Synthesis and incorporation into a-DNA of a novel conformationally constrained alpha-nucleoside analogue

We describe the synthesis and incorporation into alpha-DNA of a novel conformationally constrained alpha-nucleoside analogue. The carbohydrate part of this analogue was prepared in 4 steps from the known bicyclic precursor 1 via a stereospecific, intramolecular, Et 3B mediated radical addition to a keto-function as the key step. The thus obtained intermediate 4 was transformed stereoselectively into the corresponding alpha-nucleoside analogues 7 and 8 containing the bases adenine and thymine, and were further elaborated into the phosphoramidite building blocks 11 and 12 . Both building blocks were incorporated into alpha-oligodeoxynucleotides and their pairing behavior to parallel complementary DNA studied by UV-melting experiments. Single substitutions of alpha-deoxyribnucleoside units by the new analogues in the center of duplexes were found to be thermally destabilizing by only -0.8 to -3.1›C.

Fast Update of Conditional Simulation Ensembles

Gaussian random field (GRF) conditional simulation is a key ingredient in many spatial statistics problems for computing Monte-Carlo estimators and quantifying uncertainties on non-linear functionals of GRFs conditional on data. Conditional simulations are known to often be computer intensive, especially when appealing to matrix decomposition approaches with a large number of simulation points. This work studies settings where conditioning observations are assimilated batch sequentially, with one point or a batch of points at each stage. Assuming that conditional simulations have been performed at a previous stage, the goal is to take advantage of already available sample paths and by-products to produce updated conditional simulations at mini- mal cost. Explicit formulae are provided, which allow updating an ensemble of sample paths conditioned on n ≥ 0 observations to an ensemble conditioned on n + q observations, for arbitrary q ≥ 1. Compared to direct approaches, the proposed formulae proveto substantially reduce computational complexity. Moreover, these formulae explicitly exhibit how the q new observations are updating the old sample paths. Detailed complexity calculations highlighting the benefits of this approach with respect to state-of-the-art algorithms are provided and are complemented by numerical experiments.

Bibliotheca Judaica, Hebraica, Rabbinica : Pinczower - Porges

[Otto Harrassowitz]

Application of Ga(68) -DOTA-exendin-4 PET/CT to localise an occult insulinoma

A 49 year old female presented to our Neuroendocrine Tumour (NET) centre with recurrent severe and disabling hypoglycaemia. She had previously been extensively investigated with a clinical and biochemical diagnosis of endogenous hyperinsulinemic hypoglycaemia although the source of hormonal hypersecretion could not be localised with MRI, EUS and (111) In-Octreotide scans. After extensive discussion the patient opted for blind surgical resection undergoing a pylorus-preserving pancreaticoduodenectomy in December 2010. Histological examination of the resected operative specimen demonstrated a normal pancreas with no evidence of neuroendocrine tumour. Consistent with this, post-surgery her hypoglycaemic symptoms persisted with fasting capillary blood glucose of 2.1-6.0 mmol/l with increasing hypoglycaemia unawareness. Consequently she sought alternative clinical opinions from two European Neuroendocrine Tumour Society (ENETS) Centres of Excellence who investigated her collaboratively. This article is protected by copyright. All rights reserved.

Hypersensitivity of an Arabidopsis Sugar Signaling Mutant toward Exogenous Proline Application

In transgenic Arabidopsis a patatin class I promoter from potato is regulated by sugars and proline (Pro), thus integrating signals derived from carbon and nitrogen metabolism. In both cases a signaling cascade involving protein phosphatases is involved in induction. Other endogenous genes are also regulated by both Pro and carbohydrates. Chalcone synthase (CHS) gene expression is induced by both, whereas the Pro biosynthetic Δ1-pyrroline-5-carboxylate synthetase (P5CS) is induced by high Suc concentrations but repressed by Pro, and Pro dehydrogenase (ProDH) is inversely regulated. The mutantrsr1-1, impaired in sugar dependent induction of the patatin promoter, is hypersensitive to low levels of external Pro and develops autofluorescence and necroses. Toxicity of Pro can be ameliorated by salt stress and exogenously supplied metabolizable carbohydrates. The rsr1-1 mutant shows a reduced response regarding sugar induction of CHS andP5CS expression. ProDH expression is de-repressed in the mutant but still down-regulated by sugar. Pro toxicity seems to be mediated by the degradation intermediate Δ1-pyrroline-5-carboxylate. Induction of the patatin promoter by carbohydrates and Pro, together with the Pro hypersensitivity of the mutant rsr1-1, demonstrate a new link between carbon/nitrogen and stress responses.

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 636 - Bestätigung einer geplanten fünfbändigen Ausgabe der "Welt als Wille und Vorstellung"

u.a.: Verlagsbedingungen; Verlagsrechte; Bezahlung eines Konventionalbetrags;

Xp95 is phosphorylated within the proline rich domain during Xenopus oocyte maturation

Xp95 is the Xenopus ortholog of a conserved family of scaffold proteins that have in common an N-terminal Bro1 domain and a C-terminal proline rich domain (PRD). The regulation of this protein family is poorly understood. We previously showed that Xp95 undergoes a phosphorylation-dependant gel mobility shift during meiotic maturation of Xenopus oocytes, the only natural biological system in which post-translational modifications of this family has been demonstrated. Here we characterized Xp95 phosphorylation via two approaches. First, we tested a series of Xp95 fragments for the ability to gel-shift during oocyte maturation, and found that a fragment containing amino acids 705-786 is sufficient to cause a gel-shift. This fragment is within the N-terminal region of Xp95's PRD (N-PRD). Second, we purified phosphorylated Xp95 and by mass spectrometry found that a 5080 Da peptide which maps to N-PRD (amino acids 706-756) contains two phosphorylation sites, one of which is T745, within the conserved CIN85 binding motif. By in vitro protein interaction assays, we that T745 is critical for CIN85/Xp95 interaction, and that Xp95 phosphorylation correlates with loss of binding to CIN85. We also show that an Alix fragment (amino acids 604-789) also undergoes a gel-shift during oocyte maturation and during colcemid-induced mitotic arrest of HeLa cells. These findings indicate that Xp95/Alix is phosphorylated on the PRD during M phase induction and that the PRD phosphorylation regulates partner protein interaction. ^

Solar radiation over and under sea ice and photographic quantification of Ice algal aggregates during the POLARSTERN cruise ARK-XXVII/3 (IceArc) in summer 2012

The ice cover of the Arctic Ocean has been changing dramatically in the last decades and the consequences for the sea-ice associated ecosystem remain difficult to assess. Algal aggregates underneath sea ice have been described sporadically but the frequency and distribution of their occurrence is not well quantified. We used upward looking images obtained by a remotely operated vehicle (ROV) to derive estimates of ice algal aggregate biomass and to investigate their spatial distribution. During the IceArc expedition (ARK-XXVII/3) of RV Polarstern in late summer 2012, different types of algal aggregates were observed floating underneath various ice types in the Central Arctic basins. Our results show that the floe scale distribution of algal aggregates in late summer is very patchy and determined by the topography of the ice underside, with aggregates collecting in dome shaped structures and at the edges of pressure ridges. The buoyancy of the aggregates was also evident from analysis of the aggregate size distribution. Different approaches used to estimate aggregate biomass yield a wide range of results. This highlights that special care must be taken when upscaling observations and comparing results from surveys conducted using different methods or on different spatial scales.

Solar irradiance over and under seasonal land-fast sea ice off Barrow, Alaska, in 2010

The amount of solar radiation transmitted through Arctic sea ice is determined by the thickness and physical properties of snow and sea ice. Light transmittance is highly variable in space and time since thickness and physical properties of snow and sea ice are highly heterogeneous on variable time and length scales. We present field measurements of under-ice irradiance along transects under undeformed land-fast sea ice at Barrow, Alaska (March, May, and June 2010). The measurements were performed with a spectral radiometer mounted on a floating under-ice sled. The objective was to quantify the spatial variability of light transmittance through snow and sea ice, and to compare this variability along its seasonal evolution. Along with optical measurements, snow depth, sea ice thickness, and freeboard were recorded, and ice cores were analyzed for chlorophyll a and particulate matter. Our results show that snow cover variability prior to onset of snow melt causes as much relative spatial variability of light transmittance as the contrast of ponded and white ice during summer. Both before and after melt onset, measured transmittances fell in a range from one third to three times the mean value. In addition, we found a twentyfold increase of light transmittance as a result of partial snowmelt, showing the seasonal evolution of transmittance through sea ice far exceeds the spatial variability. However, prior melt onset, light transmittance was time invariant and differences in under-ice irradiance were directly related to the spatial variability of the snow cover.