Photoionization Rates of Cs Rydberg Atoms in a 1064 nm Far Off-Resonance Trap

Experimental measurements of photoionization rates of $nD_{5/2}$ Rydberg states of Cs ($50 \leq n \leq 75$) in a 1064 nm far off-resonance dipole trap are presented. The photoionization rates are obtained by measuring the lifetimes of Rydberg atoms produced inside of a 1064 nm far off-resonance trap and comparing the lifetimes to corresponding control experiments in a magneto-optical trap. Experimental results for the control experiments agree with recent theoretical predictions for Rydberg state lifetimes and measured photoionization rates are in agreement with transition rates calculated from a model potential.Comment: 12 pages, 4 figure

Observation of blue-shifted ultralong-range Cs2_{2} Rydberg molecules

We observe ultralong-range blue-shifted Cs$_{2}$ molecular states near $ns_{1/2}$ Rydberg states in an optical dipole trap, where $31\leq n\leq34$. The accidental near degeneracy of $(n-4)l$ and $ns$ Rydberg states for $l>2$ in Cs, due to the small fractional $ns$ quantum defect, leads to non-adiabatic coupling among these states, producing potential wells above the $ns$ thresholds. Two important consequences of admixing high angular momentum states with $ns$ states are the formation of large permanent dipole moments, $\sim 15-100\,$Debye, and accessibility of these states via two-photon association. The observed states are in excellent agreement with theory. Both projections of the total angular momentum on the internuclear axis are visible in the experiment

Ontological dependence in a spacetime-world

Priority Monism (hereafter, ‘Monism’), as defined by Jonathan Schaffer (Philos Rev 119:131–176, 2010), has a number of components. It is the view that: the cosmos exists; the cosmos is a maximal actual concrete object, of which all actual concrete objects are parts; the cosmos is basic—there is no object upon which the cosmos depends, ontologically; ontological dependence is a primitive and unanalysable relation. In a recent attack, Lowe (Spinoza on monism. Palgave Macmillan, London, pp 92–122, 2012) has offered a series of arguments to show that Monism fails. He offers up four tranches of argument, with different focuses. These focal points are: (1) being a concrete object; (2) aggregation and dependence; (3) analyses of ontological dependence; (4) Schaffer’s no-overlap principle. These are all technical notions, but each figures at the heart of a cluster of arguments that Lowe puts forward. To respond, I work through each tranche of argument in turn. Before that, in the first section, I offer a cursory statement of Monism, as Schaffer presents it in his 2010 paper, Monism: The Priority of the Whole. I then respond to each of Lowe’s criticisms in turn, deploying material from Schaffer’s 2009 paper Spacetime: the One Substance, as well as various pieces of conceptual machinery from Lowe’s own works (The possibility of metaphysics. Clarendon, Oxford, 1998, 2010) to deflect Lowe’s (Spinoza on monism. Palgave Macmillan, London, pp 92–122, 2012) attacks. In the process of defending Monism from Lowe (Spinoza on monism. Palgave Macmillan, London, pp 92–122, 2012), I end up offering some subtle refinements to Schaffer’s (Philos Rev 119:131–176, 2010) view and explain how the resulting ‘hybrid’ view fares in the wider dialectic

Followup to Columbia Investigation: Reinforced Carbon/Carbon From the Breach Location in the Wing Leading Edge Studied

Initial estimates on the temperature and conditions of the breach in the Space Shuttle Columbia's wing focused on analyses of the slag deposits. These deposits are complex mixtures of the reinforced carbon/carbon (RCC) constituents, insulation material, and wing structural materials. Identification of melted/solidified Cerachrome insulation (Thermal Ceramics, Inc., Augusta, GA) indicated that the temperatures at the breach had exceeded 1760 C

The Invisible Thin Red Line

The aim of this paper is to argue that the adoption of an unrestricted principle of bivalence is compatible with a metaphysics that (i) denies that the future is real, (ii) adopts nomological indeterminism, and (iii) exploits a branching structure to provide a semantics for future contingent claims. To this end, we elaborate what we call Flow Fragmentalism, a view inspired by Kit Fine (2005)’s non-standard tense realism, according to which reality is divided up into maximally coherent collections of tensed facts. In this way, we show how to reconcile a genuinely A-theoretic branching-time model with the idea that there is a branch corresponding to the thin red line, that is, the branch that will turn out to be the actual future history of the world

Immodest and proud

In his ‘Ambitious, Yet Modest, Metaphysics’, Hofweber (Metametaphysics, Oxford University Press, Oxford, pp 260–289, 2009a) puts forward arguments against positions in metaphysics that he describes as ‘immodest’; a position he identifies as defended by Jonathan Lowe. In this paper I reply to Hofweber’s arguments, offering a defence of immodest metaphysics of the type practiced by Lowe (The possibility of metaphysics, Oxford University Press, Oxford, 1998) inter alia

Flagellin Acting Via TLR5 is the Major Activator of Key Signaling Pathways Leading to NF-kappa B and Proinflammatory Gene Program activation in intestinal epithelial cells

BACKGROUND: Infection of intestinal epithelial cells by pathogenic Salmonella leads to activation of signaling cascades that ultimately initiate the proinflammatory gene program. The transcription factor NF-kappa B is a key regulator/activator of this gene program and is potently activated. We explored the mechanism by which Salmonella activates NF-kappa B during infection of cultured intestinal epithelial cells and found that flagellin produced by the bacteria and contained on them leads to NF-kappa B activation in all the cells; invasion of cells by the bacteria is not required to activate NF-kappa B. RESULTS: Purified flagellin activated the mitogen activated protein kinase (MAPK), stress-activated protein kinase (SAPK) and I kappa B kinase (IKK) signaling pathways that lead to expression of the proinflammatory gene program in a temporal fashion nearly identical to that of infection of intestinal epithelial cells by Salmonella. Flagellin expression was required for Salmonella invasion of host cells and it activated NF-kappa B via toll-like receptor 5 (TLR5). Surprisingly, a number of cell lines found to be unresponsive to flagellin express TLR5 and expression of exogenous TLR5 in these cells induces NF-kappa B activity in response to flagellin challenge although not robustly. Conversely, overexpression of dominant-negative TLR5 alleles only partially blocks NF-kappa B activation by flagellin. These observations are consistent with the possibility of either a very stable TLR5 signaling complex, the existence of a low abundance flagellin co-receptor or required adapter, or both. CONCLUSION: These collective results provide the evidence that flagellin acts as the main determinant of Salmonella mediated NF-kappa B and proinflammatory signaling and gene activation by this flagellated pathogen. In addition, expression of the fli C gene appears to play an important role in the proper functioning of the TTSS since mutants that fail to express fli C are defective in expressing a subset of Sip proteins and fail to invade host cells. Flagellin added in trans cannot restore the ability of the fli C mutant bacteria to invade intestinal epithelial cells. Lastly, TLR5 expression in weak and non-responding cells indicates that additional factors may be required for efficient signal propagation in response to flagellin recognition

New synthetic routes to Triazolo-benzodiazepine analogues:expanding the scope of the bump-and-hole approach for selective Bromo and Extra-Terminal (BET) bromodomain inhibition

We describe new synthetic routes developed toward a range of substituted analogues of bromo and extra-terminal (BET) bromodomain inhibitors I-BET762/JQ1 based on the triazolo-benzodiazepine scaffold. These new routes allow for the derivatization of the methoxyphenyl and chlorophenyl rings, in addition to the diazepine ternary center and the side chain methylene moiety. Substitution at the level of the side chain methylene afforded compounds targeting specifically and potently engineered BET bromodomains designed as part of a bump and hole approach. We further demonstrate that marked selectivity for the second over the first bromodomain can be achieved with an indole derivative that exploits differential interaction with an aspartate/histidine conservative substitution on the BC loop of BET bromodomains

Flagellin acting via TLR5 is the major activator of key signaling pathways leading to NF-κB and proinflammatory gene program activation in intestinal epithelial cells

BACKGROUND: Infection of intestinal epithelial cells by pathogenic Salmonella leads to activation of signaling cascades that ultimately initiate the proinflammatory gene program. The transcription factor NF-κB is a key regulator/activator of this gene program and is potently activated. We explored the mechanism by which Salmonella activates NF-κB during infection of cultured intestinal epithelial cells and found that flagellin produced by the bacteria and contained on them leads to NF-κB activation in all the cells; invasion of cells by the bacteria is not required to activate NF-κB. RESULTS: Purified flagellin activated the mitogen activated protein kinase (MAPK), stress-activated protein kinase (SAPK) and Ikappa B kinase (IKK) signaling pathways that lead to expression of the proinflammatory gene program in a temporal fashion nearly identical to that of infection of intestinal epithelial cells by Salmonella. Flagellin expression was required for Salmonella invasion of host cells and it activated NF-κB via toll-like receptor 5 (TLR5). Surprisingly, a number of cell lines found to be unresponsive to flagellin express TLR5 and expression of exogenous TLR5 in these cells induces NF-κB activity in response to flagellin challenge although not robustly. Conversely, overexpression of dominant-negative TLR5 alleles only partially blocks NF-κB activation by flagellin. These observations are consistent with the possibility of either a very stable TLR5 signaling complex, the existence of a low abundance flagellin co-receptor or required adapter, or both. CONCLUSION: These collective results provide the evidence that flagellin acts as the main determinant of Salmonella mediated NF-κB and proinflammatory signaling and gene activation by this flagellated pathogen. In addition, expression of the fli C gene appears to play an important role in the proper functioning of the TTSS since mutants that fail to express fli C are defective in expressing a subset of Sip proteins and fail to invade host cells. Flagellin added in trans cannot restore the ability of the fli C mutant bacteria to invade intestinal epithelial cells. Lastly, TLR5 expression in weak and non-responding cells indicates that additional factors may be required for efficient signal propagation in response to flagellin recognition