Stability of Hydraulic Systems with Focus on Cavitating Pumps

Increasing use is being made of transmission matrices to characterize unsteady flows in hydraulic system components and to analyze the stability of such systems. This paper presents some general characteristics which should be examined in any experimentally measured transmission matrices and a methodology for the analysis of the stability of transmission matrices in hydraulic systems of order 2. These characteristics are then examined for cavitating pumps and the predicted instabilities (known as auto-oscillation) compared with experimental observations in a particular experimental system

Auto-Oscillation of Cavitating Inducers

This paper presents details of measurements on the instability know as auto-oscillation which occurs in systems with cavitating pumps. Specific measurements are made of onset cavitation number and auto-osciallation frequency for a range of inducers. It has been shown that auto-oscillation is a system instability caused by the active dynamic characteristics of the cavitating pump. A system anslysis is presented which utilized previously measured dynamic transfer functions for the inducers; the resulting predictions of instability are consistent with the observations. Though the onset cavitation number is a function of the entire system it is also show that, given the onset cavitation number, the auto-oscillation frequency is only weakly dependent on the system and primarily a function of the pump dynamics. Detailed measurements of the amplitude and phase of fluctuating pressures and flow rates during auto-oscillation are also presented. These strongly suggest that the pump dynamics are primarily determined by the complicated flow at inlet to the inducer which involves pre-swirl generated by a strong backflow. Some data on the non-linear effect of auto-osciallation on overall mean performance are also presented

The Effects of Inlet Flow Modification on Cavitating Inducer Performance

This paper explores the effect of inlet flow modification on the cavitating and noncavitating performance of two cavitating inducers, one of simple helical design and the other a model of the low-pressure LOX pump in the Space Shuttle Main Engine. The modifications were generated by sections of honeycomb, both uniform and nonuniform. Significant improvement in the performance over a wide range of flow coefficients resulted from the use of either honeycomb section. Measurements of the axial and swirl velocity profiles of the flows entering the inducers were made in order to try to understand the nature of the inlet flow and the manner in which it is modified by the honeycomb sections

Slits Are Chemorepellents Endogenous to Hypothalamus and Steer Thalamocortical Axons into Ventral Telencephalon

Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA pathfinding. We show that Slit chemorepellents are the hypothalamic chemorepellent and act through Robos to steer TCAs into ventral telencephalon. During TCA pathfinding, Slit1 and Slit2 are expressed in hypothalamus and ventral thalamus and Robo1 and Robo2 are expressed in dorsal thalamus. In collagen gel cocultures of dorsal thalamus and Slit2-expressing cells, axon number and length are decreased on the explant side facing Slit2-expressing cells, overall axon outgrowth is diminished, and axons turn away from the Slit2-expressing cells. Thus, Slit2 is an inhibitor and chemorepellent for dorsal thalamic axons. Collagen gel cocultures of dorsal thalamus with sections of live diencephalon, with and without the hypothalamus portion overlaid with Robo2-fc-expressing cells to block Slit function, identify Slits as the hypothalamic chemorepellent. Thus, Slits are chemorepellents for TCAs endogenous to hypothalamus and steer TCAs from diencephalon into ventral telencephalon, a critical pathfinding event defective in Slit and Robo2 mutant mice

Virtual screening for inhibitors of the human TSLP:TSLPR interaction

The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Ra), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP: TSLPR complex to investigate the drugability of this complex. Two commercially available fragment libraries were screened computationally for possible inhibitors and a selection of fragments was subsequently tested in vitro. The screening setup consisted of two orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a biochemical assay based on a TSLP: alkaline phosphatase fusion protein. Four fragments pertaining to diverse chemical classes were identified to reduce TSLP: TSLPR complex formation to less than 75% in millimolar concentrations. We have used unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound. This work provides a proof-ofprinciple for use of fragments in the inhibition of TSLP: TSLPR complexation

Midline Signalling Systems Direct the Formation of a Neural Map by Dendritic Targeting in the Drosophila Motor System

During embryonic development of the motor system of Drosophila, motorneurons target their dendrites to different regions along the body axis in response to midline guidance cues

The APEX Quantitative Proteomics Tool: Generating protein quantitation estimates from LC-MS/MS proteomics results

Mass spectrometry (MS) based label-free protein quantitation has mainly focused on analysis of ion peak heights and peptide spectral counts. Most analyses of tandem mass spectrometry (MS/MS) data begin with an enzymatic digestion of a complex protein mixture to generate smaller peptides that can be separated and identified by an MS/MS instrument. Peptide spectral counting techniques attempt to quantify protein abundance by counting the number of detected tryptic peptides and their corresponding MS spectra. However, spectral counting is confounded by the fact that peptide physicochemical properties severely affect MS detection resulting in each peptide having a different detection probability. Lu et al. (2007) described a modified spectral counting technique, Absolute Protein Expression (APEX), which improves on basic spectral counting methods by including a correction factor for each protein (called O(i) value) that accounts for variable peptide detection by MS techniques. The technique uses machine learning classification to derive peptide detection probabilities that are used to predict the number of tryptic peptides expected to be detected for one molecule of a particular protein (O(i)). This predicted spectral count is compared to the protein's observed MS total spectral count during APEX computation of protein abundances. Results: The APEX Quantitative Proteomics Tool, introduced here, is a free open source Java application that supports the APEX protein quantitation technique. The APEX tool uses data from standard tandem mass spectrometry proteomics experiments and provides computational support for APEX protein abundance quantitation through a set of graphical user interfaces that partition thparameter controls for the various processing tasks. The tool also provides a Z-score analysis for identification of significant differential protein expression, a utility to assess APEX classifier performance via cross validation, and a utility to merge multiple APEX results into a standardized format in preparation for further statistical analysis. Conclusion: The APEX Quantitative Proteomics Tool provides a simple means to quickly derive hundreds to thousands of protein abundance values from standard liquid chromatography-tandem mass spectrometry proteomics datasets. The APEX tool provides a straightforward intuitive interface design overlaying a highly customizable computational workflow to produce protein abundance values from LC-MS/MS datasets.National Institute of Allergy and Infectious Diseases (NIAID) N01-AI15447National Institutes of HealthNational Science Foundation, the Welsh and Packard FoundationsInternational Human Frontier Science ProgramCenter for Systems and Synthetic Biolog

Evidence That Descending Cortical Axons Are Essential for Thalamocortical Axons to Cross the Pallial-Subpallial Boundary in the Embryonic Forebrain

Developing thalamocortical axons traverse the subpallium to reach the cortex located in the pallium. We tested the hypothesis that descending corticofugal axons are important for guiding thalamocortical axons across the pallial-subpallial boundary, using conditional mutagenesis to assess the effects of blocking corticofugal axonal development without disrupting thalamus, subpallium or the pallial-subpallial boundary. We found that thalamic axons still traversed the subpallium in topographic order but did not cross the pallial-subpallial boundary. Co-culture experiments indicated that the inability of thalamic axons to cross the boundary was not explained by mutant cortex developing a long-range chemorepulsive action on thalamic axons. On the contrary, cortex from conditional mutants retained its thalamic axonal growth-promoting activity and continued to express Nrg-1, which is responsible for this stimulatory effect. When mutant cortex was replaced with control cortex, corticofugal efferents were restored and thalamic axons from conditional mutants associated with them and crossed the pallial-subpallial boundary. Our study provides the most compelling evidence to date that cortical efferents are required to guide thalamocortical axons across the pallial-subpallial boundary, which is otherwise hostile to thalamic axons. These results support the hypothesis that thalamic axons grow from subpallium to cortex guided by cortical efferents, with stimulation from diffusible cortical growth-promoting factors

Contrasting patterns of evolutionary constraint and novelty revealed by comparative sperm proteomic analysis in Lepidoptera

Background: Rapid evolution is a hallmark of reproductive genetic systems and arises through the combined processes of sequence divergence, gene gain and loss, and changes in gene and protein expression. While studies aiming to disentangle the molecular ramifications of these processes are progressing, we still know little about the genetic basis of evolutionary transitions in reproductive systems. Here we conduct the first comparative analysis of sperm proteomes in Lepidoptera, a group that exhibits dichotomous spermatogenesis, in which males produce a functional fertilization-competent sperm (eupyrene) and an incompetent sperm morph lacking nuclear DNA (apyrene). Through the integrated application of evolutionary proteomics and genomics, we characterize the genomic patterns potentially associated with the origination and evolution of this unique spermatogenic process and assess the importance of genetic novelty in Lepidopteran sperm biology. Results: Comparison of the newly characterized Monarch butterfly (Danaus plexippus) sperm proteome to those of the Carolina sphinx moth (Manduca sexta) and the fruit fly (Drosophila melanogaster) demonstrated conservation at the level of protein abundance and post-translational modification within Lepidoptera. In contrast, comparative genomic analyses across insects reveals significant divergence at two levels that differentiate the genetic architecture of sperm in Lepidoptera from other insects. First, a significant reduction in orthology among Monarch sperm genes relative to the remainder of the genome in non-Lepidopteran insect species was observed. Second, a substantial number of sperm proteins were found to be specific to Lepidoptera, in that they lack detectable homology to the genomes of more distantly related insects. Lastly, the functional importance of Lepidoptera specific sperm proteins is broadly supported by their increased abundance relative to proteins conserved across insects. Conclusions: Our results identify a burst of genetic novelty amongst sperm proteins that may be associated with the origin of heteromorphic spermatogenesis in ancestral Lepidoptera and/or the subsequent evolution of this system. This pattern of genomic diversification is distinct from the remainder of the genome and thus suggests that this transition has had a marked impact on lepidopteran genome evolution. The identification of abundant sperm proteins unique to Lepidoptera, including proteins distinct between specific lineages, will accelerate future functional studies aiming to understand the developmental origin of dichotomous spermatogenesis and the functional diversification of the fertilization incompetent apyrene sperm morph