Glacial forcing of central Indonesian hydroclimate since 60,000 y B.P.

The Indo-Pacific warm pool houses the largest zone of deep atmospheric convection on Earth and plays a critical role in global climate variations. Despite the region’s importance, changes in Indo-Pacific hydroclimate on orbital timescales remain poorly constrained. Here we present high-resolution geochemical records of surface runoff and vegetation from sediment cores fromLake Towuti, on the island of Sulawesi in central Indonesia, that continuously span the past 60,000 y.We show that wet conditions and rainforest ecosystems on Sulawesi present during marine isotope stage 3 (MIS3) and the Holocene were interrupted by severe drying between ∼33,000 and 16,000 y B.P. when Northern Hemisphere ice sheets expanded and global temperatures cooled. Our record reveals little direct influence of precessional orbital forcing on regional climate, and the similarity between MIS3 and Holocene climates observed in Lake Towuti suggests that exposure of the Sunda Shelf has a weaker influence on regional hydroclimate and terrestrial ecosystems than suggested previously. We infer that hydrological variability in this part of Indonesia varies strongly in response to high-latitude climate forcing, likely through reorganizations of the monsoons and the position of the intertropical convergence zone. These findings suggest an important role for the tropical western Pacific in amplifying glacial–interglacial climate variability.

Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type?1 diabetes; a randomized controlled trial

To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes.

Climate forcing reconstructions for use in the PMIP simulations of the last millennium

Simulations of climate over the Last Millennium (850–1850 CE) have been incorporated into the third phase of the Paleoclimate Modelling Intercomparison Project (PMIP3). The drivers of climate over this period are chiefly orbital, solar, volcanic, changes in land use/land cover and some variation in greenhouse gas levels. While some of these effects can be easily defined, the reconstructions of solar, volcanic and land use-related forcing are more uncertain. We describe here the approach taken in defining the scenarios used in PMIP3, document the forcing reconstructions and discuss likely implications.

Climate forcing reconstructions for use in PMIP simulations of the Last Millennium (v1

We update the forcings for the PMIP3 experiments for the Last Millennium to include new assessments of historical land use changes and discuss new suggestions for calibrating solar activity proxies to total solar irradiance.

Design and in vitro characterization of highly sst2-selective somatostatin antagonists suitable for radiotargeting

Radiolabeled sst 2 and sst 3 antagonists are better candidates for tumor targeting than agonists with comparable binding characteristics (Ginj, M.; Zhang, H.; Waser, B.; Cescato, R.; Wild, D.; Erchegyi, J.; Rivier, J.; Mäcke, H. R.; Reubi, J. C. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 16436-16441.). Because most of the neuroendocrine tumors express sst 2, we used the known antagonists acetyl- pNO 2Phe (2)- c[ dCys (3)-Tyr (7)- dTrp (8)-Lys (9)-Thr (10)-Cys (14)]- dTyr (15)-NH 2 ( 1) (Bass, R. T.; Buckwalter, B. L.; Patel, B. P.; Pausch, M. H.; Price, L. A.; Strnad, J.; Hadcock, J. R. Mol. Pharmacol. 1996, 50, 709-715. Bass, R. T.; Buckwalter, B. L.; Patel, B. P.; Pausch, M. H.; Price, L. A.; Strnad, J.; Hadcock, J. R. Mol. Pharmacol. 1997, 51, 170; Erratum.) and H-Cpa (2)- c[ dCys (3)-Tyr (7)- dTrp (8)-Lys (9)-Thr (10)-Cys (14)]-2Nal (15)-NH 2 ( 7) (Hocart, S. J.; Jain, R.; Murphy, W. A.; Taylor, J. E.; Coy, D. H. J. Med. Chem. 1999, 42, 1863-1871.) as leads for analogues with increased sst 2 binding affinity and selectivity. Among the 32 analogues reported here, DOTA- pNO 2Phe (2)- c[ dCys (3)-Tyr (7)- dAph (8)(Cbm)-Lys (9)-Thr (10)-Cys (14)- dTyr (15)-NH 2 ( 3) and DOTA-Cpa (2)- c[ dCys (3)-Aph (7)(Hor)- dAph (8)(Cbm)-Lys (9)-Thr (10)-Cys (14)]- dTyr (15)-NH 2 ( 31) had the highest sst 2 binding affinity and selectivity. All of the analogues tested kept their sst 2 antagonistic properties (i.e., did not affect calcium release in vitro and competitively antagonized the agonistic effect of [Tyr (3)]octreotide). Moreover, in an immunofluorescence-based internalization assay, the new analogues prevented sst 2 internalization induced by the sst 2 agonist [Tyr (3)]octreotide without being active by themselves. In conclusion, several analogues (in particular 3, 31, and 32) have outstanding sst 2 binding and functional antagonistic properties and, because of their DOTA moiety, are excellent candidates for in vivo targeting of sst 2-expressing cancers.