Differential loss of chromosome 11q in familial and sporadic parasympathetic paragangliomas detected by comparative genomic hybridization

Parasympathetic paragangliomas (PGLs) represent neuroendocrine tumors arising from chief cells in branchiomeric and intravagal paraganglia, which share several histological features with their sympathetic counterpart sympathoadrenal paragangliomas. In recent years, genetic analyses of the familial form of PGL have attracted considerable interest. However, the majority of paragangliomas occurs sporadically and it remains to be determined whether the pathogenesis of sporadic paraganglioma resembles that of the familial form. Furthermore, data on comparative genetic aberrations are scarce. To provide fundamental cytogenetic data on sporadic and hereditary PGLs, we performed comparative genomic hybridization using directly fluorochrome-conjugated DNA extracted from 12 frozen and 4 paraffin-embedded tumors. The comparative genomic hybridization data were extended by loss of heterozygosity analysis of chromosome 11q. DNA copy number changes were found in 10 (63%) of 16 tumors. The most frequent chromosomal imbalance involved loss of chromosome 11. Six of seven familial tumors and two of nine sporadic tumors showed loss of 11q (86% versus 22%, P = 0.012). Deletions of 11p and 5p were found in two of nine sporadic tumors. We conclude that overall DNA copy number changes are infrequent in PGLs compared to sympathetic paragangliomas and that loss of chromosome 11 may be an important event in their tumorigenesis, particularly in familial paragangliomas

Losses of chromosomes 1p and 3q are early genetic events in the development of sporadic pheochromocytomas

Despite several loss of heterozygosity studies, a comprehensive genomic survey of pheochromocytomas is still lacking. To identify DNA copy number changes which might be important in tumor development and progression and which may have diagnostic utility, we evaluated genetic aberrations in 29 sporadic adrenal and extra-adrenal pheochromocytomas (19 clinically benign tumors and 10 malignant lesions). Comparative genomic hybridization was performed using directly fluorochrome-conjugated DNA extracted from frozen (16) and paraffin-embedded (13) tumor tissues. The most frequently observed changes were losses of chromosomes 1p11-p32 (86%), 3q (52%), 6q (34%), 3p, 17p (31% each), 11q (28%), and gains of chromosomes 9q (38%) and 17q (31%). No amplification was identified and no difference between adrenal and extra-adrenal tumors was detected. Progression to malignant tumors was strongly associated with deletions of chromosome 6q (60% versus 21% in clinically benign lesions, P = 0.0368) and 17p (50% versus 21%). Fluorescence in situ hybridization confirmed the comparative genomic hybridization data of chromosomes 1p, 3q, and 6q, and revealed aneuploidy in some tumors. Our results suggest that the development of pheochromocytomas is associated with specific genomic aberrations, such as losses of 1p, 3q, and 6q and gains of 9q and 17q. In particular, tumor suppressor genes on chromosomes 1p and 3q may be involved in early tumorigenesis, and deletions of chromosomes 6q and 17p in progression to malignancy

Prospects for Constraining Cosmology with the Extragalactic Cosmic Microwave Background Temperature

Observers have demonstrated that it is now feasible to measure the cosmic microwave background (CMB) temperature at high redshifts. We explore the possible constraints on cosmology which might ultimately be derived from such measurements. Besides providing a consistency check on standard and alternative cosmologies, possibilities include: constraints on the inhomogeneity and anisotropy of the universe at intermediate redshift $z ^<_\sim 10$; an independent probe of peculiar motions with respect to the Hubble flow; and constraining the epoch of reionization. We argue that the best possibility is as a probe of peculiar motions. We show, however, that the current measurement uncertainty ($\Delta T= \pm 0.002$K) in the local present absolute CMB temperature imposes intrinsic limits on the use of such CMB temperature measurements as a cosmological probe. At best, anisotropies at intermediate redshift could only be constrained at a level of $^>_\sim 0.1$ and peculiar motions could only be determined to an uncertainty of $^>_\sim 311$ km s$^{-1}$. If the high $z$ CMB temperature can only be measured with a precision comparable to the uncertainty of the local interstellar CMB temperature, then peculiar motions could be determined to an uncertainty of $1101 (1+z)^{-1} [\Delta T_{CMB}(z)/0.01 K] km s^{-1}$.Comment: 8 pages 2 Figures, PRD Submitte

Investigating patterns of pond and lake distributions to enhance the modeling of future Arctic surface inundation

Permafrost acts as an impermeable subsurface in Arctic lowland landscapes. This hydrological barrier results in carbon-rich, water-saturated soils as well as many ponds and lakes. The rapidly warming Arctic climate very likely will affect the surface inundation in Arctic lowlands due to changes in precipitation, evapotranspiration, and permafrost degradation. Drying and wetting of the surface may occur in different regions and potentially alter the exchange of energy and carbon between the surface and the atmosphere. With increased permafrost thaw, for example, water may drain to deeper soil layers or drainage maybe enhanced due to newly forming drainage networks. Melting ground ice and subsequent inundation, on the other hand, may enhance formation of new ponds and wet areas. The current distribution of ponds and lakes in the Arctic is the result of complex interactions between climate, ground ice volume, topography, age and sediment characteristics. Because lake formation and growth processes occur at spatial scales orders of magnitude below those of the resolution for global or pan-arctic models land surface models, statistical representations of lake size distributions and other properties to inform such processes in future models are needed that can be related to macroscopic landcape properties. This study proposes basic observationally-constrained relationships to enhance the modeling of future Arctic surface inundation. We mapped ponds and lakes in 21 circum-arctic sites representing different permafrost-soil landscapes, i.e., physiographic regions with similar surface geology, regional climate, and biomes. We used high-resolution optical and radar satellite imagery with spatial resolutions of 4 m or better to create detailed water body maps and derive representative probability density functions (PDF). PDFs of ponds and lakes vary little within the same ecoregion. Significant differences, however, do occur between landscapes. We used regional permafrost-soil landscape maps of Alaska, Canada, and Siberia to upscale the water body distributions to the circum-arctic. We here present regional distribution parameters, i.e. pond and lake fractions as well as PDF moments (mean surface area, standard deviation, and skewness) and their uncertainties. Younger landscapes, that developed in the early Holocene exhibit very skewed water body distributions. These landscapes are dominated by many ponds and feature only very few large lakes. Older landscapes, on the other hand, show more larger lakes but also a higher variability in pond and lake size. For lakes smaller than 5*10⁵ m², PDFs change in a regular fashion across all sites: Relationships between mean surface area and standard deviation show a linear behaviour whereas the correlation between mean and skewness log-normal. We hypothesize that these relationships are an expression of pond and lake growth and/or lake formation in the landscapes and discuss the potential of the observed patterns to improve predictions of future distributions of Arctic ponds and lakes

Measurement of W Polarisation at LEP

The three different helicity states of W bosons produced in the reaction e+ e- -> W+ W- -> l nu q q~ at LEP are studied using leptonic and hadronic W decays. Data at centre-of-mass energies \sqrt s = 183-209 GeV are used to measure the polarisation of W bosons, and its dependence on the W boson production angle. The fraction of longitudinally polarised W bosons is measured to be 0.218 \pm 0.027 \pm 0.016 where the first uncertainty is statistical and the second systematic, in agreement with the Standard Model expectation

Search for Anomalous Couplings in the Higgs Sector at LEP

Anomalous couplings of the Higgs boson are searched for through the processes e^+ e^- -> H gamma, e^+ e^- -> e^+ e^- H and e^+ e^- -> HZ. The mass range 70 GeV < m_H < 190 GeV is explored using 602 pb^-1 of integrated luminosity collected with the L3 detector at LEP at centre-of-mass energies sqrt(s)=189-209 GeV. The Higgs decay channels H -> ffbar, H -> gamma gamma, H -> Z\gamma and H -> WW^(*) are considered and no evidence is found for anomalous Higgs production or decay. Limits on the anomalous couplings d, db, Delta(g1z), Delta(kappa_gamma) and xi^2 are derived as well as limits on the H -> gamma gamma and H -> Z gamma decay rates

Measurement of W Polarisation at LEP

The three different helicity states of W bosons produced in the reaction e+ e- -> W+ W- -> l nu q q~ at LEP are studied using leptonic and hadronic W decays. Data at centre-of-mass energies \sqrt s = 183-209 GeV are used to measure the polarisation of W bosons, and its dependence on the W boson production angle. The fraction of longitudinally polarised W bosons is measured to be 0.218 \pm 0.027 \pm 0.016 where the first uncertainty is statistical and the second systematic, in agreement with the Standard Model expectation

Neutral-Current Four-Fermion Production in e+e- Interactions at LEP

Neutral-current four-fermion production, e+e- -> ffff is studied in 0.7/fb of data collected with the L3 detector at LEP at centre-of-mass energies root(s)=183-209GeV. Four final states are considered: qqvv, qqll, llll and llvv, where l denotes either an electron or a muon. Their cross sections are measured and found to agree with the Standard Model predictions. In addition, the e+e- -> Zgamma* -> ffff process is studied and its total cross section at the average centre-of-mass energy 196.6GeV is found to be 0.29 +/- 0.05 +/- 0.03 pb, where the first uncertainty is statistical and the second systematic, in agreement with the Standard Model prediction of 0.22 pb. Finally, the mass spectra of the qqll final states are analysed to search for the possible production of a new neutral heavy particle, for which no evidence is found

Measurement of Exclusive rho+rho- Production in Mid-Virtuality Two-Photon Interactions and Study of the gamma gamma* -> rho rho Process at LEP

Exclusive rho+rho- production in two-photon collisions between a quasi-real photon, gamma, and a mid-virtuality photon, gamma*, is studied with data collected at LEP at centre-of-mass energies root(s)=183-209GeV with a total integrated luminosity of 684.8pb^-1. The cross section of the gamma gamma* -> rho+ rho- process is determined as a function of the photon virtuality, Q^2, and the two-photon centre-of-mass energy, W_gg, in the kinematic region: 0.2GeV^2 < Q^2 <0.85GeV^2 and 1.1GeV < W_gg < 3GeV. These results, together with previous L3 measurements of rho0 rho0 and rho+ rho- production, allow a study of the gamma gamma* -> rho rho process over the Q^2-region 0.2GeV^2 < Q^2 < 30 GeV^2

Bose-Einstein Correlations of Neutral and Charged Pions in Hadronic Z Decays

Bose-Einstein correlations of both neutral and like-sign charged pion pairs are measured in a sample of 2 million hadronic Z decays collected with the L3 detector at LEP. The analysis is performed in the four-momentum difference range 300 MeV < Q < 2 GeV. The radius of the neutral pion source is found to be smaller than that of charged pions. This result is in qualitative agreement with the string fragmentation model