Search for Neutrinoless Double-ß Decay in

The Majorana Collaboration is operating an array of high purity Ge detectors to search for neutrinoless double-ß decay in ^{76}Ge. The Majorana Demonstrator comprises 44.1 kg of Ge detectors (29.7 kg enriched in ^{76}Ge) split between two modules contained in a low background shield at the Sanford Underground Research Facility in Lead, South Dakota. Here we present results from data taken during construction, commissioning, and the start of full operations. We achieve unprecedented energy resolution of 2.5 keV FWHM at Q_{ßß} and a very low background with no observed candidate events in 9.95 kg yr of enriched Ge exposure, resulting in a lower limit on the half-life of 1.9×10^{25} yr (90% C.L.). This result constrains the effective Majorana neutrino mass to below 240-520 meV, depending on the matrix elements used. In our experimental configuration with the lowest background, the background is 4.0_{-2.5}^{+3.1} counts/(FWHM t yr).

A mouse model for polycystic kidney disease through a somatic in-frame deletion in the 5' end of Pkd1.

Autosomal dominant polycystic kidney disease, a leading cause of end-stage renal disease in adults, is characterized by progressive focal cyst formation in the kidney. Embryonic lethality of Pkd1-targeted mice limits the use of these mice. Here we developed a floxed allele of Pkd1 exons 2-6. Global deletion mutants developed polyhydramnios, hydrops fetalis, polycystic kidney and pancreatic disease. Somatic Pkd1 inactivation in the kidney was achieved by crossing Pkd1(flox) mice with transgenic mice expressing Cre controlled by a gamma-glutamyltranspeptidase promoter. These mutants developed cysts in both proximal and distal nephron segments and survived for about 4 weeks. Somatic loss of heterozygosity was shown in a reporter mouse strain to cause cystogenesis. Some cysts in young mice are positive for multiple tubular markers and a mesenchymal marker, suggesting a delay in tubular epithelial differentiation. A higher cell proliferation rate was observed in distal nephron segments probably accounting for the faster growth rate of distal cysts. Although we observed an overall increase in apoptosis in cystic kidneys, there was no difference between proximal or distal nephron segments. We also found increased cyclic AMP, aquaporin 2 and vasopressin type 2 receptor mRNA levels, and apical membrane translocation of aquaporin 2 in cystic kidneys, all of which may contribute to the differential cyst growth rate observed. The accelerated polycystic kidney phenotype of these mice provides an excellent model for studying molecular pathways of cystogenesis and to test therapeutic strategies.

Haploinsufficiency of the mSds3 chromatin regulator promotes chromosomal instability and cancer only upon complete neutralization of p53.

The mSin3 corepressor complex has been linked to diverse cancer signaling pathways through its capacity to regulate target gene expression via chromatin modification. mSds3, a cell essential gene, is a key component of the mSin3 complex serving to maintain its inherent histone deacetylase activity. mSds3 also serves an essential role in the establishment of pericentric heterochromatin, and genetic ablation of mSds3 results in chromosome missegregation. In contrast, mSin3A nullizygous cells show normal chromosome dynamics and cytogenetic profiles. The integral role of mSds3 in controlling chromosome segregation and mSin3-regulated transcriptional networks prompted efforts to determine the neoplastic impact of loss of one copy of mSds3 or mSin3A. In particular, we assessed whether loss of one copy of mSds3, alone or in combination with p53 mutation, results in aneuploidy and promotes a cancer-prone condition in the mouse. We observe that, in a p53 null background, loss of one mSds3 allele results in accelerated tumor onset and increased tumor burden. Notably, these mSds3(+/-) p53(-/-) tumors exhibit a more complex cytogenetic profile characterized by marked aneuploidy and centromeric associations. The presence of even one copy of p53 is sufficient to suppress the accelerated tumorigenesis in mSds3(+/-) mice, consistent with a key role for p53 in monitoring mitotic fidelity. These observations with Sds3 mutant mice contrast with mSin3A(+/-) p53(-/-) mice, which do not show an accelerated or increased tumor incidence relative to mSin3A(+/+)p53(-/-) controls, correlating with the absence of aneuploidy detected upon mSin3A genetic inactivation. This genetic study establishes that the capacity of mSds3 to cooperate with p53 deficiency in cancer predisposition relates to its specific role in chromosome segregation, rather than its central role in maintaining a functional mSin3A complex.

Accuracy of the conductance catheter for measurement of ventricular volumes seen clinically: effects of electric field homogeneity and parallel conductance.

The conductance-volume method is an important clinical tool which allows the assessment of left ventricular function in vivo. However, the accuracy of this method is limited by the homogeneity of electric field the conductance catheter produces and the parallel conductance of surrounding structures. This paper examines these sources of error in volumes seen clinically. The characteristics of electric field within a chamber were examined using computer simulation. Nonconductive and conductive models were constructed and experimental measurements obtained using both single-field (SF) and dual-field (DF) excitation. Results from computer simulations and in vitro measurements were compared to validate the purposed theoretical model of conductance-volume method. The effects of field homogeneity and significance of parallel conductance in volume measurement were then determined. The results of this study show that DF provide a more accurate measure of intraventricular volume than SF, especially at larger volumes. However, both significantly underestimate true volume at larger volumes. In addition, the parallel conductance due to the chamber wall is significant at small volumes, but diminishes at larger volumes. Furthermore, the effect of parallel conductance beyond the chamber wall may be negligible. This study demonstrates the limitations in applying current conductance technology to patients with dilated hearts.

Physicochemical interactions in processing.

Synopsis The manufacturing of toiletries is a complex procedure and many process routes are possible for a given formulation. In the past, considerable attention has been given to the design of manufacturing equipment but there has been relatively little appreciation of the influence of physicochemical interactions during processing. These interactions are likely to be particularly important during the manufacture of dispersions such as emulsions and pastes where phase and interfacial behaviour or particle interactions can be affected by the introduction of electrolytes or surface active species. For emulsions consisting of cetyl trimethyl ammonium chloride/long chain alcohol/water, the final rheological behaviour is governed by the formation of a 'frozen' lamellar structure in the continuous phase. The phase changes occurring during processing can significantly affect the degree of structure obtained. With powder dispersions, the rheology is affected by the introduction of surface active species due to deflocculation of the particles. Even in complex product systems such as toothpastes, these changes due to powder/detergent interactions are still apparent.