A Network-based Approach to Breast Cancer Systems Medicine.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women. Although recent improvements in the prevention, early detection, and treatment of breast cancer have led to a significant decrease in the mortality rate, the identification of an optimal therapeutic strategy for each patient remains a difficult task because of the heterogeneous nature of the disease. Clinical heterogeneity of breast cancer is in part explained by the vast genetic and molecular heterogeneity of this disease, which is now emerging from large-scale screening studies using \u201c-omics\u201d technologies (e.g. microarray gene expression profiling, next-generation sequencing). This genetic and molecular heterogeneity likely contributes significantly to therapy response and clinical outcome. The recent advances in our understanding of the molecular nature of breast cancer due, in particular, to the explosion of high-throughput technologies, is driving a shift away from the \u201cone-dose-fits-all\u201d paradigm in healthcare, to the new \u201cPersonalized Cancer Care\u201d paradigm. The aim of \u201cPersonalized Cancer Care\u201d is to select the optimal course of clinical intervention for individual patients, maximizing the likelihood of effective treatment and reducing the probability of adverse drug reactions, according to the molecular features of the patient. In light to this medical scenario, the aim of this project is to identify novel molecular mechanisms that are altered in breast cancer through the development of a computational pipeline, in order to propose putative biomarkers and druggable target genes for the personalized management of patients. Through the application of a Systems Biology approach to reverse engineer Gene Regulatory Networks (GRNs) from gene expression data, we built GRNs around \u201chub\u201d genes transcriptionally correlating with clinical-pathological features associated with breast tumor expression profiles. The relevance of the GRNs as putative cancer-related mechanisms was reinforced by the occurrence of mutational events related to breast cancer in the \u201chub\u201d genes, as well as in the neighbor genes. Moreover, for some networks, we observed mutually exclusive mutational patterns in the neighbors genes, thus supporting their predicted role as oncogenic mechanisms. Strikingly, a substantial fraction of GRNs were overexpressed in Triple Negative Breast Cancer patients who acquired resistance to therapy, suggesting the involvement of these networks in mechanisms of chemoresistance. In conclusion, our approach allowed us to identify cancer molecular mechanisms frequently altered in breast cancer and in chemorefractory tumors, which may suggest novel cancer biomarkers and potential drug targets for the development of more effective therapeutic strategies in metastatic breast cancer patients

Radiographic dental implants recognition for geographic evaluation in human identification

Dental implants for prosthetic rehabilitation with fixed crown or mobile partial/total dentures is a very common oral treatment among the population in Italy as elsewhere. There is a great number of implant systems of different designs. However, a catalogue of radiographic images and a description of the dental implants available in Italy would be useful in order to identify the manufacturer and the type of implant encountered in forensic casework. When an unidentified body is found with one or more implants in the jaws, and no dental record is available, clues gleaned from the type of implants used could give direction to the investigation. In this study Italian implant manufactures were contacted and asked to provide specimen implants. Digital radiographs were taken of all the implants donated at 0°, 30°, and 60° horizontal rotation, combined with -20°, -10°, 0°, +10°, and +20° vertical inclination relative to the radiographic beam and the X-ray sensor. A total of 15 images per implant were taken and examined to identify consistent, unique features that would aid in implant recognition. Only those observations made from radiographs between -10° and +10° vertical inclination would ever be used for definite identification of any implant. The information from this study should be considered a survey of the commercial distribution of dental implants in Italy through their digital radiographic images. It is also a starting point for a wider geographical evaluation of different manufacturers in other countries and continents. The radiographic images provided should help both the forensic odontologist and the prosthodontist to identify pre-existing implants which they may discover from their radiographic images

Measurements of branching fraction ratios and CP-asymmetries in suppressed B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^- decays

We report the first reconstruction in hadron collisions of the suppressed decays B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^-, sensitive to the CKM phase gamma, using data from 7 fb^-1 of integrated luminosity collected by the CDF II detector at the Tevatron collider. We reconstruct a signal for the B^- -> D(-> K^+ pi^-)K^- suppressed mode with a significance of 3.2 standard deviations, and measure the ratios of the suppressed to favored branching fractions R(K) = [22.0 \pm 8.6(stat)\pm 2.6(syst)]\times 10^-3, R^+(K) = [42.6\pm 13.7(stat)\pm 2.8(syst)]\times 10^-3, R^-(K)= [3.8\pm 10.3(stat)\pm 2.7(syst]\times 10^-3, as well as the direct CP-violating asymmetry A(K) = -0.82\pm 0.44(stat)\pm 0.09(syst) of this mode. Corresponding quantities for B^- -> D(-> K^+ pi^-)pi^- decay are also reported.Comment: 8 pages, 1 figure, accepted by Phys.Rev.D Rapid Communications for Publicatio

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV

The t t-bar production cross section (sigma[t t-bar]) is measured in proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS experiment, corresponding to an integrated luminosity of 2.3 inverse femtobarns. The measurement is performed in events with two leptons (electrons or muons) in the final state, at least two jets identified as jets originating from b quarks, and the presence of an imbalance in transverse momentum. The measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/- 2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction of the standard model.Comment: Replaced with published version. Included journal reference and DO

Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe