Late-onset uveitis-glaucoma-hyphema syndrome caused by Soemmering ring cataract.

OBJECTIVE: To propose a late-onset mechanism for uveitis-glaucoma-hyphema (UGH) syndrome caused by Soemmering ring cataract (SRC) and describe surgical outcomes. DESIGN: Retrospective interventional case series. PARTICIPANTS: Patients developing UGH from anterior displacement of a haptic from a SRC. METHODS: A retrospective chart review was conducted of all patients referred to an anterior segment surgeon (J.C.H.) for intraocular lens (IOL) reposition/exchange between January 2003 and June 2017. Inclusion criteria consisted of all eyes with (i) a diagnosis of UGH syndrome, and (ii) SRC causing anterior displacement of a sulcus-fixated haptic with iris-haptic touch. Outcome measures were change in best corrected visual acuities (BCVA) and resolution of UGH findings. RESULTS: Seven eyes of 7 patients developed UGH secondary to a SRC causing contact between the IOL optic/haptic and the iris/uvea. Diagnosis of UGH was made at a mean 9.1 years after IOL implantation; this was statistically different compared with UGH eyes with other mechanisms from our full UGH cohort (mean 5.4 years; p = 0.0367). The mean preoperative LogMAR BCVA of 0.45 improved to 0.37 after surgical intervention (p = 0.27). Resolution (or nearly full resolution) of UGH findings was achieved in all cases after SRC extraction and lens repositioning/exchange. CONCLUSIONS: Late-onset UGH syndrome can be caused by SRC. Surgical removal of the SRC with IOL repositioning within the capsular bag resolves most if not all components of UGH. Anterior segment ultrasound biomicroscopy is a helpful modality for determining if a SRC is present by demonstrating anatomic relationships commonly obscured by a miotic pupil.

Electron microscopy of silicone irrigation/aspiration tips involved in posterior capsule rupture.

We describe 2 cases of posterior capsule rupture caused by Alcon reusable silicone irrigation/aspiration (I/A) tips. Scanning electron microscopy and reflected light microscopy of these tips revealed burring of the inner metallic shafts and tears in the silicone sleeves. A review of surgical video revealed that posterior capsule ruptures caused by the I/A tips occurred when the posterior capsule was aspirated either through the aspiration port or through a tear in the silicone sleeve. Contact of the posterior capsule with the sharp metallic burrs on the inner metal tube can result in posterior capsule rupture.

Use of computational modeling combined with advanced visualization to develop strategies for the design of crop ideotypes to address food security.

Sustainable crop production is a contributing factor to current and future food security. Innovative technologies are needed to design strategies that will achieve higher crop yields on less land and with fewer resources. Computational modeling coupled with advanced scientific visualization enables researchers to explore and interact with complex agriculture, nutrition, and climate data to predict how crops will respond to untested environments. These virtual observations and predictions can direct the development of crop ideotypes designed to meet future yield and nutritional demands. This review surveys modeling strategies for the development of crop ideotypes and scientific visualization technologies that have led to discoveries in "big data" analysis. Combined modeling and visualization approaches have been used to realistically simulate crops and to guide selection that immediately enhances crop quantity and quality under challenging environmental conditions. This survey of current and developing technologies indicates that integrative modeling and advanced scientific visualization may help overcome challenges in agriculture and nutrition data as large-scale and multidimensional data become available in these fields.

Crops In Silico: Generating Virtual Crops Using an Integrative and Multi-scale Modeling Platform.

Multi-scale models can facilitate whole plant simulations by linking gene networks, protein synthesis, metabolic pathways, physiology, and growth. Whole plant models can be further integrated with ecosystem, weather, and climate models to predict how various interactions respond to environmental perturbations. These models have the potential to fill in missing mechanistic details and generate new hypotheses to prioritize directed engineering efforts. Outcomes will potentially accelerate improvement of crop yield, sustainability, and increase future food security. It is time for a paradigm shift in plant modeling, from largely isolated efforts to a connected community that takes advantage of advances in high performance computing and mechanistic understanding of plant processes. Tools for guiding future crop breeding and engineering, understanding the implications of discoveries at the molecular level for whole plant behavior, and improved prediction of plant and ecosystem responses to the environment are urgently needed. The purpose of this perspective is to introduce Crops in silico (cropsinsilico.org), an integrative and multi-scale modeling platform, as one solution that combines isolated modeling efforts toward the generation of virtual crops, which is open and accessible to the entire plant biology community. The major challenges involved both in the development and deployment of a shared, multi-scale modeling platform, which are summarized in this prospectus, were recently identified during the first Crops in silico Symposium and Workshop.

Fast Coherent Particle Advection through Time-Varying Unstructured Flow Datasets.

Tracing the paths of collections of particles through a flow field is a key step for many flow visualization and analysis methods. When a flow field is interpolated from the nodes of an unstructured mesh, the process of advecting a particle must first find which cell in the unstructured mesh contains the particle. Since the paths of nearby particles often diverge, the parallelization of particle advection quickly leads to incoherent memory accesses of the unstructured mesh. We have developed a new block advection GPU approach that reorganizes particles into spatially coherent bundles as they follow their advection paths, which greatly improves memory coherence and thus shared-memory GPU performance. This approach works best for flows that meet the CFL criterion on unstructured meshes of uniformly sized elements, small enough to fit at least two timesteps in GPU memory.

Determining pharmacological selectivity of the kappa opioid receptor antagonist LY2456302 using pupillometry as a translational biomarker in rat and human.

BACKGROUND: Selective kappa opioid receptor antagonism is a promising experimental strategy for the treatment of depression. The kappa opioid receptor antagonist, LY2456302, exhibits ~30-fold higher affinity for kappa opioid receptors over mu opioid receptors, which is the next closest identified pharmacology. METHODS: Here, we determined kappa opioid receptor pharmacological selectivity of LY2456302 by assessing mu opioid receptor antagonism using translational pupillometry in rats and humans. RESULTS: In rats, morphine-induced mydriasis was completely blocked by the nonselective opioid receptor antagonist naloxone (3mg/kg, which produced 90% mu opioid receptor occupancy), while 100 and 300 mg/kg LY2456302 (which produced 56% and 87% mu opioid receptor occupancy, respectively) only partially blocked morphine-induced mydriasis. In humans, fentanyl-induced miosis was completely blocked by 50mg naltrexone, and LY2456302 dose-dependently blocked miosis at 25 and 60 mg (minimal-to-no blockade at 4-10mg). CONCLUSIONS: We demonstrate, for the first time, the use of translational pupillometry in the context of receptor occupancy to identify a clinical dose of LY2456302 achieving maximal kappa opioid receptor occupancy without evidence of significant mu receptor antagonism.

On the visualization of social and other scale-free networks.

This paper proposes novel methods for visualizing specifically the large power-law graphs that arise in sociology and the sciences. In such cases a large portion of edges can be shown to be less important and removed while preserving component connectedness and other features (e.g. cliques) to more clearly reveal the network's underlying connection pathways. This simplification approach deterministically filters (instead of clustering) the graph to retain important node and edge semantics, and works both automatically and interactively. The improved graph filtering and layout is combined with a novel computer graphics anisotropic shading of the dense crisscrossing array of edges to yield a full social network and scale-free graph visualization system. Both quantitative analysis and visual results demonstrate the effectiveness of this approach.

Detection and quantification of anthrax lethal factor in serum by mass spectrometry.

The lethal toxin produced during Bacillus anthracis infection is a complex of protective antigen, which localizes the toxin to the cell receptor, and lethal factor (LF), a zinc-dependent endoproteinase whose known targets include five members of the mitogen-activated protein kinase kinase (MAPKK) family of response regulators. We have developed a method for detecting functional LF in serum. Anti-LF murine monoclonal antibodies immobilized on magnetic protein G beads were used to capture and concentrate the LF from serum. The captured LF was exposed to an optimized MAPKK-based peptide substrate, which it hydrolyzed into two smaller peptides. The LF cleavage products were then analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) and quantified by isotope dilution-MS. The entire analytical method can be performed in less than 4 h with detection of LF levels as low as 0.05 ng/mL. The method was used to quantify LF levels in serum from rhesus macaques infected with B. anthracis. Serum samples obtained at day 2 postinfection contained 30-250 ng/mL LF and illustrated the clear potential to detect LF earlier in the infection cycle. This method represents a highly specific and rapid diagnostic tool for early anthrax and has a potential additional role as a research tool for understanding toxemia and effects of medical countermeasures for anthrax.

RotoTexture: automated tools for texturing raw video.

We propose a video editing system that allows a user to apply a time-coherent texture to a surface depicted in the raw video from a single uncalibrated camera, including the surface texture mapping of a texture image and the surface texture synthesis from a texture swatch. Our system avoids the construction of a 3D shape model and instead uses the recovered normal field to deform the texture so that it plausibly adheres to the undulations of the depicted surface. The texture mapping method uses the nonlinear least-squares optimization of a spring model to control the behavior of the texture image as it is deformed to match the evolving normal field through the video. The texture synthesis method uses a coarse optical flow to advect clusters of pixels corresponding to patches of similarly oriented surface points. These clusters are organized into a minimum advection tree to account for the dynamic visibility of clusters. We take a rather crude approach to normal recovering and optical flow estimation, yet the results are robust and plausible for nearly diffuse surfaces such as faces and t-shirts.

Improved bioavailability of the mGlu2/3 receptor agonist LY354740 using a prodrug strategy: in vivo pharmacology of LY544344.

Numerous studies have indicated that selective agonists of group II metabotropic glutamate (mGlu) receptors, such as LY354740 [(1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate] and LY379268 [(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate], may be useful in the treatment of many psychiatric disorders, including psychosis, anxiety, and drug withdrawal. Although animal and human studies demonstrate potential therapeutic utility, poor oral bioavailability is a limiting factor in the clinical development of these compounds. Therefore, a novel prodrug approach is being pursued to increase exposure levels of active compound after oral administration. Here, we demonstrate a 10-fold increase in brain, plasma, and cerebrospinal fluid levels of LY354740 after oral prodrug administration. Furthermore, we compare the oral efficacy of the mGlu2/3 receptor agonist LY354740 and its prodrug LY544344 [(1S,2S,5R,6S)-2-[(2'S)-(2'-amino)propionyl]aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride] in rodent models of psychosis and anxiety. Phencyclidine (PCP)-induced hyperlocomotion was dose dependently inhibited in rats receiving oral administration of 30 or 100 mg/kg LY544344, whereas LY354740 did not significantly reverse PCP-mediated behaviors at doses up to 100 mg/kg. Orally administered LY544344 (30 mg/kg) and subcutaneously administered LY354740 (10 mg/kg) attenuated stress-induced hyperthermia in DBA/2 mice, with the prodrug producing anxiolytic effects at lower oral doses than the parent compound. Although oral administration of LY354740 did not significantly affect fear-induced suppression of operant responding in rats, subcutaneously administered LY354740 (10 or 20 mg/kg) and orally administered LY544344 (10 or 30 mg/kg) produced significant anxiolytic effects in this model. The present data confirm that mGlu2/3 receptor agonists produce antipsychotic and anxiolytic effects in animal behavioral models and demonstrate that oral bioavailability of LY354740 was substantially increased using a prodrug strategy.

Pharmacological characterization of stress-induced hyperthermia in DBA/2 mice using metabotropic and ionotropic glutamate receptor ligands.

RATIONALE: Accumulating evidence suggests that drugs acting on the glutamatergic system may represent promising novel therapeutic targets for the treatment of anxiety disorders. The stress-induced hyperthermia paradigm has been used widely to model some of the physiological symptoms associated with anxiety disorders and has produced results that are predictive of clinical efficacy. We have modified this paradigm to measure the autonomic consequences of stress induced by the fear of predation in mice. OBJECTIVE: To evaluate the efficacy of several classes of metabotropic and ionotropic glutamate receptor ligands, as well as known anxiolytics and psychotropic comparators, in attenuating predatory-stress-induced hyperthermia. METHODS: Male DBA/2 mice were implanted with radiotelemetric transmitters in the peritoneal cavity to measure stress-related increases in core body temperature, following placement in a novel cage containing soiled rat shavings. RESULTS: Clinically active compounds such as chlordiazepoxide (5-10 mg/kg), alprazolam (0.3-3 mg/kg), and buspirone (10-30 mg/kg) exhibited an anxiolytic profile. Assessment of glutamatergic agents indicated that the mGlu1 receptor antagonist LY456236 (10-30 mg/kg), mGlu5 receptor antagonist MPEP (10-30 mg/kg), mGlu2/3 receptor agonist LY354740 (3-10 mg/kg), mGlu2 receptor potentiator LY566332 (30 and 100 mg/kg), mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine (30-60 mg/kg), competitive NMDA receptor antagonist LY235959 (1 mg/kg), AMPA receptor antagonist GYKI-52466 (10-20 mg/kg), and glycine transporter-1 (GlyT-1) inhibitor ALX-5407 (3-10 mg/kg) dose-dependently attenuated stress-induced hyperthermia. The AMPA receptor potentiator LY451646, iGlu5 kainate receptor antagonist LY382884, glycine(B) receptor partial agonist D: -cycloserine, and GlyT-1 inhibitor ORG-24461 were ineffective in this model. CONCLUSION: Select metabotropic and ionotropic glutamate receptor ligands exhibited an anxiolytic profile, as measured by the attenuation of stress-induced hyperthermia, and may represent viable targets for the development of pharmacological treatments for anxiety-related disorders.

Newly characterized species-specific immunogenic Chlamydophila pneumoniae peptide reactive with murine monoclonal and human serum antibodies.

A monoclonal antibody (MAb) directed against an unknown Chlamydophila pneumoniae epitope has been characterized, and the respective peptide mimotope has been identified. A murine MAb specific for C. pneumoniae was used to select peptides from phage display libraries. The peptides identified from the phage display library clones reacted specifically with the respective target murine MAb and with human sera previously identified as having antibody titers to C. pneumoniae. The selected peptide mimotope sequences tended to be composed of charged residues surrounding a core of hydrophobic residues. The peptide with the best binding could inhibit >95% of binding to the MAb, suggesting that the selected peptide binds the paratope of the respective MAb. The peptide reacted with human sera previously determined by microimmunofluorescence to have anti-C. pneumoniae antibodies. The peptide was competitively competed with the MAb against Renografin-purified, sonicated C. pneumoniae in an enzyme-linked immunosorbent assay and with whole-cell C. pneumoniae in an indirect fluorescence assay format, demonstrating its potential utility in the development of diagnostics. The use of this novel peptide may allow investigators to establish standardized assays free from cross-reactive Chlamydia trachomatis and Chlamydophila psittaci epitopes and immunoreactivity.