AEGIS autonomous targeting for ChemCam on Mars Science Laboratory: Deployment and results of initial science team use.

Limitations on interplanetary communications create operations latencies and slow progress in planetary surface missions, with particular challenges to narrow-field-of-view science instruments requiring precise targeting. The AEGIS (Autonomous Exploration for Gathering Increased Science) autonomous targeting system has been in routine use on NASA's Curiosity Mars rover since May 2016, selecting targets for the ChemCam remote geochemical spectrometer instrument. AEGIS operates in two modes; in autonomous target selection, it identifies geological targets in images from the rover's navigation cameras, choosing for itself targets that match the parameters specified by mission scientists the most, and immediately measures them with ChemCam, without Earth in the loop. In autonomous pointing refinement, the system corrects small pointing errors on the order of a few milliradians in observations targeted by operators on Earth, allowing very small features to be observed reliably on the first attempt. AEGIS consistently recognizes and selects the geological materials requested of it, parsing and interpreting geological scenes in tens to hundreds of seconds with very limited computing resources. Performance in autonomously selecting the most desired target material over the last 2.5 kilometers of driving into previously unexplored terrain exceeds 93% (where ~24% is expected without intelligent targeting), and all observations resulted in a successful geochemical observation. The system has substantially reduced lost time on the mission and markedly increased the pace of data collection with ChemCam. AEGIS autonomy has rapidly been adopted as an exploration tool by the mission scientists and has influenced their strategy for exploring the rover's environment.

A scripted control system for autonomous hardware-timed experiments.

We present the labscript suite, an open-source experiment control system for automating shot-based experiments and their analysis. Experiments are composed as Python code, which is used to produce low-level hardware instructions. They are queued up and executed on the hardware in real time, synchronized by a pseudoclock. Experiment parameters are manipulated graphically, and analysis routines are run as new data are acquired. With this system, we can easily automate exploration of parameter spaces, including closed-loop optimization.

Interaction between nitric oxide signaling and gap junctions: effects on vascular function.

Nitric oxide signaling, through eNOS (or possibly nNOS), and gap junction communication are essential for normal vascular function. While each component controls specific aspects of vascular function, there is substantial evidence for cross-talk between nitric oxide signaling and the gap junction proteins (connexins), and more recently, protein-protein association between eNOS and connexins. This review will examine the evidence for interaction between these pathways in normal and diseased arteries, highlight the questions that remain about the mechanisms of their interaction, and explore the possible interaction between nitric oxide signaling and the newly discovered pannexin channels. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

Saphenous vein peripherally inserted central catheters: Technique, indications and safety issues.

This article describes the technique of saphenous vein peripherally inserted central catheter placement, which is used as an alternative site for venous access in our institution, and examines saphenous vein peripherally inserted central catheter safety issues and indications. Three end-stage renal failure patients, two patients diagnosed with malignancy and one renal transplant patient had a saphenous peripherally inserted central catheter (inserted between March 2004 and March 2006 for antibiotics or chemotherapy. The average duration of placement was 16.2 days (range 3-42 days). All insertions were carried out successfully, with an average screening time of 81.2 s. None of the patients experienced any major complications. Two patients developed localized cellulitis at the insertion site.

Usefulness of muscle denervation as an MRI sign of peripheral nerve pathology.

Peripheral nerve disorders may be classified into compressive or entrapment neuropathies and non-compressive neuropathies. Muscle denervation recognized on MRI may be a useful sign in the diagnosis of peripheral nerve disorders. Acute or subacute denervation results in prolonged T2 relaxation time, producing increased signal in skeletal muscle on short tau inversion-recovery and fat-suppressed T2-weighted images. Chronic denervation produces fatty atrophy of skeletal muscles, resulting in increased muscle signal on T1-weighted images. This review will outline and illustrate the various ways that muscle denervation as seen on MRI may assist in the diagnosis and localization of peripheral nerve disorders.

Expression of vascular endothelial growth factor (VEGF) in normal oral mucosa, oral dysplasia and oral squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine implicated in tumour vasculogenesis. A significant increase in vascularity occurs during the transition from normal oral mucosa (NOM), through dysplasia, to squamous cell carcinoma (SCC). This study investigated the presence of VEGF in NOM, oral dysplasia and SCC. The correlation between VEGF expression and the grade of dysplasia or differentiation of SCC was also examined. Specimens consisting of NOM, oral dysplastic lesions and oral SCC were stained using standard immunohistochemistry methods to determine VEGF expression. Statistical analysis indicated an up-regulation of VEGF during the transition from NOM, through dysplasia to SCC. There was also a significant difference in expression according to differentiation of SCC, but not grade of dysplasia. As VEGF is a potent mediator of vascular development, these results suggest that VEGF may play an important role in the maintenance of a blood supply for developing pre-cancerous and invasive oral lesions.

General and oral health implications of cannabis use.

Cannabis, commonly known as marijuana, is the most frequently used illicit drug in Australia. Therefore, oral health care providers are likely to encounter patients who are regular users. An upward trend in cannabis use is occurring in Australia, with 40 per cent of the population aged 14 and above having used the drug. There are three main forms of cannabis: marijuana, hash and hash oil, all of which contain the main psychoactive constituent delta-9-tetrahydrocannabinol (THC). Cannabis is most commonly smoked, however it can be added to foods. THC from cannabis enters the bloodstream and exerts its effects on the body via interaction with endogenous receptors. Cannabis affects almost every system of the body, particularly the cardiovascular, respiratory and immune systems. It also has acute and chronic effects on the mental health of some users. Therefore, chronic abuse is a concern because of its negative effects on general physical and mental health. Cannabis abusers generally have poorer oral health than non-users, with an increased risk of dental caries and periodontal diseases. Cannabis smoke acts as a carcinogen and is associated with dysplastic changes and pre-malignant lesions within the oral mucosa. Users are also prone to oral infections, possibly due to the immunosuppressive effects. Dental treatment on patients intoxicated on cannabis can result in the patient experiencing acute anxiety, dysphoria and psychotic-like paranoiac thoughts. The use of local anaesthetic containing epinephrine may seriously prolong tachycardia already induced by an acute dose of cannabis. Oral health care providers should be aware of the diverse adverse effects of cannabis on general and oral health and incorporate questions about patients' patterns of use in the medical history.

TNFalpha and IL10 SNPs act together to predict disease behaviour in Crohn's disease.

BACKGROUND: The cytokines tumour necrosis factor (TNF)alpha and interleukin (IL)10 have been implicated in the pathogenesis of Crohn's disease (CD), with increased concentrations reported in patients with active disease. However, limited data exist on their effects on disease phenotype in the same population. Certain single nucleotide polymorphisms (SNPs) within the promoter region of the IL10 (-1082G/A, -592C/A) and TNFalpha (-308G/A, -857C/T) genes have been associated with altered levels of circulating IL10 and TNFalpha. METHODS: We conducted an Australian based case-control study (304 CD patients; 231 healthy controls) of these four SNPs. Further investigation of two SNPs was conducted using a logistic regression analysis. RESULTS: We identified a possible association of both IL10 SNPs and TNFalpha-857 with CD. Further investigation of a relationship with disease severity showed a significant association of higher producing IL10-1082G and TNFalpha-857C alleles with stricturing behaviour, which was strongest when these alleles were combined and persisted after multivariate analysis (p = 0.007; odds ratio (OR) 2.37, 95% CI 1.26 to 4.43). In addition, the TNFalpha-857CC genotype was independently associated with familial CD (p = 0.03; OR 3.12; 95% CI 1.15 to 8.46). CONCLUSION: These two SNPs may help to predict disease behaviour in CD patients, which may be clinically useful in shaping treatment of the disease at an earlier stage.

Controlling the physical behavior and biological performance of liposome formulations through use of surface grafted poly(ethylene glycol).

The presence of poly(ethylene glycol) (PEG) at the surface of a liposomal carrier has been clearly shown to extend the circulation lifetime of the vehicle. To this point, the extended circulation lifetime that the polymer affords has been attributed to the reduction or prevention of protein adsorption. However, there is little evidence that the presence of PEG at the surface of a vehicle actually reduces total serum protein binding. In this review we examine all aspects of PEG in order to gain a better understanding of how the polymer fulfills its biological role. The physical and chemical properties of the polymer are explored and compared to properties of other hydrophilic polymers. An evidence based assessment of several in vitro protein binding studies as well as in vivo pharmacokinetics studies involving PEG is included. The ability of PEG to prevent the self-aggregation of liposomes is considered as a possible means by which it extends circulation longevity. Also, a "dysopsonization" phenomenon where PEG actually promotes binding of certain proteins that then mask the vehicle is discussed.

Inactivation of platelet-derived growth factor-BB following modification by ADP-ribosyltransferase.

1. Arginine-specific ADP-ribosyltransferase (ART1) is expressed on the surface of a number of cell types, and catalyses the transfer of ADP-ribose from NAD(+) to target proteins. We investigated whether extracellular proteins such as growth factors may serve as substrates for this enzyme, with subsequent alteration in their biological activity. Experiments were performed with rat skeletal muscle membranes and V79 Chinese hamster lung fibroblasts with doxycycline-inducible expression of human ART. 2. From a panel of growth factors, platelet-derived growth factor-BB (PDGF-BB) was found to be the best substrate for ART1, whereas the structural homologue PDGF-AA was not a substrate. Under conditions of maximum labelling 5 mol ADP-ribose was incorporated per mol of PDGF-BB. 3. Purified (ADP-ribosyl)-PDGF-BB did not stimulate a mitogenic or chemotactic response in human pulmonary smooth muscle cells, and showed a reduced capacity to bind to PDGF receptors in competition binding experiments, when compared to unmodified PDGF-BB. 4. PDGF-dependent [(3)H-methyl]-thymidine incorporation was measured in the ART1-transfected fibroblast cell line at physiological concentrations of PDGF-BB, and without addition of extracellular NAD(+). Fibroblasts expressing human ART1 at the cell surface showed reduced mitogenic responses to PDGF-BB, but not to PDGF-AA. This loss of mitogenic response in cells expressing ART1 activity was reversed by the addition of agmatine (an ART1 substrate). 5. In conclusion, we propose that PDGF-BB-dependent signalling may be regulated by post-translational modification of the growth factor by ART1 at the cell surface. This has been demonstrated in membranes of rat skeletal muscle, and the reaction confirmed in ART1-transfected fibroblasts.

Topographic distribution and developmental timecourse of auditory event-related potentials in two subtypes of attention-deficit hyperactivity disorder.

The effect of age on the topographic distribution of auditory event-related potentials (ERPs) recorded during a two-tone discrimination, or oddball, task was examined in two subtypes of attention deficit/hyperactivity disorder (AD/HD) as defined by the most recent diagnostic manual, DSM-IV. EEG was recorded at 17 sites from AD/HD predominantly inattentive type (n=50) and AD/HD combined type (n=50) subjects aged from 8 to 17 years 11 months. ERP components were quantified at each site. Results revealed topographic differences from controls (n=50) that were common to both subtypes (e.g. target and standard P2 amplitude, and standard P2 latency) or unique to a particular subtype of AD/HD (Inattentive type: target N1, N2, P3b and standard N2 amplitude, target P2 latency; Combined type: target N1, P2, N2 and P3b amplitude, target N2 and standard N1 latency). These group differences showed different age effects. The across-region results revealed differing patterns of abnormal component development for each subtype, indicating a qualitative difference in information processing stage deficits in each of these AD/HD subtypes.

Gene families from the Arabidopsis thaliana pollen coat proteome.

The pollen extracellular matrix contains proteins mediating species specificity and components needed for efficient pollination. We identified all proteins >10 kilodaltons in the Arabidopsis pollen coating and showed that most of the corresponding genes reside in two genomic clusters. One cluster encodes six lipases, whereas the other contains six lipid-binding oleosin genes, including GRP17, a gene that promotes efficient pollination. Individual oleosins exhibit extensive divergence between ecotypes, but the entire cluster remains intact. Analysis of the syntenic region in Brassica oleracea revealed even greater divergence, but a similar clustering of the genes. Such allelic flexibility may promote speciation in plants.

Surface-associated serum proteins inhibit the uptake of phosphatidylserine and poly(ethylene glycol) liposomes by mouse macrophages.

Serum proteins, acting as opsonins, are believed to contribute significantly to liposome-macrophage cell association and thus regulate liposome uptake by cells of the mononuclear phagocytic system (MPS). We studied the effect of serum protein on binding and uptake of phosphatidylglycerol-, phosphatidylserine-, cardiolipin-, and N,N-dioleyl-N,N-dimethylammonium chloride- (DODAC) containing as well as poly(ethylene glycol)- (PEG) containing liposomes by mouse bone marrow macrophages in vitro. Consistent with the postulated surface-shielding properties of PEG, protein-free uptake of liposomes containing 5 mol% PEG and either 20 mol% anionic phosphatidylserine or 20 mol% cationic DODAC was equivalent to uptake of neutral liposomes. In contrast to previous reports indicating that protein adsorption to liposomes increases uptake by macrophages, the presence of bound serum protein did not increase the uptake of these liposomes by cultured macrophages. Rather, we found that pre-incubating liposomes with serum reduced the uptake of liposomes containing phosphatidylserine. Surprisingly, serum treatment of PEG-containing liposomes also significantly reduced liposome uptake by macrophages. It is postulated that, in the case of phosphatidylserine liposomes, the bound serum protein can provide a non-specific surface-shielding property that reduces the charge-mediated interactions between liposomes and bone marrow macrophage cells. In addition, incubation of PEG-bearing liposomes with serum can result in a change in the properties of the PEG, resulting in a surface that is better protected against interactions with cells.

The value of MRI in the assessment of an elbow injury in a neonate.

We describe the use of MRI to establish the exact diagnosis in a swollen elbow in a neonate. Urgent diagnosis was needed for medical and social reasons. We accomplished this without the use of an invasive procedure or anaesthesia for a fracture that is recognised to be difficult to diagnose in patients of this age group.

Obstetric risk factors for postnatal depression in urban and rural community samples.

OBJECTIVE: The objective of this study was to examine obstetric risk factors for postnatal depression in an urban and rural community sample, with concurrent consideration of personality, psychiatric history and recent life events. METHODS: This was a prospective study with women planning to give birth in one of the four participating hospitals recruited antenatally. Obstetric information was obtained from the New South Wales Midwives Data Collection, completed shortly after delivery. Personality, psychiatric history and life-events information were obtained from a questionnaire, administered within 1 week postpartum. Depression status was assessed at 8 weeks postpartum using the Edinburgh Postnatal Depression Scale. RESULTS: Complete data were obtained from 490 women. Several non-obstetric risk factors for the development of postnatal depression at 8 weeks postpartum were reported including: sociodemographic (up to technical college level education, rented housing, receiving a pension/benefit), personality (those who described themselves as either nervy, shy/selfconscious, obsessional, angry or a worrier), psychiatric history (familial history of mental illness, personal history of depression or anxiety or a history of depression in the participant's mother) and recent life-events (major health problem, arguments with partner and friends/relatives). None of the obstetric variables were significantly associated with increased risk for postnatal depression, but several showed marginally significant increases (multiparous women, antepartum haemorrhage, forceps and caesarean section deliveries). CONCLUSIONS: The results emphasize the importance of psychosocial risk factors for postnatal depression and suggest that most obstetric factors during pregnancy and birth do not significantly increase risk for this depression. Early identification of potential risk for postnatal depression should include assessment of sociodemography, personality, psychiatric history and recent life events, as well as past and present obstetric factors.

Nasal bilevel positive airway pressure therapy in children with a sleep-related breathing disorder and attention-deficit hyperactivity disorder: effects on electrophysiological measures of brain function.

OBJECTIVE: To examine the effect of nasal bilevel positive airway pressure (BiPAP) treatment for concurrent sleep-related breathing disorders (SRBDs) and attention-deficit hyperactivity disorder (ADHD) on electrophysiological measures of spontaneous brain activity and auditory stimulus processing. METHODS: Nineteen children diagnosed with both SRBD and ADHD participated. Electroencephalogram (EEG) activity was recorded during a resting period and an auditory oddball task before beginning BiPAP treatment, after 6 months on treatment, and after a subsequent 1 week non-treatment period. Treatment effects on EEG and event-related potentials (ERPs) to target stimuli were examined via topographic analysis. RESULTS: Thirteen of the initial 19 children completed 6 months of BiPAP therapy, with six lost mainly due to compliance problems. Children on BiPAP therapy showed a significant decrease in slow-wave (delta and theta) and an increase in fast wave (beta) EEG activity. The P3 component of the ERP showed treatment effects in amplitude and latency. CONCLUSIONS: The electrophysiological data suggest that SRBDs may contribute to ADHD symptomatology. Treatment of SRBD with BiPAP therapy in children with concurrent ADHD can lead to significant changes, in the direction of normalization, of the typical electrophysiological features of ADHD.

Kupffer cells do not play a role in governing the efficacy of liposomal mitoxantrone used to treat a tumor model designed to assess drug delivery to liver.

A tumor model designed to assess liposome-mediated drug delivery to liver has been used in an attempt to better understand the mechanism of activity of liposomal mitoxantrone, a liposomal anticancer drug formulation that appears to be uniquely effective in treating this tumor model. Reductions in liposomal mitoxantrone accumulation in the liver were achieved either by use of poly(ethylene)glycol (PEG)-modified lipids or by methods designed to deplete liver phagocytes, a method referred to as hepatic mononuclear phagocytic system (MPS) blockade. A 2-fold reduction in mitoxantrone delivery to the liver was obtained using a mitoxantrone formulation with PEG-modified lipids, and a 3-fold reduction was obtained when liposomal mitoxantrone was given to animals pretreated to induce hepatic MPS blockade. Results demonstrate that the liposomal mitoxantrone formulation prepared with PEG-modified lipids was significantly less active than the formulations that did not contain PEG lipids, with median survival times of 17 days and 100% 60-day survival, respectively. In contrast, hepatic MPS blockade had no effect on the therapeutic activity of 1,2-dimyristoyl phosphatidylcholine/cholesterol (DMPC/Chol) mitoxantrone (100% 60-day survival). These data suggest that the hepatic MPS does not play a role in mediating the therapeutic activity of DMPC/Chol mitoxantrone in the treatment of liver localized disease. Results with formulations prepared with a PEG-stabilized surface, however, suggest that nonspecific methods to decrease liposome cell interactions inhibit the therapeutic activity of DMPC/Chol mitoxantrone.

In vitro characterization of the anticancer activity of membrane-active cationic peptides. I. Peptide-mediated cytotoxicity and peptide-enhanced cytotoxic activity of doxorubicin against wild-type and p-glycoprotein over-expressing tumor cell lines.

Cationic amphipathic peptides, such as the defensins and cecropins, induce cell death in prokaryotic and eukaryotic cells by increasing membrane permeability. Increased permeability may lead to cell lysis or, alternatively, may produce subtle changes in the membrane's barrier function that promote cell death. The in vitro cytotoxic and lytic activity of short mammalian-derived extended-helical cationic peptides and insect-derived alpha-helical peptides was measured in this study with the objective of establishing the anticancer potential of these agents. Two specific aims were addressed: (i) to assess the activity of peptides against non-malignant cells (sheep erythrocytes and human umbilical vein endothelial cells) versus tumor cells; and (ii) to characterize the cytotoxic activity using multidrug-resistant tumor cell lines in the presence and absence of the anthracycline doxorubicin. Cell lysis assays demonstrated that the lytic activity of the peptides tested was 2->50 times more cytotoxic to tumor cells than to non-malignant cells. Further, the cytotoxic activity of these peptides was equivalent when tested against sensitive and multidrug-resistant cell lines. In addition to their inherent cytotoxic activity, these membrane-active peptides can also augment the in vitro cytotoxic activity of doxorubicin against multidrug-resistant tumor cells.

Detection of feigned recognition memory impairment using the old/new effect of the event-related potential.

Twenty-four undergraduate university students with no known neurological disorders completed the Recognition Memory Test (Warrington, A., 1984. Recognition Memory Test manual. Windsor, Berkshire: NFER-Nelson.) while event-related potentials (ERPs) were recorded. Twelve subjects were instructed to feign a recognition memory deficit (malingering group), while the remainder served as controls. The malingerers performed poorly on the test compared to the control group. The 'old/new effect', an ERP measure thought to reflect recognition memory processes, did not differ between the groups, indicating recognition of previously learned material in the malingering group despite poor test performance. The study also revealed a second, early, old/new effect, maximal at left frontal sites in the malingering relative to the control group, suggesting task-related processing differences between the two groups. These effects appear to be of potential value in the detection of malingering of cognitive impairment in the clinical situation.