Clipping versus coiling for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis of prospective studies

Neurosurgical clipping and endovascular coiling are both standard therapies to prevent rebleeding after aneurysmal subarachnoid hemorrhage (aSAH). However, controversy still exists about which is the optimal treatment. This meta-analysis aims to assess the effectiveness and safety of two treatments with high-quality evidence. Web of Science, Cochrane Library, EMBASE, Pubmed, Sinomed, China National Knowledge Infrastructure, and Wanfang Data databases were systematically searched on August 5, 2021. Randomized controlled trials (RCTs) and prospective cohort studies that evaluated the effectiveness and safety of clipping versus coiling in aSAH patients at discharge or within 1-year follow-up period were eligible. No restriction was set on the publication date. Meta-analyses were conducted to calculate the pooled estimates and 95% confidence intervals (CI) of relative risk (RR). Eight RCTs and 20 prospective cohort studies were identified. Compared to coiling, clipping was associated with a lower rebleeding rate at discharge (RR: 0.52, 95% CI: 0.29––0.94) and a higher aneurysmal occlusion rate (RR: 1.33, 95% CI: 1.19–1.48) at 1-year follow-up. In contrast, coiling reduced the vasospasm rate at discharge (RR: 1.45, 95% CI: 1.23–1.71) and 1-year poor outcome rate (RR: 1.27, 95% CI: 1.16–1.39). Subgroup analyses presented that among patients with a poor neurological condition at admission, no statistically significant outcome difference existed between the two treatments. The overall prognosis was better among patients who received coiling, but this advantage was not significant among patients with a poor neurological condition at admission. Therefore, the selection of treatment modality for aSAH patients should be considered comprehensively

Distributed Proximity-Aware Peer Clustering in BitTorrent-Like Peer-to-Peer Networks

International Conference on Embedded and Ubiquitous Computing (EUC 2006), Seoul, Korea, 1-4 Aug 2006In this paper, we propose a hierarchical architecture for grouping peers into clusters in a large-scale BitTorrent-like underlying overlay network in such a way that clusters are evenly distributed and that the peers within are relatively close together. We achieve this by constructing the CBT (Clustered BitTorrent) system with two novel algorithms: a peer joining algorithm and a super-peer selection algorithm. Proximity and distribution are determined by the measurement of distances among peers. Performance evaluations demonstrate that the new architecture achieves better results than a randomly organized BitTorrent network, improving the system scalability and efficiency while retaining the robustness and incentives of original BitTorrent paradigm.Department of Computin

In the Shadow of the Transiting Disk: Imaging epsilon Aurigae in Eclipse

Eclipses of the single-line spectroscopic binary star, epsilon Aurigae, provide an opportunity to study the poorly-defined companion. We used the MIRC beam combiner on the CHARA array to create interferometric images during eclipse ingress. Our results demonstrate that the eclipsing body is a dark disk that is opaque and tilted, and therefore exclude alternative models for the system. These data constrain the geometry and masses of the components, providing evidence that the F-star is not a massive supergiant star.Comment: As submitted to Nature. Published in Nature April 8, 2010

Kub5-Hera(RPRD1B) deficiency promotes “BRCAness” and vulnerability to PARP inhibition in BRCA-proficient breast cancers

Purpose: Identification of novel strategies to expand the use of PARP inhibitors beyond BRCA deficiency is of great interest in personalized medicine. Here, we investigated the unannotated role of Kub5-Hera(RPRD1B) (K-H) in homologous recombination (HR) repair and its potential clinical significance in targeted cancer therapy. Experimental Design: Functional characterization of K-H alterations on HR repair of double-strand breaks (DSB) were assessed by targeted gene silencing, plasmid reporter assays, immunofluorescence, and Western blots. Cell survival with PARP inhibitors was evaluated through colony-forming assays and statistically analyzed for correlation with K-H expression in various BRCA1/2 nonmutated breast cancers. Gene expression microarray/qPCR analyses, chromatin immunoprecipitation, and rescue experiments were used to investigate molecular mechanisms of action. Results: K-H expression loss correlates with rucaparib LD50 values in a panel of BRCA1/2 nonmutated breast cancers. Mechanistically, K-H depletion promotes BRCAness, where extensive upregulation of PARP1 activity was required for the survival of breast cancer cells. PARP inhibition in these cells led to synthetic lethality that was rescued by wild-type K-H reexpression, but not by a mutant K-H (p.R106A) that weakly binds RNAPII. K-H mediates HR by facilitating recruitment of RNAPII to the promoter region of a critical DNA damage response and repair effector, cyclin-dependent kinase 1 (CDK1). Conclusions: Cancer cells with low K-H expression may have exploitable BRCAness properties that greatly expand the use of PARP inhibitors beyond BRCA mutations. Our results suggest that aberrant K-H alterations may have vital translational implications in cellular responses/survival to DNA damage, carcinogenesis, and personalized medicine. (C) 2018 AACR

Experimental realisation of Shor's quantum factoring algorithm using qubit recycling

Quantum computational algorithms exploit quantum mechanics to solve problems exponentially faster than the best classical algorithms. Shor's quantum algorithm for fast number factoring is a key example and the prime motivator in the international effort to realise a quantum computer. However, due to the substantial resource requirement, to date, there have been only four small-scale demonstrations. Here we address this resource demand and demonstrate a scalable version of Shor's algorithm in which the n qubit control register is replaced by a single qubit that is recycled n times: the total number of qubits is one third of that required in the standard protocol. Encoding the work register in higher-dimensional states, we implement a two-photon compiled algorithm to factor N=21. The algorithmic output is distinguishable from noise, in contrast to previous demonstrations. These results point to larger-scale implementations of Shor's algorithm by harnessing scalable resource reductions applicable to all physical architectures.Comment: 7 pages, 3 figure

A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

Respiratory Insufficiency Correlated Strongly with Mortality of Rodents Infected with West Nile Virus

West Nile virus (WNV) disease can be fatal for high-risk patients. Since WNV or its antigens have been identified in multiple anatomical locations of the central nervous system of persons or rodent models, one cannot know where to investigate the actual mechanism of mortality without careful studies in animal models. In this study, depressed respiratory functions measured by plethysmography correlated strongly with mortality. This respiratory distress, as well as reduced oxygen saturation, occurred beginning as early as 4 days before mortality. Affected medullary respiratory control cells may have contributed to the animals' respiratory insufficiency, because WNV antigen staining was present in neurons located in the ventrolateral medulla. Starvation or dehydration would be irrelevant in people, but could cause death in rodents due to lethargy or loss of appetite. Animal experiments were performed to exclude this possibility. Plasma ketones were increased in moribund infected hamsters, but late-stage starvation markers were not apparent. Moreover, daily subcutaneous administration of 5% dextrose in physiological saline solution did not improve survival or other disease signs. Therefore, infected hamsters did not die from starvation or dehydration. No cerebral edema was apparent in WNV- or sham-infected hamsters as determined by comparing wet-to-total weight ratios of brains, or by evaluating blood-brain-barrier permeability using Evans blue dye penetration into brains. Limited vasculitis was present in the right atrium of the heart of infected hamsters, but abnormal electrocardiograms for several days leading up to mortality did not occur. Since respiratory insufficiency was strongly correlated with mortality more than any other pathological parameter, it is the likely cause of death in rodents. These animal data and a poor prognosis for persons with respiratory insufficiency support the hypothesis that neurological lesions affecting respiratory function may be the primary cause of human WNV-induced death

Regulation of Neuronal Cell Death by c-Abl-Hippo/MST2 Signaling Pathway

BACKGROUND: Mammalian Ste20-like kinases (MSTs) are the mammalian homologue of Drosophila hippo and play critical roles in regulation of cell death, organ size control, proliferation and tumorigenesis. MSTs exert pro-apoptotic function through cleavage, autophosphorylation and in turn phosphorylation of downstream targets, such as Histone H2B and FOXO (Forkhead box O). Previously we reported that protein kinase c-Abl mediates oxidative stress-induced neuronal cell death through phosphorylating MST1 at Y433, which is not conserved among mammalian MST2, Drosophila Hippo and C.elegans cst-1/2. METHODOLOGY/PRINCIPAL FINDINGS: Using immunoblotting, in vitro kinase and cell death assay, we demonstrate that c-Abl kinase phosphorylates MST2 at an evolutionarily conserved site, Y81, within the kinase domain. We further show that the phosphorylation of MST2 by c-Abl leads to the disruption of the interaction with Raf-1 proteins and the enhancement of homodimerization of MST2 proteins. It thereby enhances the MST2 activation and induces neuronal cell death. CONCLUSIONS/SIGNIFICANCE: The identification of the c-Abl tyrosine kinase as a novel upstream activator of MST2 suggests that the conserved c-Abl-MST signaling cascade plays an important role in oxidative stress-induced neuronal cell death

Promiscuity and preferences of metallothioneins: the cell rules

Metalloproteins are essential for many cellular functions, but it has not been clear how they distinguish between the different metals to bind the correct ones. A report in BMC Biology finds that preferences of two metallothionein isoforms for two different cations are due to inherent properties of these usually less discriminating proteins. Here these observations are discussed in the context of the cellular mechanisms that regulate metal binding to proteins