Advances in understanding genome maintenance

A report from the Abcam genome stability conference 'Maintenance of Genome Stability', Jolly Beach Resort, Antigua, 8-11 March 2010

Cyber Threats Facing Autonomous and Connected Vehicles: Future Challenges

Vehicles are currently being developed and sold with increasing levels of connectivity and automation. As with all networked computing devices, increased connectivity often results in a heightened risk of a cyber security attack. Furthermore, increased automation exacerbates any risk by increasing the opportunities for the adversary to implement a successful attack. In this paper, a large volume of publicly accessible literature is reviewed and compartmentalised based on the vulnerabilities identified and mitigation techniques developed. This review highlighted that the majority of research is reactive and vulnerabilities are often discovered by friendly adversaries (white-hat hackers). Many gaps in the knowledge base were identified. Priority should be given to address these knowledge gaps to minimise future cyber security risks in the connected and autonomous vehicle sector

A biomechanical evaluation of taping and bracing in reducing knee joint translation and rotation

We used five randomly selected cadaver specimens to evaluate the Anderson Knee Stabler and the Lenox Hill Knee Brace, individually and in combination with an anterior cruciate ligament protective tape method. Re duction of total laxity, as well as a defined pathologic anterior-posterior translation and internal-external ro tation, was tested after the anterior cruciate and medial collateral ligaments of the specimens had been sec tioned. Displacements were produced pneumatically; loads were applied to the tibia with the knee in 50° of flexion. The tape and Lenox Hill Brace combination showed the greatest reduction in both anterior-posterior trans lation and internal-external rotation. The Lenox Hill Brace and the tape method used individually both re stricted anterior-posterior translation and internal-ex ternal rotation better than the Stabler Brace alone. This study provides objective evidence of the restraining capabilities of these protective systems that may prove to be beneficial in the clinical setting.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67165/2/10.1177_036354659202000409.pd

Optical and mechanical design of the extreme AO coronagraphic instrument MagAO-X

Here we review the current optical mechanical design of MagAO-X. The project is post-PDR and has finished the design phase. The design presented here is the baseline to which all the optics and mechanics have been fabricated. The optical/mechanical performance of this novel extreme AO design will be presented here for the first time. Some highlights of the design are: 1) a floating, but height stabilized, optical table; 2) a Woofer tweeter (2040 actuator BMC MEMS DM) design where the Woofer can be the current f/16 MagAO ASM or, more likely, fed by the facility f/11 static secondary to an ALPAO DM97 woofer; 3) 22 very compact optical mounts that have a novel locking clamp for additional thermal and vibrational stability; 4) A series of four pairs of super-polished off-axis parabolic (OAP) mirrors with a relatively wide FOV by matched OAP clocking; 5) an advanced very broadband (0.5-1.7micron) ADC design; 6) A Pyramid (PWFS), and post-coronagraphic LOWFS NCP wavefront sensor; 7) a vAPP coronagraph for starlight suppression. Currently all the OAPs have just been delivered, and all the rest of the optics are in the lab. Most of the major mechanical parts are in the lab or instrument, and alignment of the optics has occurred for some of the optics (like the PWFS) and most of the mounts. First light should be in 2019A.Comment: 10 pages, proc. SPIE 10703, Adaptive Optics IV, Austin TX, June 201

Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells

Recognition and repair of damaged DNA occurs within the context of chromatin. The key protein components of chromatin are histones, whose post-translational modifications control diverse chromatin functions. Here, we report our findings from a large-scale screen for DNA-damage-responsive histone modifications in human cells. We have identified specific phosphorylations and acetylations on histone H3 that decrease in response to DNA damage. Significantly, we find that DNA-damage-induced changes in H3S10p, H3S28p and H3.3S31p are a consequence of cell-cycle re-positioning rather than DNA damage per se. In contrast, H3K9Ac and H3K56Ac, a mark previously uncharacterized in human cells, are rapidly and reversibly reduced in response to DNA damage. Finally, we show that the histone acetyl-transferase GCN5/KAT2A acetylates H3K56 in vitro and in vivo. Collectively, our data indicate that though most histone modifications do not change appreciably after genotoxic stress, H3K9Ac and H3K56Ac are reduced in response to DNA damage in human cells

Multiple sediment incorporation events in a continental magmatic arc: Insight from the metasedimentary rocks of the northern North Cascades, Washington (USA)

The rheology and composition of arc crust and the overall evolution of continental magmatic arcs can be affected by sediment incorporation events. The exhumed Cretaceous–Eocene North Cascades arc exposes abundant meta­ sedimentary rocks that were incorporated into the arc during multiple events. This study uses field relationships, detrital zircon geochronology, bulk rock geo­ chemistry, geothermometry, and quartz­in­garnet geobarometry to distinguish approximate contacts and emplacement depths for different metasedimentary units to better understand their protolith incorporation history and impact on the arc. The Skagit Gneiss Complex is one of the main deep crustal units of the North Cascades arc. It includes metasedimentary rocks with distinct detrital zircon signatures: Proterozoic–Cretaceous (Group 1) or Triassic–Cretaceous (Group 2) zircon populations. Both metasedimentary groups achieved near­ peak metamorphic conditions of 640–800 °C and 5.5–7.9 kbar; several Group 2 samples reveal the higher pressures. A third group of metasedimentary rocks, which was previously interpreted as metamorphosed equivalents of backarc sediments (Group 3), exhibited unimodal Triassic or bimodal Late Jurassic– Early Cretaceous detrital zircon signatures and achieved near­peak conditions of 570–700 °C and 8.7–10.5 kbar. The combined field and analytical data indi­ cate that protoliths of Group 1 and Group 2 metasedimentary rocks were successively deposited in a forearc basin and underthrusted into the arc as a relatively coherent body. Group 3 backarc sediments were incorporated into the arc along a transpressional step­over zone. The incorporation of both forearc and backarc sediments was likely facilitated by arc magmatism that weakened arc crust in combination with regional transpression

Intrathecal enzyme replacement for Hurler syndrome: biomarker association with neurocognitive outcomes.

PurposeAbnormalities in cerebrospinal fluid (CSF) have been reported in Hurler syndrome, a fatal neurodegenerative lysosomal disorder. While no biomarker has predicted neurocognitive response to treatment, one of these abnormalities, glycosaminoglycan nonreducing ends (NREs), holds promise to monitor therapeutic efficacy. A trial of intrathecal enzyme replacement therapy (ERT) added to standard treatment enabled tracking of CSF abnormalities, including NREs. We evaluated safety, biomarker response, and neurocognitive correlates of change.MethodsIn addition to intravenous ERT and hematopoietic cell transplantation, patients (N = 24) received intrathecal ERT at four peritransplant time points; CSF was evaluated at each point. Neurocognitive functioning was quantified at baseline, 1 year, and 2 years posttransplant. Changes in CSF biomarkers and neurocognitive function were evaluated for an association.ResultsOver treatment, there were significant decreases in CSF opening pressure, biomarkers of disease activity, and markers of inflammation. Percent decrease in NRE from pretreatment to final intrathecal dose posttransplant was positively associated with percent change in neurocognitive score from pretreatment to 2 years posttransplant.ConclusionIntrathecal ERT was safe and, in combination with standard treatment, was associated with reductions in CSF abnormalities. Critically, we report evidence of a link between a biomarker treatment response and neurocognitive outcome in Hurler syndrome