Quantum Effects in Black Hole Interiors

The Weyl curvature inside a black hole formed in a generic collapse grows, classically without bound, near to the inner horizon, due to partial absorption and blueshifting of the radiative tail of the collapse. Using a spherical model, we examine how this growth is modified by quantum effects of conformally coupled massless fields.Comment: 13 pages, 1 figure (not included), RevTe

High-throughput sequencing of gastric cancer patients : unravelling genetic predispositions towards an early-onset subtype

Background: Gastric cancer is the fourth most common cause of cancer-related death. Currently, it is broadly accepted that the molecular complexity and heterogeneity of gastric cancer, both inter- and intra-tumor, display important barriers for finding specific biomarkers for the early detection and diagnosis of this malignancy. Early-onset gastric cancer is not as prevalent as conventional gastric carcinoma, but it is a preferable model for studying the genetic background, as young patients are less exposed to environmental factors, which influence cancer development. Aim: The main objective of this study was to reveal age-dependent genotypic characteristics of gastric cancer subtypes, as well as conduct mutation profiling for the most frequent alterations in gastric cancer development, using targeted next-generation sequencing technology. Patients and methods: The study group included 53 patients, consisting of 18 patients with conventional gastric cancer and 35 with an early-onset subtype. The DNA of all index cases was used for next-generation sequencing, employing a panel of 94 genes and 284 single nucleotide polymorphisms (SNPs) (TruSight Cancer Panel, Illumina), which is characteristic for common and rare types of cancer. Results: From among the 53 samples processed for sequencing, we were able to identify seven candidate genes (STK11, RET, FANCM, SLX4, WRN, MEN1, and KIT) and nine variants among them: one splice_acceptor, four synonymous, and four missense variants. These were selected for the age-dependent differentiation of gastric cancer subtypes. We found four variants with C-Score ≥ 10, as 10% of the most deleterious substitutions: rs1800862 (RET), rs10138997 (FANCM), rs2230009 (WRN), and rs2959656 (MEN1). We identified 36 different variants, among 24 different genes, which were the most frequent genetic alterations among study subjects. We found 16 different variants among the genes that were present in 100% of the total cohort: SDHB (rs2746462), ALK (rs1670283), XPC (rs2958057), RECQL4 (rs4925828; rs11342077, rs398010167; rs2721190), DDB2 (rs326212), MEN1 (rs540012), AIP (rs4930199), ATM (rs659243), HNF1A (rs1169305), BRCA2 (rs206075; rs169547), ERCC5 (rs9514066; rs9514067), and FANCI (rs7183618). Conclusions: The technology of next-generation sequencing is a useful tool for studying the development and progression of gastric carcinoma in a high-throughput way. Our study revealed that early-onset gastric cancer has a different mutation frequency profile in certain genes compared to conventional subtype

Low frequency of HER2 amplification and overexpression in early onset gastric cancer

BACKGROUND: The recent ToGA trial results indicated that trastuzumab is a new, effective, and well-tolerated treatment for HER2-positive gastric cancer (GC). Although GC mainly affects older patients, fewer than 10% of GC patients are considered early-onset (EOGC) (presenting at the age of 45 years or younger). These EOGC show different clinicopathological and molecular profiles compared to late onset GC suggesting that they represent a separate entity within gastric carcinogenesis. In light of potential trastuzumab benefit, subpopulations of GC such as EOGC (versus late onset) should be evaluated for their frequency of amplification and overexpression using currently available techniques. METHODS: Tissue microarray (TMA) blocks of 108 early onset GC and 91 late onset GC were stained by immunohistochemistry (IHC, Hercep test, DAKO) and chromogenic in situ hybridization (CISH, SPoT-Light, Invitrogen). RESULTS: Overall, we found only 5% HER2 high level amplification and 3% HER2 3+ overexpression (6/199). In addition, 8 patients (4%) showed a low level CISH amplification and 9 patients (4.5%) showed a 2+ IHC score. IHC and CISH showed 92% concordance and CISH showed less heterogeneity than IHC. In 2/199 cases (1%), IHC showed clinically relevant heterogeneity between TMA cores, but all cases with focal IHC 3+ expression were uniformly CISH high level amplified. Early onset GCs showed a significantly lower frequency of HER2 amplification (2%) and overexpression (0%) than late onset GCs (8% and 7% respectively) (p = 0.085 and p = 0.008 respectively). Proximal GC had more HER2 amplification (9% versus 3%) and overexpression (7% versus 2%) than distal tumours although this difference was not significant (p = 0.181 and p = 0.182 respectively). HER2 CISH showed more high level amplification in the intestinal type (7%, 16% if low-level included) compared to the mixed (5%, 5% if low-level included) and diffuse type (3%, 4% if low-level included) GCs (p = 0.029). A similar association was seen for HER2 IHC and histologic type (p = 0.008). Logistic regression indicated a significant association between HER2 expression and age, which remained significant when adjusted for both location and histological type. CONCLUSIONS: Even focal HER2 overexpression in GC points to uniform HER2 amplification by CISH. We show for the first time that early onset GC has a lower frequency of HER2 amplification and overexpression than late onset GC, and confirm that intestinal type GC shows the highest rate of HER2 amplification and overexpression

New Types of Thermodynamics from (1+1)(1+1)-Dimensional Black Holes

For normal thermodynamic systems superadditivity $\S$, homogeneity \H and concavity \C of the entropy hold, whereas for $(3+1)$-dimensional black holes the latter two properties are violated. We show that $(1+1)$-dimensional black holes exhibit qualitatively new types of thermodynamic behaviour, discussed here for the first time, in which \C always holds, \H is always violated and $\S$ may or may not be violated, depending of the magnitude of the black hole mass. Hence it is now seen that neither superadditivity nor concavity encapsulate the meaning of the second law in all situations.Comment: WATPHYS-TH93/05, Latex, 10 pgs. 1 figure (available on request), to appear in Class. Quant. Gra

Conservation Laws and 2D Black Holes in Dilaton Gravity

A very general class of Lagrangians which couple scalar fields to gravitation and matter in two spacetime dimensions is investigated. It is shown that a vector field exists along whose flow lines the stress-energy tensor is conserved, regardless of whether or not the equations of motion are satisfied or if any Killing vectors exist. Conditions necessary for the existence of Killing vectors are derived. A new set of 2D black hole solutions is obtained for one particular member within this class of Lagrangians. One such solution bears an interesting resemblance to the 2D string-theoretic black hole, yet contains markedly different thermodynamic properties.Comment: 11 pgs. WATPHYS-TH92/0

Cosmological Models in Two Spacetime Dimensions

Various physical properties of cosmological models in (1+1) dimensions are investigated. We demonstrate how a hot big bang and a hot big crunch can arise in some models. In particular, we examine why particle horizons do not occur in matter and radiation models. We also discuss under what circumstances exponential inflation and matter/radiation decoupling can happen. Finally, without assuming any particular equation of state, we show that physical singularities can occur in both untilted and tilted universe models if certain assumptions are satisfied, similar to the (3+1)-dimensional cases.Comment: 22 pgs., 2 figs. (available on request) (revised version contains `paper.tex' macro file which was omitted in earlier version

Atmospheric Effects on Neutron Star Parameter Constraints with NICER

We present an analysis of the effects of uncertainties in the atmosphere models on the radius, mass, and other neutron star parameter constraints for the NICER observations of rotation-powered millisecond pulsars. To date, NICER has applied the X-ray pulse profile modeling technique to two millisecond-period pulsars: PSR J0030+0451 and the high-mass pulsar PSR J0740+6620. These studies have commonly assumed a deep-heated fully-ionized hydrogen atmosphere model, although they have explored the effects of partial-ionization and helium composition in some cases. Here we extend that exploration and also include new models with partially ionized carbon composition, externally heated hydrogen, and an empirical atmospheric beaming parametrization to explore deviations in the expected anisotropy of the emitted radiation. None of the studied atmosphere cases have any significant influence on the inferred radius of PSR J0740+6620, possibly due to its X-ray faintness, tighter external constraints, and/or viewing geometry. In the case of PSR J0030+0451 both the composition and ionization state could significantly alter the inferred radius. However, based on the evidence (prior predictive probability of the data), partially ionized hydrogen and carbon atmospheres are disfavored. The difference in the evidence for ionized hydrogen and helium atmospheres is too small to be decisive for most cases, but the inferred radius for helium models trends to larger sizes around or above 14-15 km. External heating or deviations in the beaming that are less than $5\,\%$ at emission angles smaller than 60 degrees, on the other hand, have no significant effect on the inferred radius.Comment: 26 pages, 12 figures (2 of which are figure sets), 3 tables. Accepted for publication in Ap

Self-completeness and spontaneous dimensional reduction

A viable quantum theory of gravity is one of the biggest challenges facing physicists. We discuss the confluence of two highly expected features which might be instrumental in the quest of a finite and renormalizable quantum gravity -- spontaneous dimensional reduction and self-completeness. The former suggests the spacetime background at the Planck scale may be effectively two-dimensional, while the latter implies a condition of maximal compression of matter by the formation of an event horizon for Planckian scattering. We generalize such a result to an arbitrary number of dimensions, and show that gravity in higher than four dimensions remains self-complete, but in lower dimensions it is not. In such a way we established an "exclusive disjunction" or "exclusive or" (XOR) between the occurrence of self-completeness and dimensional reduction, with the goal of actually reducing the unknowns for the scenario of the physics at the Planck scale. Potential phenomenological implications of this result are considered by studying the case of a two-dimensional dilaton gravity model resulting from dimensional reduction of Einstein gravity.Comment: 12 pages, 3 figures; v3: final version in press on Eur. Phys. J. Plu