Validation of a Predictive Model for Survival in Patients With Advanced Cancer: Secondary Analysis of RTOG 9714.

BackgroundThe objective of this study was to validate a simple predictive model for survival of patients with advanced cancer.MethodsPrevious studies with training and validation datasets developed a model predicting survival of patients referred for palliative radiotherapy using three readily available factors: primary cancer site, site of metastases and Karnofsky performance score (KPS). This predictive model was used in the current study, where each factor was assigned a value proportional to its prognostic weight and the sum of the weighted scores for each patient was survival prediction score (SPS). Patients were also classified according to their number of risk factors (NRF). Three risk groups were established. The Radiation Therapy and Oncology Group (RTOG) 9714 data was used to provide an additional external validation set comprised of patients treated among multiple institutions with appropriate statistical tests.ResultsThe RTOG external validation set comprised of 908 patients treated at 66 different radiation facilities from 1998 to 2002. The SPS method classified all patients into the low-risk group. Based on the NRF, two distinct risk groups with significantly different survival estimates were identified. The ability to predict survival was similar to that of the training and previous validation datasets for both the SPS and NRF methods.ConclusionsThe three variable NRF model is preferred because of its relative simplicity

Ionic and electronic properties of the topological insulator Bi2_2Te2_2Se investigated using β\beta-detected nuclear magnetic relaxation and resonance of 8^8Li

We report measurements on the high temperature ionic and low temperature electronic properties of the 3D topological insulator Bi$_2$Te$_2$Se using ion-implanted $^8$Li $\beta$-detected nuclear magnetic relaxation and resonance. With implantation energies in the range 5-28 keV, the probes penetrate beyond the expected range of the topological surface state, but are still within 250 nm of the surface. At temperatures above ~150 K, spin-lattice relaxation measurements reveal isolated $^8$Li$^{+}$ diffusion with an activation energy $E_{A} = 0.185(8)$ eV and attempt frequency $\tau_{0}^{-1} = 8(3) \times 10^{11}$ s$^{-1}$ for atomic site-to-site hopping. At lower temperature, we find a linear Korringa-like relaxation mechanism with a field dependent slope and intercept, which is accompanied by an anomalous field dependence to the resonance shift. We suggest that these may be related to a strong contribution from orbital currents or the magnetic freezeout of charge carriers in this heavily compensated semiconductor, but that conventional theories are unable to account for the extent of the field dependence. Conventional NMR of the stable host nuclei may help elucidate their origin.Comment: 17 pages, 12 figures, submitted to Phys. Rev.

The interaction between maternal immune activation and alpha 7 nicotinic acetylcholine receptor in regulating behaviors in the offspring

Mutation of human chromosome 15q13.3 increases the risk for autism and schizophrenia. One of the noteworthy genes in 15q13.3 is CHRNA7, which encodes the nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) associated with schizophrenia in clinical studies and rodent models. This study investigates the role of α7nAChR in maternal immune activation (MIA) mice model, a murine model of environmental risk factor for autism and schizophrenia. We provided choline, a selective α7nAChR agonist among its several developmental roles, in the diet of C57BL/6N wild-type dams throughout the gestation and lactation period and induced MIA at mid-gestation. The adult offspring behavior and gene expression profile in the maternal splenic-placenta-fetal brain axis at mid-gestation were investigated. We found that choline supplementation prevented several MIA behavioral abnormalities in the wild-type offspring. Pro-inflammatory cytokine interleukin-6 (IL-6) and Chrna7 gene expression in the wild-type fetal brain were elevated by poly(I:C) injection and were suppressed by gestational choline supplementation. We further investigated the gene expression level of IL-6 in Chrna7 mutant mice. We found that the basal level of IL-6 was higher in Chrna7 mutant fetal brain, which suggests that α7nAChR may serve an anti-inflammatory role in the fetal brain during development. Lastly, we induced MIA in Chrna7+/− offspring. The Chrna7+/− offspring were more vulnerable to MIA, with increased behavioral abnormalities. Our study shows that α7nAChR modulates inflammatory response affecting the fetal brain and demonstrates its effects on offspring behavior development after maternal infection

Fidelity of Target Site Duplication and Sequence Preference during Integration of Xenotropic Murine Leukemia Virus-Related Virus

Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a new human retrovirus associated with prostate cancer and chronic fatigue syndrome. The causal relationship of XMRV infection to human disease and the mechanism of pathogenicity have not been established. During retrovirus replication, integration of the cDNA copy of the viral RNA genome into the host cell chromosome is an essential step and involves coordinated joining of the two ends of the linear viral DNA into staggered sites on target DNA. Correct integration produces proviruses that are flanked by a short direct repeat, which varies from 4 to 6 bp among the retroviruses but is invariant for each particular retrovirus. Uncoordinated joining of the two viral DNA ends into target DNA can cause insertions, deletions, or other genomic alterations at the integration site. To determine the fidelity of XMRV integration, cells infected with XMRV were clonally expanded and DNA sequences at the viral-host DNA junctions were determined and analyzed. We found that a majority of the provirus ends were correctly processed and flanked by a 4-bp direct repeat of host DNA. A weak consensus sequence was also detected at the XMRV integration sites. We conclude that integration of XMRV DNA involves a coordinated joining of two viral DNA ends that are spaced 4 bp apart on the target DNA and proceeds with high fidelity

Efficient unidirectional proxy re-encryption

Office of Research, Singapore Management Universit

Efficient Unidirectional Proxy Re-Encryption

Proxy re-encryption (PRE) allows a semi-trusted proxy to convert a ciphertext originally intended for Alice into one encrypting the same plaintext for Bob. The proxy only needs a re-encryption key given by Alice, and cannot learn anything about the plaintext encrypted. This adds flexibility in various applications, such as confidential email, digital right management and distributed storage. In this paper, we study unidirectional PRE, which the re-encryption key only enables delegation in one direction but not the opposite. In PKC 2009, Shao and Cao proposed a unidirectional PRE assuming the random oracle. However, we show that it is vulnerable to chosen-ciphertext attack (CCA). We then propose an efficient unidirectional PRE scheme (without resorting to pairings). We gain high efficiency and CCA-security using the ``token-controlled encryption\u27\u27 technique, under the computational Diffie-Hellman assumption, in the random oracle model and a relaxed but reasonable definition

A compactness theorem for complete Ricci shrinkers

We prove precompactness in an orbifold Cheeger-Gromov sense of complete gradient Ricci shrinkers with a lower bound on their entropy and a local integral Riemann bound. We do not need any pointwise curvature assumptions, volume or diameter bounds. In dimension four, under a technical assumption, we can replace the local integral Riemann bound by an upper bound for the Euler characteristic. The proof relies on a Gauss-Bonnet with cutoff argument.Comment: 28 pages, final version, to appear in GAF

Activity of iridium pyridine-based nanophotoswitches in retina

Purpose : Nanophotoswitches (NPSs) offer a new tool for optical stimulation of neuronal activity, in vitro and potentially in vivo. Our group previously reported a ruthenium bipyridine-based NPS (Rubpy-C17) that, after injection into the eyes of photoreceptor degenerated blind rats, elicited electrical activity in the contralateral superior colliculus upon light exposure. Compared with the ruthenium complexes, the family of iridium complexes has been more widely used in clinics, owing to its biosafety profile. We have thus synthesized and tested Irbpy-C17, an analog of Rubpy-C17 with the ruthenium core replaced by iridium. Methods : Rubpy molecules can be visualized by their luminescence upon visible wavelength illumination. To examine membrane incorporation, fluorescence imaging of HEK cells was obtained after incubation with Irbpy-C17. Activity of Irbpy-C17 was studied by MEA recording from wholemount retina after intravitreal injection. The test molecules were administered into the vitreous of blind RCS rats at the concentration of 200 µM. Animals were kept in dark after injection until the surgical dissection of retina. Acutely isolated retina was mounted on the MEA with the ganglion cell layer facing down to capture the spiking activity in response to light stimuli. Results : Irbpy-C17 exhibited good membrane incorporation similar to that of Rubpy-C17. Interestingly, despite that Irbpy-C17 elicited minimal light response initially, subsequent application of synaptic blocker cocktail that pharmacologically isolated RGCs substantially enhanced the light activation of RGCs (1.8 ± 0.3 fold increase in spike frequency). In comparison with the 3-hour incubation between injection and dissection, prolonged 24-hour incubation led to a more pronounced 2.5 ± 0.5 fold increase in spike frequency. Conclusions : Our data suggest that Irbpy-C17 may act on multiple components of the retinal neural circuitry that could suppress its direct action on RGCs via synaptic transmission. These molecules intravitreally administered remain stable and active in the ocular environment up to at least one day post injection. These data will prompt us to further study the iridium complexes in parallel with the ruthenium counterparts, particularly for the underlying mechanism of their differential behavior. The NPSs obviates the need for gene manipulation or toxic UV illumination, highlighting its potential in generating high-acuity prosthetic vision in the blind