An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma

The incidence of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is increasing and implicated in more than 60% of all oropharyngeal carcinomas (OPSCCs). Although whole-genome, transcriptome, and proteome analyses have identified altered signaling pathways in HPV-induced HNSCCs, additional tools are needed to investigate the unique pathobiology of OPSCC. Herein, bioinformatics analyses of human HPV(+) HNSCCs revealed that all tumors express full-length E6 and identified molecular subtypes based on relative E6 and E7 expression levels. To recapitulate the levels, stoichiometric ratios, and anatomic location of E6/E7 expression, we generated a genetically engineered mouse model whereby balanced expression of E6/E7 is directed to the oropharyngeal epithelium. The addition of a mutant PIK3CAE545K allele leads to the rapid development of pre-malignant lesions marked by immune cell accumulation, and a subset of these lesions progress to OPSCC. This mouse provides a faithful immunocompetent model for testing treatments and investigating mechanisms of immunosuppression

Density functional study of Aun_n (n=2-20) clusters: lowest-energy structures and electronic properties

We have investigated the lowest-energy structures and electronic properties of the Au$_n$(n=2-20) clusters based on density functional theory (DFT) with local density approximation. The small Au$_n$ clusters adopt planar structures up to n=6. Tabular cage structures are preferred in the range of n=10-14 and a structural transition from tabular cage-like structure to compact near-spherical structure is found around n=15. The most stable configurations obtained for Au$_{13}$ and Au$_{19}$ clusters are amorphous instead of icosahedral or fcc-like, while the electronic density of states sensitively depend on the cluster geometry. Dramatic odd-even alternative behaviors are obtained in the relative stability, HOMO-LUMO gaps and ionization potentials of gold clusters. The size evolution of electronic properties is discussed and the theoretical ionization potentials of Au$_n$ clusters compare well with experiments.Comment: 6 pages, 7 figure

Biomarkers and longitudinal changes in lumbar spine degeneration and low back pain: the Johnston County Osteoarthritis Project

Objective: To determine if baseline biomarkers are associated with longitudinal changes in the worsening of disc space narrowing (DSN), vertebral osteophytes (OST), and low back pain (LBP). Design: Paired baseline (2003–2004) and follow-up (2006–2010) lumbar spine radiographs from the Johnston County Osteoarthritis Project were graded for severity of DSN and OST. LBP severity was self-reported. Concentrations of analytes (cytokines, proteoglycans, and neuropeptides) were quantified by immunoassay. Pressure-pain threshold (PPT), a marker of sensitivity to pressure pain, was measured with a standard dolorimeter. Binary logistic regression models were used to estimate odd ratios (OR) and 95% confidence intervals (CI) of biomarker levels with DSN, OST, or LBP. Interactions were tested between biomarker levels and the number of affected lumbar spine levels or LBP. Results: We included participants (n = 723) with biospecimens, PPT, and paired lumbar spine radiographic data. Baseline Lumican, a proteoglycan reflective of extracellular matrix changes, was associated with longitudinal changes in DSN worsening (OR = 3.19 [95% CI 1.22, 8.01]). Baseline brain-derived neuropathic factor, a neuropeptide, (OR = 1.80 [95% CI 1.03, 3.16]) was associated with longitudinal changes in OST worsening, which may reflect osteoclast genesis. Baseline hyaluronic acid (OR = 1.31 [95% CI 1.01, 1.71]), indicative of systemic inflammation, and PPT (OR = 1.56 [95% CI 1.02, 2.31]) were associated with longitudinal increases in LBP severity. Conclusion: These findings suggest that baseline biomarkers are associated with longitudinal changes occurring in structures of the lumbar spine (DSN vs OST). Markers of inflammation and perceived pressure pain sensitivity were associated with longitudinal worsening of LBP

Seesaw tau lepton mass and calculable neutrino masses in a 3-3-1 model

In a version of the 3-3-1 model proposed by Duong and Ma the introduction of the scalar sextet for giving mass to the charged leptons is avoided by adding a singlet charged lepton. We show that in this case the $\tau$ lepton gains mass through a seesaw--like mechanism. Besides we show how to generate neutrino masses at the tree and at the 1-loop level with the respective Maki-Nakagawa-Sakata leptonic mixing matrices.Comment: revtex, 5 pages and one eps figure. Published versio

Inflammatory, Structural, and Pain Biochemical Biomarkers May Reflect Radiographic Disc Space Narrowing: The Johnston County Osteoarthritis Project

The purpose of this work is to determine the relationship between biomarkers of inflammation, structure, and pain with radiographic disc space narrowing (DSN) in community-based participants. A total of 74 participants (37 cases and 37 controls) enrolled in the Johnston County Osteoarthritis Project during 2006–2010 were selected. The cases had at least mild radiographic DSN and low back pain (LBP). The controls had neither radiographic evidence of DSN nor LBP. The measured analytes from human serum included N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, IL-17, IL-6, BDNF, OPG, and NPY. A standard dolorimeter measured pressure-pain threshold. The coefficients of variation were used to evaluate inter- and intra-assay reliability. Participants with similar biomarker profiles were grouped together using cluster analysis. The binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) in propensity score-matched models. Significant associations were found between radiographic DSN and OPG (RR = 3.90; 95% CI: 1.83, 8.31), IL-6 (RR = 2.54; 95% CI: 1.92, 3.36), and NPY (RR = 2.06 95% CI: 1.62, 2.63). Relative to a cluster with low levels of biomarkers, a cluster representing elevated levels of OPG, RANTES, Lumican, Keratin-19, and NPY (RR = 3.04; 95% CI: 1.22, 7.54) and a cluster representing elevated levels of NPY (RR = 2.91; 95% CI: 1.15, 7.39) were significantly associated with radiographic DSN. Clinical Significance: These findings suggest that individual and combinations of biochemical biomarkers may reflect radiographic DSN. This is just one step toward understanding the relationships between biochemical biomarkers and DSN that may lead to improved intervention delivery

Measurement of double beta decay of 100Mo to excited states in the NEMO 3 experiment

The double beta decay of 100Mo to the 0^+_1 and 2^+_1 excited states of 100Ru is studied using the NEMO 3 data. After the analysis of 8024 h of data the half-life for the two-neutrino double beta decay of 100Mo to the excited 0^+_1 state is measured to be T^(2nu)_1/2 = [5.7^{+1.3}_{-0.9}(stat)+/-0.8(syst)]x 10^20 y. The signal-to-background ratio is equal to 3. Information about energy and angular distributions of emitted electrons is also obtained. No evidence for neutrinoless double beta decay to the excited 0^+_1 state has been found. The corresponding half-life limit is T^(0nu)_1/2(0^+ --> 0^+_1) > 8.9 x 10^22 y (at 90% C.L.). The search for the double beta decay to the 2^+_1 excited state has allowed the determination of limits on the half-life for the two neutrino mode T^(2nu)_1/2(0^+ --> 2^+_1) > 1.1 x 10^21 y (at 90% C.L.) and for the neutrinoless mode T^(0nu)_1/2(0^+ --> 2^+_1) > 1.6 x 10^23 y (at 90% C.L.).Comment: 23 pages, 7 figures, 4 tables, submitted to Nucl. Phy

Phenomenology of flavor-mediated supersymmetry breaking

The phenomenology of a new economical SUSY model that utilizes dynamical SUSY breaking and gauge-mediation (GM) for the generation of the sparticle spectrum and the hierarchy of fermion masses is discussed. Similarities between the communication of SUSY breaking through a messenger sector, and the generation of flavor using the Froggatt-Nielsen (FN) mechanism are exploited, leading to the identification of vector-like messenger fields with FN fields, and the messenger U(1) as a flavor symmetry. An immediate consequence is that the first and second generation scalars acquire flavor-dependent masses, but do not violate FCNC bounds since their mass scale, consistent with effective SUSY, is of order 10 TeV. We define and advocate a minimal flavor-mediated model (MFMM), recently introduced in the literature, that successfully accommodates the small flavor-breaking parameters of the standard model using order one couplings and ratios of flavon field vevs. The mediation of SUSY breaking occurs via two-loop log-enhanced GM contributions, as well as several one-loop and two-loop Yukawa-mediated contributions for which we provide analytical expressions. The MFMM is parameterized by a small set of masses and couplings, with values restricted by several model constraints and experimental data. The next-to-lightest sparticle (NLSP) always has a decay length that is larger than the scale of a detector, and is either the lightest stau or the lightest neutralino. Similar to ordinary GM models, the best collider search strategies are, respectively, inclusive production of at least one highly ionizing track, or events with many taus plus missing energy. In addition, D^0 - \bar{D}^0 mixing is also a generic low energy signal. Finally, the dynamical generation of the neutrino masses is briefly discussed.Comment: 54 pages, LaTeX, 8 figure

Association of Biomarkers with Individual and Multiple Body Sites of Pain: The Johnston County Osteoarthritis Project

Introduction: Biochemical biomarkers may provide insight into musculoskeletal pain reported at individual or multiple body sites. The purpose of this study was to determine if biomarkers or pressure-pain threshold (PPT) were associated with individual or multiple sites of pain. Methods: This cross-sectional analysis included 689 community-based participants. Self-reported symptoms (ie, pain, aching, or stiffness) were ascertained about the neck, upper back/thoracic, low back, shoulders, elbows, wrist, hands, hips, knees, ankles, and feet. Measured analytes included CXCL-6, RANTES, HA, IL-6, BDNF, OPG and NPY. A standard dolorimeter measured PPT. Logistic regression was used determine the association between biomarkers and PPT with individual and summed sites of pain. Results: Increased IL-6 and HA were associated with knee pain (OR=1.30, 95% CI 1.03, 1.64) and (OR=1.32, 95% CI 1.01, 1.73) respectively; HA was also associated with elbow/wrist/hand pain (OR=1.60, 95% CI 1.22, 2.09). Those with increased NPY levels were less likely to have shoulder pain (OR=0.56, 95% CI 0.33, 0.93). Biomarkers HA (OR=1.50, 95% CI 1.07, 2.10), OPG (OR=1.74, 95% CI 1.00, 3.03), CXCL-6 (OR=1.75, 95% CI 1.02, 3.01) and decreased PPT (OR=3.97, 95% CI 2.22, 7.12) were associated with multiple compared to no sites of pain. Biomarker HA (OR=1.57, 95% CI 1.06, 2.32) and decreased PPT (OR=3.53, 95% CI 1.81, 6.88) were associated with multiple compared to a single site of pain. Conclusion: Biomarkers of inflammation (HA, OPG, IL-6 and CXCL-6), pain (NPY) and PPT may help to understand the etiology of single and multiple pain sites

Power-spectrum analysis of Super-Kamiokande solar neutrino data, taking into account asymmetry in the error estimates

The purpose of this article is to carry out a power-spectrum analysis (based on likelihood methods) of the Super-Kamiokande 5-day dataset that takes account of the asymmetry in the error estimates. Whereas the likelihood analysis involves a linear optimization procedure for symmetrical error estimates, it involves a nonlinear optimization procedure for asymmetrical error estimates. We find that for most frequencies there is little difference between the power spectra derived from analyses of symmetrized error estimates and from asymmetrical error estimates. However, this proves not to be the case for the principal peak in the power spectra, which is found at 9.43 yr-1. A likelihood analysis which allows for a "floating offset" and takes account of the start time and end time of each bin and of the flux estimate and the symmetrized error estimate leads to a power of 11.24 for this peak. A Monte Carlo analysis shows that there is a chance of only 1% of finding a peak this big or bigger in the frequency band 1 - 36 yr-1 (the widest band that avoids artificial peaks). On the other hand, an analysis that takes account of the error asymmetry leads to a peak with power 13.24 at that frequency. A Monte Carlo analysis shows that there is a chance of only 0.1% of finding a peak this big or bigger in that frequency band 1 - 36 yr-1. From this perspective, power spectrum analysis that takes account of asymmetry of the error estimates gives evidence for variability that is significant at the 99.9% level. We comment briefly on an apparent discrepancy between power spectrum analyses of the Super-Kamiokande and SNO solar neutrino experiments.Comment: 13 pages, 2 tables, 6 figure

Lorentz and CPT Violation in Neutrinos

A general formalism is presented for violations of Lorentz and CPT symmetry in the neutrino sector. The effective hamiltonian for neutrino propagation in the presence of Lorentz and CPT violation is derived, and its properties are studied. Possible definitive signals in existing and future neutrino-oscillation experiments are discussed. Among the predictions are direction-dependent effects, including neutrino-antineutrino mixing, sidereal and annual variations, and compass asymmetries. Other consequences of Lorentz and CPT violation involve unconventional energy dependences in oscillation lengths and mixing angles. A variety of simple models both with and without neutrino masses are developed to illustrate key physical effects. The attainable sensitivities to coefficients for Lorentz violation in the Standard-Model Extension are estimated for various types of experiments. Many experiments have potential sensitivity to Planck-suppressed effects, comparable to the best tests in other sectors. The lack of existing experimental constraints, the wide range of available coefficient space, and the variety of novel effects imply that some or perhaps even all of the existing data on neutrino oscillations might be due to Lorentz and CPT violation.Comment: 25 pages REVTe