Flotillins and the PHB domain protein family: Rafts, worms and anaesthetics

While our understanding of lipid microdomains has advanced in recent years, many aspects of their formation and dynamics are still unclear. In particular, the molecular determinants that facilitate the partitioning of integral membrane proteins into lipid raft domains are yet to be clarified. This review focuses on a family of raft-associated integral membrane proteins, termed flotillins, which belongs to a larger class of integral membrane proteins that carry an evolutionarily conserved domain called the prohibitin homology (PHB) domain. A number of studies now suggest that eucaryotic proteins carrying this domain have affinity for lipid raft domains. The PHB domain is carried by a diverse array of proteins including stomatin, podocin, the archetypal PHB protein, prohibitin, lower eucaryotic proteins such as the Dictyostelium discoideum proteins vacuolin A and vacuolin B and the Caenorhabditis elegans proteins unc-1, unc-24 and mec-2. The presence of this domain in some procaryotic proteins suggests that the PHB domain may constitute a primordial lipid recognition motif. Recent work has provided new insights into the trafficking and targeting of flotillin and other PHB domain proteins. While the function of this large family of proteins remains unclear, studies of the C. elegans PHB proteins suggest possible links to a class of volatile anaesthetics raising the possibility that these lipophilic agents could influence lipid raft domains. This review will discuss recent insights into the cell biology of flotillins and the large family of evolutionarily conserved PHB domain proteins.

Quadriceps activity and movement reactions in response to unpredictable sagittal support-surface translations in women with patellofemoral pain

Patellofemoral pain (PFP) may be related to unfavorable knee joint loading. Delayed and/or reduced activity of vastus medialis obliquus (VMO) and different movement patterns have been identified in individuals with PFP in some studies, whereas other studies have failed to show a difference compared to non-affected controls. The discrepancy between study results may depend on the different tasks that have been investigated. No previous study has investigated these variables in postural responses to unpredictable perturbations in PFP. Whole body three dimensional kinematics and surface EMG of quadriceps muscles activation was studied in postural responses to unpredictable support surface translations in 17 women with PFP who were pain free at the time of testing, and 17 matched healthy controls. The results of the present study showed earlier onset of VMO activity and associated changes in kinematics to anterior platform translation in the PFP subjects. We suggest that the relative timing between the portions quadriceps muscles may be task specific and part of an adapted response in attempt to reduce knee joint loading. This learned response appears to remain even when the pain is no longer present.

The lattice solid model to simulate the physics of rocks and earthquakes: Incorporation of friction

The particle-based lattice solid model developed to study the physics of rocks and the nonlinear dynamics of earthquakes is refined by incorporating intrinsic friction between particles. The model provides a means for studying the causes of seismic wave attenuation, as well as frictional heat generation, fault zone evolution, and localisation phenomena. A modified velocity-Verlat scheme that allows friction to be precisely modelled is developed. This is a difficult computational problem given that a discontinuity must be accurately simulated by the numerical approach (i.e., the transition from static to dynamical frictional behaviour). This is achieved using a half time step integration scheme. At each half time step, a nonlinear system is solved to compute the static frictional forces and states of touching particle-pairs. Improved efficiency is achieved by adaptively adjusting the time step increment, depending on the particle velocities in the system. The total energy is calculated and verified to remain constant to a high precision during simulations. Numerical experiments show that the model can be applied to the study of earthquake dynamics, the stick-slip instability, heat generation, and fault zone evolution. Such experiments may lead to a conclusive resolution of the heat flow paradox and improved understanding of earthquake precursory phenomena and dynamics. (C) 1999 Academic Press.

Globalisation and security in the Taiwan Straits

Only recently the Sino-Taiwanese issue has again been in the headlines of the international media. On Saturday, 3 August 2002, Taiwan's President Chen Shui-bian insisted in a passionate speech that there is 'one country on each side' of the Taiwan Strait. He went even further by calling for new legislation that would allow a referendum to be held on changing the island's current international status, saying that this would be a 'basic human right'. Chen's remarks resulted in a furious response from the mainland. Although the conflict between Beijing and Taipei can be interpreted as a legacy of the Chinese Civil War, the tensions intensified during the 1990s. The following article suggests that the linkages and dynamics between the globalization process and international security are increasingly important for a better understanding of the development of relations at the international level in general and in the China-Taiwan conflict in particular.

Management role in employee participation:a comparative study of multi-national enterprises in India and the U.K.

This research is an Anglo-Indian comparative case study. It studies managerial action in the participation arena of two British multi-nationals i.e. Cadbury Limited and ICI plc. The research was carried out in matched pairs of factories of the above named companies, located in the Midlands of the UK and in Bombay in India. The data for this research was collected through semi-structured interviews with managers and non-management actors, study of company documents and non-participant observation of some participation forums. The research conceptualises the idea of a `participation arena' consisting of the structures, processes, purposes and dynamics of participation. This arena is visualised as broadly reflecting the organisation structure and can be divided into corporate, unit and shopfloor level. Managerial action in this arena is examined in terms of interaction between three sets of factors i.e. company business objectives, strategies and policies; managerial values of power and control; and the responses of unions. Similarities and differences between management action in the home and host plants of the two multi-national companies are also examined. The major findings of the research are as follows. There is significant difference between the participation arena of the parent and the subsidiary company. The latter is marked by absence of higher level participation forums and lack of opportunity for employees to discuss, let alone influence, key decisions. This results from parent company control over key activities of the subsidiary. The similarities in management action in the participation arenas of the two companies in both countries can be attributed to the operation of the three sets of factors mentioned above. Nevertheless, the particular circumstances of each company are a greater influence on managerial action than the national context. Finally, future areas of research in this field are explored.

Finite element analysis of the statics of and vibrations in axisymmetric shells

The finite element process is now used almost routinely as a tool of engineering analysis. From early days, a significant effort has been devoted to developing simple, cost effective elements which adequately fulfill accuracy requirements. In this thesis we describe the development and application of one of the simplest elements available for the statics and dynamics of axisymmetric shells . A semi analytic truncated cone stiffness element has been formulated and implemented in a computer code: it has two nodes with five degrees of freedom at each node, circumferential variations in displacement field are described in terms of trigonometric series, transverse shear is accommodated by means of a penalty function and rotary inertia is allowed for. The element has been tested in a variety of applications in the statics and dynamics of axisymmetric shells subjected to a variety of boundary conditions. Good results have been obtained for thin and thick shell cases .

Molecular dynamics simulations:bring biomolecular structures alive on a computer

The molecular dynamics (MD) simulations play a very important role in science today. They have been used successfully in binding free-energy calculations and rational design of drugs and vaccines. MD simulations can help visualize and understand structures and dynamics at an atomistic level when combined with molecular graphics programs. The molecular and atomistic properties can be displayed on a computer in a time-dependent way, which opens a road toward a better understanding of the relationship of structure, dynamics, and function. In this chapter, the basics of MD are explained, together with a step-by-step description of setup and running an MD simulation.

Tear analysis and lens-tear interactions:Part I. Protein fingerprinting with microfluidic technology

The purpose of this work is to establish the application of a fully automated microfluidic chip based protein separation assay in tear analysis. It is rapid, requires small sample volumes and is vastly superior to, and more convenient than, comparable conventional gel electrophoresis assays. The protein sizing chip technology was applied to three specific fields of analysis. Firstly tear samples were collected regularly from subjects establishing the baseline effects of tear stimulation, tear state and patient health. Secondly tear samples were taken from lens wearing eyes and thirdly the use of microfluidic technology was assessed as a means to investigate a novel area of tear analysis, which we have termed the 'tear envelope'. Utilising the Agilent 2100 Bioanalyzer in combination with the Protein 200 Plus LabChip kit, these studies investigated tear proteins in the range of 14-200 kDa. Particular attention was paid to the relative concentrations of lysozyme, tear lipocalin, secretory IgA (sIgA), IgG and lactoferrin, together with the overall tear electropherogram 'fingerprint'. Furthermore, whilst lens-tear interaction studies are generally thought of as an investigation into the effects of tears components on the contact lens material, i.e. deposition studies, this report addresses the reverse phenomenon-the effect of the lens, and particularly the newly inserted lens, on the tear fluid composition and dynamics. The use of microfluidic technology provides a significant advance in tear studies and should prove invaluable in tear diagnostics and contact lens performance analysis.

Species differential regulation of COX2 can be described by an NFκB-dependent logic AND gate

Cyclooxygenase 2 (COX2), a key regulatory enzyme of the prostaglandin/eicosanoid pathway, is an important target for anti-inflammatory therapy. It is highly induced by pro-inflammatory cytokines in a Nuclear factor kappa B (NFκB)-dependent manner. However, the mechanisms determining the amplitude and dynamics of this important pro-inflammatory event are poorly understood. Furthermore, there is significant difference between human and mouse COX2 expression in response to the inflammatory stimulus tumor necrosis factor alpha (TNFα). Here, we report the presence of a molecular logic AND gate composed of two NFκB response elements (NREs) which controls the expression of human COX2 in a switch-like manner. Combining quantitative kinetic modeling and thermostatistical analysis followed by experimental validation in iterative cycles, we show that the human COX2 expression machinery regulated by NFκB displays features of a logic AND gate. We propose that this provides a digital, noise-filtering mechanism for a tighter control of expression in response to TNFα, such that a threshold level of NFκB activation is required before the promoter becomes active and initiates transcription. This NFκB-regulated AND gate is absent in the mouse COX2 promoter, most likely contributing to its differential graded response in promoter activity and protein expression to TNFα. Our data suggest that the NFκB-regulated AND gate acts as a novel mechanism for controlling the expression of human COX2 to TNFα, and its absence in the mouse COX2 provides the foundation for further studies on understanding species-specific differential gene regulation.

Nonlinear multicore waveguiding structures with balanced gain and loss

We study existence, stability, and dynamics of linear and nonlinear stationary modes propagating in radially symmetric multicore waveguides with balanced gain and loss. We demonstrate that, in general, the system can be reduced to an effective PT-symmetric dimer with asymmetric coupling. In the linear case, we find that there exist two modes with real propagation constants before an onset of the PT-symmetry breaking while other modes have always the propagation constants with nonzero imaginary parts. This leads to a stable (unstable) propagation of the modes when gain is localized in the core (ring) of the waveguiding structure. In the case of nonlinear response, we show that an interplay between nonlinearity, gain, and loss induces a high degree of instability, with only small windows in the parameter space where quasistable propagation is observed. We propose a novel stabilization mechanism based on a periodic modulation of both gain and loss along the propagation direction that allows bounded light propagation in the multicore waveguiding structures.

The big 4 in Bangladesh:caught between the global and the local

Purpose- This article explores the work practices of Big 4 firms in Bangladesh with the aim of exploring the extent to which Global Professional Service Firms can be thought of as being genuinely ‘global’. Methodology/Approach- Interviews were undertaken with the vast majority of Big 4 partners in Bangladesh. These interviews explored a number of themes related to the professional service work context in Bangladesh and the relationship between local and global firms. Findings- The central finding of this paper is that although the Big 4 have a long-established presence in Bangladesh, local societal factors heavily influence the realities of work for accountants there. In most cases the Big 4 firms establish correspondent firms (instead of full member firms) in Bangladesh and tend to offer restricted service lines. Additionally, the paper identifies professional, commercial and cultural barriers to greater Big 4 involvement in the local market. Conceptually, the chief contribution of this paper is to explore how the effects of globalising capitalism and standardised ‘best practices’ in global professional service work are mediated through the societal effects of Bangladeshi society, resulting in the Big 4 having only a tentative presence in the Bangladeshi market. Research implications- The findings cast doubt on the extent to which self-styled Global Professional Service firms are truly ‘global’ in nature. Future work examining the Big 4, or accounting more generally, in the context of globalization, would do well to pay greater attention to the experience of professionals in emerging markets. Originality/Value- Whilst there has been much work looking at accounting and accountants in the context of globalization, this work has tended to privilege ‘core’ western empirical settings. Very little is known about Professional Service Firms in ‘peripheral’ or emerging markets. Furthermore, this study extends the application of the System, Society and Dominance framework by mapping the interactions and dynamics of these three sources of influence in the setting of PSFs.

Mechanistic studies on the degradation of gasoline oxygenates by advanced oxidation technologies and the reaction of 4-methyl-1,2,4-triazoline-3,5-dione with tetracyclopropylethylene

Gasoline oxygenates (MTBE, methyl tert-butyl ether; DIPE, di-isopropyl ether; ETBE, ethyl tert-butyl ether; TAME, tert-amyl ether) are added to gasoline to boost octane and enhance combustion. The combination of large scale use, high water solubility and only minor biodegradability has now resulted in a significant gasoline oxygenate contamination occurring in surface, ground, and drinking water systems. Combination of hydroxyl radical formation and the pyrolytic environment generated by ultrasonic irradiation (665 kHz) leads to the rapid degradation of MTBE and other gasoline oxygenates in aqueous media. ^ The presence of oxygen promotes the degradation processes by rapid reaction with carbon centered radicals indicating radical processes involving O 2 are significant pathways. A number of the oxidation products were identified. The formation of products (alcohols, ketones, aldehydes, esters, peroxides, etc) could be rationalized by mechanisms which involve hydrogen abstraction by OH radical and/or pyrolysis to form carboncentered radicals which react with oxygen and follow standard oxidation chain processes. ^ The reactions of N-substituted R-triazolinediones (RTAD; R = CH 3 or phenyl) have attracted considerable interest because they exhibit a number of unusual mechanistic characteristics that are analogous to the reactions of singlet oxygen (1O2) and offer an easy way to provide C-N bond(s) formation. The reactions of triazolinedione with olefins have been widely studied and aziridinium imides are generally accepted to be the reactive intermediates. ^ We observed the rapid formation of an unusual intermediate upon mixing tetracyclopropylethylene with 4-methyl-1,2,4-triazoline-3,5-dione in CDCl 3. Detailed characterization by NMR (proton, 13C, 2-D NMRs) indicates the intermediate is 5,5,6,6-tetracyclopropyl-3-methyl-5,6-dihydro-oxazolo[3,2- b][1,2,4]-triazolium-2-olate. Such products are extremely rare and have not been studied. Upon warming the intermediate is converted to 2 + 2 diazetidine (major) and ene product (minor). ^ To further explore the kinetics and dynamics of the reaction activation energies were obtained using Arrhenius plots. Activation energies for the formation of the intermediate from reactants, and 2+2 adduct from the intermediate were determined as 7.48 kcal moll and 19.8 kcal mol−1 with their pre-exponential values of 2.24 × 105 dm 3 mol−1 sec−1 and 2.75 × 108 sec−1, respectively, meaning net slow reactions because of low pre-exponential values caused by steric hindrance. ^

Cross sections and Rosenbluth separations from kaon electroproduction on protons up to Q2 = 2.35 (GeV/c)2

The kaon electroproduction reaction H(e, e ′K+)Λ was studied as a function of the four momentum transfer, Q2, for different values of the virtual photon polarization parameter. Electrons and kaons were detected in coincidence in two High Resolution Spectrometers (HRS) at Jefferson Lab. Data were taken at electron beam energies ranging from 3.4006 to 5.7544 GeV. The kaons were identified using combined time of flight information and two Aerogel Čerenkov detectors used for particle identification. For different values of Q2 ranging from 1.90 to 2.35 GeV/c2 the center of mass cross sections for the Λ hyperon were determined for 20 kinematics and the longitudinal, σ L, and transverse, σT, terms were separated using the Rosenbluth separation technique. ^ Comparisons between available models and data have been studied. The comparison supports the t-channel dominance behavior for kaon electroproduction. All models seem to underpredict the transverse cross section. An estimate of the kaon form factor has been explored by determining the sensitivity of the separated cross sections to variations of the kaon EM form factor. From comparison between models and data we can conclude that interpreting the data using the Regge model is quite sensitive to a particular choice for the EM form factors. The data from the E98-108 experiment extends the range of the available kaon electroproduction cross section data to an unexplored region of Q2 where no separations have ever been performed. ^

Spatial, geomorphological, and seasonal variability of CDOM in estuaries of the Florida Coastal Everglades

This paper demonstrates the usefulness of fluorescence techniques for long-term monitoring and assessment of the dynamics (sources, transport and fate) of chromophoric dissolved organic matter (CDOM) in highly compartmentalized estuarine regions with non-point water sources. Water samples were collected monthly from a total of 73 sampling stations in the Florida Coastal Everglades (FCE) estuaries during 2001 and 2002. Spatial and seasonal variability of CDOM characteristics were investigated for geomorphologically distinct sub-regions within Florida Bay (FB), the Ten Thousand Islands (TTI), and Whitewater Bay (WWB). These variations were observed in both quantity and quality of CDOM. TOC concentrations in the FCE estuaries were generally higher during the wet season (June–October), reflecting high freshwater loadings from the Everglades in TTI, and a high primary productivity of marine biomass in FB. Fluorescence parameters suggested that the CDOM in FB is mainly of marine/microbial origin, while for TTI and WWB a terrestrial origin from Everglades marsh plants and mangroves was evident. Variations in CDOM quality seemed mainly controlled by tidal exchange/mixing of Everglades freshwater with Florida Shelf waters, tidally controlled releases of CDOM from fringe mangroves, primary productivity of marine vegetation in FB and diagenetic processes such as photodegradation (particularly for WWB). The source and dynamics of CDOM in these subtropical estuaries is complex and found to be influenced by many factors including hydrology, geomorphology, vegetation cover, landuse and biogeochemical processes. Simple, easy to measure, high sample throughput fluorescence parameters for surface waters can add valuable information on CDOM dynamics to long-term water quality studies which can not be obtained from quantitative determinations alone.

Magnetic nanoparticle-based targeted drug delivery for treatment of neuro-AIDS and drug addiction

Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain results in several mild-to-severe neuro-immunological complications termed neuroAIDS. One-tenth of HIV-infected population is addicted to recreational drugs such as opiates, alcohol, nicotine, marijuana, etc. which share common target-areas in the brain with HIV. Interestingly, intensity of neuropathogenesis is remarkably enhanced due to exposure of recreational drugs during HIV infection. Current treatments to alleviate either the individual or synergistic effects of abusive drugs and HIV on neuronal modulations are less effective at CNS level, basically due to impermeability of therapeutic molecules across blood-brain barrier (BBB). Despite exciting advancement of nanotechnology in drug delivery, existing nanovehicles such as dendrimers, polymers, micelles, etc. suffer from the lack of adequate BBB penetrability before the drugs are engulfed by the reticuloendothelial system cells as well as the uncertainty that if and when the nanocarrier reaches the brain. Therefore, in order to develop a fast, target-specific, safe, and effective approach for brain delivery of anti-addiction, anti-viral and neuroprotective drugs, we exploited the potential of magnetic nanoparticles (MNPs) which, in recent years, has attracted significant importance in biomedical applications. We hypothesize that under the influence of external (non-invasive) magnetic force, MNPs can deliver these drugs across BBB in most effective manner. Accordingly, in this dissertation, I delineated the pharmacokinetics and dynamics of MNPs bound anti-opioid, anti-HIV and neuroprotective drugs for delivery in brain. I have developed a liposome-based novel magnetized nanovehicle which, under the influence of external magnetic forces, can transmigrate and effectively deliver drugs across BBB without compromising its integrity. It is expected that the developed nanoformulations may be of high therapeutic significance for neuroAIDS and for drug addiction as well.