in the Kennebec River. Although these behaviors are common for Atlantic sturgeon, regular coastal migrations of shortnose sturgeon have not been documented previously in this region. These results have important implications for future dam removals as well as for rangewide and river-specific shortnose sturgeon management.

Increment thickness versus dentin bond strength of bulk fill flowables

Objectives: The aim was to investigate the influence of increment thickness on shear bond strength (SBS) to dentin of a conventional and two bulk fill flowable composites. Methods: A total of 135 specimens of ground human dentin were produced (n=15/group; 3 increment thicknesses; 3 flowable composites) and the dentin surfaces were treated with the adhesive system OptiBond FL (Kerr) according to manufacturer’s instructions. Split Teflon molds (inner diameter: 3.6 mm) of 2 mm, 4 mm, or 6 mm height allowing three increment thicknesses were clamped on the dentin surfaces and filled with either the conventional flowable Filtek Supreme XTE ((XTE); 3M ESPE) or the bulk fill flowables Filtek Bulk Fill ((FBF); 3M ESPE) or SDR ((SDR); DENTSPLY Caulk). The flowable composites were light-cured for 20 s (Demi LED; Kerr) and the specimens stored for 24 h (37°C, 100% humidity). Specimens were then subjected to a SBS-test in a universal testing machine at a cross-head speed of 1 mm/min (Zwick Z010; Zwick GmbH & Co.). SBS-values were statistically analysed with a nonparametrical ANOVA followed by exact Wilcoxon rank sum tests (α=0.05). Failure mode of the specimens was determined under a stereomicroscope at 25× magnification. Results: SBS-values (MPa) at 2 mm/4 mm/6 mm increment thicknesses (mean value [standard deviation]) were for XTE: 18.8 [2.6]/17.6 [1.6]/16.7 [3.1], for FBF: 20.6 [2.7]/17.8 [2.7]/18.7 [2.9], and for SDR: 21.7 [2.6]/18.5 [2.6]/20.3 [3.0]. For all three flowable composites, 2 mm increments yielded the highest SBS-values whereas for increments of 4 mm and 6 mm no differences were detected. All specimens presented failure modes involving cohesive failure in dentin. Conclusion: The influence of increment thickness on dentin SBS was less pronounced than expected. However, the high number of cohesive failures in dentin, reflecting the efficiency of the adhesive system, suggests a limited discriminatory power of the SBS-test.

Influence of increment thickness on microhardness and dentin bond strength of bulk fill resin composites

OBJECTIVES To investigate the influence of increment thickness on Vickers microhardness (HV) and shear bond strength (SBS) to dentin of a conventional and four bulk fill resin composites. METHODS HV and SBS were determined on specimens of the conventional resin composite Filtek Supreme XTE (XTE) and the bulk fill resin composites SDR (SDR), Filtek Bulk Fill (FBF), x-tra fil (XFIL), and Tetric EvoCeram Bulk Fill (TEBF) after 24h storage. HV was measured either as profiles at depths up to 6mm or at the bottom of 2mm/4mm/6mm thick resin composite specimens. SBS of 2mm/4mm/6mm thick resin composite increments was measured to dentin surfaces of extracted human molars treated with the adhesive system OptiBond FL, and the failure mode was stereomicroscopically determined at 40× magnification. HV profiles and failure modes were descriptively analysed whereas HV at the bottom of resin composite specimens and SBS were statistically analysed with nonparametric ANOVA followed by Wilcoxon rank sum tests (α=0.05). RESULTS HV profiles (medians at 2mm/4mm/6mm): XTE 105.6/88.8/38.3, SDR 34.0/35.5/36.9, FBF 36.4/38.7/37.1, XFIL 103.4/103.9/101.9, TEBF 63.5/59.7/51.9. HV at the bottom of resin composite specimens (medians at 2mm/4mm/6mm): XTE (p<0.0001) 105.5>85.5>31.1, SDR (p=0.10) 25.8=21.9=26.0, FBF (p=0.16) 26.6=25.3=28.9, XFIL (p=0.18) 110.5=107.2=101.9, TEBF (p<0.0001) 63.0>54.9>48.2. SBS (MPa, medians at 2mm/4mm/6mm): XTE (p<0.0001) 23.9>18.9=16.7, SDR (p=0.26) 24.6=22.7=23.4, FBF (p=0.11) 21.4=20.3=22.0, x-tra fil (p=0.55) 27.0=24.0=23.6, TEBF (p=0.11) 21.0=20.7=19.0. The predominant SBS failure mode was cohesive failure in dentin. SIGNIFICANCE At increasing increment thickness, HV and SBS decreased for the conventional resin composite but generally remained constant for the bulk fill resin composites.

«Gesundheitsrecht am Puls der Zeit» : Bericht zum Symposium der Privaten Universität im Fürstentum Liechtenstein vom 22. November 2013

Am 22. November 2013 führte die Private Universität im Fürstentum Liechtenstein (UFL) bereits zum vierten Mal ihr jährliches Symposium zum Gesundheitsrecht durch. Es war dem Thema «Ökonomie und Gesundheit – Was darf uns unsere Gesundheit kosten?» gewidmet. In Triesen (FL) trafen sich Fachleute aus Liechtenstein und der Schweiz, um verschiedene Facetten der Finanzierung des Gesundheitssystems interdisziplinär zu erörtern und mit einem kritischen Publikum zu diskutieren.

Ökonomie und Gesundheit: Was darf uns unsere Gesundheit kosten?

Der Sammelband ist die Frucht des von der UFL im November 2013 in Triesen FL veranstalteten Symposiums «Gesundheitsrecht am Puls der Zeit». Die Beiträge widmen sich der Gesundheitsversorgung und ihren Kosten aus dem Blickwinkel verschiedener Disziplinen. Aus der Warte von Gesundheitsökonomie, Ethik, Medizin und Recht setzen sich die Autorinnen und Autoren unter anderem mit medizinischen und pflegerischen Leistungen, dem Zugang zu teuren Medikamenten bei seltenen Krankheiten, den Folgen von krankheitsbedingten Absenzen am Arbeitsplatz und den Anreizen, denen die mit der Behandlung von kranken, behinderten und betagten Menschen beschäftigten Fachleute ausgesetzt sind, auseinander. Im Vordergrund dieser Betrachtungen zu Qualität, Fairness und Wirtschaftlichkeit des Gesundheitssystems, der Zusammenarbeit verschiedener Leistungserbringer vor, während und nach einer Behandlung im Spital sowie des betrieblichen Gesundheitsmanagements stehen Beispiele aus Liechtenstein und aus der Schweiz.

"Gesundheitsrecht am Puls der Zeit" - Die Symposien der UFL

Einleitungskapitel im Sammelband des von der Privaten Universität im Fürstentum Liechtenstein (UFL) im November 2013 in Triesen FL veranstalteten Symposiums «Gesundheitsrecht am Puls der Zeit» zum Thema "Ökonomie und Gesundheit - Was darf uns unsere Gesundheit kosten?"

Der gantz judisch Glaub : mit sampt einer gründlichen vnd warhafftigen anzeigunge aller Satzungen, Ceremonien, Gebetten, heimliche vnd öffentliche Gebreuch, deren sich die Juden halten, durch das gantz Jar ; mit schönen vnd gegründten Argumenten wider jhren Glauben

durch Anthonium Margaritham Hebreischen Leser, der löblichen Vniuersitet vnd Fürstlichen Stadt Leiptzig, beschrieben vnd an tag gegeben

Der gantz jüdisch Glaub : mit sampt einer gründlichen vnd warhafftigen anzaygunge, aller Satzungen, Ceremonien, Gebetten ...

durch Anthonium Margaritham beschrieben u. an tag gegeben