Cigarette Smoking and p16INK4α Gene Promoter Hypermethylation in Non-Small Cell Lung Carcinoma Patients: A Meta-Analysis

BACKGROUND:Aberrant methylation of promoter DNA and transcriptional repression of specific tumor suppressor genes play an important role in carcinogenesis. Recently, many studies have investigated the association between cigarette smoking and p16(INK4α) gene hypermethylation in lung cancer, but could not reach a unanimous conclusion. METHODS AND FINDINGS:Nineteen cross-sectional studies on the association between cigarette smoking and p16(INK4α) methylation in surgically resected tumor tissues from non-small cell lung carcinoma (NSCLC) patients were identified in PubMed database until June 2011. For each study, a 2×2 cross-table was extracted. In total, 2,037 smoker and 765 nonsmoker patients were pooled with a fixed-effects model weighting for the inverse of the variance. Overall, the frequency of p16(INK4α) hypermethylation was higher in NSCLC patients with smoking habits than that in non-smoking patients (OR = 2.25, 95% CI = 1.81-2.80). The positive association between cigarette smoking and p16(INK4α) hypermethylation was similar in adenocarcinoma and squamous-cell carcinoma. In the stratified analyses, the association was stronger in Asian patients and in the studies with larger sample sizes. CONCLUSION:Cigarette smoking is positively correlated to p16(INK4α) gene hypermethylation in NSCLC patients

GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy

We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range. The Gamma-Ray Imaging, Polarimetry and Spectroscopy (GRIPS) mission addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate $\gamma$-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.Comment: to appear in Exp. Astron., special vol. on M3-Call of ESA's Cosmic Vision 2010; 25 p., 25 figs; see also www.grips-mission.e

Quantum and classical confinement of resonant states in a trilayer graphene Fabry-Pérot interferometer

The advent of few-layer graphene has given rise to a new family of two-dimensional systems with emergent electronic properties governed by relativistic quantum mechanics. The multiple carbon sublattices endow the electronic wavefunctions with pseudospin, a lattice analogue of the relativistic electron spin, whereas the multilayer structure leads to electric-field-effect tunable electronic bands. Here we use these properties to realize giant conductance oscillations in ballistic trilayer graphene Fabry-Pérot interferometers, which result from phase coherent transport through resonant bound states beneath an electrostatic barrier. We confine these states by selectively decoupling them from the leads, resulting in transport via non-resonant states and suppression of the giant oscillations. The confinement is achieved both classically, by manipulating quasiparticle momenta with a magnetic field, and quantum mechanically, by locally varying the pseudospin character of the carrier wavefunctions. Our results illustrate the unique potential of trilayer graphene as a versatile platform for electron optics and pseudospintronics.United States. Office of Naval Research (GATE MURI)National Science Foundation (U.S.) (Career Award DMR-0845287)Conselho Nacional de Pesquisas (Brazil

Two Nuclear Localization Signals in USP1 Mediate Nuclear Import of the USP1/UAF1 Complex

The human deubiquitinase USP1 plays important roles in cancer-related processes, such as the DNA damage response, and the maintenance of the undifferentiated state of osteosarcoma cells. USP1 deubiquitinase activity is critically regulated by its interaction with the WD40 repeat-containing protein UAF1. Inhibiting the function of the USP1/UAF1 complex sensitizes cancer cells to chemotherapy, suggesting that this complex is a relevant anticancer target. Intriguingly, whereas UAF1 has been reported to locate in the cytoplasm, USP1 is a nuclear protein, although the sequence motifs that mediate its nuclear import have not been functionally characterized. Here, we identify two nuclear localization signals (NLSs) in USP1 and show that these NLSs mediate the nuclear import of the USP1/UAF1 complex. Using a cellular relocation assay based on these results, we map the UAF1-binding site to a highly conserved 100 amino acid motif in USP1. Our data support a model in which USP1 and UAF1 form a complex in the cytoplasm that subsequently translocates to the nucleus through import mediated by USP1 NLSs. Importantly, our findings have practical implications for the development of USP1-directed therapies. First, the UAF1-interacting region of USP1 identified here might be targeted to disrupt the USP1/UAF1 interaction with therapeutic purposes. On the other hand, we describe a cellular relocation assay that can be easily implemented in a high throughput setting to search for drugs that may dissociate the USP1/UAF1 complex

Time-related improvement of survival in resectable gastric cancer: the role of Japanese-style gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy

BACKGROUND: We investigated the change of prognosis in resected gastric cancer (RGC) patients and the role of radical surgery and adjuvant chemotherapy. METHODS: We retrospectively analyze the outcome of 426 consecutive patients from 1975 to 2002, divided into 2 time-periods (TP) cohort: Before 1990 (TP1, n = 207) and 1990 or after (TP2; n= 219). Partial gastrectomy and D1-lymphadenetomy was predominant in TP1 and total gastrectomy with D2-lymphadenectomy it was in TP2. Adjuvant chemotherapy consisted of mitomycin C (MMC), 10–20 mg/m2 iv 4 courses or MMC plus Tegafur 500 mg/m2 for 6 months. RESULTS: Positive nodes were similar in TP2/TP1 patients with 56%/59% respectively. Total gastrectomy was done in 56%/45% of TP2/TP1 respectively. Two-drug adjuvant chemotherapy was administered in 65%/18% of TP2/TP1 respectively. Survival at 5 years was 66% for TP2 versus 42% for TP1 patients (p < 0.0001). Survival by stages II, IIIA y IIIB for TP2 versus TP1 patients was 70 vs. 51% (p = 0.0132); 57 vs. 22% (p = 0.0008) y 30 vs. 15% (p = 0.2315) respectively. Multivariate analysis showed that age, stage of disease and period of treatment were independent variables. CONCLUSION: The global prognosis and that of some stages have improved in recent years with case RGC patients treated with surgery and adjuvant chemotherapy

Quantum and classical confinement of resonant states in a trilayer graphene Fabry-Pérot interferometer

The advent of few-layer graphene has given rise to a new family of two-dimensional systems with emergent electronic properties governed by relativistic quantum mechanics. The multiple carbon sublattices endow the electronic wavefunctions with pseudospin, a lattice analogue of the relativistic electron spin, whereas the multilayer structure leads to electric-field-effect tunable electronic bands. Here we use these properties to realize giant conductance oscillations in ballistic trilayer graphene Fabry-Pérot interferometers, which result from phase coherent transport through resonant bound states beneath an electrostatic barrier. We confine these states by selectively decoupling them from the leads, resulting in transport via non-resonant states and suppression of the giant oscillations. The confinement is achieved both classically, by manipulating quasiparticle momenta with a magnetic field, and quantum mechanically, by locally varying the pseudospin character of the carrier wavefunctions. Our results illustrate the unique potential of trilayer graphene as a versatile platform for electron optics and pseudospintronics.United States. Office of Naval Research (GATE MURI)National Science Foundation (U.S.) (Career Award DMR-0845287)Conselho Nacional de Pesquisas (Brazil

Properties of Graphene: A Theoretical Perspective

In this review, we provide an in-depth description of the physics of monolayer and bilayer graphene from a theorist's perspective. We discuss the physical properties of graphene in an external magnetic field, reflecting the chiral nature of the quasiparticles near the Dirac point with a Landau level at zero energy. We address the unique integer quantum Hall effects, the role of electron correlations, and the recent observation of the fractional quantum Hall effect in the monolayer graphene. The quantum Hall effect in bilayer graphene is fundamentally different from that of a monolayer, reflecting the unique band structure of this system. The theory of transport in the absence of an external magnetic field is discussed in detail, along with the role of disorder studied in various theoretical models. We highlight the differences and similarities between monolayer and bilayer graphene, and focus on thermodynamic properties such as the compressibility, the plasmon spectra, the weak localization correction, quantum Hall effect, and optical properties. Confinement of electrons in graphene is nontrivial due to Klein tunneling. We review various theoretical and experimental studies of quantum confined structures made from graphene. The band structure of graphene nanoribbons and the role of the sublattice symmetry, edge geometry and the size of the nanoribbon on the electronic and magnetic properties are very active areas of research, and a detailed review of these topics is presented. Also, the effects of substrate interactions, adsorbed atoms, lattice defects and doping on the band structure of finite-sized graphene systems are discussed. We also include a brief description of graphane -- gapped material obtained from graphene by attaching hydrogen atoms to each carbon atom in the lattice.Comment: 189 pages. submitted in Advances in Physic

A novel logistic-NARX model as a classifier for dynamic binary classification

System identification and data-driven modeling techniques have seen ubiquitous applications in the past decades. In particular, parametric modeling methodologies such as linear and nonlinear autoregressive with exogenous input models (ARX and NARX) and other similar and related model types have been preferably applied to handle diverse data-driven modeling problems due to their easy-to-compute linear-in-the-parameter structure, which allows the resultant models to be easily interpreted. In recent years, several variations of the NARX methodology have been proposed that improve the performance of the original algorithm. Nevertheless, in most cases, NARX models are applied to regression problems where all output variables involve continuous or discrete-time sequences sampled from a continuous process, and little attention has been paid to classification problems where the output signal is a binary sequence. Therefore, we developed a novel classification algorithm that combines the NARX methodology with logistic regression and the proposed method is referred to as logistic-NARX model. Such a combination is advantageous since the NARX methodology helps to deal with the multicollinearity problem while the logistic regression produces a model that predicts categorical outcomes. Furthermore, the NARX approach allows for the inclusion of lagged terms and interactions between them in a straight forward manner resulting in interpretable models where users can identify which input variables play an important role individually and/or interactively in the classification process, something that is not achievable using other classification techniques like random forests, support vector machines, and k-nearest neighbors. The efficiency of the proposed method is tested with five case studies