Phase I study of dose escalation to dominant intraprostatic lesions using high-dose-rate brachytherapy.

PurposeRadiation dose escalation for prostate cancer improves biochemical control but is limited by toxicity. Magnetic resonance spectroscopic imaging (MRSI) can define dominant intraprostatic lesions (DIL). This phase I study evaluated dose escalation to MRSI-defined DIL using high-dose-rate (HDR) brachytherapy.Material and methodsEnrollment was closed early due to low accrual. Ten patients with prostate cancer (T2a-3b, Gleason 6-9, PSA < 20) underwent pre-treatment MRSI, and eight patients had one to three DIL identified. The eight enrolled patients received external beam radiation therapy to 45 Gy and HDR brachytherapy boost to the prostate of 19 Gy in 2 fractions. MRSI images were registered to planning CT images and DIL dose-escalated up to 150% of prescription dose while maintaining normal tissue constraints. The primary endpoint was genitourinary (GU) toxicity.ResultsThe median total DIL volume was 1.31 ml (range, 0.67-6.33 ml). Median DIL boost was 130% of prescription dose (range, 110-150%). Median urethra V120 was 0.15 ml (range, 0-0.4 ml) and median rectum V75 was 0.74 ml (range, 0.1-1.0 ml). Three patients had acute grade 2 GU toxicity, and two patients had late grade 2 GU toxicity. No patients had grade 2 or higher gastrointestinal toxicity, and no grade 3 or higher toxicities were noted. There were no biochemical failures with median follow-up of 4.9 years (range, 2-8.5 years).ConclusionsDose escalation to MRSI-defined DIL is feasible. Toxicity was low but incompletely assessed due to limited patients' enrollment

Nexus solitons in the center vortex picture of QCD

It is very plausible that confinement in QCD comes from linking of Wilson loops to finite-thickness vortices with magnetic fluxes corresponding to the center of the gauge group. The vortices are solitons of a gauge-invariant QCD action representing the generation of gluon mass. There are a number of other solitonic states of this action. We discuss here what we call nexus solitons, in which for gauge group SU(N), up to N vortices meet a a center, or nexus, provided that the total flux of the vortices adds to zero (mod N). There are fundamentally two kinds of nexuses: Quasi-Abelian, which can be described as composites of Abelian imbedded monopoles, whose Dirac strings are cancelled by the flux condition; and fully non-Abelian, resembling a deformed sphaleron. Analytic solutions are available for the quasi-Abelian case, and we discuss variational estimates of the action of the fully non-Abelian nexus solitons in SU(2). The non-Abelian nexuses carry Chern-Simons number (or topological charge in four dimensions). Their presence does not change the fundamentals of confinement in the center-vortex picture, but they may lead to a modified picture of the QCD vacuum.Comment: LateX, 24 pages, 2 .eps figure

Phosphorylation of the actin binding protein Drebrin at S647 and is regulated by neuronal activity and PTEN

Defects in actin dynamics affect activity-dependent modulation of synaptic transmission and neuronal plasticity, and can cause cognitive impairment. A salient candidate actin-binding protein linking synaptic dysfunction to cognitive deficits is Drebrin (DBN). However, the specific mode of how DBN is regulated at the central synapse is largely unknown. In this study we identify and characterize the interaction of the PTEN tumor suppressor with DBN. Our results demonstrate that PTEN binds DBN and that this interaction results in the dephosphorylation of a site present in the DBN C-terminus - serine 647. PTEN and pS647-DBN segregate into distinct and complimentary compartments in neurons, supporting the idea that PTEN negatively regulates DBN phosphorylation at this site. We further demonstrate that neuronal activity increases phosphorylation of DBN at S647 in hippocampal neurons in vitro and in ex vivo hippocampus slices exhibiting seizure activity, potentially by inducing rapid dissociation of the PTEN:DBN complex. Our results identify a novel mechanism by which PTEN is required to maintain DBN phosphorylation at dynamic range and signifies an unusual regulation of an actin-binding protein linked to cognitive decline and degenerative conditions at the CNS synapse

Center vortices and confinement vs. screening

We study adjoint and fundamental Wilson loops in the center-vortex picture of confinement, for gauge group SU(N) with general N. There are N-1 distinct vortices, whose properties, including collective coordinates and actions, we study. In d=2 we construct a center-vortex model by hand so that it has a smooth large-N limit of fundamental-representation Wilson loops and find, as expected, confinement. Extending an earlier work by the author, we construct the adjoint Wilson-loop potential in this d=2 model for all N, as an expansion in powers of $\rho/M^2$, where $\rho$ is the vortex density per unit area and M is the vortex inverse size, and find, as expected, screening. The leading term of the adjoint potential shows a roughly linear regime followed by string breaking when the potential energy is about 2M. This leading potential is a universal (N-independent at fixed fundamental string tension $K_F$) of the form $(K_F/M)U(MR)$, where R is the spacelike dimension of a rectangular Wilson loop. The linear-regime slope is not necessarily related to $K_F$ by Casimir scaling. We show that in d=2 the dilute vortex model is essentially equivalent to true d=2 QCD, but that this is not so for adjoint representations; arguments to the contrary are based on illegal cumulant expansions which fail to represent the necessary periodicity of the Wilson loop in the vortex flux. Most of our arguments are expected to hold in d=3,4 also.Comment: 29 pages, LaTex, 1 figure. Minor changes; references added; discussion of factorization sharpened. Major conclusions unchange

Structural Parameters of the M87 Globular Clusters

We derive structural parameters for ~2000 globular clusters in the giant Virgo elliptical M87 using extremely deep Hubble Space Telescope images in F606W (V) and F814W (I) taken with the ACS/WFC. The cluster scale sizes (half-light radii r_h) and ellipticities are determined from PSF-convolved King-model profile fitting. We find that the r_h distribution closely resembles the inner Milky Way clusters, peaking at r_h~2.5 pc and with virtually no clusters more compact than r_h ~ 1 pc. The metal-poor clusters have on average an r_h 24% larger than the metal-rich ones. The cluster scale size shows a gradual and noticeable increase with galactocentric distance. Clusters are very slightly larger in the bluer waveband V a possible hint that we may be beginning to see the effects of mass segregation within the clusters. We also derived a color magnitude diagram for the M87 globular cluster system which show a striking bimodal distribution.Comment: ApJ accepte

Relativistic center-vortex dynamics of a confining area law

We offer a physicists' proof that center-vortex theory requires the area in the Wilson-loop area law to involve an extremal area. Area-law dynamics is determined by integrating over Wilson loops only, not over surface fluctuations for a fixed loop. Fluctuations leading to to perimeter-law corrections come from loop fluctuations as well as integration over finite -thickness center-vortex collective coordinates. In d=3 (or d=2+1) we exploit a contour form of the extremal area in isothermal which is similar to d=2 (or d=1+1) QCD in many respects, except that there are both quartic and quadratic terms in the action. One major result is that at large angular momentum \ell in d=3+1 the center-vortex extremal-area picture yields a linear Regge trajectory with Regge slope--string tension product \alpha'(0)K_F of 1/(2\pi), which is the canonical Veneziano/string value. In a curious effect traceable to retardation, the quark kinetic terms in the action vanish relative to area-law terms in the large-\ell limit, in which light-quark masses \sim K_F^{1/2} are negligible. This corresponds to string-theoretic expectations, even though we emphasize that the extremal-area law is not a string theory quantum-mechanically. We show how some quantum trajectory fluctuations as well as non-leading classical terms for finite mass yield corrections scaling with \ell^{-1/2}. We compare to old semiclassical calculations of relativistic q\bar{q} bound states at large \ell, which also yield asymptotically-linear Regge trajectories, finding agreement with a naive string picture (classically, not quantum-mechanically) and disagreement with an effective-propagator model. We show that contour forms of the area law can be expressed in terms of Abelian gauge potentials, and relate this to old work of Comtet.Comment: 20 pages RevTeX4 with 3 .eps figure

Complete plastid genome sequences of Drimys, Liriodendron, and Piper: implications for the phylogenetic relationships of magnoliids

BACKGROUND: The magnoliids with four orders, 19 families, and 8,500 species represent one of the largest clades of early diverging angiosperms. Although several recent angiosperm phylogenetic analyses supported the monophyly of magnoliids and suggested relationships among the orders, the limited number of genes examined resulted in only weak support, and these issues remain controversial. Furthermore, considerable incongruence resulted in phylogenetic reconstructions supporting three different sets of relationships among magnoliids and the two large angiosperm clades, monocots and eudicots. We sequenced the plastid genomes of three magnoliids, Drimys (Canellales), Liriodendron (Magnoliales), and Piper (Piperales), and used these data in combination with 32 other angiosperm plastid genomes to assess phylogenetic relationships among magnoliids and to examine patterns of variation of GC content. RESULTS: The Drimys, Liriodendron, and Piper plastid genomes are very similar in size at 160,604, 159,886 bp, and 160,624 bp, respectively. Gene content and order are nearly identical to many other unrearranged angiosperm plastid genomes, including Calycanthus, the other published magnoliid genome. Overall GC content ranges from 34–39%, and coding regions have a substantially higher GC content than non-coding regions. Among protein-coding genes, GC content varies by codon position with 1st codon > 2nd codon > 3rd codon, and it varies by functional group with photosynthetic genes having the highest percentage and NADH genes the lowest. Phylogenetic analyses using parsimony and likelihood methods and sequences of 61 protein-coding genes provided strong support for the monophyly of magnoliids and two strongly supported groups were identified, the Canellales/Piperales and the Laurales/Magnoliales. Strong support is reported for monocots and eudicots as sister clades with magnoliids diverging before the monocot-eudicot split. The trees also provided moderate or strong support for the position of Amborella as sister to a clade including all other angiosperms. CONCLUSION: Evolutionary comparisons of three new magnoliid plastid genome sequences, combined with other published angiosperm genomes, confirm that GC content is unevenly distributed across the genome by location, codon position, and functional group. Furthermore, phylogenetic analyses provide the strongest support so far for the hypothesis that the magnoliids are sister to a large clade that includes both monocots and eudicots

Center Vortices, Nexuses, and the Georgi-Glashow Model

In a gauge theory with no Higgs fields the mechanism for confinement is by center vortices, but in theories with adjoint Higgs fields and generic symmetry breaking, such as the Georgi-Glashow model, Polyakov showed that in d=3 confinement arises via a condensate of 't Hooft-Polyakov monopoles. We study the connection in d=3 between pure-gauge theory and the theory with adjoint Higgs by varying the Higgs VEV v. As one lowers v from the Polyakov semi- classical regime v>>g (g is the gauge coupling) toward zero, where the unbroken theory lies, one encounters effects associated with the unbroken theory at a finite value v\sim g, where dynamical mass generation of a gauge-symmetric gauge- boson mass m\sim g^2 takes place, in addition to the Higgs-generated non-symmetric mass M\sim vg. This dynamical mass generation is forced by the infrared instability (in both 3 and 4 dimensions) of the pure-gauge theory. We construct solitonic configurations of the theory with both m,M non-zero which are generically closed loops consisting of nexuses (a class of soliton recently studied for the pure-gauge theory), each paired with an antinexus, sitting like beads on a string of center vortices with vortex fields always pointing into (out of) a nexus (antinexus); the vortex magnetic fields extend a transverse distance 1/m. An isolated nexus with vortices is continuously deformable from the 't Hooft-Polyakov (m=0) monopole to the pure-gauge nexus-vortex complex (M=0). In the pure-gauge M=0 limit the homotopy $\Pi_2(SU(2)/U(1))=Z_2$ (or its analog for SU(N)) of the 't Hooft monopoles is no longer applicable, and is replaced by the center-vortex homotopy $\Pi_1(SU)N)/Z_N)=Z_N$.Comment: 27 pages, LaTeX, 3 .eps figure