Planning the Future of U.S. Particle Physics (Snowmass 2013): Chapter 6: Accelerator Capabilities

These reports present the results of the 2013 Community Summer Study of the APS Division of Particles and Fields ("Snowmass 2013") on the future program of particle physics in the U.S. Chapter 6, on Accelerator Capabilities, discusses the future progress of accelerator technology, including issues for high-energy hadron and lepton colliders, high-intensity beams, electron-ion colliders, and necessary R&D for future accelerator technologies.Comment: 26 page

Euclidean Approach to the Entropy for a Scalar Field in Rindler-like Space-Times

The off-shell entropy for a massless scalar field in a D-dimensional Rindler-like space-time is investigated within the conical Euclidean approach in the manifold C_\be\times\M^N, C_\be being the 2-dimensional cone, making use of the zeta-function regularisation. Due to the presence of conical singularities, it is shown that the relation between the zeta-function and the heat kernel is non trivial and, as first pointed out by Cheeger, requires a separation between small and large eigenvalues of the Laplace operator. As a consequence, in the massless case, the (naive) non existence of the Mellin transform is by-passed by the Cheeger's analytical continuation of the zeta-function on manifold with conical singularities. Furthermore, the continuous spectrum leads to the introduction of smeared traces. In general, it is pointed out that the presence of the divergences may depend on the smearing function and they arise in removing the smearing cutoff. With a simple choice of the smearing function, horizon divergences in the thermodynamical quantities are recovered and these are similar to the divergences found by means of off-shell methods like the brick wall model, the optical conformal transformation techniques or the canonical path integral method.Comment: 17 pages, LaTex. A sign error corrected and few comments adde

A Magnetic Transition Probed by the Ce Ion in Square-Lattice Antiferromagnet CeMnAsO

We examined the magnetic properties of the square-lattice antiferromagnets CeMnAsO and LaMnAsO and their solid solutions La1-xCexMnAsO by resistivity, magnetic susceptibility, and heat capacity measurements below room temperature. A first-order phase transition is observed at 34.1 K, below which the ground-state doublet of the Ce ion splits by 3.53 meV. It is likely that Mn moments already ordered above room temperature are reoriented at the transition, as reported for related compounds, such as NdMnAsO and PrMnSbO. This transition generates a large internal magnetic field at the Ce site in spite of the fact that simple Heisenberg interactions should be cancelled out at the Ce site owing to geometrical frustration. The transition takes place at nearly the same temperature with the substitution of La for Ce up to 90%. The Ce moment does not undergo long-range order by itself, but is parasitically induced at the transition, serving as a good probe for detecting the magnetism of Mn spins in a square lattice.Comment: 11 pages, 5 figures, to be published in J. Phys. Soc. Jp

Quantum Fields in Hyperbolic Space-Times with Finite Spatial Volume

The one-loop effective action for a massive self-interacting scalar field is investigated in $4$-dimensional ultrastatic space-time $R \times H^3/\Gamma$, $H^3/\Gamma$ being a non-compact hyperbolic manifold with finite volume. Making use of the Selberg trace formula, the $\zeta$-function related to the small disturbance operator is constructed. For an arbitrary gravitational coupling, it is found that $\zeta(s)$ has a simple pole at $s=0$. The one-loop effective action is analysed by means of proper-time regularisations and the one-loop divergences are explicitly found. It is pointed out that, in this special case, also $\zeta$-function regularisation requires a divergent counterterm, which however is not necessary in the free massless conformal invariant coupling case. Finite temperature effects are studied and the high-temperature expansion is presented. A possible application to the problem of the divergences of the entanglement entropy for a free massless scalar field in a Rindler-like space-time is briefly discussed.Comment: 13 pages, LaTex. The contribution of hyperbolic elements has been added. Other minor corrections and reference

Boundary relations and generalized resolvents of symmetric operators

The Kre\u{\i}n-Naimark formula provides a parametrization of all selfadjoint exit space extensions of a, not necessarily densely defined, symmetric operator, in terms of maximal dissipative (in \dC_+) holomorphic linear relations on the parameter space (the so-called Nevanlinna families). The new notion of a boundary relation makes it possible to interpret these parameter families as Weyl families of boundary relations and to establish a simple coupling method to construct the generalized resolvents from the given parameter family. The general version of the coupling method is introduced and the role of boundary relations and their Weyl families for the Kre\u{\i}n-Naimark formula is investigated and explained.Comment: 47 page

Tamoxifen enhances the cytotoxic effects of nelfinavir in breast cancer cells

Introduction: The HIV protease inhibitor nelfinavir is currently under investigation as a new anti-cancer drug. Several studies have shown that nelfinavir induces cell cycle arrest, endoplasmic reticulum stress, autophagy, and apoptosis in cancer cells. In the present article, the effect of nelfinavir on human breast cancer cells is examined and potential combination treatments are investigated. Methods: The effects of nelfinavir and tamoxifen on the human breast cancer cell lines MCF7, T47 D, MDA-MB-453, and MDA-MB-435 were tested by analysing their influence on cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay), apoptosis (annexin binding, poly(ADP-ribose) polymerase cleavage), autophagy (autophagy marker light chain 3B expression), endoplasmic reticulum stress (binding protein and activating transcription factor 3 expression), and the occurrence of oxidative stress (intracellular glutathione level). Results: Nelfinavir induced apoptosis in all four breast cancer cell lines tested, although the extent of autophagy and endoplasmic reticulum stress varied among the cell lines. The concentration of nelfinavir needed for an efficient induction of apoptosis in breast cancer cells could be reduced from 15 mu g/ml to 6 mu g/ml when combined with tamoxifen. At a concentration of 6 mu g/ml, tamoxifen substantially enhanced the endoplasmic reticulum stress reaction in those cell lines that responded to nelfinavir with binding protein (BiP) upregulation (MCF7, T47D), and enhanced autophagy in cell lines that responded to nelfinavir treatment with autophagy marker light chain 3B upregulation (MDA-MB-453). Although tamoxifen has been described to be able to induce oxidative stress at concentrations similar to those applied in this study (6 mu g/ml), we observed that nelfinavir but not tamoxifen reduced the intracellular glutathione level of breast cancer cells within hours of application by up to 32%, suggesting the induction of oxidative stress was an early event and an additional cause of the apoptosis induced by nelfinavir. Conclusions: The results demonstrate that nelfinavir may be an effective drug against breast cancer and could be combined with tamoxifen to enhance its efficacy against breast cancer cells. Moreover, the cytotoxic effect of a tamoxifen and nelfinavir combination was independent of the oestrogen receptor status of the analysed breast cancer cells, suggesting a potential benefit of a combination of these two drugs even in patients with no hormone-responsive tumours. We therefore recommend that clinical studies on nelfinavir with breast cancer patients should include this drug combination to analyse the therapeutic efficacy as well as the safety and tolerability of this potential treatment option

Harnessing RNA sequencing for global, unbiased evaluation of two new adjuvants for dendritic-cell immunotherapy

Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing (RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC-vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and Frühsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine-RNA complexes (pRNA) and CpG-P. We found that GM-CSF and pRNA had similar effects on their target cells, whereas pRNA and CpG-P induced stronger type I interferon (IFN) expression than FSME. In general, the pathways most affected by all stimuli were related to immune activity and cell migration. GM-CSF stimulation, however, also induced a significant increase of genes related to nonsense-mediated decay, indicating a possible deleterious effect of this stimulus. Taken together, the two novel stimuli appear to be promising alternatives. Our study demonstrates how RNA-seq based investigation of changes in a large number of genes and gene groups can be exploited for fast and unbiased, global evaluation of clinical-grade stimuli, as opposed to the general limited evaluation of a pre-specified set of genes, by which one might miss important biological effects that are detrimental for vaccine efficacy

Two Regional Mental Health Treatment Facilities

One of the major social programs of the 1960s was the development of community mental health centers. As with most early attempts at evaluation, the results were pessimistic. This article reanalyzes one of the earliest, and best-known, evaluations of a community-based treatment facility. Following the conceptual framework of Campbell and his associates, it was found that the various threats to the validity of the findings indicate a consistent and systematic bias against detecting a positive effect for the new mental health center. In light of recent federal legislation mandating formal evaluations, appropriate procedures are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68090/2/10.1177_0193841X7900300403.pd