Clonal karyotype evolution involving ring chromosome 1 with myelodysplastic syndrome subtype RAEB-t progressing into acute leukemia

s Karyotypic evolution is a well-known phenomenon in patients with malignant hernatological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hernatological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes {[}46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome{[}46,XY,r(1),+8,-21/45,XY,r(1),+8,-21,-22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient's HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient's clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor's PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hernatological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease. Copyright (c) 2006 S. Karger AG, Basel

Thermal production of axino Dark Matter

We reconsider thermal production of axinos in the early universe, adding: a) missed terms in the axino interaction; b) production via gluon decays kinematically allowed by thermal masses; c) a precise modeling of reheating. We find an axino abunance a few times larger than previous computations.Comment: 6 pages, 2 figures. Final version, to appear on JHE

Breakdown of the adiabatic limit in low dimensional gapless systems

It is generally believed that a generic system can be reversibly transformed from one state into another by sufficiently slow change of parameters. A standard argument favoring this assertion is based on a possibility to expand the energy or the entropy of the system into the Taylor series in the ramp speed. Here we show that this argumentation is only valid in high enough dimensions and can break down in low-dimensional gapless systems. We identify three generic regimes of a system response to a slow ramp: (A) mean-field, (B) non-analytic, and (C) non-adiabatic. In the last regime the limits of the ramp speed going to zero and the system size going to infinity do not commute and the adiabatic process does not exist in the thermodynamic limit. We support our results by numerical simulations. Our findings can be relevant to condensed-matter, atomic physics, quantum computing, quantum optics, cosmology and others.Comment: 11 pages, 5 figures, to appear in Nature Physics (originally submitted version

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB

The Cosmology of Composite Inelastic Dark Matter

Composite dark matter is a natural setting for implementing inelastic dark matter - the O(100 keV) mass splitting arises from spin-spin interactions of constituent fermions. In models where the constituents are charged under an axial U(1) gauge symmetry that also couples to the Standard Model quarks, dark matter scatters inelastically off Standard Model nuclei and can explain the DAMA/LIBRA annual modulation signal. This article describes the early Universe cosmology of a minimal implementation of a composite inelastic dark matter model where the dark matter is a meson composed of a light and a heavy quark. The synthesis of the constituent quarks into dark mesons and baryons results in several qualitatively different configurations of the resulting dark matter hadrons depending on the relative mass scales in the system.Comment: 31 pages, 4 figures; references added, typos correcte

Proportions of the aesthetic African-Caribbean face : idealized ratios, comparison with the golden proportion and perceptions of attractiveness

Abstract Background In the absence of clear guidelines for facial aesthetic surgery, most surgeons rely on expert intuitive judgement when planning aesthetic and reconstructive surgery. One of the most famous theories regarding “ideal” facial proportions is that of the golden proportion. However, there are conflicting opinions as to whether it can be used to assess facial attractiveness. The aim of this investigation was to assess facial ratios of professional black models and to compare the ratios with the golden proportion. Methods Forty photographs of male and female professional black models were collected. Observers were asked to assign a score from 1 to 10 (1 = not very attractive, 10 = very attractive). A total of 287 responses were analysed for grading behaviour according to various demographic factors by two groups of observers. The best graded photographs were compared with the least well-graded photographs to identify any differences in their facial ratios. The models’ facial ratios were calculated and compared with the golden proportion. Results Differences in grading behaviour were observed amongst the two assessment groups. Only one out of the 12 facial ratios was not significantly different from the golden proportion. Conclusions Only one facial ratio was observed to be similar to the golden proportion in professional model facial photographs. No correlation was found between facial ratios in professional black models with the golden proportion. It is proposed that an individualistic treatment for each ratio is a rather better method to guide future practice

Discovery of a Non-Peptidic Inhibitor of West Nile Virus NS3 Protease by High-Throughput Docking

An estimated 2.5 billion people are at risk of diseases caused by dengue and West Nile virus. As of today, there are neither vaccines to prevent nor drugs to cure the severe infections caused by these viruses. The NS3 protease is one of the most promising targets for drug development against West Nile virus because it is an essential enzyme for viral replication and because success has been demonstrated with the closely related hepatitis C virus protease. We have discovered a small molecule that inhibits the NS3 protease of West Nile virus by computer-aided high-throughput docking, and validated it using three experimental techniques. The inhibitor has potential to be developed to a drug candidate to combat West Nile virus infections

Provision of artificial warrens as a means to enhance native wild rabbit populations: what type of warren and where should they be sited?

In Spain, wild rabbits are essential for some highly endangered species, and, therefore, many actions have been undertaken to increase their populations. In the present study, artificial warrens are provided as a means to increase shelter for native wild rabbit populations in a given area. We evaluate the use of three types of warrens by rabbits and the effect on that use of five habitat characteristics at two spatial scales (500 × 500-m grids and 25-m plots). To evaluate that use, we identified pre-established signs at the entrances to each warren, and based on this, we calculated occupancy rate and activity. Our results indicate that rabbit abundance within a grid is the only variable which simultaneously explains both the greater occupancy and the higher activity in the artificial warrens located in that grid. Some 73.2% of the grids showed signs of rabbit use at the time of the evaluation. However, the pre-existing rabbit populations within the grids were not quantified and, hence, we cannot state that the warrens contributed to an increase in the rabbit abundance. Regarding the habitat, our results reveal that warrens should be situated in grids with food coverage of less than 50%, while the use of each individual refuge is greater where food availability in the immediate surroundings is at least 20% and shelter at least 50%. The tube warrens showed significantly greater rabbit use than the other types while there was little difference between the stone and pallet warrens in terms of use

The Cosmological Constant

This is a review of the physics and cosmology of the cosmological constant. Focusing on recent developments, I present a pedagogical overview of cosmology in the presence of a cosmological constant, observational constraints on its magnitude, and the physics of a small (and potentially nonzero) vacuum energy.Comment: 50 pages. Submitted to Living Reviews in Relativity (http://www.livingreviews.org/), December 199