Stability of extemporaneously prepared ophthalmic solutions for mydriasis

Purpose Results of an evaluation of the physical and chemical stability of extemporaneously prepared adult and pediatric ophthalmic solutions containing combinations of phenylephrine, tropicamide, and cyclopentolate are reported. Methods A stability study was conducted to help determine the feasibility of innovative formulations to meet an unmet clinical need for combination mydriatic ophthalmic eyedrops. An adult mydriatic ophthalmic solution containing phenylephrine hydrochloride 2.5% and tropicamide 1.0% and a pediatric formulation containing phenylephrine hydrochloride 2.5%, tropicamide 0.5%, and cyclopentolate hydrochloride 0.5% were prepared using proper aseptic techniques. Triplicate samples of each formulation were stored for 60 days at refrigeration temperatures (2–8 °C) and analyzed on day 0 and days 7, 14, 28, and 60. At each time point, the stability samples were assessed by visual inspection, pH measurement, and stability-indicating high-performance liquid chromatography (HPLC) analysis. Results Over the 60-day storage period, there was no significant change in the visual appearance or pH level of any of the adult or pediatric solution samples. The results of HPLC analysis indicated that all samples retained 97–102% of the initial drug concentrations for up to 60 days. Conclusion Both adult and pediatric ophthalmic formulations containing combinations of phenylephrine, tropicamide, and cyclopentolate were stable physically and chemically for up to 60 days when stored at refrigeration temperatures (2–8 °C)

Ninja data analysis with a detection pipeline based on the Hilbert-Huang Transform

The Ninja data analysis challenge allowed the study of the sensitivity of data analysis pipelines to binary black hole numerical relativity waveforms in simulated Gaussian noise at the design level of the LIGO observatory and the VIRGO observatory. We analyzed NINJA data with a pipeline based on the Hilbert Huang Transform, utilizing a detection stage and a characterization stage: detection is performed by triggering on excess instantaneous power, characterization is performed by displaying the kernel density enhanced (KD) time-frequency trace of the signal. Using the simulated data based on the two LIGO detectors, we were able to detect 77 signals out of 126 above SNR 5 in coincidence, with 43 missed events characterized by signal to noise ratio SNR less than 10. Characterization of the detected signals revealed the merger part of the waveform in high time and frequency resolution, free from time-frequency uncertainty. We estimated the timelag of the signals between the detectors based on the optimal overlap of the individual KD time-frequency maps, yielding estimates accurate within a fraction of a millisecond for half of the events. A coherent addition of the data sets according to the estimated timelag eventually was used in a characterization of the event.Comment: Accepted for publication in CQG, special issue NRDA proceedings 200

Protein kinase C-dependent signaling controls the midgut epithelial barrier to malaria parasite infection in anopheline mosquitoes.

Anopheline mosquitoes are the primary vectors of parasites in the genus Plasmodium, the causative agents of malaria. Malaria parasites undergo a series of complex transformations upon ingestion by the mosquito host. During this process, the physical barrier of the midgut epithelium, along with innate immune defenses, functionally restrict parasite development. Although these defenses have been studied for some time, the regulatory factors that control them are poorly understood. The protein kinase C (PKC) gene family consists of serine/threonine kinases that serve as central signaling molecules and regulators of a broad spectrum of cellular processes including epithelial barrier function and immunity. Indeed, PKCs are highly conserved, ranging from 7 isoforms in Drosophila to 16 isoforms in mammals, yet none have been identified in mosquitoes. Despite conservation of the PKC gene family and their potential as targets for transmission-blocking strategies for malaria, no direct connections between PKCs, the mosquito immune response or epithelial barrier integrity are known. Here, we identify and characterize six PKC gene family members--PKCδ, PKCε, PKCζ, PKD, PKN, and an indeterminate conventional PKC--in Anopheles gambiae and Anopheles stephensi. Sequence and phylogenetic analyses of the anopheline PKCs support most subfamily assignments. All six PKCs are expressed in the midgut epithelia of A. gambiae and A. stephensi post-blood feeding, indicating availability for signaling in a tissue that is critical for malaria parasite development. Although inhibition of PKC enzymatic activity decreased NF-κB-regulated anti-microbial peptide expression in mosquito cells in vitro, PKC inhibition had no effect on expression of a panel of immune genes in the midgut epithelium in vivo. PKC inhibition did, however, significantly increase midgut barrier integrity and decrease development of P. falciparum oocysts in A. stephensi, suggesting that PKC-dependent signaling is a negative regulator of epithelial barrier function and a potential new target for transmission-blocking strategies

STEPS - an approach for human mobility modeling

In this paper we introduce Spatio-TEmporal Parametric Stepping (STEPS) - a simple parametric mobility model which can cover a large spectrum of human mobility patterns. STEPS makes abstraction of spatio-temporal preferences in human mobility by using a power law to rule the nodes movement. Nodes in STEPS have preferential attachment to favorite locations where they spend most of their time. Via simulations, we show that STEPS is able, not only to express the peer to peer properties such as inter-ontact/contact time and to reflect accurately realistic routing performance, but also to express the structural properties of the underlying interaction graph such as small-world phenomenon. Moreover, STEPS is easy to implement, exible to configure and also theoretically tractable

Study of Space Station propulsion system resupply and repair Final report

Resupply and repair capabilities for orbital space station bipropellant propulsion syste

Plaque complement activation and cognitive loss in Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Complement activation is increased in Alzheimer's disease (AD), but its significance is unclear. The objective of this study was to determine the relationship between complement activation and cognition during the development of AD.</p> <p>Methods</p> <p>iC3b, C9, Bielschowsky, and Gallyas staining was performed on aged normal (n = 17), mild cognitively impaired (n = 12), and AD (n = 17–18) inferior temporal gyrus specimens. Plaques were counted in 10× fields with high numbers of Bielschowsky-stained plaques. One-way ANOVA was used to determine between-group differences for plaque counts and measures of cognitive function, and linear regression was used to evaluate global cognition as a function of Bielschowsky-stained plaques. Terms for iC3b- and C9-stained plaques were then added sequentially as additional predictors in a "mediation analysis" model.</p> <p>Results</p> <p>Complement was detected on plaques in all groups, and on neurofibrillary tangles only in AD specimens. iC3b, C9, and Bielschowsky-stained plaque counts increased 2.5- to 3-fold in AD vs. other groups (all <it>p </it>≤ 0.01). C9 staining was present on some diffuse plaques, as well as on neuritic plaques. Bielschowsky-stained and complement-stained plaque counts were highly correlated, and were negatively correlated with cognitive measures. When the Bielschowsky plaque count was used as a predictor, its correlations with cognitive measures were statistically significant, but when iC3b and C9 plaque counts were added as additional predictors, these correlations were no longer significant. This loss of significance was attributed to multicollinearity, i.e., high correlations between Bielschowsky-stained and complement-stained plaque counts.</p> <p>Conclusion</p> <p>Both early-stage (iC3b) and late-stage (C9) complement activation occurs on neocortical plaques in subjects across the cognitive spectrum; contrary to previous reports, C9 is present on some diffuse plaques. Because of high correlations between complement-stained and Bielschowsky-stained plaque counts, quantitative assessment of the extent to which complement activation may mediate the relationship between plaques and cognitive function could not be performed. Additional studies with animal models of AD (if late-stage complement activation can be demonstrated), or possibly a trial in AD patients with an inhibitor of late-stage complement activation, may be necessary to determine the significance of this process in AD.</p

Complement activation in the Parkinson's disease substantia nigra: an immunocytochemical study

BACKGROUND: Inflammatory processes are increased in the Parkinson's disease (PD) brain. The long-term use of nonsteroidal anti-inflammatory drugs has been associated, in retrospective studies, with decreased risk for PD, suggesting that inflammation may contribute to development of this disorder. The objective of this study was to determine the extent of complement activation, a major inflammatory mechanism, in PD. METHODS: Substantia nigra specimens from young normal subjects (n = 11–13), aged normal subjects (n = 24–28), and subjects with PD (n = 19–20), Alzheimer's disease (AD; n = 12–13), and dementia with Lewy bodies (DLB; n = 9) were stained for iC3b and C9, representing early- and late-stage complement activation, respectively. Numbers of iC3b(+), C9(+), and total melanized neurons in each section were counted in a blinded fashion. Nonparametric analyses were used to evaluate differences between groups and to evaluate correlations between complement staining, numbers of melanized neurons, and the duration of PD. RESULTS: Lewy bodies in both PD and DLB specimens stained for iC3b and C9. Staining was also prominent on melanized neurons. The percentage of iC3b(+ )neurons was significantly increased in PD vs. aged normal and AD specimens, and in young normal vs. aged normal specimens. C9 immunoreactivity was significantly increased in PD vs. AD specimens, but unlike iC3b, the increased C9 staining in PD and young normal specimens did not achieve statistical significance vs. aged normal specimens. iC3b and C9 staining in PD specimens was not correlated with the numbers of remaining melanized neurons, nor with the duration of PD. CONCLUSION: Complement activation occurs on Lewy bodies and melanized neurons in the PD substantia nigra. Early complement activation (iC3b) is increased on melanized neurons in PD vs. aged normal specimens, and late-stage complement activation (C9) also tends to increase. This latter finding suggests that complement activation may contribute to loss of dopaminergic neurons in some individuals with PD. Complement activation on melanized neurons appears to decrease with normal aging, suggesting a possible neuroprotective role for this process in the normal substantia nigra

Possibilities for Measurement and Compensation of Stray DC Electric Fields Acting on Drag-Free Test Masses

DC electric fields can combine with test mass charging and thermal dielectric voltage noise to create significant force noise acting on the drag-free test masses in the LISA (Laser Interferometer Space Antenna) gravitational wave mission. This paper proposes a simple technique to measure and compensate average stray DC potentials at the mV level, yielding substantial reduction in this source of force noise. We discuss the attainable resolution for both flight and ground based experiments.Comment: To be published in Advances in Space Research, COSPAR 2002 conference proceedings (6 pages, 3 figures

LC-MS proteomics analysis of the iInsulin/IGF-1-deficient Caenorhabditis elegans daf-2(e1370) mutant reveals extensive restructuring of intermediary metabolism

The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC-MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediary metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid beta-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity

Comparing global seismic tomography models using the varimax Principal Component Analysis

Global seismic tomography has greatly progressed in the past decades, with many global Earth models being produced by different research groups. Objective, statistical methods are crucial for the quantitative interpretation of the large amount of information encapsulated by the models as well as for unbiased model comparisons. We propose here to use a rotated version of the Principal Component Analysis (PCA) to compress the information, in order to ease the geological interpretation and model comparison. The method generates between 7 to 15 principal components (PC) for each of the seven tested global tomography models, capturing more than 97 % of the total variance of the model. Each PC consists of a vertical profile, to which a horizontal pattern is associated by projection. The depth profiles and the horizontal patterns enable examining the key characteristics of the main components of the models. Most of the information in the models is associated with a few features: Large Low Shear Velocity Provinces (LLSVPs) in the lowermost mantle, subduction signals and low velocity anomalies likely associated with mantle plumes in the upper and lower mantle, and ridges and cratons in the uppermost mantle. Importantly, all models highlight several independent components in the lower mantle that make between 36 % and 69 % of the total variance, depending on the model, which suggests that the lower mantle is more complex than traditionally assumed. Overall, we find that the varimax PCA is a useful additional tool for the quantitative comparison and interpretation of tomography models