Tests of the Gravitational Inverse-Square Law

We review recent experimental tests of the gravitational inverse-square law and the wide variety of theoretical considerations that suggest the law may break down in experimentally accessible regions.Comment: 81 pages, 10 figures, submitted by permission of the Annual Review of Nuclear and Particle Science. Final version of this material is scheduled to appear in the Annual Review of Nuclear and Particle Science Vol. 53, to be published in December 2003 by Annual Reviews, http://AnnualReviews.or

Effects of religious vs. standard cognitive behavioral therapy on therapeutic alliance: A randomized clinical trial

Background: Treatments that integrate religious clients' beliefs into therapy may enhance the therapeutic alliance (TA) in religious clients. Objective: Compare the effects of religiously integrated cognitive behavioral therapy (RCBT) and standard CBT (SCBT) on TA in adults with major depression and chronic medical illness. Method: Multi-site randomized controlled trial in 132 participants, of whom 108 (SCBT = 53, RCBT = 55) completed the Revised Helping Alliance Questionnaire (HAQ-II) at 4, 8, and 12 weeks. Trajectory of change in scores over time was compared between groups. Results: HAQ-II score at 4 weeks predicted a decline in depressive symptoms over time independent of treatment group (B = −0.06, SE = 0.02, p = 0.002, n = 108). There was a marginally significant difference in HAQ-II scores at 4 weeks that favored RCBT (p = 0.076); however, the mixed effects model indicated a significant group by time interaction that favored the SCBT group (B = 1.84, SE = 0.90, degrees of freedom = 181, t = 2.04, p = 0.043, d = 0.30). Conclusions: While RCBT produces a marginally greater improvement in TA initially compared with SCBT, SCBT soon catches up

Physicochemical-guided design of cathelicidin-derived peptides generates membrane active variants with therapeutic potential.

The spread of multi-drug resistance and the slow pace at which antibiotics come onto the market are undermining our ability to treat human infections, leading to high mortality rates. Aiming to overcome this global crisis, antimicrobial peptides are considered promising alternatives to counter bacterial infections with multi-drug resistant bacteria. The cathelicidins comprise a well-studied class of AMPs whose members have been used as model molecules for sequence modifications, aiming at enhanced biological activities and stability, along with reduced toxic effects on mammalian cells. Here, we describe the antimicrobial activities, modes of action and structural characterization of two novel cathelicidin-like peptides, named BotrAMP14 and CrotAMP14, which were re-designed from snake batroxicidin and crotalicidin, respectively. BotrAMP14 and CrotAMP14 showed broad-spectrum antibacterial activity against susceptible microorganisms and clinical isolates with minimal inhibitory concentrations ranging from 2-35.1 μM. Moreover, both peptides had low cytotoxicity against Caco-2 cells in vitro. In addition, in vivo toxicity against Galleria mellonella moth larvae revealed that both peptides led to>76% larval survival after 144 h. Microscopy studies suggest that BotrAMP14 and CrotAMP14 destabilize E. coli membranes. Furthermore, circular dichroism and molecular dynamics simulations indicate that, in a membrane-like environment, both peptides adopt α-helical structures that interact with bilayer phospholipids through hydrogen bonds and electrostatic interaction. Thus, we concluded that BotrAMP14 and CrotAMP14 are helical membrane active peptides, with similar antibacterial properties but lower cytotoxicity than the larger parent peptides batroxicidin and crotalicidin, having advantages for drug development strategies

Top and Bottom Seesaw from Supersymmetric Strong Dynamics

We propose a top and bottom seesaw model with partial composite top and bottom quarks. Such composite quarks and topcolor gauge bosons are bound states from supersymmetric strong dynamics by Seiberg duality. Supersymmetry breaking also induces the breaking of topcolor into the QCD gauge coupling. The low energy description of our model reduces to a complete non-minimal extension of the top seesaw model with bottom seesaw. The non-minimal nature is crucial for Higgs mixings and the appearance of light Higgs fields. The Higgs fields are bound states of partial composite particles with the lightest one compatible with a 125 GeV Higgs field which was discovered at the LHC.Comment: Minor changes, Published Versio

Immune Correlates of Protection Against Human Cytomegalovirus Acquisition, Replication, and Disease

Human cytomegalovirus (HCMV) is the most common infectious cause of infant birth defects and an etiology of significant morbidity and mortality in solid organ and hematopoietic stem cell transplant recipients. There is tremendous interest in developing a vaccine or immunotherapeutic to reduce the burden of HCMV-associated disease, yet after nearly a half-century of research and development in this field we remain without such an intervention. Defining immune correlates of protection is a process that enables targeted vaccine/immunotherapeutic discovery and informed evaluation of clinical performance. Outcomes in the HCMV field have previously been measured against a variety of clinical end points, including virus acquisition, systemic replication, and progression to disease. Herein we review immune correlates of protection against each of these end points in turn, showing that control of HCMV likely depends on a combination of innate immune factors, antibodies, and T-cell responses. Furthermore, protective immune responses are heterogeneous, with no single immune parameter predicting protection against all clinical outcomes and stages of HCMV infection. A detailed understanding of protective immune responses for a given clinical end point will inform immunogen selection and guide preclinical and clinical evaluation of vaccines or immunotherapeutics to prevent HCMV-mediated congenital and transplant disease

Bayesian inference of biochemical kinetic parameters using the linear noise approximation

Background Fluorescent and luminescent gene reporters allow us to dynamically quantify changes in molecular species concentration over time on the single cell level. The mathematical modeling of their interaction through multivariate dynamical models requires the deveopment of effective statistical methods to calibrate such models against available data. Given the prevalence of stochasticity and noise in biochemical systems inference for stochastic models is of special interest. In this paper we present a simple and computationally efficient algorithm for the estimation of biochemical kinetic parameters from gene reporter data. Results We use the linear noise approximation to model biochemical reactions through a stochastic dynamic model which essentially approximates a diffusion model by an ordinary differential equation model with an appropriately defined noise process. An explicit formula for the likelihood function can be derived allowing for computationally efficient parameter estimation. The proposed algorithm is embedded in a Bayesian framework and inference is performed using Markov chain Monte Carlo. Conclusion The major advantage of the method is that in contrast to the more established diffusion approximation based methods the computationally costly methods of data augmentation are not necessary. Our approach also allows for unobserved variables and measurement error. The application of the method to both simulated and experimental data shows that the proposed methodology provides a useful alternative to diffusion approximation based methods

Inter-calibration of a proposed new primary reference standard AA-ETH Zn for zinc isotopic analysis

We have prepared a large volume of pure, concentrated and homogenous zinc standard solution. This new standard solution is intended to be used as a primary reference standard for the zinc isotope community, and to serve as a replacement for the nearly exhausted current reference standard, the so-called JMC-Lyon Zn. The isotopic composition of this new zinc standard (AA-ETH Zn) has been determined through an inter-laboratory calibration exercise, calibrated against the existing JMC-Lyon standard, as well as the certified Zn reference standard IRMM-3702. The data show that the new standard is isotopically indistinguishable from the IRMM-3702 zinc standard, with a weighted δ66/64Zn value of 0.28 ± 0.02‰ relative to JMC-Lyon. We suggest that this new standard be assigned a δ66/64Zn value of +0.28‰ for reporting of future Zn isotope data, with the rationale that all existing published Zn isotope data are presented relative to the JMC-Lyon standard. Therefore our proposed presentation allows for a direct comparison with all previously published data, and that are directly traceable to a certified reference standard, IRMM-3702 Zn. This standard will be made freely available to all interested labs through contact with the corresponding author

The Conformal Sector of F-theory GUTs

D3-brane probes of exceptional Yukawa points in F-theory GUTs are natural hidden sectors for particle phenomenology. We find that coupling the probe to the MSSM yields a new class of N = 1 conformal fixed points with computable infrared R-charges. Quite surprisingly, we find that the MSSM only weakly mixes with the strongly coupled sector in the sense that the MSSM fields pick up small exactly computable anomalous dimensions. Additionally, we find that although the states of the probe sector transform as complete GUT multiplets, their coupling to Standard Model fields leads to a calculable threshold correction to the running of the visible sector gauge couplings which improves precision unification. We also briefly consider scenarios in which SUSY is broken in the hidden sector. This leads to a gauge mediated spectrum for the gauginos and first two superpartner generations, with additional contributions to the third generation superpartners and Higgs sector.Comment: v2: 51 pages, 2 figures, remark added, typos correcte

Cosmic strings from pseudo-anomalous Fayet-Iliopoulos U(1) in D3/D7 brane inflation

We examine the consequences of recent developments on Fayet-Iliopoulos (FI) terms for D-term inflationary models. There is currently no known way to couple constant FI terms to supergravity consistently; only field-dependent FI terms are allowed. These are natural in string theory and we argue that the FI term in D3/D7 inflation turns out to be of this type, corresponding to a pseudo-anomalous U(1). T he anomaly is canceled by the Green-Schwarz mechanism in 4 dimensions. Inflation proceeds as usual, except that the scale is set by the GS parameter. Cosmic strings resulting from a pseudo-anomalous U(1) have potentially interesting characteristics. Originally expected to be global, they turn out to be local in the string theory context and can support currents. We outline the nature of these strings, discuss bounds on their formation, and summarize resulting cosmological consequences.Comment: 10 pages; minor changes to match published versio