Preleukemia: one name, many meanings.

Definition of preleukemia has evolved. It was first used to describe the myelodysplastic syndrome (MDS) with a propensity to progress to acute myeloid leukemia (AML). Individuals with germline mutations of either RUNX1, CEBPA, or GATA2 can also be called as preleukemic because they have a markedly increased incidence of evolution into AML. Also, alkylating chemotherapy or radiation can cause MDS/preleukemia, which nearly always progress to AML. More recently, investigators noted that AML patients who achieved complete morphological remission after chemotherapy often have clonal hematopoiesis predominantly marked by either DNMT3A, TET2 or IDH1/2 mutations, which were also present at diagnosis of AML. This preleukemic clone represents involvement of an early hematopoietic stem cells, which is resistant to standard therapy. The same clonal hematopoietic mutations have been identified in older 'normal' individuals who have a modest increased risk of developing frank AML. These individuals have occasionally been said, probably inappropriately, to have a preleukemia clone. Our evolving understanding of the term preleukemia has occurred by advancing technology including studies of X chromosome inactivation, cytogenetics and more recently deep nucleotide sequencing

Symmetric Allocations for Distributed Storage

We consider the problem of optimally allocating a given total storage budget in a distributed storage system. A source has a data object which it can code and store over a set of storage nodes; it is allowed to store any amount of coded data in each node, as long as the total amount of storage used does not exceed the given budget. A data collector subsequently attempts to recover the original data object by accessing each of the nodes independently with some constant probability. By using an appropriate code, successful recovery occurs when the total amount of data in the accessed nodes is at least the size of the original data object. The goal is to find an optimal storage allocation that maximizes the probability of successful recovery. This optimization problem is challenging because of its discrete nature and nonconvexity, despite its simple formulation. Symmetric allocations (in which all nonempty nodes store the same amount of data), though intuitive, may be suboptimal; the problem is nontrivial even if we optimize over only symmetric allocations. Our main result shows that the symmetric allocation that spreads the budget maximally over all nodes is asymptotically optimal in a regime of interest. Specifically, we derive an upper bound for the suboptimality of this allocation and show that the performance gap vanishes asymptotically in the specified regime. Further, we explicitly find the optimal symmetric allocation for a variety of cases. Our results can be applied to distributed storage systems and other problems dealing with reliability under uncertainty, including delay tolerant networks (DTNs) and content delivery networks (CDNs).Comment: 7 pages, 3 figures, extended version of an IEEE GLOBECOM 2010 pape

A Pan1/End3/Sla1 complex links Arp2/3-mediated actin assembly to sites of clathrin-mediated endocytosis.

More than 60 highly conserved proteins appear sequentially at sites of clathrin-mediated endocytosis in yeast and mammals. The yeast Eps15-related proteins Pan1 and End3 and the CIN85-related protein Sla1 are known to interact with each other in vitro, and they all appear after endocytic-site initiation but before endocytic actin assembly, which facilitates membrane invagination/scission. Here we used live-cell imaging in parallel with genetics and biochemistry to explore comprehensively the dynamic interactions and functions of Pan1, End3, and Sla1. Our results indicate that Pan1 and End3 associate in a stable manner and appear at endocytic sites before Sla1. The End3 C-terminus is necessary and sufficient for its cortical localization via interaction with Pan1, whereas the End3 N-terminus plays a crucial role in Sla1 recruitment. We systematically examined the dynamic behaviors of endocytic proteins in cells in which Pan1 and End3 were simultaneously eliminated, using the auxin-inducible degron system. The results lead us to propose that endocytic-site initiation and actin assembly are separable processes linked by a Pan1/End3/Sla1 complex. Finally, our study provides mechanistic insights into how Pan1 and End3 function with Sla1 to coordinate cargo capture with actin assembly

Development and validation of the crew-station system-integration research facility

The various issues associated with the use of integrated flight management systems in aircraft were discussed. To address these issues a fixed base integrated flight research (IFR) simulation of a helicopter was developed to support experiments that contribute to the understanding of design criteria for rotorcraft cockpits incorporating advanced integrated flight management systems. A validation experiment was conducted that demonstrates the main features of the facility and the capability to conduct crew/system integration research

Why Do Protein Structures Recur?

Protein tertiary structures exhibit an observable degeneracy in nature. This paper examines the connection between a protein motif\u27s abundance in nature and its designability as measured by in silico methods. After generating a set of protein structures, we evaluated each structure\u27s abundance in nature, ratio of possible contacts (contact degree) and in silico designability. Our results showed that any two or these metrics are moderately correlated. Together abundance and contact degree produced the strongest correlation with in silico designability. Our results suggest that abundance is indeed an indicator of designability. Furthermore, abundance and contact degree appear to correlate with some distinct components of in silico designability

Simulating spin-charge separation with light

In this work we show that stationary light-matter excitations generated inside a hollow one-dimensional waveguide filled with atoms, can be made to generate a photonic two-component Lieb Liniger model. We explain how to prepare and drive the atomic system to a strongly interacting regime where spin-charge separation could be possible. We then proceed by explaining how to measure the corresponding effective spin and charge densities and velocities through standard optical methods based in measuring dynamically the emitted photon intensities or by analyzing the photon spectrum. The relevant interactions exhibit the necessary tunability both to generate and efficiently observe spin charge separation with current technology.Comment: 4 pages. Comments welcom

Haze in the Klang Valley of Malaysia

Continuous measurements of dry aerosol light scattering (Bsp) were made at two sites in the Klang Valley of Malaysia between December 1998 and December 2000. In addition 24-h PM2.5 samples were collected on a one-day-in-six cycle and the chemical composition of the aerosol was determined. Periods of excessive haze were defined as 24-h average Bsp values greater than 150 Mm-1 and these occurred on a number of occasions, between May and September 1999, during May 2000, and between July and September 2000. The evidence for smoke being a significant contributor to aerosol during periods of excessive haze is discussed and includes features of the aerosol chemistry, the diurnal cycle of Bsp, and the coincidence of forest fires on Sumatra during the southwest (SW) monsoon period, as well as transport modelling for one week of the southwest Monsoon of 2000. The study highlights that whilst transboundary smoke is a major contributor to poor visibility in the Klang Valley, smoke from fires on Peninsular Malaysia is also a contributor, and at all times, the domestic source of secondary particle production is present