Salvage Fractionated Stereotactic Re-irradiation (FSRT) for Patients with Recurrent High Grade Gliomas Progressed after Bevacizumab Treatment

Purpose/Objectives: Bevacizumab failure is a major clinical problem in the manage- ment of high grade gliomas (HGG), with a median overall survival of less than 4 months (m). This study evaluated the efficacy of fractionated stereotactic re-irradiation (FSRT) for patients with HGG after progression on Bevacizumab. Materials/Methods: Retrospective review was conducted of patients treated with FSRT after progression on bevacizumab. A total of 36 patients were identified. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed. Results: Among the 36 patients, 31 patients had recurrent glioblastoma, and 5 patients had recurrent anaplastic astrocytoma. The median time from initial bevacizumab treatment to FSRT was 8.5 m (range 2.3 – 32.0 m). The median plan target volume for FSRT was 27.5 cc (range 1.95 – 165 cc). With a median follow up of 20.4 m, the overall survival of the patients since initial diagnosis was also 24.9 m. The median overall survival after initiation of bevacizumab was 13.4 months. The median overall survival from FSRT was 4.8 m. FSRT treatment was well tolerated with no Grade \u3e3 toxicity. Conclusions: Favorable outcomes were observed in patients with recurrent HGG who received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for selected patients with recurrent HGG amenable to FSRT, who had failed bevacizumab treatment

Complete Genome Sequence of Mesorhizobium ciceri bv. biserrulae Strain WSM1284, an Efficient Nitrogen-Fixing Microsymbiont of the Pasture Legume Biserrula pelecinus.

We report the complete genome sequence of Mesorhizobium ciceri bv. biserrulae strain WSM1284, a nitrogen-fixing microsymbiont of the pasture legume Biserrula pelecinus The genome consists of 6.88 Mb distributed between a single chromosome (6.33 Mb) and a single plasmid (0.55 Mb)

Complete Genome Sequence of Mesorhizobium ciceri Strain CC1192, an Efficient Nitrogen-Fixing Microsymbiont of Cicer arietinum.

We report the complete genome sequence of Mesorhizobium ciceri strain CC1192, an efficient nitrogen-fixing microsymbiont of Cicer arietinum (chickpea). The genome consists of 6.94 Mb distributed between a single chromosome (6.29 Mb) and a plasmid (0.65 Mb)

Cue-Dependent Inhibition in Posttraumatic Stress Disorder and Attention- Deficit/Hyperactivity Disorder

Objective Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are common among military veterans, but the comorbidity of these two psychiatric disorders remains largely unstudied. Evaluating response inhibition and cue-dependent learning as behavioral and neurocognitive mechanisms underlying ADHD/PTSD can inform etiological models and development of tailored interventions. Method A cued go/no-go task evaluated response inhibition in 160 adult males. Participants were recruited from the community and a Veterans Administration medical center. Four diagnostic groups were identified: ADHD-only, PTSD-only, ADHD + PTSD, controls. Results Group differences were observed across most indices of inhibitory functioning, reaction time, and reaction time variability, whereby PTSD-only and ADHD + PTSD participants demonstrated deficits relative to controls. No cue dependency effects were observed. Conclusion Finding complement prior work on neurocognitive mechanisms underlying ADHD, PTSD, and ADHD + PTSD. Lack of expected group differences for the ADHD-only group may be due to limited power. Additional work is needed to better characterize distinctions among clinical groups, as well as to test effects among women and youth

Nucleotide Excision Repair- and Polymerase Eta-Mediated Error-Prone Removal of Mitomycin C Interstrand Cross-Links

Interstrand cross-links (ICLs) make up a unique class of DNA lesions in which both strands of the double helix are covalently joined, precluding strand opening during replication and transcription. The repair of DNA ICLs has become a focus of study since ICLs are recognized as the main cytotoxic lesion inflicted by an array of alkylating compounds used in cancer treatment. As is the case for double-strand breaks, a damage-free homologous copy is essential for the removal of ICLs in an error-free manner. However, recombination-independent mechanisms may exist to remove ICLs in an error-prone fashion. We have developed an in vivo reactivation assay that can be used to examine the removal of site-specific mitomycin C-mediated ICLs in mammalian cells. We found that the removal of the ICL from the reporter substrate could take place in the absence of undamaged homologous sequences in repair-proficient cells, suggesting a cross-link repair mechanism that is independent of homologous recombination. Systematic analysis of nucleotide excision repair mutants demonstrated the involvement of transcription-coupled nucleotide excision repair and a partial requirement for the lesion bypass DNA polymerase eta encoded by the human POLH gene. From these observations, we propose the existence of a recombination-independent and mutagenic repair pathway for the removal of ICLs in mammalian cells

Gallium Arsenide (GaAs) Quantum Photonic Waveguide Circuits

Integrated quantum photonics is a promising approach for future practical and large-scale quantum information processing technologies, with the prospect of on-chip generation, manipulation and measurement of complex quantum states of light. The gallium arsenide (GaAs) material system is a promising technology platform, and has already successfully demonstrated key components including waveguide integrated single-photon sources and integrated single-photon detectors. However, quantum circuits capable of manipulating quantum states of light have so far not been investigated in this material system. Here, we report GaAs photonic circuits for the manipulation of single-photon and two-photon states. Two-photon quantum interference with a visibility of 94.9 +/- 1.3% was observed in GaAs directional couplers. Classical and quantum interference fringes with visibilities of 98.6 +/- 1.3% and 84.4 +/- 1.5% respectively were demonstrated in Mach-Zehnder interferometers exploiting the electro-optic Pockels effect. This work paves the way for a fully integrated quantum technology platform based on the GaAs material system.Comment: 10 pages, 4 figure

G-Quadruplex Dynamics Contribute To Regulation Of Mitochondrial Gene Expression

Single-stranded DNA or RNA sequences rich in guanine (G) can adopt non-canonical structures known as G-quadruplexes (G4). Mitochondrial DNA (mtDNA) sequences that are predicted to form G4 are enriched on the heavy-strand and have been associated with formation of deletion breakpoints. Increasing evidence supports the ability of mtDNA to form G4 in cancer cells; however, the functional roles of G4 structures in regulating mitochondrial nucleic acid homeostasis in non-cancerous cells remain unclear. Here, we demonstrate by live cell imaging that the G4-ligand RHPS4 localizes primarily to mitochondria at low doses. We find that low doses of RHPS4 do not induce a nuclear DNA damage response but do cause an acute inhibition of mitochondrial transcript elongation, leading to respiratory complex depletion. We also observe that RHPS4 interferes with mtDNA levels or synthesis both in cells and isolated mitochondria. Importantly, a mtDNA variant that increases G4 stability and anti-parallel G4-forming character shows a stronger respiratory defect in response to RHPS4, supporting the conclusion that mitochondrial sensitivity to RHPS4 is G4-mediated. Taken together, our results indicate a direct role for G4 perturbation in mitochondrial genome replication, transcription processivity, and respiratory function in normal cells