Compilation of somatic mutations of the CDKN2 gene in human cancers : non-random distribution of base substitutions

The CDKN2 gene, encoding the cyclin-dependent kinase inhibitor p16, is a tumour suppressor gene that maps to chromosome band 9p21-p22. The most common mechanism of inactivation of this gene in human cancers is through homozygous deletion; however, in a smaller proportion of tumours and tumour cell lines intragenic mutations occur. In this study we have compiled a database of over 120 published point mutations in the CDKN2 gene from a wide variety of tumour types. A further 50 deletions, insertions, and splice mutations in CDKN2 have also been compiled. Furthermore, we have standardised the numbering of all mutations according to the full-length 156 amino acid form of p16. From this study we are able to define several hot spots, some of which occur at conserved residues within the ankyrin domains of p16. While many of the hotspots are shared by a number of cancers, the relative importance of each position varies, possibly reflecting the role of different carcinogens in the development of certain tumours. As reported previously, the mutational spectrum of CDKN2 in melanomas differs from that of internal malignancies and supports the involvement of UV in melanoma tumorigenesis. Notably, 52% of all substitutions in melanoma-derived samples occurred at just six nucleotide positions. Nonsense mutations comprise a comparatively high proportion of mutations present in the CDKN2 gene, and possible explanations for this are discussed.

Developing a knowledge base for enterprise system success: the role of management and operational staff

Knowledge base is one of the emerging concepts in the Knowledge Management area. As there exists no agreed- upon standard definition of a knowledge base, this paper defines a knowledge base in terms of our research of Enterprise Systems (ES). The knowledge base is defined with reference to Learning Network Theory. Using this theoretical framework, we investigate the roles of management and operational staff in organisations and how their interactions can create a better ES-knowledge base to contribute to ES success. We focus on the post- implementation phase of ES as part of the ES lifecycle. Our findings will facilitate future research directions and contribute to better understandings of how the knowledge base can be integrated and how this integration leads to Enterprise System success.

Effect of cold water immersion on repeated cycling performance and limb blood flow

The purpose of the present study was to compare the effects of cold water immersion (CWI) and active recovery (ACT) on resting limb blood flow, rectal temperature and repeated cycling performance in the heat. Ten subjects completed two testing sessions separated by 1 week; each trial consisted of an initial all-out 35-min exercise bout, one of two 15-min recovery interventions (randomised: CWI or ACT), followed by a 40-min passive recovery period before repeating the 35-min exercise bout. Performance was measured as the change in total work completed during the exercise bouts. Resting limb blood flow, heart rate, rectal temperature and blood lactate were recorded throughout the testing sessions. There was a significant decline in performance after ACT (mean (SD) −1.81% (1.05%)) compared with CWI where performance remained unchanged (0.10% (0.71%)). Rectal temperature was reduced after CWI (36.8°C (1.0°C)) compared with ACT (38.3°C (0.4°C)), as was blood flow to the arms (CWI 3.64 (1.47) ml/100 ml/min; ACT 16.85 (3.57) ml/100 ml/min) and legs (CW 4.83 (2.49) ml/100 ml/min; ACT 4.83 (2.49) ml/100 ml/min). Leg blood flow at the end of the second exercise bout was not different between the active (15.25 (4.33) ml/100 ml/min) and cold trials (14.99 (4.96) ml/100 ml/min), whereas rectal temperature (CWI 38.1°C (0.3°C); ACT 38.8°C (0.2°C)) and arm blood flow (CWI 20.55 (3.78) ml/100 ml/min; ACT 23.83 (5.32) ml/100 ml/min) remained depressed until the end of the cold trial. These findings indicate that CWI is an effective intervention for maintaining repeat cycling performance in the heat and this performance benefit is associated with alterations in core temperature and limb blood flow.

Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients

Background: High-flow nasal cannulae (HFNC) create positive oropharyngeal airway pressure but it is unclear how their use affects lung volume. Electrical impedance tomography (EIT) allows assessment of changes in lung volume by measuring changes in lung impedance. Primary objectives were to investigate the effects of HFNC on airway pressure (Paw) and end-expiratory lung volume (EELV), and to identify any correlation between the two. Secondary objectives were to investigate the effects of HFNC on respiratory rate (RR), dyspnoea, tidal volume and oxygenation; and the interaction between body mass index (BMI) and EELV. Methods: Twenty patients prescribed HFNC post-cardiac surgery were investigated. Impedance measures, Paw, PaO2/FiO2 ratio, RR and modified Borg scores were recorded first on low flow oxygen (nasal cannula or Hudson face mask) and then on HFNC. Results: A strong and significant correlation existed between Paw and end-expiratory lung impedance (EELI) (r=0.7, p<0.001). Compared with low flow oxygen, HFNC significantly increased EELI by 25.6% (95% CI 24.3, 26.9) and Paw by 3.0 cmH2O (95% CI 2.4, 3.7). RR reduced by 3.4 breaths per minute (95% CI 1.7, 5.2) with HFNC use, tidal impedance variation increased by 10.5% (95% CI 6.1, 18.3) and PaO2/FiO2 ratio improved by 30.6 mmHg (95% CI 17.9, 43.3). HFNC improved subjective dyspnoea scoring (p=0.023). Increases in EELI were significantly influenced by BMI, with larger increases associated with higher BMIs (p<0.001). Conclusions: This study suggests that HFNC improve dyspnoea and oxygenation by increasing both EELV and tidal volume, and are most beneficial in patients with higher BMIs.

Natural convection flow in a porous enclosure with localized heating from below

Natural convection flow in a two-dimensional fluid saturated porous enclosure with localized heating from below, symmetrical cooling from the sides and the top and rest of the bottom walls are insulated, has been investigated numerically. Darcy’s law for porous media along with the energy equation based on the 1st law of thermodynamics has been considered. Implicit finite volume method with TDMA solver is used to solve the governing equations. Localized heating is simulated by a centrally located isothermal heat source on the bottom wall, and four different values of the dimensionless heat source length, 1/5, 2/5, 3/5 and 4/5 are considered. The effect of heat source length and the Rayleigh number on streamlines and isotherms are presented, as well as the variation of the local rate of heat transfer in terms of the local Nusselt number from the heated wall. Finally, the average Nusselt number at the heated part of the bottom wall has been shown against Rayleigh number for the non-dimensional heat source length.

Data flow analysis of embedded program expressions

Data flow analysis techniques can be used to help assess threats to data confidentiality and integrity in security critical program code. However, a fundamental weakness of static analysis techniques is that they overestimate the ways in which data may propagate at run time. Discounting large numbers of these false-positive data flow paths wastes an information security evaluator's time and effort. Here we show how to automatically eliminate some false-positive data flow paths by precisely modelling how classified data is blocked by certain expressions in embedded C code. We present a library of detailed data flow models of individual expression elements and an algorithm for introducing these components into conventional data flow graphs. The resulting models can be used to accurately trace byte-level or even bit-level data flow through expressions that are normally treated as atomic. This allows us to identify expressions that safely downgrade their classified inputs and thereby eliminate false-positive data flow paths from the security evaluation process. To validate the approach we have implemented and tested it in an existing data flow analysis toolkit.

Natural convection in a triangular enclosure due to non-uniform cooling on top

Natural convection in a triangular enclosure subject to non-uniformly cooling at the inclined surfaces and uniformly heating at the base is investigated numerically. The numerical simulations of the unsteady flows over a range of Rayleigh numbers and aspect ratios are carried out using Finite Volume Method. Since the upper surface is cooled and the bottom surface is heated, the air flow in the enclosure is potentially unstable to Rayleigh Benard instability. It is revealed that the transient flow development in the enclosure can be classified into three distinct stages; an early stage, a transitional stage and a steady stage. It is also found that the flow inside the enclosure strongly depends on the governing parameters, Rayleigh number and aspect ratio. The asymmetric behaviour of the flow about the geometric centre line is discussed in detailed. The heat transfer through the roof and the ceiling as a form of Nusselt number is also reported in this study.

Mixed convection laminar flow along a horizontal plate subject to streamwise sinusoidal surface temperature

Mixed convection of a two-dimensional laminar incompressible flow along a horizontal flat plate with streamwise sinusoidal surface temperature has been numerically investigated for different values of Rayleigh number and Reynolds number for constant values of Prandtl number, amplitude and frequency of periodic temperature. The numerical scheme is based on the finite element method adapted to rectangular non-uniform mesh elements by a non-linear parametric solution algorithm. The fluid considered in this study is air. The results are obtained for the Rayleigh number and Reynolds number ranging from 102 to 104 and 1 to 100, respectively, with constant physical properties for the fluid medium considered. Velocity and temperature profiles, streamlines, isotherms, and average Nusselt numbers are presented to observe the effect of the investigating parameters on fluid flow and heat transfer characteristics. The present results show that the convective phenomena are greatly influenced by the variation of Rayleigh numbers and Reynolds number.

Flow regime transition criteria for two-phase flow at reduced gravity conditions

Flow regime transition criteria are of practical importance for two-phase flow analyses at reduced gravity conditions. Here, flow regime transition criteria which take the friction pressure loss effect into account were studied in detail. Criteria at reduced gravity conditions were developed by extending an existing model with various experimental datasets taken at microgravity conditions showed satisfactory agreement. Sample computations of the model were performed at various gravity conditions, such as 0.196, 1.62, 3.71, and 9.81 m/s2 corresponding to micro-gravity and lunar, Martian and Earth surface gravity, respectively. It was found that the effect of gravity on bubbly-slug and slug-annular (churn) transitions in a two-phase flow system was more pronounced at low liquid flow conditions, whereas the gravity effect could be ignored at high mixture volumetric flux conditions. While for the annular flow transitions due to flow reversal and onset of dropset entrainment, higher superficial gas velocity was obtained at higher gravity level.

Effect of MHD and heat generation on natural convection flow in an open square cavity under microgravity condition

Purpose - Thermo-magnetic convection and heat transfer of paramagnetic fluid placed in a micro-gravity condition (g = 0) and under a uniform vertical gradient magnetic field in an open square cavity with three cold sidewalls have been studied numerically. Design/methodology/approach - This magnetic force is proportional to the magnetic susceptibility and the gradient of the square of the magnetic induction. The magnetic susceptibility is inversely proportional to the absolute temperature based on Curie’s law. Thermal convection of a paramagnetic fluid can therefore take place even in zero-gravity environment as a direct consequence of temperature differences occurring within the fluid due to a constant internal heat generation placed within a magnetic field gradient. Findings - Effects of magnetic Rayleigh number, Ra, Prandtl number, Pr, and paramagnetic fluid parameter, m, on the flow pattern and isotherms as well as on the heat absorption are presented graphically. It is found that the heat transfer rate is suppressed in increased of the magnetic Rayleigh number and the paramagnetic fluid parameter for the present investigation. Originality/value - It is possible to control the buoyancy force by using the super conducting magnet. To the best knowledge of the author no literature related to magnetic convection for this configuration is available.

MHD natural convection flow from an isothermal horizontal circular cylinder under consideration of temperature dependent viscosity

Magnetohydrodynamic (MHD) natural convection laminar flow from an iso-thermal horizontal circular cylinder immersed in a fluid with viscosity proportional to a linear function of temperature will be discussed with numerical simulations. The governing boundary layer equations are transformed into a non-dimensional form and the resulting nonlinear system of partial differential equa-tions are reduced to convenient form, which are solved numerically by two very efficient methods, namely, (i) Implicit finite difference method together with Keller box scheme and (ii) Direct numerical scheme. Numerical results are presented by velocity and temperature distributions of the fluid as well as heat transfer characteristics, namely the shearing stress and the local heat transfer rate in terms of the local skin-friction coefficient and the local Nusselt number for a wide range of magnetohydrodynamic parameter, viscosity-variation parameter and viscous dissipation parameter. MHD flow in this geometry with temperature dependent viscosity is absent in the literature. The results obtained from the numerical simulations have been veri-fied by two methodologies.

Field study of air change and flow rate in six automobiles

For many people, a relatively large proportion of daily exposure to a multitude of pollutants may occur inside an automobile. A key determinant of exposure is the amount of outdoor air entering the cabin (i.e. air change or flow rate). We have quantified this parameter in six passenger vehicles ranging in age from 18 years to <1 year, at three vehicle speeds and under four different ventilation settings. Average infiltration into the cabin with all operable air entry pathways closed was between 1 and 33.1 air changes per hour (ACH) at a vehicle speed of 60 km/h, and between 2.6 and 47.3 ACH at 110 km/h, with these results representing the most (2005 Volkswagen Golf) and least air-tight (1989 Mazda 121) vehicles, respectively. Average infiltration into stationary vehicles parked outdoors varied between ~0 and 1.4 ACH and was moderately related to wind speed. Measurements were also performed under an air recirculation setting with low fan speed, while airflow rate measurements were conducted under two non-recirculate ventilation settings with low and high fan speeds. The windows were closed in all cases, and over 200 measurements were performed. The results can be applied to estimate pollutant exposure inside vehicles.

Scheduling a flow-shop with combined buffer conditions

In this paper, No-Wait, No-Buffer, Limited-Buffer, and Infinite-Buffer conditions for the flow-shop problem (FSP) have been investigated. These four different buffer conditions have been combined to generate a new class of scheduling problem, which is significant for modelling many real-world scheduling problems. A new heuristic algorithm is developed to solve this strongly NP-hard problem. Detailed numerical implementations have been analysed and promising results have been achieved.

Internet-enabled international entrepreneurship : a conceptual exploration of the link between a firm’s resource base, dynamic capabilities and international market performance

It has been suggested that the accumulation of valuable resources and capabilities, such as Internet application, is not enough to support a firm’s sustainable competitive advantage, especially for high technology-mediated firms; which often operate in fast changing dynamic environments. While the idea of ‘Internet-enabled resources and capabilities’ has been recognised by RBV theorists, the notion has largely been ignored in conceptual and empirical studies. Given this finding, a conceptual framework is constructed and research issues are then developed in order to focus attention on the relationship between, the Internet and a firm’s resource base, dynamic capabilities and international market performance. We postulate that successful Internet-enabled market performance arises from those international entrepreneurial-oriented firms which encompass: international vision, international business experience, Internet-international marketing capabilities and international networking capabilities. Recommendations for future theory development are presented, along with the implications for international entrepreneurial managers in Australian small and medium sized firms

Tax concessions for charities : competitive neutrality, the tax base and "public goods" choice

It is argued that concerns arise about the integrity and fairness of the taxation regime where charitable organizations, which avail themselves of the tax exemption status while undertaking commercial activities, compete directly with the for-profit sector. The appropriateness of the tax concessions granted to charitable organizations is considered in respect of income derived from commercial activities. It is principally argued that the traditional line of reasoning for imposing limitations on tax concessions focuses on an incorrect underlying inquiry. Traditionally, it is argued that limitations should be imposed because of unfair competition, lack of competitive neutrality, or an arbitrary decision relating to a lack of deserving. However, it is argued that a more appropriate question from which to base any limitations is one which considers the value attached to the integrity of the taxation regime as a whole, and the tax base specifically compared to the public good of charities. When the correct underlying question is asked, sound taxation policy ensues, as a less arbitrary approach may be adopted to limit the scope of tax concessions available to charitable organizations.