B-cell Prolymphocytic Leukemia in a Young Male

B-cell prolymphocytic leukemia [B-PLL] is a neoplasm of B prolymphocytes affecting the peripheral blood, bone marrow and spleen. The principal disease characteristics are massive splenomegaly with absent or minimal peripheral lymphadenopathy and a rapidly rising lymphocyte count. Here, we report a case of B-PLL in a 42 year old male who had come for routine health check up

Mapping the Energy Cascade in the North Atlantic Ocean: The Coarse-graining Approach

This is the final version of the article. Available from AMS via the DOI in this record.A coarse-graining framework is implemented to analyze nonlinear processes, measure energy transfer rates and map out the energy pathways from simulated global ocean data. Traditional tools to measure the energy cascade from turbulence theory, such as spectral flux or spectral transfer rely on the assumption of statistical homogeneity, or at least a large separation between the scales of motion and the scales of statistical inhomogeneity. The coarse-graining framework allows for probing the fully nonlinear dynamics simultaneously in scale and in space, and is not restricted by those assumptions. This paper describes how the framework can be applied to ocean flows. Energy transfer between scales is not unique due to a gauge freedom. Here, it is argued that a Galilean invariant subfilter scale (SFS) flux is a suitable quantity to properly measure energy scale-transfer in the Ocean. It is shown that the SFS definition can yield answers that are qualitatively different from traditional measures that conflate spatial transport with the scale-transfer of energy. The paper presents geographic maps of the energy scale-transfer that are both local in space and allow quasi-spectral, or scale-by-scale, dynamics to be diagnosed. Utilizing a strongly eddying simulation of flow in the North Atlantic Ocean, it is found that an upscale energy transfer does not hold everywhere. Indeed certain regions, near the Gulf Stream and in the Equatorial Counter Current have a marked downscale transfer. Nevertheless, on average an upscale transfer is a reasonable mean description of the extra-tropical energy scale-transfer over regions of O(10^3) kilometers in size.Financial support was provided by IGPPS at Los Alamos National Laboratory (LANL) and NSF grant OCE-1259794. HA was also supported through DOE grants de-sc0014318, de-na0001944, and the LANL LDRD program through project number 20150568ER. MH was also supported through the HiLAT project of the Regional and Global Climate Modeling program of the DOE’s Office of Science, and GKV was also supported by NERC, the Marie Curie Foundation and the Royal Society (Wolfson Foundation). This research used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231

Building SO(10) models from F-theory

We revisit local F-theory SO(10) and SU(5) GUTs and analyze their properties within the framework of the maximal underlying E_8 symmetry in the elliptic fibration. We consider the symmetry enhancements along the intersections of seven-branes with the GUT surface and study in detail the embedding of the abelian factors undergoing monodromies in the covering gauge groups. We combine flux data from the successive breaking of SO(10) to SU(5) gauge symmetry and subsequently to the Standard Model one, and further constrain the parameters determining the models' particle spectra. In order to eliminate dangerous baryon number violating operators we propose ways to construct matter parity like symmetries from intrinsic geometric origin. We study implementations of the resulting constrained scenario in specific examples obtained for a variety of monodromies.Comment: 53 page

Survival Motor Neuron (SMN) protein is required for normal mouse liver development

Spinal Muscular Atrophy (SMA) is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Decreased levels of, cell-ubiquitous, SMN protein is associated with a range of systemic pathologies reported in severe patients. Despite high levels of SMN protein in normal liver, there is no comprehensive study of liver pathology in SMA. We describe failed liver development in response to reduced SMN levels, in a mouse model of severe SMA. The SMA liver is dark red, small and has: iron deposition; immature sinusoids congested with blood; persistent erythropoietic elements and increased immature red blood cells; increased and persistent megakaryocytes which release high levels of platelets found as clot-like accumulations in the heart. Myelopoiesis in contrast, was unaffected. Further analysis revealed significant molecular changes in SMA liver, consistent with the morphological findings. Antisense treatment from birth with PMO25, increased lifespan and ameliorated all morphological defects in liver by postnatal day 21. Defects in the liver are evident at birth, prior to motor system pathology, and impair essential liver function in SMA. Liver is a key recipient of SMA therapies, and systemically delivered antisense treatment, completely rescued liver pathology. Liver therefore, represents an important therapeutic target in SMA

Plasticity facilitates sustainable growth in the commons

In the commons, communities whose growth depends on public goods, individuals often rely on surprisingly simple strategies, or heuristics, to decide whether to contribute to the common good (at risk of exploitation by free-riders). Although this appears a limitation, here we show how four heuristics lead to sustainable growth by exploiting specific environmental constraints. The two simplest ones --contribute permanently or switch stochastically between contributing or not-- are first shown to bring sustainability when the public good efficiently promotes growth. If efficiency declines and the commons is structured in small groups, the most effective strategy resides in contributing only when a majority of individuals are also contributors. In contrast, when group size becomes large, the most effective behavior follows a minimal-effort rule: contribute only when it is strictly necessary. Both plastic strategies are observed in natural systems what presents them as fundamental social motifs to successfully manage sustainability

Time-Energy Tradeoffs for Evacuation by Two Robots in the Wireless Model

Two robots stand at the origin of the infinite line and are tasked with searching collaboratively for an exit at an unknown location on the line. They can travel at maximum speed $b$ and can change speed or direction at any time. The two robots can communicate with each other at any distance and at any time. The task is completed when the last robot arrives at the exit and evacuates. We study time-energy tradeoffs for the above evacuation problem. The evacuation time is the time it takes the last robot to reach the exit. The energy it takes for a robot to travel a distance $x$ at speed $s$ is measured as $xs^2$. The total and makespan evacuation energies are respectively the sum and maximum of the energy consumption of the two robots while executing the evacuation algorithm. Assuming that the maximum speed is $b$, and the evacuation time is at most $cd$, where $d$ is the distance of the exit from the origin, we study the problem of minimizing the total energy consumption of the robots. We prove that the problem is solvable only for $bc \geq 3$. For the case $bc=3$, we give an optimal algorithm, and give upper bounds on the energy for the case $bc>3$. We also consider the problem of minimizing the evacuation time when the available energy is bounded by $\Delta$. Surprisingly, when $\Delta$ is a constant, independent of the distance $d$ of the exit from the origin, we prove that evacuation is possible in time $O(d^{3/2}\log d)$, and this is optimal up to a logarithmic factor. When $\Delta$ is linear in $d$, we give upper bounds on the evacuation time.Comment: This is the full version of the paper with the same title which will appear in the proceedings of the 26th International Colloquium on Structural Information and Communication Complexity (SIROCCO'19) L'Aquila, Italy during July 1-4, 201

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size

Dynamics on expanding spaces: modeling the emergence of novelties

Novelties are part of our daily lives. We constantly adopt new technologies, conceive new ideas, meet new people, experiment with new situations. Occasionally, we as individuals, in a complicated cognitive and sometimes fortuitous process, come up with something that is not only new to us, but to our entire society so that what is a personal novelty can turn into an innovation at a global level. Innovations occur throughout social, biological and technological systems and, though we perceive them as a very natural ingredient of our human experience, little is known about the processes determining their emergence. Still the statistical occurrence of innovations shows striking regularities that represent a starting point to get a deeper insight in the whole phenomenology. This paper represents a small step in that direction, focusing on reviewing the scientific attempts to effectively model the emergence of the new and its regularities, with an emphasis on more recent contributions: from the plain Simon's model tracing back to the 1950s, to the newest model of Polya's urn with triggering of one novelty by another. What seems to be key in the successful modelling schemes proposed so far is the idea of looking at evolution as a path in a complex space, physical, conceptual, biological, technological, whose structure and topology get continuously reshaped and expanded by the occurrence of the new. Mathematically it is very interesting to look at the consequences of the interplay between the "actual" and the "possible" and this is the aim of this short review.Comment: 25 pages, 10 figure

Activated prothrombin complex in the management of direct thrombin inhibitor-associated intracerebral haemorrhage.

Intracerebral haematoma expansion independently predicts poor functional outcome and mortality. Therefore, it is important to act quickly to arrest this expansion. Whilst a direct antidote to dabigatran remains in development, the use of factor VIII inhibitor bypassing activity may offer a practical strategy for arresting haemorrhage in individuals taking direct thrombin inhibitors.NRE is supported by a Research Training Fellowship from The Dunhill Medical Trust [grant number RTF44/0114].This is the author accepted manuscript. The final version is available from Oxford University Press at http://dx.doi.org/10.1093/qjmed/hcv219