A stacking-fault based microscopic model for platelets in diamond

We propose a new microscopic model for the $\{001\}$ planar defects in diamond commonly called platelets. This model is based on the formation of a metastable stacking fault, which can occur because of the ability of carbon to stabilize in different bonding configurations. In our model the core of the planar defect is basically a double layer of three-fold coordinated $sp^2$ carbon atoms embedded in the common $sp^3$ diamond structure. The properties of the model were determined using {\it ab initio} total energy calculations. All significant experimental signatures attributed to the platelets, namely, the lattice displacement along the $[001]$ direction, the asymmetry between the $[110]$ and the $[1\bar{1}0]$ directions, the infrared absorption peak $B^\prime$, and broad luminescence lines that indicate the introduction of levels in the band gap, are naturally accounted for in our model. The model is also very appealing from the point of view of kinetics, since naturally occurring shearing processes will lead to the formation of the metastable fault.Comment: 5 pages, 4 figures. Submitted for publication on August 2nd, 200

The prismatic Sigma 3 (10-10) twin bounday in alpha-Al2O3 investigated by density functional theory and transmission electron microscopy

The microscopic structure of a prismatic $\Sigma 3$ $(10\bar{1}0)$ twin boundary in \aal2o3 is characterized theoretically by ab-initio local-density-functional theory, and experimentally by spatial-resolution electron energy-loss spectroscopy in a scanning transmission electron microscope (STEM), measuring energy-loss near-edge structures (ELNES) of the oxygen $K$-ionization edge. Theoretically, two distinct microscopic variants for this twin interface with low interface energies are derived and analysed. Experimentally, it is demonstrated that the spatial and energetical resolutions of present high-performance STEM instruments are insufficient to discriminate the subtle differences of the two proposed interface variants. It is predicted that for the currently developed next generation of analytical electron microscopes the prismatic twin interface will provide a promising benchmark case to demonstrate the achievement of ELNES with spatial resolution of individual atom columns

Density functional theory calculations of the carbon ELNES of small diameter armchair and zigzag nanotubes: core-hole, curvature and momentum transfer orientation effects

We perform density functional theory calculations on a series of armchair and zigzag nanotubes of diameters less than 1nm using the all-electron Full-Potential(-Linearised)-Augmented-Plane-Wave (FPLAPW) method. Emphasis is laid on the effects of curvature, the electron beam orientation and the inclusion of the core-hole on the carbon electron energy loss K-edge. The electron energy loss near-edge spectra of all the studied tubes show strong curvature effects compared to that of flat graphene. The curvature induced $\pi-\sigma$ hybridisation is shown to have a more drastic effect on the electronic properties of zigzag tubes than on those of armchair tubes. We show that the core-hole effect must be accounted for in order to correctly reproduce electron energy loss measurements. We also find that, the energy loss near edge spectra of these carbon systems are dominantly dipole selected and that they can be expressed simply as a proportionality with the local momentum projected density of states, thus portraying the weak energy dependence of the transition matrix elements. Compared to graphite, the ELNES of carbon nanotubes show a reduced anisotropy.Comment: 25 pages, 15 figures, revtex4 submitted for publication to Phys. Rev.

Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers.: CYCLON-induced Rituximab resistance

International audienceImmuno-chemotherapy elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumours in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that autonomously drives aggressive tumour growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma

Excellent outcomes of laparoscopic esophagomyotomy for achalasia in patients older than 60 years of age

The effectiveness of an esophagomyotomy for dysphagia in elderly patients with achalasia has been questioned. This study was designed to provide an answer. A total of 162 consecutive patients with achalasia who had a laparoscopic myotomy and Dor fundoplication and who were available for follow-up interview were divided by age: <60 years (range, 14–59; 118 patients), and ≥60 years (range, 60–93; 44 patients). Primary outcome measures were severity of dysphagia, regurgitation, heartburn, and chest pain before and after the operation as assessed on a four-point Likert scale, and the need for postoperative dilatation or revisional surgery. Follow-up averaged 64 months. Older patients had less dysphagia (mean score 3.6 vs. 3.9; P < 0.01) and less chest pain (1.0 vs. 1.8; P < 0.01). Regurgitation (3.0 vs. 3.2; P = not significant (NS)) and heartburn (1.6 vs. 2.0, P = NS) were similar. Older patients were no different in degree of esophageal dilation, manometric findings, number of previous pneumatic dilatations, or previous botulinum toxin therapy. None of the older patients had previously had an esophagomyotomy, whereas 14% of younger patients had (P < 0.01). After laparoscopic myotomy, older patients had better relief of dysphagia (mean score 1.0 vs 1.6; P < 0.01), less heartburn (0.8 vs. 1.1; P = 0.03), and less chest pain (0.2 vs. 0.8, P < 0.01). Complication rates were similar. Older patients did not require more postoperative dilatations (22 patients vs. 10 patients; P = 0.7) or revisional surgery for recurrent or persistent symptoms (3 vs. 1 patients; P = 0.6). Satisfaction scores did not differ, and more than 90% of patients in both groups said in retrospect they would have undergone the procedure if they had known beforehand how it would turn out. This retrospective review with long follow-up supports laparoscopic esophagomyotomy as first-line therapy in older patients with achalasia. They appeared to benefit even more than younger patients

Mast Cells Express 11 beta-hydroxysteroid Dehydrogenase Type 1: A Role in Restraining Mast Cell Degranulation:a role in restraining mast cell degranulation

Mast cells are key initiators of allergic, anaphylactic and inflammatory reactions, producing mediators that affect vascular permeability, angiogenesis and fibrosis. Glucocorticoid pharmacotherapy reduces mast cell number, maturation and activation but effects at physiological levels are unknown. Within cells, glucocorticoid concentration is modulated by the 11β-hydroxysteroid dehydrogenases (11β-HSDs). Here we show expression and activity of 11β-HSD1, but not 11β-HSD2, in mouse mast cells with 11β-HSD activity only in the keto-reductase direction, regenerating active glucocorticoids (cortisol, corticosterone) from inert substrates (cortisone, 11-dehydrocorticosterone). Mast cells from 11β-HSD1-deficient mice show ultrastructural evidence of increased activation, including piecemeal degranulation and have a reduced threshold for IgG immune complex-induced mast cell degranulation. Consistent with reduced intracellular glucocorticoid action in mast cells, levels of carboxypeptidase A3 mRNA, a glucocorticoid-inducible mast cell-specific transcript, are lower in peritoneal cells from 11β-HSD1-deficient than control mice. These findings suggest that 11β-HSD1-generated glucocorticoids may tonically restrain mast cell degranulation, potentially influencing allergic, anaphylactic and inflammatory responses