HORMONAL-REGULATION OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 IN CULTURED MONKEY SERTOLI CELLS

Sertoli cells play a central role in the control and maintenance of spermatogenesis. Isolated Sertoli cells of mouse and rat testes have been shown to secrete plasminogen activator (PA) and a plasminogen activator inhibitor type-1 (PAI-1) in culture. In this study, we have investigated the hormonal regulation of PA and PAI-1 activities in cultured monkey Sertoli cells. Sertoli cells (5x10(5) cells/well) isolated from infant rhesus monkey testes were preincubated at 35 degrees C for 16 h in 24-well plates precoated with poly(D-lysine) (5 mu g/cm(2)) in 0.5 mi McCoy's 5a medium containing 5% of fetal calf serum and further incubated for 48 h in 0.5 mi serum-free medium with or without various hormones or other compounds, PA as well as PAI-1 activities in the conditioned media were assayed by fibrin overlay and reverse fibrin autography techniques respectively. The Sertoli cells in vitro secreted only tissue-type PA (tPA), no detectable amount of urokinase-type PA (uPA) could be observed, Monkey Sertoli cells were also capable of secreting PAI-1, Immunocytochemical studies indicated that both tPA and PAI-1 positive staining localized in the Sertoli cells, spermatids and residual bodies of the seminiferous epithelium; Northern blot analysis further confirmed the presence of both tPA and PAI-1 mRNA in monkey Sertoli cells. Addition of follicle-stimulating hormone (FSH) or cyclic adenosine monophosphate (cAMP) derivatives or cAMP-generating agents and gonadotrophin-releasing hormone (GnRH) agonist or phorbol ester (PMA) to the cell culture significantly increased tPA activity. PAI-1 activity in the culture was also enhanced by these reagents except 8-bromo-dibutyryl-cAMP, forskolin and 3-isobutyl-1-methylxanthin (MIX) which greatly stimulated tPA activity, whereas decreased PAI-1 activity, implying that neutralization of PAI-1 activity by tile high level of tPA in the conditioned media may occur. These data suggest that increased intracellular signals which activate protein kinase A (PKA), or protein kinase C (PKC) can modulate Sertoli cell tPA and PAI-1 activities, The concomitant induction of PA and PAI-1 by the same reagents in the Sertoli cells may reflect a finely tuned regulatory mechanism in which PAI-1 could limit the excession of the proteolysis.

Expression, purification and characterization of recombinant Jerdonitin, a P-II class snake venom metalloproteinase comprising metalloproteinase and disintegrin domains

Jerdonitin is a P-II class snake venom metalloproteinase comprising metalloproteinase and disintegrin domains. In this study, we established a high-level expression system in Pichia pastoris and developed a purification strategy for the recombinant Jerdonitin. This recombinant Jerdonitin degraded fibrinogen at a level of activity comparable with its wild type. The effects of recombinant Jerdonitin on inhibiting ADP-induced human platelet aggregation were in a dose-dependent manner with an IC50 of 248 nM. In addition, we reported here that Jerdonitin can significantly inhibit the growth of several cell lines, including human liver cancer cells (Bel7402), human leukemia cells (K562) and human gastric carcinoma cells (BGC823). This study offers recombinant Jerdonitin that will be valuable for further functional and structural studies of Jerdonitin. (C) 2009 Elsevier Ltd. All rights reserved.

Displacement and mixing ventilation driven by opposing wind and buoyancy

The effect of an opposing wind on the stratification and flow produced by a buoyant plume rising from a heat source on the floor of a ventilated enclosure is investigated. Ventilation openings located at high level on the windward side of the enclosure and at low level on the leeward side allow a wind-driven flow from high to low level, opposite to the buoyancy-driven flow. One of two stable steady flow regimes is established depending on a dimensionless parameter F that characterizes the relative magnitudes of the wind-driven and buoyancy-driven velocities within the enclosure, and on the time history of the flow. A third, unstable steady flow solution is identified. For small opposing winds (small F) a steady, two-layer stratification and displacement ventilation is established. Exterior fluid enters through the lower leeward openings and buoyant interior fluid leaves through the upper windward openings. As the wind speed increases, the opposing wind may cause a reversal in the flow direction. In this case, cool exterior fluid enters through the high windward openings and mixes the interior fluid, which exits through the leeward openings. There are now two possibilities. If the rate of heat input by the source exceeds the rate of heat loss through the leeward openings, the temperature of the interior increases and this flow reversal is only maintained temporarily. The buoyancy force increases with time, the flow reverts to its original direction, and steady two-layer displacement ventilation is re-established and maintained. In this regime, the increase in wind speed increases the depth and temperature of the warm upper layer, and reduces the ventilation flow rate. If, on the other hand, the heat loss exceeds the heat input, the interior cools and the buoyancy-driven flow decreases. The reversed flow is maintained, the stratification is destroyed and mixing ventilation occurs. Further increases in wind speed increase the ventilation rate and decrease the interior temperature. The transitions between the two ventilation flow patterns exhibit hysteresis. The change from displacement ventilation to mixing ventilation occurs at a higher F than the transition from mixing to displacement. Further, we find that the transition from mixing to displacement ventilation occurs at a fixed value of F, whereas the transition from displacement to mixing flow is dependent on the details of the time history of the flow and the geometry of the openings, and is not determined solely by the value of F. Theoretical models that predic t the steady stratification profiles and flow rates for the displacement and mixing ventilation, and the transitions between them, are presented and compared with measurements from laboratory experiments. The transition between these ventilation patterns completely changes the internal environment, and we discuss some of the implications for the natural ventilation of buildings. © 2004 Cambridge University Press.

The Impact of Contract Type on Service Provider Information Requirements

This paper is concerned with the role of information in the servitization of manufacturing which has led to “the innovation of an organisation’s capabilities and processes as equipment manufacturers seek to offer services around their products” (Neely 2009, Baines et al 2009). This evolution has resulted in an information requirement (IR) shift as companies move from discrete provision of equipment and spare parts to long-term service contracts guaranteeing prescribed performance levels. Organisations providing such services depend on a very high level of availability and quality of information throughout the service life-cycle (Menor et al 2002). This work focuses on whether, for a proposed contract based around complex equipment, the Information System is capable of providing information at an acceptable quality and requires the IRs to be examined in a formal manner. We apply a service information framework (Cuthbert et al 2008, McFarlane & Cuthbert 2012) to methodically assess IRs for different contract types to understand the information gap between them. Results from case examples indicate that this gap includes information required for the different contract types and a set of contract-specific IRs. Furthermore, the control, ownership and use of information differs across contract types as the boundary of operation and responsibility changes.

An ngram-based statistical machine translation decoder

In this paper we describe MARIE, an Ngram-based statistical machine translation decoder. It is implemented using a beam search strategy, with distortion (or reordering) capabilities. The underlying translation model is based on an Ngram approach, extended to introduce reordering at the phrase level. The search graph structure is designed to perform very accurate comparisons, what allows for a high level of pruning, improving the decoder efficiency. We report several techniques for efficiently prune out the search space. The combinatory explosion of the search space derived from the search graph structure is reduced by limiting the number of reorderings a given translation is allowed to perform, and also the maximum distance a word (or a phrase) is allowed to be reordered. We finally report translation accuracy results on three different translation tasks.

Identification of Cj1051c as a Major determinant for the restriction barrier of Campylobacter jejuni StrainNCTC11168

Campylobacter jejuni is a leading cause of human diarrheal illness in the world, and research on it has benefitted greatly by the completion of several genome sequences and the development of molecular biology tools. However, many hurdles remain for a full understanding of this unique bacterial pathogen. One of the most commonly used strains for genetic work with C. jejuni is NCTC11168. While this strain is readily transformable with DNA for genomic recombination, transformation with plasmids is problematic. In this study, we have identified a determinant of this to be cj1051c, predicted to encode a restriction-modification type IIG enzyme. Knockout mutagenesis of this gene resulted in a strain with a 1,000-fold-enhanced transformation efficiency with a plasmid purified from a C. jejuni host. Additionally, this mutation conferred the ability to be transformed by plasmids isolated from an Escherichia coli host. Sequence analysis suggested a high level of variability of the specificity domain between strains and that this gene may be subject to phase variation. We provide evidence that cj1051c is active in NCTC11168 and behaves as expected for a type IIG enzyme. The identification of this determinant provides a greater understanding of the molecular biology of C. jejuni as well as a tool for plasmid work with strain NCTC11168. © 2012, American Society for Microbiology.

Active control of the accordion modes of a submerged hull

Active vibration control of a submerged hull is presented. A submarine hull can be idealised as a ring stiffened finite cylinder with applied fluid loading. At low frequencies, rotation of the propeller results in discrete tones at the blade passing frequency and its harmonics. The low frequency axial and radial vibration modes of the submerged body can result in a high level of radiated noise. Global hull modes are difficult to attenuate since passive control techniques such as damping materials are not practical due to size and weight constraints. This work investigates active vibration control of a submarine hull for attenuation of the structural and acoustic responses. Based on a feedforward algorithm at tonal frequencies, active vibration suppression of the axial and radial hull displacements are investigated. The effect of the various control arrangements on the structure-borne radiated noise is examined. Numerical simulations of the control performance are presented.

Characterising the information requests of aerospace engineering designers

During product development, engineering designers raise several information requests that make them search through human and documentary sources. This paper reports research to characterise, in detail, these requests for designers working in a major aerospace engineering company. The research found that at a high level, a distinction can be made between requests to acquire information and to process information. The former are raised to access design and domain information. The latter, instead, are formed to define designs. For researchers, this study extends existing knowledge of information requests by characterising key differences in their nature and explaining how they are used in the design process. For practitioners, these findings can be used as a basis to understand the diverseness of information requests and how to channel efforts to support designers in information seeking. In particular, the research indicates that a strategy to support designers should enable the development of engineering communities that share information effectively and the introduction of techniques that facilitate the documentation of information. © 2012 Springer-Verlag London Limited.

Quality practices and problems in free software projects

Free software and open source projects are often perceived to be of high quality. It has been suggested that the high level of quality found in some free software projects is related to the open development model which promotes peer review. While the quality of some free software projects is comparable to, if not better than, that of closed source software, not all free software projects are successful and of high quality. Even mature and successful projects face quality problems; some of these are related to the unique characteristics of free software and open source as a distributed development model led primarily by volunteers. In exploratory interviews performed with free software and open source developers, several common quality practices as well as actual quality problems have been identified. The results of these interviews are presented in this paper in order to take stock of the current status of quality in free software projects and to act as a starting point for the implementation of quality process improvement strategies.

Inverse induction motor modelling of a submarine propulsion system

An inherent trade-off exists in simulation model development and employment: a trade-off between the level of detail simulated and the simulation models computational cost. It is often desirable to simulate a high level of detail to a high degree of accuracy. However, due to the nature of design optimisation, which requires a large number of design evaluations, the application of such simulation models can be prohibitively expensive. A induction motor modelling approache to reduce the computational cost while maintaining a high level of detail and accuracy in the final design is presented. © 2012 IEEE.

Model-based influences on humans' choices and striatal prediction errors.

The mesostriatal dopamine system is prominently implicated in model-free reinforcement learning, with fMRI BOLD signals in ventral striatum notably covarying with model-free prediction errors. However, latent learning and devaluation studies show that behavior also shows hallmarks of model-based planning, and the interaction between model-based and model-free values, prediction errors, and preferences is underexplored. We designed a multistep decision task in which model-based and model-free influences on human choice behavior could be distinguished. By showing that choices reflected both influences we could then test the purity of the ventral striatal BOLD signal as a model-free report. Contrary to expectations, the signal reflected both model-free and model-based predictions in proportions matching those that best explained choice behavior. These results challenge the notion of a separate model-free learner and suggest a more integrated computational architecture for high-level human decision-making.

A combined nonfertile and UO2 PWR fuel assembly for actinide waste minimization

A new combined Non Fertile and Uranium (CONFU) fuel assembly is proposed to limit the actinides that need long-term high-level waste storage from the pressurized water reactor (PWR) fuel cycle. In the CONFU assembly concept, ∼20% of the UO2 fuel pins are replaced with fertile free fuel hosting the transuranic elements (TRUs) generated in the previous cycle. This leads to a fuel cycle sustainable with respect to net TRU generation, and the amount and radiotoxicity of the nuclear waste can be significantly reduced in comparison with the conventional once-through UO2 fuel cycle. It is shown that under the constraints of acceptable power peaking limits, the CONFU assembly exhibits negative reactivity feedback coefficients comparable in values to those of the reference UO2 fuel. Feasibility of the PWR core operation and control with complete TRU recycle has been shown based on full-core three-dimensional neutronic simulation. However, gradual buildup of small amounts of Cm and Cf challenges fuel reprocessing and fabrication due to the high spontaneous fission rates of these nuclides and heat generation by some Pu, Am, and Cm isotopes. Feasibility of the processing steps becomes more attainable if the time between discharge and reprocessing is 20 yr or longer.

Polymer film packaging for food: An environmental assessment

Plastics packaging is ubiquitous in the food industry, fulfilling a range of functions including a significant role in reducing food waste. The public perception of packaging, however, is dominated by end-of-life aspects, when the packaging becomes waste often found littering urban, rural and marine environments. A balanced analysis of the role of packaging demands that the whole lifecycle is examined, looking not only at the packaging itself but also at the product being packaged. This paper focuses on packaging in the meat and cheese industry, analysing the impact of films and bags. The functions of packaging are defined and the environmental impact of delivering these functions is assessed. The influence of packaging on levels of waste and energy consumption elsewhere in the system is examined, including the contentious issue of end-of-life for packaging. Strategies for minimizing the environmental impact of the packaging itself involve reduction in the amount of material used (thinner packaging), rather than emphasizing end-of-life issues. Currently, with polymer recycling not at a high level, evidence suggests that this strategy is justifiable. Biodegradable polymers may have some potential for improving environmental performance, but are still problematic. The conclusion is that although current packaging is in some ways wasteful and inefficient, the alternatives are even less desirable. © 2013 Elsevier B.V. All rights reserved.

IGBT converters conducted EMI analysis by controlled multiple-slope switching waveform approximation

IGBTs realise high-performance power converters. Unfortunately, with fast switching of the IGBT-free wheel diode chopper cell, such circuits are intrinsic sources of high-level EMI. Therefore, costly EMI filters or shielding are normally needed on the load and supply side. In order to design these EMI suppression components, designers need to predict the EMI level with reasonable accuracy for a given structure and operating mode. Simplifying the transient IGBT switching current and voltage into a multiple slope switching waveform approximation offers a feasible way to estimate conducted EMI with some accuracy. This method is dependent on the availability of high-fidelity measurements. Also, that multiple slope approximation needs careful and time-costly IGBT parameters optimisation process to approach the real switching waveform. In this paper, Active Voltage Control Gate Drive(AVC GD) is employed to shape IGBT switching into several defined slopes. As a result, Conducted EMI prediction by multiple slope switching approximation could be more accurate, less costly but more friendly for implementation. © 2013 IEEE.

The closed thorium-transuranic fuel cycle in reduced-moderation PWRs and BWRs

Multiple recycle of long-lived actinides has the potential to greatly reduce the required storage time for spent nuclear fuel or high level nuclear waste. This is generally thought to require fast reactors as most transuranic (TRU) isotopes have low fission probabilities in thermal reactors. Reduced-moderation LWRs are a potential alternative to fast reactors with reduced time to deployment as they are based on commercially mature LWR technology. Thorium (Th) fuel is neutronically advantageous for TRU multiple recycle in LWRs due to a large improvement in the void coefficient. If Th fuel is used in reduced-moderation LWRs, it appears neutronically feasible to achieve full actinide recycle while burning an external supply of TRU, with related potential improvements in waste management and fuel utilization. In this paper, the fuel cycle of TRU-bearing Th fuel is analysed for reduced-moderation PWRs and BWRs (RMPWRs and RBWRs). RMPWRs have the advantage of relatively rapid implementation and intrinsically low conversion ratios, which is desirable to maximize the TRU burning rate. However, it is challenging to simultaneously satisfy operational and fuel cycle constraints. An RBWR may potentially take longer to implement than an RMPWR due to more extensive changes from current BWR technology. However, the harder neutron spectrum can lead to favourable fuel cycle performance. A two-stage TRU burning cycle, where the first stage is Th-Pu MOX in a conventional PWR feeding a second stage continuous burn in RMPWR or RBWR, is technically reasonable, although it is more suitable for the RBWR implementation. In this case, the fuel cycle performance is relatively insensitive to the discharge burn-up of the first stage. © 2013 Elsevier Ltd. All rights reserved.