Sonographic and cyst fluid cytological changes after EUS-guided pancreatic cyst ablation

Background and Aims The effect of EUS-guided pancreatic cyst ablation (PCA) on sonographic morphology and cyst fluid cytology is unknown. The aim of this study is to evaluate morphological, cytological and change in cyst fluid DNA after PCA. Methods In a prospective single center study, consecutive patients with suspected benign 10 to 50 mm pancreatic cysts underwent baseline EUS-FNA and EUS-PCA followed 2 to 3 months later by repeat EUS, cyst fluid analysis and possible repeat PCA. Surveillance imaging after ablation was performed at least annually and classified as complete (CR), partial (PR), or persistent with <5%, 5% to 25%, and 25% of the original cyst volume, respectively. Results 36 patients underwent EUS-PCA with ethanol alone (n = 8) or ethanol and paclitaxel (n = 28) and CR occurred in 19 (56%). After EUS-PCA, EUS showed an increase in wall diameter in 68%, decreased number of septations in 24%, increased debris in 24%, loss of mural nodule or novel calcification in 21%, and alteration of fluid viscosity in 48%. Follow-up cytology showed increased epithelial cellularity in 27%, loss or decreased cellular atypia in 15%, and increased or appearance of macrophages in 24% and inflammatory cells in 15%. Post-ablation DNA amount increased and quality decreased in 71% each. Between the CR and non-CR patients, there was no significant difference in frequency of sonographic or cytological features. In the CR group, mean DNA quantity was significantly increased after ablation (p=0.023) without a change in quality (p=0.136) Conclusions EUS-PCA induces morphological and cytological changes of the pancreatic cysts none of which appear to predict overall imaging-defined response to ablation

Physico-chemical requirements and kinetics of membrane fusion of flavivirus-like particles.

Flaviviruses deliver their RNA genome into the host-cell cytoplasm by fusing their lipid envelope with a cellular membrane. Expression of the flavivirus pre-membrane and envelope glycoprotein genes in the absence of other viral genes results in the spontaneous assembly and secretion of virus-like particles (VLPs) with membrane fusion activity. Here, we examined the physico-chemical requirements for membrane fusion of VLPs from West Nile and Japanese encephalitis viruses. In a bulk fusion assay, optimal hemifusion (or lipid mixing) efficiencies were observed at 37 °C. Fusion efficiency increased with decreasing pH; half-maximal hemifusion was attained at pH 5.6. The anionic lipids bis(monoacylglycero)phosphate and phosphatidylinositol-3-phosphate, when present in the target membrane, significantly enhanced fusion efficiency, consistent with the emerging model that flaviviruses fuse with intermediate-to-late endosomal compartments, where these lipids are most abundant. In a single-particle fusion assay, VLPs catalysed membrane hemifusion, tracked as lipid mixing with the cellular membrane, on a timescale of 7-20 s after acidification. Lipid mixing kinetics suggest that hemifusion is a kinetically complex, multistep process.This work was supported by a Senior Research Fellowship from the Wellcome Trust, grant number 101908/Z/13/Z, to Y.M.; grant R01 GM102869 from the National Institutes of Health (NIH) to Y.M.; NIH grant NS079955 to E.R.; NIH grant T32 GM08283 to J.B.N.; and NIH grant T32 GM007223 to D.C.D. We thank Michel Ledizet, Martin Mattessich and Nathalie Bonafé (L2 Diagnostics, LLC) for helpful discussions.This is the author accepted manuscript. The final version is available from the Society for General Microbiology via http://dx.doi.org/10.1099/vir.0.00011

Overcharging a Black Hole and Cosmic Censorship

We show that, contrary to a widespread belief, one can overcharge a near extremal Reissner-Nordstrom black hole by throwing in a charged particle, as long as the backreaction effects may be considered negligible. Furthermore, we find that we can make the particle's classical radius, mass, and charge, as well as the relative size of the backreaction terms arbitrarily small, by adjusting the parameters corresponding to the particle appropriately. This suggests that the question of cosmic censorship is still not wholly resolved even in this simple scenario. We contrast this with attempting to overcharge a black hole with a charged imploding shell, where we find that cosmic censorship is upheld. We also briefly comment on a number of possible extensions.Comment: 26 pages, 3 figures, LaTe

Phase Transition in Conformally Induced Gravity with Torsion

We have considered the quantum behavior of a conformally induced gravity in the minimal Riemann-Cartan space. The regularized one-loop effective potential considering the quantum fluctuations of the dilaton and the torsion fields in the Coleman-Weinberg sector gives a sensible phase transition for an inflationary phase in De Sitter space. For this effective potential, we have analyzed the semi-classical equation of motion of the dilaton field in the slow-rolling regime.Comment: 7pages, no figur

Glueball spectrum and the Pomeron in the Wilson loop approach

Using a nonperturbative method based on asymptotic behaviour of Wilson loops we calculate masses of glueballs and corresponding Regge-trajectories. The only input is string tension fixed by meson Regge slope, while perturbative contributions to spin splittings are defined by standard alpha_s values. The masses of lowest glueball states are in a perfect agreement with lattice results. The leading glueball trajectory which is associated with Pomeron is discussed in details and its mixing with f and f' trajectories is taken into account.Comment: LaTeX2e, 49 pages, 2 figure

Quantum systems in weak gravitational fields

Fully covariant wave equations predict the existence of a class of inertial-gravitational effects that can be tested experimentally. In these equations inertia and gravity appear as external classical fields, but, by conforming to general relativity, provide very valuable information on how Einstein's views carry through in the world of the quantum.Comment: 22 pages. To be published in Proceedings of the 17th Course of the International School of Cosmology and Gravitation "Advances in the interplay between quantum and gravity physics" edited by V. De Sabbata and A. Zheltukhin, Kluwer Academic Publishers, Dordrech

COBE constraints on inflation models with a massive non-minimal scalar field

We derive power spectra of the scalar- and tensor-type structures generated in an inflation model based on a massive non-minimally coupled scalar field with the strong coupling assumption. We make analyses in both the original-frame and the conformally transformed Einstein-frame. We derive contributions of both structures to the anisotropy of the cosmic microwave background radiation, and compare the contributions with the four-year COBE-DMR data. Previous study showed that sufficient amount of inflation requires a small coupling parameter. In such a case the spectra become near Zeldovich spectra, and the gravitational wave contribution becomes negligible compared with the scalar-type contribution which is testable in future CMBR experiments.Comment: 4 pages, no figure, To appear in Phys. Rev.

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification

Hamiltonian dynamics and Noether symmetries in Extended Gravity Cosmology

We discuss the Hamiltonian dynamics for cosmologies coming from Extended Theories of Gravity. In particular, minisuperspace models are taken into account searching for Noether symmetries. The existence of conserved quantities gives selection rule to recover classical behaviors in cosmic evolution according to the so called Hartle criterion, that allows to select correlated regions in the configuration space of dynamical variables. We show that such a statement works for general classes of Extended Theories of Gravity and is conformally preserved. Furthermore, the presence of Noether symmetries allows a straightforward classification of singularities that represent the points where the symmetry is broken. Examples of nonminimally coupled and higher-order models are discussed.Comment: 20 pages, Review paper to appear in EPJ

From the Big Bang Theory to the Theory of a Stationary Universe

We consider chaotic inflation in the theories with the effective potentials phi^n and e^{\alpha\phi}. In such theories inflationary domains containing sufficiently large and homogeneous scalar field \phi permanently produce new inflationary domains of a similar type. We show that under certain conditions this process of the self-reproduction of the Universe can be described by a stationary distribution of probability, which means that the fraction of the physical volume of the Universe in a state with given properties (with given values of fields, with a given density of matter, etc.) does not depend on time, both at the stage of inflation and after it. This represents a strong deviation of inflationary cosmology from the standard Big Bang paradigm. We compare our approach with other approaches to quantum cosmology, and illustrate some of the general conclusions mentioned above with the results of a computer simulation of stochastic processes in the inflationary Universe.Comment: No changes to the file, but original figures are included. They substantially help to understand this paper, as well as eternal inflation in general, and what is now called the "multiverse" and the "string theory landscape." High quality figures can be found at http://www.stanford.edu/~alinde/LLMbigfigs