132 research outputs found
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 Au (n=2-20) clusters: lowest-energy structures and electronic properties
We have investigated the lowest-energy structures and electronic properties
of the Au(n=2-20) clusters based on density functional theory (DFT) with
local density approximation. The small Au 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 and Au 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 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 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
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