2D-Based 3D Volume Retrieval Using Singular Value Decomposition of Detected Regions

In this paper, a novel 3D retrieval model to retrieve medical volumes using 2D images as input is proposed. The main idea consists of applying a multi–scale detection of saliency of image regions. Then, the 3D volumes with the regions for each of the scales are associated with a set of projections onto the three canonical planes. The 3D shape is indirectly represented by a 2D–shape descriptor so that the 3D–shape matching is transformed into measuring similarity between 2D–shapes. The shape descriptor is defined by the set of the k largest singular values of the 2D images and Euclidean distance between the vector descriptors is used as a similarity measure. The preliminary results obtained on a simple database show promising performance with a mean average precision (MAP) of 0.82 and could allow using the approach as part of a retrieval system in clinical routine

Metal A and Metal B Sites of Nuclear RNA Polymerases Pol IV and Pol V Are Required for siRNA-Dependent DNA Methylation and Gene Silencing

Plants are unique among eukaryotes in having five multi-subunit nuclear RNA polymerases: the ubiquitous RNA polymerases I, II and III plus two plant-specific activities, nuclear RNA polymerases IV and V (previously known as Polymerases IVa and IVb). Pol IV and Pol V are not required for viability but play non-redundant roles in small interfering RNA (siRNA)-mediated pathways, including a pathway that silences retrotransposons and endogenous repeats via siRNA-directed DNA methylation. RNA polymerase activity has not been demonstrated for Polymerases IV or V in vitro, making it unclear whether they are catalytically active enzymes. Their largest and second-largest subunit sequences have diverged considerably from Pol I, II and III in the vicinity of the catalytic center, yet retain the invariant Metal A and Metal B amino acid motifs that bind magnesium ions essential for RNA polymerization. By using site-directed mutagenesis in conjunction with in vivo functional assays, we show that the Metal A and Metal B motifs of Polymerases IV and V are essential for siRNA production, siRNA-directed DNA methylation, retrotransposon silencing, and the punctate nuclear localization patterns typical of both polymerases. Collectively, these data show that the minimal core sequences of polymerase active sites, the Metal A and B sites, are essential for Pol IV and Pol V biological functions, implying that both are catalytically active

Demographic and indication-specific characteristics have limited association with social network engagement: evidence from 24,954 members of four health care support groups

Background: Digital health social networks (DHSNs) are widespread, and the consensus is that they contribute to wellness by offering social support and knowledge sharing. The success of a DHSN is based on the number of participants and their consistent creation of externalities through the generation of new content. To promote network growth, it would be helpful to identify characteristics of superusers or actors who create value by generating positive network externalities. Objective: The aim of the study was to investigate the feasibility of developing predictive models that identify potential superusers in real time. This study examined associations between posting behavior, 4 demographic variables, and 20 indication-specific variables. Methods: Data were extracted from the custom structured query language (SQL) databases of 4 digital health behavior change interventions with DHSNs. Of these, 2 were designed to assist in the treatment of addictions (problem drinking and smoking cessation), and 2 for mental health (depressive disorder, panic disorder). To analyze posting behavior, 10 models were developed, and negative binomial regressions were conducted to examine associations between number of posts, and demographic and indication-specific variables. Results: The DHSNs varied in number of days active (3658-5210), number of registrants (5049-52,396), number of actors (1085-8452), and number of posts (16,231-521,997). In the sample, all 10 models had low R2 values (.013-.086) with limited statistically significant demographic and indication-specific variables. Conclusions: Very few variables were associated with social network engagement. Although some variables were statistically significant, they did not appear to be practically significant. Based on the large number of study participants, variation in DHSN theme, and extensive time-period, we did not find strong evidence that demographic characteristics or indication severity sufficiently explain the variability in number of posts per actor. Researchers should investigate alternative models that identify superusers or other individuals who create social network externalities

High-Yield Expression of Heterologous [FeFe] Hydrogenases in Escherichia coli

BACKGROUND: The realization of hydrogenase-based technologies for renewable H(2) production is presently limited by the need for scalable and high-yielding methods to supply active hydrogenases and their required maturases. PRINCIPAL FINDINGS: In this report, we describe an improved Escherichia coli-based expression system capable of producing 8-30 mg of purified, active [FeFe] hydrogenase per liter of culture, volumetric yields at least 10-fold greater than previously reported. Specifically, we overcame two problems associated with other in vivo production methods: low protein yields and ineffective hydrogenase maturation. The addition of glucose to the growth medium enhances anaerobic metabolism and growth during hydrogenase expression, which substantially increases total yields. Also, we combine iron and cysteine supplementation with the use of an E. coli strain upregulated for iron-sulfur cluster protein accumulation. These measures dramatically improve in vivo hydrogenase activation. Two hydrogenases, HydA1 from Chlamydomonas reinhardtii and HydA (CpI) from Clostridium pasteurianum, were produced with this improved system and subsequently purified. Biophysical characterization and FTIR spectroscopic analysis of these enzymes indicate that they harbor the H-cluster and catalyze H(2) evolution with rates comparable to those of enzymes isolated from their respective native organisms. SIGNIFICANCE: The production system we describe will facilitate basic hydrogenase investigations as well as the development of new technologies that utilize these prolific H(2)-producing enzymes. These methods can also be extended for producing and studying a variety of oxygen-sensitive iron-sulfur proteins as well as other proteins requiring anoxic environments

Compliance assessment of ambulatory Alzheimer patients to aid therapeutic decisions by healthcare professionals

<p>Abstract</p> <p>Background</p> <p>Compliance represents a major determinant for the effectiveness of pharmacotherapy. Compliance reports summarising electronically compiled compliance data qualify healthcare needs and can be utilised as part of a compliance enhancing intervention. Nevertheless, evidence-based information on a sufficient level of compliance is scarce complicating the interpretation of compliance reports. The purpose of our pilot study was to determine the compliance of ambulatory Alzheimer patients to antidementia drugs under routine therapeutic use using electronic monitoring. In addition, the forgiveness of donepezil (i.e. its ability to sustain adequate pharmacological response despite suboptimal compliance) was characterised and evidence-based guidance for the interpretation of compliance reports was intended to be developed.</p> <p>Methods</p> <p>We determined the compliance of four different antidementia drugs by electronic monitoring in 31 patients over six months. All patients were recruited from the gerontopsychiatric clinic of a university hospital as part of a pilot study. The so called medication event monitoring system (MEMS) was employed, consisting of a vial with a microprocessor in the lid which records the time (date, hour, minute) of every opening. Daily compliance served as primary outcome measure, defined as percentage of days with correctly administered doses of medication. In addition, pharmacokinetics and pharmacodynamics of donepezil were simulated to systematically assess therapeutic undersupply also incorporating study compliance patterns. Statistical analyses were performed with SPSS and Microsoft Excel.</p> <p>Results</p> <p>Median daily compliance was 94% (range 48%-99%). Ten patients (32%) were non-compliant at least for one month. One-sixth of patients taking donepezil displayed periods of therapeutic undersupply. For 10 mg and 5 mg donepezil once-daily dosing, the estimated forgiveness of donepezil was 80% and 90% daily compliance or two and one dosage omissions at steady state, respectively. Based on the simulation findings we developed rules for the evidence-based interpretation of donepezil compliance reports.</p> <p>Conclusions</p> <p>Compliance in ambulatory Alzheimer patients was for the first time assessed under routine conditions using electronic monitoring: On average compliance was relatively high but variable between patients. The approach of pharmacokinetic/pharmacodynamic <it>in silico </it>simulations was suitable to characterise the forgiveness of donepezil suggesting evidence-based recommendations for the interpretation of compliance reports.</p

A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus

At the site of microbial infections, the significant influx of immune effector cells and the necrosis of tissue by the invading pathogen generate hypoxic microenvironments in which both the pathogen and host cells must survive. Currently, whether hypoxia adaptation is an important virulence attribute of opportunistic pathogenic molds is unknown. Here we report the characterization of a sterol-regulatory element binding protein, SrbA, in the opportunistic pathogenic mold, Aspergillus fumigatus. Loss of SrbA results in a mutant strain of the fungus that is incapable of growth in a hypoxic environment and consequently incapable of causing disease in two distinct murine models of invasive pulmonary aspergillosis (IPA). Transcriptional profiling revealed 87 genes that are affected by loss of SrbA function. Annotation of these genes implicated SrbA in maintaining sterol biosynthesis and hyphal morphology. Further examination of the SrbA null mutant consequently revealed that SrbA plays a critical role in ergosterol biosynthesis, resistance to the azole class of antifungal drugs, and in maintenance of cell polarity in A. fumigatus. Significantly, the SrbA null mutant was highly susceptible to fluconazole and voriconazole. Thus, these findings present a new function of SREBP proteins in filamentous fungi, and demonstrate for the first time that hypoxia adaptation is likely an important virulence attribute of pathogenic molds

The Contribution of Occult Precipitation to Nutrient Deposition on the West Coast of South Africa

The Strandveld mediterranean-ecosystem of the west coast of South Africa supports floristically diverse vegetation growing on mostly nutrient-poor aeolian sands and extending from the Atlantic Ocean tens of kilometers inland. The cold Benguela current upwelling interacts with warm onshore southerly winds in summer causing coastal fogs in this region. We hypothesized that fog and other forms of occult precipitation contribute moisture and nutrients to the vegetation. We measured occult precipitation over one year along a transect running inland in the direction of the prevailing wind and compared the nutrient concentrations with those in rainwater. Occult deposition rates of P, N, K, Mg, Ca, Na, Al and Fe all decreased with distance from the ocean. Furthermore, ratios of cations to Na were similar to those of seawater, suggesting a marine origin for these. In contrast, N and P ratios in occult precipitation were higher than in seawater. We speculate that this is due to marine foam contributing to occult precipitation. Nutrient loss in leaf litter from dominant shrub species was measured to indicate nutrient demand. We estimated that occult precipitation could meet the demand of the dominant shrubby species for annual N, P, K and Ca. Of these species, those with small leaves intercepted more moisture and nutrients than those with larger leaves and could take up foliar deposits of glycine, NO3-, NH4 + and Li (as tracer for K) through leaf surfaces. We conclude that occult deposition together with rainfall deposition are potentially important nutrient and moisture sources for the Strandveld vegetation that contribute to this vegetation being floristically distinct from neighbouring nutrient-poor Fynbos vegetation

The Role of Actin Turnover in Retrograde Actin Network Flow in Neuronal Growth Cones

The balance of actin filament polymerization and depolymerization maintains a steady state network treadmill in neuronal growth cones essential for motility and guidance. Here we have investigated the connection between depolymerization and treadmilling dynamics. We show that polymerization-competent barbed ends are concentrated at the leading edge and depolymerization is distributed throughout the peripheral domain. We found a high-to-low G-actin gradient between peripheral and central domains. Inhibiting turnover with jasplakinolide collapsed this gradient and lowered leading edge barbed end density. Ultrastructural analysis showed dramatic reduction of leading edge actin filament density and filament accumulation in central regions. Live cell imaging revealed that the leading edge retracted even as retrograde actin flow rate decreased exponentially. Inhibition of myosin II activity before jasplakinolide treatment lowered baseline retrograde flow rates and prevented leading edge retraction. Myosin II activity preferentially affected filopodial bundle disassembly distinct from the global effects of jasplakinolide on network turnover. We propose that growth cone retraction following turnover inhibition resulted from the persistence of myosin II contractility even as leading edge assembly rates decreased. The buildup of actin filaments in central regions combined with monomer depletion and reduced polymerization from barbed ends suggests a mechanism for the observed exponential decay in actin retrograde flow. Our results show that growth cone motility is critically dependent on continuous disassembly of the peripheral actin network

Neuronal networks provide rapid neuroprotection against spreading toxicity

Acute secondary neuronal cell death, as seen in neurodegenerative disease, cerebral ischemia (stroke) and traumatic brain injury (TBI), drives spreading neurotoxicity into surrounding, undamaged, brain areas. This spreading toxicity occurs via two mechanisms, synaptic toxicity through hyperactivity, and excitotoxicity following the accumulation of extracellular glutamate. To date, there are no fast-acting therapeutic tools capable of terminating secondary spreading toxicity within a time frame relevant to the emergency treatment of stroke or TBI patients. Here, using hippocampal neurons (DIV 15-20) cultured in microfluidic devices in order to deliver a localized excitotoxic insult, we replicate secondary spreading toxicity and demonstrate that this process is driven by GluN2B receptors. In addition to the modeling of spreading toxicity, this approach has uncovered a previously unknown, fast acting, GluN2A-dependent neuroprotective signaling mechanism. This mechanism utilizes the innate capacity of surrounding neuronal networks to provide protection against both forms of spreading neuronal toxicity, synaptic hyperactivity and direct glutamate excitotoxicity. Importantly, network neuroprotection against spreading toxicity can be effectively stimulated after an excitotoxic insult has been delivered, and may identify a new therapeutic window to limit brain damage