CORE: Augmenting Regenerating-Coding-Based Recovery for Single and Concurrent Failures in Distributed Storage Systems

Data availability is critical in distributed storage systems, especially when node failures are prevalent in real life. A key requirement is to minimize the amount of data transferred among nodes when recovering the lost or unavailable data of failed nodes. This paper explores recovery solutions based on regenerating codes, which are shown to provide fault-tolerant storage and minimum recovery bandwidth. Existing optimal regenerating codes are designed for single node failures. We build a system called CORE, which augments existing optimal regenerating codes to support a general number of failures including single and concurrent failures. We theoretically show that CORE achieves the minimum possible recovery bandwidth for most cases. We implement CORE and evaluate our prototype atop a Hadoop HDFS cluster testbed with up to 20 storage nodes. We demonstrate that our CORE prototype conforms to our theoretical findings and achieves recovery bandwidth saving when compared to the conventional recovery approach based on erasure codes.Comment: 25 page

Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC). Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further

BRAF V600E mutations in urine and plasma cell-free DNA from patients with Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare histiocytosis with a high prevalence of BRAF V600E mutation (>50% of patients). Patients with BRAF-mutant ECD can respond to BRAF inhibitors. Unfortunately, the lack of adequate archival tissue often precludes BRAF testing. We hypothesized that cell-free DNA (cfDNA) from plasma or urine can offer an alternative source of biologic material for testing. We tested for BRAF V600E mutation in cfDNA from the plasma and urine of 6 ECD patients. In patients with available archival tissue, the result of BRAF mutation analysis was concordant with plasma and urine cfDNA results in all 3 patients (100% agreement, kappa 1.00). In all 6 patients, BRAF mutation analysis of plasma and urine cfDNA was concordant in 5 of 6 patients (83% agreement, kappa 0.67). Testing for BRAF V600E mutation in plasma and urine cfDNA should be further investigated as an alternative to archival tissue mutation analysis

Very Red and Extremely Red Galaxies in the Fields of z ~ 1.5 Radio-Loud Quasars

We previously identified an excess of mostly red galaxies around 31 RLQs at z=1-2. These fields have an ERO (extremely red object, R-K>6) density 2.7 times higher than the field. Assuming the EROs are passively evolved galaxies at the quasar redshifts, they have characteristic luminosities of only ~L^*. We also present new observations of four z~1.54 RLQ fields: (1) Wide-field J & Ks data confirm an Abell richness ~2 excess within 140" of Q0835+580 but an excess only within 50" of Q1126+101. (2) In 3 fields we present deep narrow-band redshifted H-alpha observations. We detect five candidate galaxies at the quasar redshifts, a surface density 2.5x higher than the field. (3) SCUBA sub-mm observations of 3 fields detect 2 quasars and 2 galaxies with SEDs best fit as highly reddened galaxies at the quasar z. (4) H-band adaptive optics (AO) imaging is used to estimate redshifts for 2 red, bulge-dominated galaxies using the Kormendy relation. Both have structural redshifts foreground to the quasar, but these are not confirmed by photometric redshifts, possibly because their optical photometry is corrupted by scattered light from the AO guidestar. (5) We use quantitative SED fits to constrain the photometric redshifts z_ph for some galaxies. Most galaxies near Q0835+580 are consistent with being at its redshift, including a candidate very old passively evolving galaxy. Many very & extremely red objects have z_ph z_q, and dust reddening is required to fit most of them, including many objects whose fits also require relatively old stellar populations. Large reddenings of E(B-V)~0.6 are required to fit four J-K selected EROs, though all but one of them have best-fit z_ph>z_q. These objects may represent a population of dusty high-z galaxies underrepresented in optically selected samples. (Abridged)Comment: Missing object 1126.424 added to Table 4; title changed to save people the apparent trouble of reading the abstract. 38 pages, 16 figures, 2 in color; all-PostScript figure version available from http://astro.princeton.edu/~pathall/tp3.ps.g

A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen.

BACKGROUND: Hereditary microscopic haematuria often segregates with mutations of COL4A3, COL4A4 or COL4A5 but in half of families a gene is not identified. We investigated a Cypriot family with autosomal dominant microscopic haematuria with renal failure and kidney cysts. METHODS: We used genome-wide linkage analysis, whole exome sequencing and cosegregation analyses. RESULTS: We identified a novel frameshift mutation, c.4611_4612insG:p.T1537fs, in exon 49 of COL4A1. This mutation predicts truncation of the protein with disruption of the C-terminal part of the NC1 domain. We confirmed its presence in 20 family members, 17 with confirmed haematuria, 5 of whom also had stage 4 or 5 chronic kidney disease. Eleven family members exhibited kidney cysts (55% of those with the mutation), but muscle cramps or cerebral aneurysms were not observed and serum creatine kinase was normal in all individuals tested. CONCLUSIONS: Missense mutations of COL4A1 that encode the CB3 [IV] segment of the triple helical domain (exons 24 and 25) are associated with HANAC syndrome (hereditary angiopathy, nephropathy, aneurysms and cramps). Missense mutations of COL4A1 that disrupt the NC1 domain are associated with antenatal cerebral haemorrhage and porencephaly, but not kidney disease. Our findings extend the spectrum of COL4A1 mutations linked with renal disease and demonstrate that the highly conserved C-terminal part of the NC1 domain of the α1 chain of type IV collagen is important in the integrity of glomerular basement membrane in humans