Dynamic optimal control model for profit maximization of software product under the influence of promotional effort

In this paper, a decision model is presented for the sales of software product to determine the profit and marketing policy under the influence of promotional efforts. The paper focuses on dependence of the optimal profit on the promotional efforts when there is diffusion effect of demand on the sales function. An elaborate optimization policy considering the dynamic nature of production cost function is proposed and numerical example is illustrated. The paper also studies the behavior of the future profit and its impact on profit maximization model by considering the constant price during the entire planning horizon. The experimental results greatly help us to identify the contributions of each selected parameter and its weight. Some conclusions, limitations of this study and future direction are also discussed.     

Formation of embryoid bodies using dielectrophoresis

Embryoid body (EB) formation forms an important step in embryonic stem cell differentiation invivo. In murine embryonic stem cell (mESC) cultures EB formation is inhibited by the inclusion of leukaemic inhibitory factor (LIF) in the medium. Assembly of mESCs into aggregates by positive dielectrophoresis (DEP) in high field regions between interdigitated oppositely castellated electrodes was found to initiate EB formation. Embryoid body formation in aggregates formed with DEP occurred at a more rapid rate-in fact faster compared to conventional methods-in medium without LIF. However, EB formation also occurred in medium in which LIF was present when the cells were aggregated with DEP. The optimum characteristic size for the electrodes for EB formation with DEP was found to be 75-100 microns; aggregates smaller than this tended to merge, whilst aggregates larger than this tended to split to form multiple EBs. Experiments with ESCs in which green fluorescent protein (GFP) production was targeted to the mesodermal gene brachyury indicated that differentiation within embryoid bodies of this size may preferentially occur along the mesoderm lineage. As hematopoietic lineages during normal development derive from mesoderm, the finding points to a possible application of DEP formed EBs in the production of blood-based products from ESCs.     

Flow manipulation and cell immobilization for biochemical applications using thermally responsive fluids

A flow redirection and single cell immobilization method in a microfluidic chip is presented. Microheaters generated localized heating and induced poly(N-isopropylacrylamide) phase transition, creating a hydrogel that blocked a channel or immobilized a single cell. The heaters were activated in sets to redirect flow and exchange the fluid in which an immobilized cell was immersed. A yeast cell was immobilized in hydrogel and a 4′,6-diamidino-2-phenylindole (DAPI) fluorescent stain was introduced using flow redirection. DAPI diffused through the hydrogel and fluorescently labelled the yeast DNA, demonstrating in situ single cell biochemistry by means of immobilization and fluid exchange.The ability to control microfluidic flow is central to nearly all lab-on-a-chip processes. Recent developments in microfluidics either include microchannel based flow control in which microvalves are used to control the passage of fluid,¹ or are based on discrete droplet translocation in which electric fields or thermal gradients are used to determine the droplet path.^{2, 3} Reconfigurable microfluidic systems have certain advantages, including the ability to adapt downstream fluid processes such as sorting to upstream conditions and events. This is especially relevant for work with individual biomolecules and high throughput cell sorting.⁴ Additionally, reconfigurable microfluidic systems allow for rerouting flows around defective areas for high device yield or lifetime and for increasing the device versatility as a single chip design can have a variety of applications.Microvalves often form the basis of flow control systems and use magnetic, electric, piezoelectric, and pneumatic actuation methods.⁵ Many of these designs require complicated fabrication steps and can have large complex structures that limit the scalability or feasability of complex microfluidic systems. Recent work has shown how phase transition of stimuli-responsive hydrogels can be used to actuate a simple valve design.⁶ Beebe et al. demonstrated pH actuated hydrogel valves.⁷ Phase transition of thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) using a heater element was demonstrated by Richter et al.⁸ Phase transition was also achieved by using light actuation by Chen et al.⁹ Electric heating has shown a microflow response time of less than 33 ms.¹¹ Previous work¹⁰ showed the use of microheaters to induce a significant shift in the viscosity of thermosensitive hydrogel to block microchannel flow and deflect a membrane, stopping flow in another microchannel. Additionally, Yu et al.¹² demonstrated thermally actuated valves based on porous polymer monoliths with PNIPAAm. Krishnan and Erickson¹³ showed how reconfigurable optically actuated hydrogel formation can be used to dynamically create highly viscous areas and thus redirect flow with a response time of  ～ 2?s. This process can be used to embed individual biomolecules in hydrogel and suppress diffusion as also demonstrated by others.^{15, 16} Fiddes et al.¹⁴ demonstrated the use of hydrogels to transport immobilized biomolecules in a digital microfluidic system. While the design of Krishnan and Erickson is highly flexible, it requires the use of an optical system and absorption layer to generate a geometric pattern to redirect flow.This paper describes the use of an array of gold microheaters positioned in a single layer polydimethylsiloxane (PDMS) microfluidic network to dynamically control microchannel flow of PNIPAAm solution. Heat generation and thus PNIPAAm phase transition were localized as the microheaters were actuated using pulse width modulation (PWM) of an applied electric potential. Additionally, hydrogel was used to embed and immobilise individual cells, exchange the fluid parts of the microfluidic system in order to expose the cells to particular reagents to carry out an in situ biochemical process. The PDMS microchannel network and the microheater array are shown in Figure ​Figure11.Open in a separate windowFigure 1A sketch of the electrical circuit and a microscope image of the gold microheaters and the PDMS microchannels. The power to the heaters was modulated with a PWM input through a H-bridge. For clarity, the electrical circuit for only the two heaters with gelled PNIPAAm is shown (H1 and V2). There are four heaters (V1-V4) in the “vertical channels” and three heaters (H1-H3) in the “horizontal” channel.The microchannels were fabricated using a patterned mould on a silicon wafer to define PDMS microchannels, as described by DeBusschere et al.¹⁷ and based on previous work.¹⁰ A 25 × 75 mm glass microscope slide served as the remaining wall of the microchannel system as well as the substrate for the microheater array. The gold layer had a thickness of 200 nm and was deposited and patterned using E-beam evaporation and photoresist lift-off.²¹ The gold was patterned to function as connecting electrical conductors as well as the microheaters.It was crucial that the microheater array was aligned with an accuracy of  ～ 20μm with the PDMS microchannel network for good heat localization. The PDMS and glass lid were treated with plasma to activate the surface and alignment was carried out by mounting the microscope slide onto the condenser lens of an inverted microscope (TE-2000 Nikon Instruments). While imaging with a 4× objective, the x, y motorized stage aligned the microchannels to the heaters and the condenser lens was lowered for the glass substrate to contact the PDMS and seal the microchannels.Local phase transition of 10% w/w PNIPAAm solution in the microchannels was achieved by applying a 7 V potential through a H-bridge that received a PWM input at 500 Hz which was modulated using a USB controller (Arduino Mega 2650) and a matlab (Mathworks) GUI. The duty cycle of the PWM input was calibrated for each microheater to account for differences in heater resistances (25?Ω to 52?Ω) due to varying lengths of on-chip connections and slight fabrication inconsistencies, as well as for different flow conditions during device operation. Additionally, thermal cross-talk between heaters required decreasing the PWM input significantly when multiple heaters were activated simultaneously. This allowed confining the areas of cross-linked PNIPAAm to the microheaters, allowing the fluid in other areas to flow freely.By activating the heaters in sets, it was possible to redirect the flow and exchange the fluid in the central area. Figure ​Figure22 demonstrates how the flow direction in the central microchannel area was changed from a stable horizontal flow to a stable vertical flow with a 3 s response time, using only PNIPAAm phase transition. Constant pressures were applied to the inlets to the horizontal channel and to the vertical channels. Activating heaters V1-4 (Figure ​(Figure2,2, left) resulted in flow in the horizontal channel only. Likewise, activating heaters H1 and H2 allowed for flow in the vertical channel only. In this sequence, the fluid in the central microchannel area from one inlet was exchanged with fluid from the other inlet. Additionally, by activating heater H3, a particle could be immobilised during the exchange of fluid as shown in Figure ​Figure33 (top).Open in a separate windowFigure 2Switching between fluid from the horizontal and the vertical channel using hydrogel activation and flow redirection with a response time of 3 s. A pressure of 25 mbar was applied to the inlet of the horizontal channel and a pressure of 20 mbar to the vertical channel. The flow field was determined using particle image velocimetry, in which the displacement of fluorescent seed particles was determined from image pairs generated by laser pulse exposure. Processing was carried out with davis software (LaVision).Open in a separate windowFigure 3A series of microscope images near heater H3 showing: (1a)-(1c) A single yeast cell captured by local PNIPAAm phase transition and immobilized for 5 min before being released. (2a) A single yeast cell was identified for capture by embedding in hydrogel. (2b) The cell as well as the hydrogel displayed fluorescence while embedded due to the introduction of DAPI in the surrounding region. (2c) The diffusion of DAPI towards the cell as the heating power of H3 is reduced after 15 min, showing a DAPI stained yeast cell immobilized.Particle immobilisation in hydrogel and fluid exchange in the central area of the microfluidic network were used to carry out an in situ biochemical process in which a yeast cell injected through one inlet was stained in situ with a 4′,6-diamidino-2-phenylindole (DAPI) solution (Invitrogen), which attached to the DNA of the yeast cell.¹⁸ A solution of yeast cells with a concentration of 5 × 10⁷cells/ml suspended in a 10% w/w PNIPAAm solution was injected through the horizontal channel. A solution of 2μg/l DAPI in a 10% w/w PNIPAAm solution was injected through the vertical channel. A single yeast cell was identified and captured near the central heater, and by deactivating the heaters in the vertical channel, DAPI solution was introduced in the microchannels around the hydrogel. After immobilising the cell for 15 min, the heater was deactivated, releasing the cell in the DAPI solution. This process is shown in Figure ​Figure33 (bottom). The sequence of the heater activation and deactivation in order to immobilize the cell and exchange the fluid is outlined in the supplementary material.²¹Eriksen et al.¹⁵ demonstrated the diffusion of protease K in the porous hydrogel matrix,¹⁹ and it was therefore expected that DAPI fluorescent stain (molecular weight of 350 kDa, Ref. ²⁰) would also diffuse. DAPI diffusion is shown in Figure 3(2b) in which the yeast cell shows fluorescence while embedded in the hydrogel. The yeast cell was released by deactivating the central heater and activating all the others to suppress unwanted flow in the microchannel. As a result, the single cell was fully immersed in the DAPI solution. Immobilization of a single cell allows for selection of a cell that exhibits a certain trait and introduction of a new fluid while maintaining the cell position in the field of view of the microscope such that a biochemical response can be imaged continuously.In summary, a microfluidic chip capable of local heating was used to induce phase transition of PNIPAAm to hydrogel, blocking microchannel flow, and thereby allowing for reconfigurable flow. Additionally, the hydrogel was used to embed and immobilise a single yeast cell. DAPI fluorescent stain was introduced using flow redirection, and it stained the immobilized cell, showing diffusion into the hydrogel. The versatile design of this microfluidic chip permits flow redirection, and is suitable to carry out in situ biochemical reactions on individual cells, demonstrating the potential of this technology for forming large-scale reconfigurable microfluidic networks for biochemical applications.     

The BASES expert statement on exercise, immunity, and infection

An individual's level of physical activity influences their risk of infection, most likely by affecting immune function. Regular moderate exercise reduces the risk of infection compared with a sedentary lifestyle, but very prolonged bouts of exercise and periods of intensified training are associated with an increased risk of infection. There are several lifestyle, nutritional, and training strategies that can be adopted to limit the extent of exercise-induced immunodepression and minimize the risk of infection. This expert statement provides a background summarizing the evidence together with extensive conclusions and practical guidelines.     

The planarity of the stickface motion in the field hockey hit

The field hockey hit is an important but poorly understood stroke. In this study, we investigated the planarity of the stickface motion during the downswing to better characterize the kinematics and to assess the suitability of planar pendulum models for simulating the hit. Thirteen experienced female field hockey players were filmed executing hits with a single approach step, and the kinematics of the centre of the stickface were measured. A method was developed for identifying how far back from impact the stickface motion was planar. Orthogonal regression was used to fit least-squares planes to the stickface path during sections of the downswing of varying length, with each section ending at impact. A section was considered planar if the root mean square residual between the stickface path and the fitted plane was less than 0.25% of the distance travelled by the stickface during that period. On average, the stickface motion was planar for the last 83 ± 12% of its downswing path, with the length of the planar section ranging from 1.85 m to 2.70 m. The suitability of a planar model for the stickface motion was supported, but further investigation of the stick and arm kinematics is warranted.     

Anthropometric profiles of elite older triathletes in the Ironman Brazil compared with those of young Portuguese triathletes and older Brazilians

The objective of this study was to describe the anthropometric profiles of elite older triathletes participating in the 2009 Ironman Brazil and to compare their somatotype, anthropometric and body composition characteristics with those of elite young triathletes and older non-athletes. The sample consisted of 64 males, divided into three groups: (1) older triathletes (n = 17), (2) young triathletes (n = 24), and (3) older non-athletes (n = 23). Somatotype was analysed according to the Carter and Heath ( 1990 ) method. Body mass index, sum of four skinfolds, percentage body fat, body fat mass, and fat-free mass were also estimated. Older non-athletes had higher endomorphy, sum of four skinfolds, fat percentage, and body fat mass than the athletes. Older athletes who participated in the Ironman and elite young triathletes had higher fat-free mass than older non-athletes. Older triathletes and older non-athletes were considered mainly endomorphic mesomorphs and young triathletes mainly ectomorphic mesomorphs. The findings that characterize the anthropometric profile of athletes in this sports modality could be used as a reference.     

Injury rates in professional soccer players during Ramadan

Many of the socio-cultural lifestyle and dietary changes that take place during Ramadan may affect the risk of injury in athletes, but little evidence is available. The aim of the present study was to examine the effects over two consecutive years of the holy month of Ramadan on injury rates in 42 professional players of a Tunisian top-level professional soccer team. Players were retrospectively organized into fasting and non-fasting groups and monitored for 3 months: 4 weeks before Ramadan, during the month of Ramadan (4 weeks), and 4 weeks after Ramadan each year. During Ramadan, training started at 22.00 h. The circumstances (training/match) and mechanism of injury (traumatic/overuse) were recorded. No significant differences between the three periods were observed for weekly mean training load, training strain, training duration, and Hooper's Index (quality of sleep, and quantities of stress, delayed-onset muscle soreness, and fatigue). Compared with non-fasting players, fasters had a lower (P < 0.05) Hooper's Index and stress during and after Ramadan. No significant difference in injury rates was observed between fasting and non-fasting players. Nevertheless, the rates of non-contact (6.8 vs. 0.6 and 1.1) and training overuse (5.6 vs. 0.6 and 0.5) injuries were significantly higher in fasting players during the month of Ramadan than before or after Ramadan. In conclusion, Ramadan, along with the corresponding changes in nutritional habits, sleeping schedule, and socio-cultural and religious events, significantly increased overuse and non-contact injuries in fasting players despite the fact that the training load, strain, and duration were maintained.     

Design and performance analysis of PID controller for an automatic voltage regulator system using simplified particle swarm optimization

This paper presents the design and performance analysis of Proportional Integral Derivate (PID) controller for an Automatic Voltage Regulator (AVR) system using recently proposed simplified Particle Swarm Optimization (PSO) also called Many Optimizing Liaisons (MOL) algorithm. MOL simplifies the original PSO by randomly choosing the particle to update, instead of iterating over the entire swarm thus eliminating the particles best known position and making it easier to tune the behavioral parameters. The design problem of the proposed PID controller is formulated as an optimization problem and MOL algorithm is employed to search for the optimal controller parameters. For the performance analysis, different analysis methods such as transient response analysis, root locus analysis and bode analysis are performed. The superiority of the proposed approach is shown by comparing the results with some recently published modern heuristic optimization algorithms such as Artificial Bee Colony (ABC) algorithm, Particle Swarm Optimization (PSO) algorithm and Differential Evolution (DE) algorithm. Further, robustness analysis of the AVR system tuned by MOL algorithm is performed by varying the time constants of amplifier, exciter, generator and sensor in the range of ?50% to +50% in steps of 25%. The analysis results reveal that the proposed MOL based PID controller for the AVR system performs better than the other similar recently reported population based optimization algorithms.     

An approach to web-based Personal Health Records filtering using fuzzy prototypes and data quality criteria

Nowadays, new ways of managing and accessing to health-care information are continuously appearing. Web-based Personal Health Records (web PHRs) have the potential to make data about health-care available to clinicians, researchers and students in different medical contexts and applications. Therefore, the amount of web PHRs accessible through Internet has grown enormously and as a result health-care professionals are currently burdened with more and more data. It’s probable that these data, unfortunately, have not always the adequate levels of quality, making that their work cannot always be as successful as expected. As a way of alleviating this fact, the present work is focused on improving the document filtering results in the context of web PHRs management. To achieve this goal, a new kind of document filtering model is proposed. This model is based on fuzzy prototypes which are defined by means of conceptual prototypes. These prototypes are obtained by using a data quality analysis of documents. This analysis guarantees that filtered information will be relevant enough for the information user. The complete model provides an efficient strategy of document filtering that can be very useful when it is necessary to deal with a constant flow of new information.