Calcium Diluents as Matrix Forming Agents in Sustained Release Dosage Forms

The purpose of this research was to evaluate the effect of the poorly soluble diluents; calcium sulfate dihydrate, dibasic calcium phosphate dihydrate, and tribasic calcium phosphate on medicament release from solid dosage forms. Initial findings led to an investigation of the use of these diluents as matrix forming agents in the formulation of sustained release solid dosage farms. An existing single station tablet press was instrumented with a transducer strain gauge apparatus to monitor compression force applied during tablet manufacture. An automated dissolution system was used to determine medicament release from the dosage forms under investigation. These three diluents when directly compressed with drug had shown matrix forming abilities in media of pH 4.0 to 7.5. However, they do not exhibit these same abilities in O.1N HCl. The addition of Carbopol 934P (1-5%) provided a gel-like protective barrier in O.1N HCl and acacia assisted in maintaining the matrix structure in this acidic environment. In addition, medicament release appeared nearly constant over eight to ten hours. The tablets were manufactured by weighing the excipients, screening to eliminate agglomerates, blending, and compressing. Acetaminophen was chosen as model drug due to its relatively pH independent solubility profile over the range of interest. However, the system also showed the ability to sustain the release of theophylline and chlorpheniramine maleate. Results indicate promise for the use of these calcium diluents as matrix forming agents in the formulation of sustained release solid dosage forms. Medicament release can be controlled by adjustment of formulation variables and this simple process appears unaffected by several processing variables. The simplicity, novelty, and applicability of this method of achieving sustained release of medicament from solid dosage forms warrants additional investigation of its use in the formulation of pharmaceutical products

Online parameter estimation in dynamic Markov Random Fields for image sequence analysis

pre-printMarkov Random Fields (MRF) have proven to be extremely useful models for efficient and accurate image segmentation.Recent literature points to an increased effort towards incorporating useful priors (shape, geometry, context) in a MRF framework. However, topological priors, considered extremely crucial in biological and natural image sequences have been less explored. This work proposes a strategy wherein free parameters of the MRF are used to make it topology aware using a semantic graphical model working in conjunction with the MRF. Estimation of free parameters is constrained by prior knowledge of an object's topological dynamics encoded by the graphical model. Maximizing a regional conformance measure yields parameters for the frame under consideration. The application motivating this work is the tracing of neuronal structures across 3D serial section Transmission Electron Micrograph (ssTEM) stacks. Applicability of the proposed method is demonstrated by tracing 3D structures in ssTEM stacks

Familial advanced sleep-phase syndrome: a short-period circadian rhythmvariant in humans

Journal ArticleBiological circadian clocks oscillate with an approximately 24-hour period, are ubiquitous, and presumably confer a selective advantage by anticipating the transitions between day and night. The circadian rhythms of sleep, melatonin secretion and body core temperature are thought to be generated by the suprachiasmatic nucleus of the hypothalamus, the anatomic locus of the mammalian circadian clock. Autosomal semi-dominant mutations in rodents with fast or slow biological clocks (that is, short or long endogenous period lengths; tau) are associated with phase-advanced or delayed sleep-wake rhythms, respectively. These models predict the existence of familial human circadian rhythm variants but none of the human circadian rhythm disorders are known to have a familial tendency. Although a slight 'morning lark' tendency is common, individuals with a large and disabling sleep phase-advance are rare. This disorder, advanced sleep-phase syndrome, is characterized by very early sleep onset and offset; only two cases are reported in young adults. Here we describe three kindreds with a profound phase advance of the sleep-wake, melatonin and temperature rhythms associated with a very short tau. The trait segregates as an autosomal dominant with high penetrance. These kindreds represent a well-characterized familial circadian rhythm variant in humans and provide a unique opportunity for genetic analysis of human circadian physiology

Improving biochemical yields with MixoFerm

Acetyl-CoA is a primary hub for metabolism and is the building block for most biochemicals of interest. However, the yields for biochemicals derived from acety-CoA are inherently limited because of the decarboxylation of pyruvate to acetyl-CoA which releases CO2. To overcome this limitation, White Dog Labs (WDL) developed a fermentation technology call MixoFerm™ (also known as anaerobic, non-photosynthetic mixotrophy). This technology uses microorganisms capable of concurrently utilizing both organic (e.g., sugars) and inorganic (e.g., CO2) substrates. Using MixoFerm, CO2 can be fixed back into acetyl-CoA and thus improve biochemical yields (g product/g substrate consumed). Here, we demonstrate simultaneous utilization of both fructose and syngas by Clostridium ljungdahlii and Clostridium autoethanogenum. We next engineered C. ljungdahlii to produce the non-native metabolite acetone at a yield 35% greater than the theoretical maximum acetone yield without mixotrophy. Finally, we designed and generated a strain of C. ljungdahlii capable of consuming glucose, which the wild-type strain is unable to do. With the ability to improve biochemical yields, MixoFerm™ is a robust and flexible platform technology to improve process economics and product life-cycle analysi

Wind Tunnel Testing of Powered Lift, All-Wing STOL Model

Short take-off and landing (STOL) systems can offer significant capabilities to warfighters and, for civil operators thriving on maximizing efficiencies they can improve airspace use while containing noise within airport environments. In order to provide data for next generation systems, a wind tunnel test of an all-wing cruise efficient, short take-off and landing (CE STOL) configuration was conducted in the National Aeronautics and Space Administration (NASA) Langley Research Center (LaRC) 14- by 22-foot Subsonic Wind Tunnel. The test s purpose was to mature the aerodynamic aspects of an integrated powered lift system within an advanced mobility configuration capable of CE STOL. The full-span model made use of steady flap blowing and a lifting centerbody to achieve high lift coefficients. The test occurred during April through June of 2007 and included objectives for advancing the state-of-the-art of powered lift testing through gathering force and moment data, on-body pressure data, and off-body flow field measurements during automatically controlled blowing conditions. Data were obtained for variations in model configuration, angles of attack and sideslip, blowing coefficient, and height above ground. The database produced by this effort is being used to advance design techniques and computational tools for developing systems with integrated powered lift technologies

Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells.

The retinal degenerative diseases, which together constitute a leading cause of hereditary blindness worldwide, are largely untreatable. Development of reliable methods to culture complex retinal tissues from human pluripotent stem cells (hPSCs) could offer a means to study human retinal development, provide a platform to investigate the mechanisms of retinal degeneration and screen for neuroprotective compounds, and provide the basis for cell-based therapeutic strategies. In this study, we describe an in vitro method by which hPSCs can be differentiated into 3D retinas with at least some important features reminiscent of a mature retina, including exuberant outgrowth of outer segment-like structures and synaptic ribbons, photoreceptor neurotransmitter expression, and membrane conductances and synaptic vesicle release properties consistent with possible photoreceptor synaptic function. The advanced outer segment-like structures reported here support the notion that 3D retina cups could serve as a model for studying mature photoreceptor development and allow for more robust modeling of retinal degenerative disease in vitro

Production of biochemicals and biofuels with no CO2 production and improved product yields

Traditional fermentation processes for the production of the majority of biochemicals and biofuels produce CO2 because of decarboxylation reactions, which limits the final mass yields of products. To overcome this limitation, we have developed a fermentation technology called MixoFerm™ (also known as anaerobic, non-photosynthetic mixotrophy), which uses microorganisms capable of simultaneously consuming both organic (e.g., sugars) and inorganic (e.g., CO2, CO, or H2) substrates. With this technology, product mass yields for almost any biochemical or biofuel can be increased by at least 50%, and processes can be designed that result in no CO2 production. In order to achieve zero CO2 emissions for most products, exogenous reductant must be added to the system, since sugar lacks the necessary reducing energy to both fix CO2 and produce the product of interest. Here, we demonstrate concurrent consumption of both sugars and exogenously added reducing gases (CO and/or H2) to produce products of interest at enhanced mass yields and with no CO2 emissions. In addition, we have screened a library of acetogenic bacteria in order to find an optimal MixoFerm™ host strain, one that consumes both a broad range of carbohydrates and gases. From this library, we identified strains with a broader carbohydrate consumption range than traditional acetogens like C. ljungdahlii or C. autoethanogenum, and characterized their ability to grow under a variety of MixoFerm™ conditions to produce biochemicals at enhanced mass yields. With the ability to improve product yields for reduced products, especially for ethanol and other potential biofuels, MixoFerm™ is a robust and flexible platform technology to improve process economics and product life-cycle analysis

To discover a Drowned Body

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Rapid glutamate receptor 2 trafficking during retinal degeneration

<p>Abstract</p> <p>Background</p> <p>Retinal degenerations, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), are characterized by photoreceptor loss and anomalous remodeling of the surviving retina that corrupts visual processing and poses a barrier to late-stage therapeutic interventions in particular. However, the molecular events associated with retinal remodeling remain largely unknown. Given our prior evidence of ionotropic glutamate receptor (iGluR) reprogramming in retinal degenerations, we hypothesized that the edited glutamate receptor 2 (GluR2) subunit and its trafficking may be modulated in retinal degenerations.</p> <p>Results</p> <p>Adult albino Balb/C mice were exposed to intense light for 24 h to induce light-induced retinal degeneration (LIRD). We found that prior to the onset of photoreceptor loss, protein levels of GluR2 and related trafficking proteins, including glutamate receptor-interacting protein 1 (GRIP1) and postsynaptic density protein 95 (PSD-95), were rapidly increased. LIRD triggered neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites. Immunoprecipitation analysis showed interaction between KIF3A and GRIP1 as well as PSD-95, suggesting that KIF3A may mediate transport of GluR2 and its trafficking proteins to the novel dendrites. However, in areas of photoreceptor loss, GluR2 along with its trafficking proteins nearly vanished in retracted retinal neurites.</p> <p>Conclusions</p> <p>All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.</p

Wake Measurement Downstream of a Hybrid Wing Body Model with Blown Flaps

Flow-field measurements were obtained in the wake of a full-span Hybrid Wing Body model with internally blown flaps. The test was performed at the NASA Langley 14 x 22 Foot Subsonic Tunnel at low speeds. Off-body measurements were obtained with a 7-hole probe rake survey system. Three model configurations were investigated. At 0deg angle of attack the surveys were completed with 0deg and 60deg flap deflections. At 10deg angle of attack the wake surveys were completed with a slat and a 60deg flap deflection. The 7-hole probe results further quantified two known swirling regions (downstream of the outboard flap edge and the inboard/outboard flap juncture) for the 60deg flap cases with blowing. Flowfield results and the general trends are very similar for the two blowing cases at nozzle pressure ratios of 1.37 and 1.56. High downwash velocities correlated with the enhanced lift for the 60deg flap cases with blowing. Jet-induced effects are the largest at the most inboard station for all (three) velocity components due in part to the larger inboard slot height. The experimental data are being used to improve computational tools for high-lift wings with integrated powered-lift technologies