Quantitative Analysis of Cardiomyocyte Dynamics with Optical Coherence Phase Microscopy

Spectral domain optical coherence microscopy (OCM) is an interferometric imaging technique for three-dimensional reconstruction of biological samples. Phase sensitive implementation of OCM has generally been in common path interferometer configuration to obtain high phase stability, wh ich limits the numerical aperture of the imaging optics and the transverse resolution. Here, we describe the implemen tation of optical coherence phase microscope in asymmetric Linnik interferometer configuration, which provides phase stability of 0.5 milliradians along with high spatial resolution. Three-dimensional structural images and dynamic displacement images ob tained from spontaneously active cardiomyocytes demonstrate that the phase information could potentially be used for quantitative analysis of contraction dynamics, spatially resolved to sub-cellular structures

Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure

PHASED VARIANTS IMPROVE DLBCL MINIMAL RESIDUAL DISEASE DETECTION AT THE END OF THERAPY

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High-E_T dijet photoproduction at HERA

The cross section for high-E_T dijet production in photoproduction has been measured with the ZEUS detector at HERA using an integrated luminosity of 81.8 pb-1. The events were required to have a virtuality of the incoming photon, Q^2, of less than 1 GeV^2 and a photon-proton centre-of-mass energy in the range 142 < W < 293 GeV. Events were selected if at least two jets satisfied the transverse-energy requirements of E_T(jet1) > 20 GeV and E_T(jet2) > 15 GeV and pseudorapidity requirements of -1 < eta(jet1,2) < 3, with at least one of the jets satisfying -1 < eta(jet) < 2.5. The measurements show sensitivity to the parton distributions in the photon and proton and effects beyond next-to-leading order in QCD. Hence these data can be used to constrain further the parton densities in the proton and photon.Comment: 36 pages, 13 figures, 20 tables, including minor revisions from referees. Accepted by Phys. Rev.

Measurement of (anti)deuteron and (anti)proton production in DIS at HERA

The first observation of (anti)deuterons in deep inelastic scattering at HERA has been made with the ZEUS detector at a centre-of-mass energy of 300--318 GeV using an integrated luminosity of 120 pb-1. The measurement was performed in the central rapidity region for transverse momentum per unit of mass in the range 0.3<p_T/M<0.7. The particle rates have been extracted and interpreted in terms of the coalescence model. The (anti)deuteron production yield is smaller than the (anti)proton yield by approximately three orders of magnitude, consistent with the world measurements.Comment: 26 pages, 9 figures, 5 tables, submitted to Nucl. Phys.

A phase II trial to evaluate the combination of pixantrone and obinutuzumab for patients with relapsed aggressive lymphoma: Final results of the prospective, multicentre GOAL trial

The prognosis of patients with relapsed diffuse large B-cell lymphoma (DLBCL) remains poor with current options. Here we prospectively evaluated the combination of pixantrone with obinutuzumab for up to six cycles for patients with relapsed or refractory DLBCL. Overall response rate (ORR) was the primary end-point. Sixty-eight patients were evaluated, median age was 75 years, median number of prior lines was three (range 1-10), 52 patients (76.5%) were diagnosed with DLBCL and 16 (23.5%) patients had transformed indolent lymphoma or follicular lymphoma (FL) IIIB. ORR was 35.3% for all and 40% for evaluable patients (16.6% complete response), median progression-free survival (PFS) and overall survival (OS) were 2.8 months and 8 months, respectively. Analysis of the cell of origin revealed a superior course for patients with non-GCB (germinal centre B-cell-like) phenotype [median OS not reached (n.r.) vs 5.2 months]. Patients with one prior line had an improved outcome over patients treated in later lines (PFS n.r. vs 2.5 months). Disease progression was the main reason for premature termination. Adverse events were mainly haematologic. The combination treatment revealed no unexpected adverse events. Most relevant non-haematologic toxicity was infection in 28% of patients. In summary, pixantrone-obinutuzumab showed clinical activity with sometimes long-term remission; however, the trial failed to meet its primary end-point

Repeated PTZ Treatment at 25-Day Intervals Leads to a Highly Efficient Accumulation of Doublecortin in the Dorsal Hippocampus of Rats

BACKGROUND: Neurogenesis persists throughout life in the adult mammalian brain. Because neurogenesis can only be assessed in postmortem tissue, its functional significance remains undetermined, and identifying an in vivo correlate of neurogenesis has become an important goal. By studying pentylenetetrazole-induced brain stimulation in a rat model of kindling we accidentally discovered that 25±1 days periodic stimulation of Sprague-Dawley rats led to a highly efficient increase in seizure susceptibility. METHODOLOGY/PRINCIPAL FINDINGS: By EEG, RT-PCR, western blotting and immunohistochemistry, we show that repeated convulsive seizures with a periodicity of 25±1 days led to an enrichment of newly generated neurons, that were BrdU-positive in the dentate gyrus at day 25±1 post-seizure. At the same time, there was a massive increase in the number of neurons expressing the migratory marker, doublecortin, at the boundary between the granule cell layer and the polymorphic layer in the dorsal hippocampus. Some of these migrating neurons were also positive for NeuN, a marker for adult neurons. CONCLUSION/SIGNIFICANCE: Our results suggest that the increased susceptibility to seizure at day 25±1 post-treatment is coincident with a critical time required for newborn neurons to differentiate and integrate into the existing hippocampal network, and outlines the importance of the dorsal hippocampus for seizure-related neurogenesis. This model can be used as an in vivo correlate of neurogenesis to study basic questions related to neurogenesis and to the neurogenic mechanisms that contribute to the development of epilepsy

Search for R-Parity Violating Decays of Supersymmetric Particles in e+e−e^{+}e^{-} Collisions at Centre-of-Mass Energies near 183 GeV

Searches for pair-production of supersymmetric particles under the assumption that R-parity is violated via a single dominant $LL{\bar E}$, $LQ{\bar D}$ or ${\bar U} {\bar D} {\bar D}$ coupling are performed using the data collected by the \ALEPH\ collaboration at centre-of-mass energies of 181--184~\gev. The observed candidate events in the data are in agreement with the Standard Model expectations. Upper limits on the production cross-sections and lower limits on the masses of charginos, sleptons, squarks and sneutrinos are de rived

Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem cell transplantation

We investigated the role of copy number alterations to refine risk stratification in adult Philadelphia chromosome positive (Ph)+ ALL treated with tyrosine kinase inhibitors (TKI) and allogeneic stem cell transplantation (aSCT). 97 Ph+ ALL patients (median age 41 years, range 18-64 years) within the prospective multicenter GMALL studies 06/99 (n=8) and 07/2003 (n=89) were analysed. All patients received TKI and aSCT in first complete remission (CR1). Copy number analysis was performed with SNP arrays and validated by multiplex ligation-dependent probe amplification (MLPA). The frequencies of recurrently deleted genes were: IKZF1, 76%, CDKN2A/2B, 45%, PAX5, 43%, BTG1, 18%, EBF1, 13%, ETV6, 5%, RB, 14%. In univariate analyses, the presence of CDKN2A/2B deletions had a negative impact on all endpoints: overall survival (p=0.023), disease free survival (p=0.012) and remission duration (p=0.036). The negative predictive value of CDKN2A/2B deletions was retained in multivariable analysis along with other factors such as timing of TKI therapy, intensity of conditioning, achieving remission after induction phase I and BTG1 deletions. We therefore conclude that acquired genomic CDKN2A/2B deletions identify a subgroup of Ph+ ALL patients, who have an inferior prognosis despite aSCT in CR1. Their poor outcome was attributable primarily to a high relapse rate after aSCT