On-orbit assembly using superquadric potential fields

The autonomous on-orbit assembly of a large space structure is presented using a method based on superquadric artificial potential fields. The final configuration of the elements which form the structure is represented as the minimum of some attractive potential field. Each element of the structure is then considered as presenting an obstacle to the others using a superquadric potential field attached to the body axes of the element. A controller is developed which ensures that the global potential field decreases monotonically during the assembly process. An error quaternion representation is used to define both the attractive and superquadric obstacle potentials allowing the final configuration of the elements to be defined through both relative position and orientation. Through the use of superquadric potentials, a wide range of geometric objects can be represented using a common formalism, while collision avoidance can make use of both translational and rotation maneuvers to reduce total maneuver cost for the assembly process

Hospitalization rates in patients switched from oral anti-psychotics to aripiprazole once-monthly: final efficacy analysis

Abstract Objective: To compare hospitalization rates in patients with schizophrenia treated prospectively with aripiprazole once-monthly 400 mg (AOM 400; an extended-release injectable suspension) vs the same patients\u27 retrospective rates with their prior oral anti-psychotic therapy. Research design and methods: Multi-center, open-label, mirror-image, naturalistic study in a community setting in North America. Patients who required a change in treatment and/or would benefit from long-acting injectable anti-psychotic therapy were treated prospectively for 6 months with AOM 400. Retrospective data on hospitalization rates were obtained. Clinical trial registration: ClinicalTrials.gov: NCT01432444. Main outcome measures: The proportion of patients with \u3e/=1 psychiatric inpatient hospitalization with oral anti-psychotic therapy examined retrospectively (months -4 to -1 before oral conversion) and after switching to AOM 400 (months 4-6 after initiating AOM 400). Results: Psychiatric hospitalization rates were significantly lower when patients were treated with AOM 400 compared with oral anti-psychotic therapy both in the 3-month primary efficacy sample (2.7% [n = 9/336] vs 27.1% [n = 91/336], respectively; p \u3c 0.0001) and in the total sample (6-month prospective rate: 8.8% [n = 38/433] vs 6-month retrospective rate: 38.1% [n = 165/433]; p \u3c 0.0001). Discontinuations due to adverse events (AEs) during cross-titration were lower in patients cross-titrated on oral aripiprazole for \u3e1 and(2.9% [n = 7/239]) compared with patients cross-titrated fo

Effects of aripiprazole once-monthly on domains of personal and social performance: Results from 2 multicenter, randomized, double-blind studies

Objective: To assess the effects of maintenance therapy with aripiprazole once-monthly 400 mg on personal and social functioning. Methods: Data were analyzed from 2 randomized, double-blind trials of patients with schizophrenia requiring chronic antipsychotic treatment. One study was a 52-week trial of aripiprazole once-monthly 400 mg versus placebo; the other was a 38-week trial of aripiprazole once-monthly 400 mg, oral aripiprazole (10-30 mg daily), and aripiprazole once-monthly 50 mg (subtherapeutic dose to test assay sensitivity). Functioning was assessed using the Personal and Social Performance (PSP) scale, comprising 4 domain subscales. Results: In the 52-week study, 403 patients stabilized on aripiprazole once-monthly 400 mg were randomized to receive aripiprazole once-monthly 400 mg (n=269) or placebo (n=134). In the 38-week study, 662 patients stabilized on oral aripiprazole were randomized to receive aripiprazole once-monthly 400 mg (n=265), oral aripiprazole (n=266), or aripiprazole once-monthly 50 mg (subtherapeutic dose; n=131). In the 52-week study, mean changes from baseline were significantly worsened with placebo compared with aripiprazole once-monthly 400 mg for PSP total score (

Seminaphthofluorescein-Based Fluorescent Probes for Imaging Nitric Oxide in Live Cells

Fluorescent turn-on probes for nitric oxide based on seminaphthofluorescein scaffolds were prepared and spectroscopically characterized. The Cu(II) complexes of these fluorescent probes react with NO under anaerobic conditions to yield a 20–45-fold increase in integrated emission. The seminaphthofluorescein-based probes emit at longer wavelengths than the parent FL1 and FL2 fluorescein-based generations of NO probes, maintaining emission maxima between 550 and 625 nm. The emission profiles depend on the excitation wavelength; maximum fluorescence turn-on is achieved at excitations between 535 and 575 nm. The probes are highly selective for NO over other biologically relevant reactive nitrogen and oxygen species including NO3–, NO2–, HNO, ONOO–, NO2, OCl–, and H2O2. The seminaphthofluorescein-based probes can be used to visualize endogenously produced NO in live cells, as demonstrated using Raw 264.7 macrophages.National Science Foundation (U.S.) (CHE-0611944)National Institutes of Health (U.S.) (K99GM092970

Enemies Within: Redefining the insider threat in organizational security policy

The critical importance of electronic information exchanges in the daily operation of most large modern organizations is causing them to broaden their security provision to include the custodians of exchanged data – the insiders. The prevailing data loss threat model mainly focuses upon the criminal outsider and mainly regards the insider threat as ‘outsiders by proxy’, thus shaping the relationship between the worker and workplace in information security policy. A policy that increasingly takes the form of social policy for the information age as it acquires the power to include and exclude sections of society and potentially to re-stratify it? This article draws upon empirical sources to critically explore the insider threat in organizations. It looks at the prevailing threat model before deconstructing ‘the insider’ into various risk profiles, including the well-meaning insider, before drawing conclusions about what the building blocks of information security policy around the insider might be

Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. © 2013 McEvoy et al

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

An Important Role for Syndecan-1 in Herpes Simplex Virus Type-1 Induced Cell-to-Cell Fusion and Virus Spread

Herpes simplex virus type-1 (HSV-1) is a common human pathogen that relies heavily on cell-to-cell spread for establishing a lifelong latent infection. Molecular aspects of HSV-1 entry into host cells have been well studied; however, the molecular details of the spread of the virus from cell-to-cell remain poorly understood. In the past, the role of heparan sulfate proteoglycans (HSPG) during HSV-1 infection has focused solely on the role of HS chains as an attachment receptor for the virus, while the core protein has been assumed to perform a passive role of only carrying the HS chains. Likewise, very little is known about the involvement of any specific HSPGs in HSV-1 lifecycle. Here we demonstrate that a HSPG, syndecan-1, plays an important role in HSV-1 induced membrane fusion and cell-to-cell spread. Interestingly, the functions of syndecan-1 in fusion and spread are independent of the presence of HS on the core protein. Using a mutant CHO-K1 cell line that lacks all glycosaminoglycans (GAGs) on its surface (CHO-745) we demonstrate that the core protein of syndecan-1 possesses the ability to modulate membrane fusion and viral spread. Altogether, we identify a new role for syndecan-1 in HSV-1 pathogenesis and demonstrate HS-independent functions of its core protein in viral spread

Re-imagining Navan Fort : new light on the evolution of a major ceremonial centre in Northern Europe

Peer reviewedPublisher PD