Towards the Chalonge 16th Paris Cosmology Colloquium 2012: Highlights and Conclusions of the Chalonge 15th Paris Cosmology Colloquium 2011

The Chalonge 15th Paris Cosmology Colloquium 2011 was held on 20-22 July in the historic Paris Observatory's Perrault building, in the Chalonge School spirit combining real cosmological/astrophysical data and hard theory predictive approach connected to them in the Warm Dark Matter Standard Model of the Universe: News and reviews from Herschel, QUIET, Atacama Cosmology Telescope (ACT), South Pole Telescole (SPT), Planck, PIXIE, the JWST, UFFO, KATRIN and MARE experiments; astrophysics, particle and nuclear physics warm dark matter (DM) searches and galactic observations, related theory and simulations, with the aim of synthesis, progress and clarification. Philippe Andre, Peter Biermann, Pasquale Blasi, Daniel Boyanovsky, Carlo Burigana, Hector de Vega, Joanna Dunkley, Gerry Gilmore, Alexander Kashlinsky, Alan Kogut, Anthony Lasenby, John Mather, Norma Sanchez, Alexei Smirnov, Sylvaine Turck-Chieze present here their highlights of the Colloquium. Ayuki Kamada and Sinziana Paduroiu present here their poster highlights. LambdaWDM (Warm Dark Matter) is progressing impressively over LambdaCDM whose galactic scale crisis and decline are staggering. The International School Daniel Chalonge issued an statement of strong support to the James Webb Space Telescope (JSWT). The Daniel Chalonge Medal 2011 was awarded to John C. Mather, Science PI of the JWST. Summary and conclusions are presented by H. J. de Vega, M. C. Falvella and N. G. Sanchez. Overall, LambdaWDM and keV scale DM particles deserve dedicated astronomical and laboratory experimental searches, theoretical work and simulations. KATRIN experiment in the future could perhaps adapt its set-up to look to keV scale sterile neutrinos. It will be a a fantastic discovery to detect dark matter in a beta decay. Photos of the Colloquium are included. (Abridged)Comment: 65 pages, 21 figure

Towards the Chalonge 17th Paris Cosmology Colloquium 2013: highlights and conclusions of the Chalonge 16th Paris Cosmology Colloquium 2012

LWDM (Warm Dark Matter) is progressing impressively.The galactic scale crisis and decline of LCDM+baryons are staggering. The 16th Paris Chalonge Colloquium 2012 combined real cosmological/astrophysical data and hard theory predictive approach in the LWDM Standard Model. News and reviews from ACT,WMAP,SPT,QUIET,Planck,Herschel,JWST,UFFO,KATRIN and MARE experiments; astrophysics, particle and nuclear physics WDM searches, galactic observations, related theory and simulations, with the aim of synthesis and clarification. Here highlights by P Biermann, C Burigana, C Conselice, A Cooray, H de Vega, C Giunti & M Laveder, J Kormendi & K Freeman, E Ma, J Mather, L Page, G Smoot, N Sanchez. Summary and conclusions by de Vega, Falvella and Sanchez. Data confirm primordial CMB gaussianity. Effective (Ginsburg-Landau) Inflation theory predicts r about 0.04-0.05, negligeable running of ns, the inflation energy scale (GUT scale) and the set of CMB observables in agreement with the data. WMAP9 and Planck measurements are compatible with one or two Majorana sterile neutrinos in the eV mass scale. Cored (non cusped) DM halos and keV WDM are strongly favored by theory and observations, Wimps are strongly disfavoured. LambdaCDM with baryons do not work at small scales. Inside galaxy cores, quantum WDM effects are important. Quantum WDM calculations (Thomas-Fermi) provide galaxy masses, velocity dispersions and cored profiles and their sizes in agreement with observations. A WDM fermion of about 2 keV naturally reproduces galaxy, large scale and cosmological observations. WDM keV particles deserve dedicated astronomical and laboratory searches, theoretical work and numerical simulations. KATRIN can be adapted to look to keV scale sterile neutrinos. It will be a fantastic discovery to detect dark matter in beta decay. Photos of the Colloquium are includedComment: 58 pages, 15 figures. arXiv admin note: substantial text overlap with arXiv:1203.3562, arXiv:1305.7452, arXiv:1009.3494, arXiv:1304.075

Highlights and Conclusions of the Chalonge 14th Paris Cosmology Colloquium 2010: `The Standard Model of the Universe: Theory and Observations'

The Chalonge 14th Paris Cosmology Colloquium was held on 22-24 July 2010 in Paris Observatory on the Standard Model of the Universe: News from WMAP7, BICEP, QUAD, SPT, AMI, ACT, Planck, QUIJOTE and Herschel; dark matter (DM) searches and galactic observations; related theory and simulations. %aiming synthesis, progress and clarification. P Biermann, D Boyanovsky, A Cooray, C Destri, H de Vega, G Gilmore, S Gottlober, E Komatsu, S McGaugh, A Lasenby, R Rebolo, P Salucci, N Sanchez and A Tikhonov present here their highlights of the Colloquium. Inflection points emerged: LambdaWDM (Warm DM) emerges impressively over LambdaCDM whose galactic scale problems are ever-increasing. Summary and conclusions by H. J. de Vega, M. C. Falvella and N. G. Sanchez stress among other points: (i) Primordial CMB gaussianity is confirmed. Inflation effective theory predicts a tensor to scalar ratio 0.05-0.04 at reach/border line of next CMB observations, early fast-roll inflation provides lowest multipoles depression. SZ amplitudes are smaller than expected: CMB and X-ray data agree but intracluster models need revision and relaxed/non-relaxed clusters distinction. (ii) cosmic ray positron excess is explained naturally by astrophysical processes, annihilating/decaying dark matter needs growing tailoring. (iii) Cored (non cusped) DM halos and warm (keV scale mass) DM are increasingly favored from theory and observations, naturally producing observed small scale structures, wimps turn strongly disfavoured. LambdaWDM 1 keV simulations well reproduce observations. Evidence that LambdaCDM does not work at small scales is staggering. P Biermann presents his live minutes of the Colloquium and concludes that a keV sterile neutrino is the most interesting DM candidate. Photos of the Colloquium are included.Comment: 58 pages, 20 figures. Three contributions added: G. Gilmore, S. Gottlober and E. Komats

Clinical and genetic factors associated with kidney tubular dysfunction in a real-life single centre cohort of HIV-positive patients

BACKGROUND: Tenofovir (TDF) is one of the most widely used antiretroviral drug. Despite the high degree of tolerability a small percentage of patients experienced alteration in tubular function during TDF use. Intracellular TDF disposition is regulated by ATP-binding cassette (ABC) drug efflux transporters and, a reduced transport activity may be implicated in accumulation of TDF into the cells. The aim of our study was to assess the major determinants of TDF associated tubular dysfunction (KTD) in a real-life setting including the usefulness of single-nucleotide polymorphisms (SNPs) mapping into ABCC2, ABCC4 and ABCC10 genes. METHODS: We retrospectively analyzed all HIV positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan from April 2013 to June 2016. All patients treated with TDF who underwent a genotypization for the functional variants mapping in ABCC2 rs717620 (-24 C > T), ABCC4 rs1751034 (3463 A > G) and ABCC10 rs2125739 (T > C) were evaluated. KTD was defined as the presence of urine phosphate wasting and/or proteinuria at 24 h urine analysis. RESULTS: One hundred fifty-eight patients were genotyped, of which 42 (26.6%) experienced signs of KTD. No statistical significant differences were observed among patients with or without KTD regarding age, gender, ethnicity and comorbidities (hypertension and diabetes). The percentage of patients with KTD was higher among those with "GG" genotype at rs1751034 of ABCC4 compared to patients without KTD [6 (14.3%) vs 4 (3.5%), p = 0.01]. No statistical significant differences were observed regarding the distribution of ABCC2 and ABCC10 SNPs. Carriers of "G" allele in homozygous status at rs1751034 of ABCC4 showed a significant association with KTD (Odds Ratio 4.67, 95% CI 1.25-17.46, p = 0.02) in bivariate analysis, but this association was lost in multivariable analysis. A significant association between bone diseases and KTD was observed (Odds Ratio 3.178, 95%CI 1.529-6.603, p = 0.002). CONCLUSIONS: According to our results ABCC4 rs1751034 could be a genetic determinant of KTD; however validation studies are needed for therapy personalization. Noteworthy, a strong association between bone disease and KTD was also observed

The Origin of the Universe as Revealed Through the Polarization of the Cosmic Microwave Background

Modern cosmology has sharpened questions posed for millennia about the origin of our cosmic habitat. The age-old questions have been transformed into two pressing issues primed for attack in the coming decade: How did the Universe begin? and What physical laws govern the Universe at the highest energies? The clearest window onto these questions is the pattern of polarization in the Cosmic Microwave Background (CMB), which is uniquely sensitive to primordial gravity waves. A detection of the special pattern produced by gravity waves would be not only an unprecedented discovery, but also a direct probe of physics at the earliest observable instants of our Universe. Experiments which map CMB polarization over the coming decade will lead us on our first steps towards answering these age-old questions.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 212 author available at http://cmbpol.uchicago.ed

Planck pre-launch status: Low Frequency Instrument calibration and expected scientific performance

We give the calibration and scientific performance parameters of the Planck Low Frequency Instrument (LFI) measured during the ground cryogenic test campaign. These parameters characterise the instrument response and constitute our best pre-launch knowledge of the LFI scientific performance. The LFI shows excellent $1/f$ stability and rejection of instrumental systematic effects; measured noise performance shows that LFI is the most sensitive instrument of its kind. The set of measured calibration parameters will be updated during flight operations through the end of the mission.Comment: Accepted for publications in Astronomy and Astrophysics. Astronomy & Astrophysics, 2010 (acceptance date: 12 Jan 2010

Ethnic differences in frequencies of gene polymorphisms in the MYCL1 region and modulation of lung cancer patients' survival

Linkage disequilibrium (LD) analysis to refine a region associated with lung cancer progression on chromosome 1p34 identified a 106 kb LD block that includes MYCL1, TRIT1 (tRNA isopentenyltransferase 1) and MFSD2 (major facilitator superfamily domain-containing 2). Case-only association study on SNPs mapping in TRIT1 and MFSD2 indicated that the rare Leu allele (frequency: 0.04) of the TRIT1 Phe202Leu variation predicts short survival as compared to the common Phe/Phe genotype (hazard ratio (HR)=1.7; 95% CI, 1.03-2.86; P=0.039) in 335 Italian lung adenocarcinoma samples. A replication study in an independent population of 246 Norwegian lung cancer patients confirmed the significant association of the Phe202Leu polymorphism with patients' survival, but the rare allele was associated with better survival rate (HR=0.5; 95% CI, 0.26-0.91; P=0.023). The rare allele of TRIT1 Phe202Leu SNP was approximately seven-fold more frequent in Asian than in Caucasian subjects and three additional SNPs in the TRIT1 and MFSD2 genes showed ethnic differences in allelic frequencies. These results suggest that polymorphisms in the MYCL1 LD region affect lung cancer survival but that the functional element(s) may show population-specific patterns

Undetected toxicity risk in pharmacogenetic testing for dihydropyrimidine dehydrogenase

Fluoropyrimidines, the mainstay agents for the treatment of colorectal cancer, alone or as a part of combination therapies, cause severe adverse reactions in about 10%-30% of patients. Dihydropyrimidine dehydrogenase (DPD), a key enzyme in the catabolism of 5-fluorouracil, has been intensively investigated in relation to fluoropyrimidine toxicity, and several DPD gene (DPYD) polymorphisms are associated with decreased enzyme activity and increased risk of fluoropyrimidine-related toxicity. In patients carrying non-functional DPYD variants (c.1905+1G>A, c.1679T>G, c.2846A>T), fluoropyrimidines should be avoided or reduced according to the patients' homozygous or heterozygous status, respectively. For other common DPYD variants (c.496A>G, c.1129-5923C>G, c.1896T>C), conflicting data are reported and their use in clinical practice still needs to be validated. The high frequency of DPYD polymorphism and the lack of large prospective trials may explain differences in studies' results. The epigenetic regulation of DPD expression has been recently investigated to explain the variable activity of the enzyme. DPYD promoter methylation and its regulation by microRNAs may affect the toxicity risk of fluoropyrimidines. The studies we reviewed indicate that pharmacogenetic testing is promising to direct personalised dosing of fluoropyrimidines, although further investigations are needed to establish the role of DPD in severe toxicity in patients treated for colorectal cancer

Nicotinic acetylcholine receptor variants associated with susceptibility to chronic obstructive pulmonary disease: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>Only 10-15% of smokers develop chronic obstructive pulmonary disease (COPD) which indicates genetic susceptibility to the disease. Recent studies suggested an association between COPD and polymorphisms in <it>CHRNA </it>coding subunits of nicotinic acetylcholine receptor. Herein, we performed a meta-analysis to clarify the impact of <it>CHRNA </it>variants on COPD.</p> <p>Methods</p> <p>We searched Web of Knowledge and Medline from 1990 through June 2011 for COPD gene studies reporting variants on <it>CHRNA</it>. Pooled odds ratios (ORs) were calculated using the major allele or genotype as reference group.</p> <p>Results</p> <p>Among seven reported variants in <it>CHRNA</it>, rs1051730 was finally analyzed with sufficient studies. Totally 3460 COPD and 11437 controls from 7 individual studies were pooled-analyzed. A-allele of rs1051730 was associated with an increased risk of COPD regardless of smoking exposure (pooled OR = 1.26, 95% CI 1.18-1.34, p < 10^-5). At the genotypic level, the ORs gradually increased per A-allele (OR = 1.27 and 1.50 for GA and AA respectively, p < 10^-5). Besides, AA genotype exhibited an association with reduced FEV1% predicted (mean difference 3.51%, 95%CI 0.87-6.16%, p = 0.009) and increased risk of emphysema (OR 1.93, 95%CI 1.29-2.90, p = 0.001).</p> <p>Conclusions</p> <p>Our findings suggest that rs1051730 in <it>CHRNA </it>is a susceptibility variant for COPD, in terms of both airway obstruction and parenchyma destruction.</p

Genetic and epigenetic alterations of Ras signalling pathway in colorectal neoplasia: analysis based on tumour clinicopathological features

Activation of RAS signalling induced by K-ras/BRAF mutations is a hallmark of colorectal tumours. In addition, Ras association domain families 1 and 2 (RASSF1 and RASSF2), the negative regulators of K-ras, are often inactivated by methylation of the promoter region in those tumours. However, reports showing differences in the occurrence of these alterations on the basis of tumour characteristics have been scarce. We analysed K-ras/BRAF mutations and the methylation status of RASSF1 and RASSF2 promoter regions in 120 colorectal adenomas with respect to their clinicopathological features. K-ras/BRAF mutations and RASSF2 methylation were observed in 49 (41%) and 30 (25%) of the samples, respectively, while RASSF1 methylation was observed in only 3 (2.5%). Adenomas with RASSF2 methylation often carried K-ras/BRAF mutations simultaneously (22 out of 30, P<0.01). Multivariate analysis revealed that the concomitance of these alterations was frequently observed in serrated adenomas (odds ratio (OR) 11.11; 95% confidence interval (CI) 1.96–63.00), but rarely in adenomas located in the sigmoid or descending colon (OR 0.13; 95% CI 0.03–0.58). A comparison between adenomas and cancers showed a significantly higher prevalence of these alterations in cancers than in adenomas in the proximal colon (58 vs 27%, P=0.02). Frequency and the time point of the occurrence of Ras signalling disorders differ according to colorectal neoplasia's characteristics, particularly the location