Tensor hypercontraction: A universal technique for the resolution of matrix elements of local, finite-range NN-body potentials in many-body quantum problems

Configuration-space matrix elements of N-body potentials arise naturally and ubiquitously in the Ritz-Galerkin solution of many-body quantum problems. For the common specialization of local, finite-range potentials, we develop the eXact Tensor HyperContraction (X-THC) method, which provides a quantized renormalization of the coordinate-space form of the N-body potential, allowing for a highly separable tensor factorization of the configuration-space matrix elements. This representation allows for substantial computational savings in chemical, atomic, and nuclear physics simulations, particularly with respect to difficult "exchange-like" contractions.Comment: Third version of the manuscript after referee's comments. In press in PRL. Main text: 4 pages, 2 figures, 1 table; Supplemental material (also included): 14 pages, 2 figures, 2 table

pMel17 is recognised by monoclonal antibodies NKI-beteb, HMB-45 and HMB-50 and by anti-melanoma CTL.

Recently, we cloned the cDNA encoding the melanocyte lineage-specific antigen gp100 and demonstrated that gp100 is recognised by three different monoclonal antibodies (MAbs) used to diagnose malignant melanoma. In addition, we showed that tumour-infiltrating lymphocytes (TIL 1200) from a melanoma patient reacted specifically with cells transfected with the gp100 cDNA. Molecular characterisation of the gp100 cDNA revealed that the gp100 antigen is highly homologous, but not identical, to another melanocyte-specific protein, pMel17. Here, we report that cells transfected with pMel17 cDNA also react with all three MAbs used to diagnose malignant melanoma, NKI-beteb, HMB-45 and HMB-50. Moreover, pMel17 transfectants are specifically lysed by TIL1200. These data demonstrate that antigenic processing of both gp100 and pMel17 give rise to peptides seen by anti-melanoma cytotoxic T lymphocytes (CTL) and are therefore potential targets for immunotherapy of malignant melanoma

MR Imaging of Prostate Cancer: Diffusion Weighted Imaging and (3D) Hydrogen 1 (1H) MR Spectroscopy in Comparison with Histology

Purpose. To evaluate retrospectively the impact of diffusion weighted imaging (DWI) and (3D) hydrogen 1 (1H) MR-spectroscopy (MRS) on the detection of prostatic cancer in comparison to histological examinations. Materials and Methods: 50 patients with suspicion of prostate cancer underwent a MRI examination at a 1.5T scanner. The prostate was divided into sextants. Regions of interest were placed in each sextant to evaluate the apparent diffusion coefficient (ADC)-values. The results of the DWI as well as MRS were compared retrospectively with the findings of the histological examination. Sensitivity and specificity of ADC and metabolic ratio (MET)—both separately and in combination—for identification of tumor tissue was computed for variable discrimination thresholds to evaluate its receiver operator characteristic (ROC). An association between ADC, MET and Gleason score was tested by the non-parametric Spearman ρ-test. Results. The average ADC-value was 1.65 ± 0.32mm2/s × 10−3 in normal tissue and 0.96±0.24 mm2/s × 10−3 in tumor tissue (mean ± 1 SD). MET was 0.418 ± 0.431 in normal tissue and 2.010 ± 1.649 in tumor tissue. The area under the ROC curve was 0.966 (95%-confidence interval 0.941–0.991) and 0.943 (0.918–0.968) for DWI and MRS, respectively. There was a highly significant negative correlation between ADC-value and the Gleason score in the tumor-positive tissue probes (n = 62, ρ = −0.405, P = .001). MRS did not show a significant correlation with the Gleason score (ρ = 0.117, P = .366). By using both the DWI and MRS, the regression model provided sensitivity and specificity for detection of tumor of 91.9% and 98.3%, respectively. Conclusion. The results of our study showed that both DWI and MRS should be considered as an additional and complementary tool to the T2-weighted MRI for detecting prostate cancer

The Yin and Yang of kidney development and Wilms’ tumours

Wilms’ tumor, or nephroblastoma, is the most common pediatric renal cancer. The tumors morphologically resemble embryonic kidneys with a disrupted architecture and are associated with undifferentiated metanephric precursors. Here, we discuss genetic and epigenetic findings in Wilms’ tumor in the context of renal development. Many of the genes implicated in Wilms’ tumorigenesis are involved in the control of nephron progenitors or the microRNA (miRNA) processing pathway. Whereas the first group of genes has been extensively studied in normal development, the second finding suggests important roles for miRNAs in general—and specific miRNAs in particular—in normal kidney development that still await further analysis. The recent identification of Wilms’ tumor cancer stem cells could provide a framework to integrate these pathways and translate them into new or improved therapeutic interventions

Activation of podocyte Notch mediates early Wt1 glomerulopathy

The Wilms' tumor suppressor gene, WT1, encodes a zinc finger protein that regulates podocyte development and is highly expressed in mature podocytes. Mutations in the WT1 gene are associated with the development of renal failure due to the formation of scar tissue within glomeruli, the mechanisms of which are poorly understood. Here, we used a tamoxifen-based CRE-LoxP system to induce deletion of Wt1 in adult mice to investigate the mechanisms underlying evolution of glomerulosclerosis. Podocyte apoptosis was evident as early as the fourth day post-induction and increased during disease progression, supporting a role for Wt1 in mature podocyte survival. Podocyte Notch activation was evident at disease onset with upregulation of Notch1 and its transcriptional targets, including Nrarp. There was repression of podocyte FoxC2 and upregulation of Hey2 supporting a role for a Wt1/FoxC2/Notch transcriptional network in mature podocyte injury. The expression of cleaved Notch1 and HES1 proteins in podocytes of mutant mice was confirmed in early disease. Furthermore, induction of podocyte HES1 expression was associated with upregulation of genes implicated in epithelial mesenchymal transition, thereby suggesting that HES1 mediates podocyte EMT. Lastly, early pharmacological inhibition of Notch signaling ameliorated glomerular scarring and albuminuria. Thus, loss of Wt1 in mature podocytes modulates podocyte Notch activation, which could mediate early events in WT1-related glomerulosclerosis

An inducible CiliaGFP mouse model for in vivo visualization and analysis of cilia in live tissue

BACKGROUND: Cilia are found on nearly every cell type in the mammalian body, and have been historically classified as either motile or immotile. Motile cilia are important for fluid and cellular movement; however, the roles of non-motile or primary cilia in most tissues remain unknown. Several genetic syndromes, called the ciliopathies, are associated with defects in cilia structure or function and have a wide range of clinical presentations. Much of what we know about the formation and maintenance of cilia comes from model systems like C. elegans and Chalmydomonas. Studies of mammalian cilia in live tissues have been hampered by difficulty visualizing them. RESULTS: To facilitate analyses of mammalian cilia function we generated an inducible Cilia(GFP) mouse by targeting mouse cDNA encoding a cilia-localized protein somatostatin receptor 3 fused to GFP (Sstr3::GFP) into the ROSA26 locus. In this system, Sstr3::GFP is expressed from the ubiquitous ROSA26 promoter after Cre mediated deletion of an upstream Neo cassette flanked by lox P sites. Fluorescent cilia labeling was observed in a variety of live tissues and after fixation. Both cell-type specific and temporally regulated cilia labeling were obtained using multiple Cre lines. The analysis of renal cilia in anesthetized live mice demonstrates that cilia commonly lay nearly parallel to the apical surface of the tubule. In contrast, in more deeply anesthetized mice the cilia display a synchronized, repetitive oscillation that ceases upon death, suggesting a relationship to heart beat, blood pressure or glomerular filtration. CONCLUSIONS: The ability to visualize cilia in live samples within the Cilia(GFP) mouse will greatly aid studies of ciliary function. This mouse will be useful for in vivo genetic and pharmacological screens to assess pathways regulating cilia motility, signaling, assembly, trafficking, resorption and length control and to study cilia regulated physiology in relation to ciliopathy phenotypes