Secondary Electron Yield Measurements of Fermilab's Main Injector Vacuum Vessel

We discuss the progress made on a new installation in Fermilab's Main Injector that will help investigate the electron cloud phenomenon by making direct measurements of the secondary electron yield (SEY) of samples irradiated in the accelerator. In the Project X upgrade the Main Injector will have its beam intensity increased by a factor of three compared to current operations. This may result in the beam being subject to instabilities from the electron cloud. Measured SEY values can be used to further constrain simulations and aid our extrapolation to Project X intensities. The SEY test-stand, developed in conjunction with Cornell and SLAC, is capable of measuring the SEY from samples using an incident electron beam when the samples are biased at different voltages. We present the design and manufacture of the test-stand and the results of initial laboratory tests on samples prior to installation.Comment: 3 pp. 3rd International Particle Accelerator Conference (IPAC 2012) 20-25 May 2012, New Orleans, Louisian

Random close packing of granular matter

We propose an interpretation of the random close packing of granular materials as a phase transition, and discuss the possibility of experimental verification.Comment: 6 page

1,2,6-thiadiazinones as novel narrow spectrum calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) inhibitors

We demonstrate for the first time that 4H-1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4H-1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water molecules in the active site. Since the TDZ analogues showed reduced promiscuity compared to their 2,4-dianilinopyrimidine counter parts, they represent starting points for development of highly selective kinase inhibitors

Radiofrequency Ablation Resulting in Left Lobe Hypertrophy and Improved Resectability

Surgical resection for colorectal liver metastases may only be considered when an adequate functional residual volume can be preserved. Selective portal venous embolisation may be used to increase this volume, whilst chemotherapy and radiofrequency ablation (RFA) can be used to treat inoperable lesions. A 73-year-old man with liver metastasis proceeded to surgery, with the intention to perform a right hemi-hepatectomy. Unexpectedly at laparotomy, despite adequate pre-operative imaging, both the right and middle hepatic veins were involved. At that time extended right hemi-hepatectomy was contraindicated by insufficient residual volume and RFA was performed. Follow-up imaging revealed atrophy of the lesion. Significantly, there was also left lateral lobe hypertrophy sufficient to permit resection, which was performed without complication. Thrombosis of intra-hepatic portal veins is a recognised complication of RFA but here it appears to have been beneficial. The case highlights the need for regular review of unresectable hepatic disease by a liver surgeon and could suggest new modalities of portal embolisation

Exponential Time Complexity of Weighted Counting of Independent Sets

We consider weighted counting of independent sets using a rational weight x: Given a graph with n vertices, count its independent sets such that each set of size k contributes x^k. This is equivalent to computation of the partition function of the lattice gas with hard-core self-repulsion and hard-core pair interaction. We show the following conditional lower bounds: If counting the satisfying assignments of a 3-CNF formula in n variables (#3SAT) needs time 2^{\Omega(n)} (i.e. there is a c>0 such that no algorithm can solve #3SAT in time 2^{cn}), counting the independent sets of size n/3 of an n-vertex graph needs time 2^{\Omega(n)} and weighted counting of independent sets needs time 2^{\Omega(n/log^3 n)} for all rational weights x\neq 0. We have two technical ingredients: The first is a reduction from 3SAT to independent sets that preserves the number of solutions and increases the instance size only by a constant factor. Second, we devise a combination of vertex cloning and path addition. This graph transformation allows us to adapt a recent technique by Dell, Husfeldt, and Wahlen which enables interpolation by a family of reductions, each of which increases the instance size only polylogarithmically.Comment: Introduction revised, differences between versions of counting independent sets stated more precisely, minor improvements. 14 page

Azimuthal Modulational Instability of Vortices in the Nonlinear Schr\"odinger Equation

We study the azimuthal modulational instability of vortices with different topological charges, in the focusing two-dimensional nonlinear Schr{\"o}dinger (NLS) equation. The method of studying the stability relies on freezing the radial direction in the Lagrangian functional of the NLS in order to form a quasi-one-dimensional azimuthal equation of motion, and then applying a stability analysis in Fourier space of the azimuthal modes. We formulate predictions of growth rates of individual modes and find that vortices are unstable below a critical azimuthal wave number. Steady state vortex solutions are found by first using a variational approach to obtain an asymptotic analytical ansatz, and then using it as an initial condition to a numerical optimization routine. The stability analysis predictions are corroborated by direct numerical simulations of the NLS. We briefly show how to extend the method to encompass nonlocal nonlinearities that tend to stabilize solutions.Comment: 8 pages, 6 figures, in press for Optics Communication

Indestructibility of Vopenka's Principle

We show that Vopenka's Principle and Vopenka cardinals are indestructible under reverse Easton forcing iterations of increasingly directed-closed partial orders, without the need for any preparatory forcing. As a consequence, we are able to prove the relative consistency of these large cardinal axioms with a variety of statements known to be independent of ZFC, such as the generalised continuum hypothesis, the existence of a definable well-order of the universe, and the existence of morasses at many cardinals.Comment: 15 pages, submitted to Israel Journal of Mathematic

In depth analysis of kinase cross screening data to identify CaMKK2 inhibitory scaffolds

The calcium/calmodulin‐dependent protein kinase kinase 2 (CAMKK2) activates CAMK1, CAMK4, AMPK, and AKT, leading to numerous physiological responses. The deregulation of CAMKK2 is linked to several diseases, suggesting the utility of CAMKK2 inhibitors for oncological, metabolic and inflammatory indications. In this work, we demonstrate that STO‐609, frequently described as a selective inhibitor for CAMKK2, potently inhibits a significant number of other kinases. Through an analysis of literature and public databases, we have identified other potent CAMKK2 inhibitors and verified their activities in differential scanning fluorimetry and enzyme inhibition assays. These inhibitors are potential starting points for the development of selective CAMKK2 inhibitors and will lead to tools that delineate the roles of this kinase in disease biology.252CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP465651/2014-32013/50724-5; 2014/50897-0; 2019/14275-

The Impact of New EUV Diagnostics on CME-Related Kinematics

We present the application of novel diagnostics to the spectroscopic observation of a Coronal Mass Ejection (CME) on disk by the Extreme Ultraviolet Imaging Spectrometer (EIS) on the Hinode spacecraft. We apply a recently developed line profile asymmetry analysis to the spectroscopic observation of NOAA AR 10930 on 14-15 December 2006 to three raster observations before and during the eruption of a 1000km/s CME. We see the impact that the observer's line-of-sight and magnetic field geometry have on the diagnostics used. Further, and more importantly, we identify the on-disk signature of a high-speed outflow behind the CME in the dimming region arising as a result of the eruption. Supported by recent coronal observations of the STEREO spacecraft, we speculate about the momentum flux resulting from this outflow as a secondary momentum source to the CME. The results presented highlight the importance of spectroscopic measurements in relation to CME kinematics, and the need for full-disk synoptic spectroscopic observations of the coronal and chromospheric plasmas to capture the signature of such explosive energy release as a way of providing better constraints of CME propagation times to L1, or any other point of interest in the heliosphere.Comment: Accepted to appear in Solar Physics Topical Issue titled "Remote Sensing of the Inner Heliosphere". Manuscript has 14 pages, 5 color figures. Movies supporting the figures can be found in http://download.hao.ucar.edu/pub/mscott/papers/Weathe

Reverse-Engineering a Transcriptional Enhancer: A Case Study in Drosophila

Abstract Enhancers, or cis-regulatory elements, are the principal determinants of spatiotemporal patterning of gene expression. For reasons of clinical and research utility, it is desirable to build customized enhancers that drive novel gene expression patterns, but currently, we largely rely on “found” genomic elements. Synthetic enhancers, assembled from transcription factor binding sites taken from natural signal-regulated enhancers, generally fail to behave like their wild-type counterparts when placed in transgenic animals, suggesting that important aspects of enhancer function are still unexplored. As a step toward the creation of a truly synthetic regulatory element, we have undertaken an extensive structure–function study of an enhancer of the Drosophila decapentaplegic (dpp) gene that drives expression in the developing visceral mesoderm (VM). Although considerable past efforts have been made to dissect the dppVM enhancer, transgenic experiments presented here indicate that its activity cannot be explained by the known regulators alone. dppVM contains multiple, previously uncharacterized, regulatory sites, some of which exhibit functional redundancy. The results presented here suggest that even the best-studied enhancers must be further dissected before they can be fully understood, and before faithful synthetic elements based on them can be created. Implications for developmental genetics, mathematical modeling, and therapeutic applications are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63213/1/ten.tea.2008.0074.pd