The centrosome is the major microtubule organizing centre (MTOC) in animal cells. Most microtubules (MTs) emanate from the centrosome, where gamma-tubulin ring complexes (gammaTuRCs) act as templates for MT nucleation. During interphase, the centrosome organizes a MT array that imparts shape and polarity to the cell and is essential for intracellular transport and positioning of organelles such as the Golgi apparatus. During mitosis, centrosomes ensure bipolarity and correct orientation of the spindle by forming the spindle poles. In order to switch from the interphasic to the mitotic state, the centrosome undergoes a structural reorganization, termed maturation, which is mainly characterized by an increase in MT nucleation activity.
A full appreciation of how centrosomes contribute to cellular functions requires the isolation and characterization of unknown centrosome-associated molecules. Here we describe the identification and characterization of a novel centrosomal component, the human protein Nlp (ninein-like protein) related to the previously characterized MT-anchoring protein ninein.
In the first part of the present thesis we describe the identification of Nlp as a novel centrosomal substrate of Polo-like kinase 1 (Plk1), an important regulator of mitosis whose activity is required for centrosome maturation. Nlp interacts with two distinct gammaTuRC components, gamma-tubulin and hGCP4, and stimulates MT nucleation. Plk1 phosphorylates Nlp and disrupts its centrosomal association. Overexpression of an Nlp mutant lacking Plk1 phosphorylation sites induces defects in mitotic spindle formation. We propose that Nlp acts as a gammaTuRC binding protein (GTBP), contributing to the MT nucleation activity of the centrosome during interphase. At the onset of mitosis, the displacement of Nlp from the centrosome triggered by Plk1 phosphorylation could represent an important step in the maturation process which allows the centrosome to switch from the interphasic to the mitotic state.
Thus, we conclude that Nlp, as well as the related protein ninein, plays an important role in MT organization. However the function of these two proteins possibly diverged during evolution: whilst Nlp gained a more prominent role in MT nucleation, ninein became principally involved in MT anchoring.
In the second part of this thesis we report the initial characterization of the molecular mechanisms underlying the ability of Nlp and ninein to induce the fragmentation of the Golgi apparatus when overexpressed in human cells. We show that the ability of these two centrosomal proteins to affect the organization of the Golgi clearly depends on their capacity to associate with the cytoplasmic dynein-dynactin complex, a molecular motor complex primarly involved in the maintainance of Golgi architecture. We propose that the excess of Nlp and ninein could induce the disruption of the Golgi apparatus by sequestering the dynein-dynactin complexes.
Future investigations should be aimed at understanding whether the dissociation of the Golgi apparatus from the centrosome induced by the excess of Nlp and ninein could interfere with cell migration and cell polarization processes, which require a highly coordinated action of these two organelles. Cell migration and cell polarization represent critical events for immune responses as well as for embryonic development, invasive growth and metastasis. Thus, our findings raise the interesting possibility that an upregulation in the expression levels of structural centrosomal proteins could represent the molecular basis for developmental disorders and malfunctioning of the immune system and, on the other hand, modulate the acquisition of invasive properties by neoplastic cells.


Background: There is limited understanding of the relationship between single tablet regimen (STR) use and non-HIV related health outcomes among patients with HIV infection. It is unclear if STR use may assist HIV-infected patients with comorbidity control. The purpose of the present study was to compare the frequency of achieving or maintaining cardiometabolic comorbidity control between STR and multiple tablet regimen (MTR) recipients.
Methods and findings: A retrospective cohort study, employing repeated subject sampling, was performed among adult HIV-infected Veterans' Affairs patients who received antiretroviral therapy within the Upstate New York Veterans' Affairs Healthcare Network. Inclusion criteria were: 1) age ≥ 18 years, 2) documentedHIV-infection, 3) antiretroviral therapy for ≥ 3 months with ≥ 3 active agents, and 4) baseline and on-treatment measurements of blood pressure, glucose, lipid laboratory values or any combination thereof. Data collected for each subject included demographics, comorbidities, medication history and select laboratory values. The primary outcomes of this study were control of blood pressure, glucose and/or lipids, defined using national guidelines. There were a total of 1,202 subjects who received either a STR (n=165; 13.7%) or MTR (n=1,037; 86.3%). The mean ± standard deviation (SD) age of subjects was 50.6 ± 8.9 years. In the multivariate analyses, significant differences were not observed in either achieving or maintaining control of any of the cardiometabolic comorbidities evaluated between recipients of STRs and MTRs after adjustment for outcomespecific confounding variables.
Conclusion: For all study endpoints, there did not appear to be meaningful differences between STR/MTRs and patients' ability to achieve control of HIV comorbidities after adjustment for confounding factors. Future studies should seek to further evaluate the impact of ART regimen type on both HIV and non-HIV health outcomes as newer STR products are adopted into standard practice.


The paper has a theoretical part and an applied one. The theoretical part covers the four first sections. The first section makes a historical overview over text automatization. The second section introduces a more cooperative relation between man-machine productions. The third section approaches such cooperation into writing. The fourth section is the link to the communicative-expressive-creative machines, and presents the way communication is modeled by social scholars. Differently, the applied part of the paper has five sections. The fifth section depicts how computer science scholars model communication, its origin and evolution, while the sixth section shows experiments with communicative robots. The seventh section works with the artificial creativity, whereas the eighth section brings examples of artificial artists. The final section deals with a more specific project, artificial writing.


This study simulated the natural convection of dissolved carbon dioxide (CO_2) in a small-scale heterogeneous saline formation using the state module ECO2N equation in the TOUGHREACT model. A one-way downscaling approach that involves using a series of sub-models in simulation procedures was proposed to efficiently simulate problems with high-scale discrepancies. This study evaluated the effects of different degrees of small-scale permeability variations on the vertical migration of dissolved CO_2. The sequential Gaussian simulation model was used to generate unconditional random permeability fields for different natural logarithm of permeability (lnk) variations (i.e., lnk variances and correlations in x and z directions). The results showed an identical transition zone of dissolved CO_2 near the top boundary, where a constant CO_2 gas saturation was specified. The local permeability variations can trigger fingerings and enhance the vertical convection of the dissolved CO_2. The number of fingerings depends on the variations in permeability near the front interface of the dissolved CO_2 (i.e., the bottom edge of the transition zone for the dissolved CO_2). However, the fingering patterns and developments are constrained by the permeability variations along the fingering paths. At the same mean lnk permeability the convection fluxes increase with an increase in lnk variances. However, an increase in lateral correlations (i.e., increase in the correlation lengths in the x direction) can slightly reduce the convection fluxes at the same lnk variance. The highly variable flux rates of the dissolved CO_2 occur early and the variations in the flux rate decrease with time.


Anxiety disorders, such as posttraumatic stress disorder (PTSD), are characterized by a high prevalence and debilitating symptoms. However, the current first-line treatment for these conditions, which consists of selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy, alongside symptomatic treatment with benzodiazepines, does not represent by far a functional solution for all affected patients. Therefore, identifying and characterizing novel candidates for alternative anxiolytic therapies are a crucial focus of psychiatric and neurobiological research.
This study focuses on Neuropeptide S (NPS), a newly identified endogenous neuropeptide that has been shown to exert strong anxiolytic effects upon intracerebral injection in rodents. In an approach that combines basic research with incipient clinically relevant application, novel mechanisms and brain targets of NPS-mediated anxiolytic effects were identified, and a noninvasive application procedure also applicable in patients, namely the intranasal administration, was established for the first time for NPS in mouse models.
In a first step, the feasibility of intranasal NPS delivery was established in mice using fluorophore-coupled NPS to allow intracerebral tracking. This method permitted for the first time tracking of intranasally applied substances within the brain at a single-cell resolution. These results not only proved the applicability of intranasal NPS administration in the mouse, but also allowed identification and characterization of hitherto undescribed cerebral NPS target cells, which were shown to be most likely exclusively neurons. Moreover, specific uptake of fluorescently labeled NPS in the hippocampus provided the first direct evidence linking this brain region, a well-known major player in the regulation of fear expression, to the NPS circuitry. Further investigation into the functional role of the hippocampus in NPS-elicited anxiolytic effects revealed that local microinjections of NPS into the ventral CA1 (vCA1) region are sufficient to elicit anxiolysis in C57BL6/N mice on the elevated plus maze (EPM).
In a second step, behavioral and molecular effects of intranasal NPS treatment were characterized in C57BL/6N mice. Intranasal application of NPS was shown here to produce anxiolytic effects similar to those described by others after intracerebral injection. This finding represents the basis for the implementation of a future NPS-based therapy via nasal sprays in patients suffering from anxiety disorders. Furthermore, the molecular effects of NPS treatment on cerebral protein expression were examined here for the first time. This research led to identification of novel downstream targets of NPS-mediated regulation in the hippocampus and the prefrontal cortex. These new targets include proteins involved in the glutamatergic system and in synaptic plasticity, both of which are known to be dysregulated in anxiety disorders.
Finally, the effects of intranasal NPS treatment, hitherto described only in non-pathological animal models, were examined for the first time in mouse models of anxiety disorders, namely the high anxiety behavior (HAB) mice and a mouse model of PTSD. In HAB mice, NPS treatment elicited anxiolytic effects similar to those observed in C57BL/6N mice. In the mouse model of PTSD, NPS counteracted disease-related changes in expression levels of hippocampal synaptic proteins.
To sum up, this work expands the current state-of-knowledge concerning the molecular and mechanistic background of NPS-mediated anxiolysis by characterizing the role of the hippocampus in the NPS circuitry and by identifying novel downstream targets of NPS. The data on anxiolytic effects of intranasal NPS treatment especially in mouse models of anxiety disorders furthermore establishes the therapeutic potential of NPS as a novel anxiolytic treatment.


We study the effects of homebuyers' beliefs about future house prices on mortgage leverage choice. We show that, from a theoretical perspective, the relationship between homebuyers' beliefs and leverage choice is ambiguous, and depends on the magnitude of a "collateral adjustment friction" that reduces homebuyers' willingness to adjust their house size in response to beliefs about house price changes. When households primarily maximize the levered return of their property investment and the collateral adjustment friction is small, more optimistic homebuyers take on more leverage to purchase larger houses and profit from the greater perceived price appreciation. On the other hand, when considerations such as family size pin down the desired property size and the collateral adjustment friction is large, more optimistic homebuyers take on less leverage to finance that property of fixed size, since they perceive a higher marginal cost of borrowing. To determine which scenario better describes the data, we empirically investigate the cross-sectional relationship between beliefs and leverage in the U.S. housing market. Our data combine mortgage financing information and a housing expectation survey with anonymized social network data from Facebook. The survey documents that an individual's belief distribution about future house price changes is affected by the recent house price experiences of her geographically-distant friends, allowing us to exploit these experiences as quasi-orthogonal shifters of individuals' beliefs. We show that more optimistic homebuyers choose lower leverage, consistent with a sizable collateral adjustment friction. As predicted by the model, the magnitude of the cross-sectional relationship between beliefs and leverage choice is larger during periods when households expect prices to fall on average. JEL Codes: E44, G12, D12, D84, R21


Although various risk assessment approaches have been adopted for landfill waste disposal sites, there are still wide-ranging knowledge gaps and limitations which need addressing by developing a holistic risk assessment methodology. This paper conceptually presents only a framework of such a risk analysis methodology for landfill leachate in a holistic format, thereby attempting to bridge these knowledge gaps. The conceptual framework or structure does not only draw together various sections and sub-sections of holistic risk assessment in one place but also categorizes and arranges them in a logical sequence. The holistic structure is to assist in performing the process of a risk analysis from start to end. Also, in order to place Risk Assessment (RA) in a broader perspective of the decision-making process, relationships between Risk Management (RM), Hazard Assessment (HA), and Risk Estimation (R Esti) are also presented. Although this paper attempts to cover the whole of the risk analysis methodology in the form of a fundamental framework, the study does not engage in in-depth detail of sections and sub-sections of the methodology due to brevity.


AIM
To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and risk of HCC.

METHODS
One hundred and seventy cases of HCC and 276 control subjects free of HCC and cirrhosis were selected for this study. Serum HBV DNA level was measured using fluorescein quantitative polymerase chain reaction at study entry and the last visit.

RESULTS
In a binary unconditional logistic regression analysis adjusted for age, cigarette smoking, alcohol consumption and family history of chronic liver diseases, the adjusted odds ratios (95% confidence intervals) of HCC in patients with increasing HBV DNA level were 2.834 (1.237-6.492), 48.403 (14.392-162.789), 42.252 (14.784-120.750), and 14.819 (6.992-31.411) for HBV DNA levels > or = 10(4) to < 10(5); > or = 10(5) to < 10(6); > or = 10(6) to < 10(7); > or = 10(7) copies/mL, respectively. Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with those at the last visit. The HBV DNA levels measured at the two time points did not differ significantly.

CONCLUSION
The findings of this study provide strong longitudinal evidence of an increased risk of HCC associated with persistent elevation of serum HBV DNA level in the 10(4)-10(7) range.


After introducing the liquid scintillation counting (LSC) method and graphite target preparation for accelerator mass spectrometry (AMS) measurements in the Zagreb Radiocarbon Laboratory, the existing database software designed only for gas proportional counting (GPC) (using a DOS operating system) could not satisfy the requirements for parallel conduction of several techniques. This has been enabled recently by the development of the new relational database ZAGRADA, which—using SQL scripts and constraints defined by primary and foreign keys—enforces high data integrity and provides better performances in data filtering and sorting. The structural scheme of this database conceptually comprises 4 basic modules with data on the samples, chemical pretreatment and preparation, measurements and data on the final results. A user-friendly graphical user interface has been designed to perform various actions and data manipulation to the database. The implementation of a new database for 14C samples has significant contribution to scientific research performed in the Radiocarbon and Tritium Laboratory and to quality assurance and quality control, and will enable better and easier communication with customers.


A level-set method for computations of interfacial flows with insoluble sur- factants with electric fields is presented. The discontinuities at the interface are captured in a sharp manner using the ghost-fluid method. The accuracy of the method is tested and compared to the standard level-set method. The method is then used to study the combined eect of insoluble surfactants and electric fields on the motion and deformation of a falling drop. It is found that the surfactant generally reduces the deformation and the terminal velocity of the drop. This reduction is most pronounced in the nearly spherical regime where the drop behavior is similar to a solid sphere due to the interface immobi- lization caused by the presence of a surfactant. The electric field increases the terminal velocity by stretching the drop in the direction of the electric field. This eect is largest for the surfactant-covered drop, which is deformed more due to the lower average interfacial tension.


Accurate and updated road network data is vital in many urban applications, such as car-sharing, and logistics. The traditional approach to identifying the road network, i.e., field survey, requires a significant amount of time and effort. With the wide usage of GPS embedded devices, a huge amount of trajectory data has been generated by different types of mobile objects, which provides a new opportunity to extract the underlying road network. However, the existing trajectory-based map recovery approaches require many empirical parameters and do not utilize the prior knowledge in existing maps, which over-simplifies or over-complicates the reconstructed road network. To this end, we propose a deep learning-based map generation framework, i.e., DeepMG, which learns the structure of the existing road network to overcome the noisy GPS positions. More specifically, DeepMG extracts features from trajectories in both spatial view and transition view and uses a convolutional deep neural network T2RNet to infer road centerlines. After that, a trajectory-based post-processing algorithm is proposed to refine the topological connectivity of the recovered map. Extensive experiments on two real-world trajectory datasets confirm that DeepMG significantly outperforms the state-of-the-art methods.


The basal ganglia network has been implicated in the control of adaptive behavior, possibly by integrating motor learning and motivational processes. Both positive and negative reinforcement appear to shape our behavioral adaptation by modulating the function of the basal ganglia. Here, we examined a transgenic mouse line (G2CT) in which synaptic transmissions onto the medium spiny neurons (MSNs) of the basal ganglia are depressed. We found that the level of collaterals from direct pathway MSNs in the external segment of the globus pallidus (GPe) ('bridging collaterals') was decreased in these mice, and this was accompanied by behavioral inhibition under stress. Furthermore, additional manipulations that could further decrease or restore the level of the bridging collaterals resulted in an increase in behavioral inhibition or active behavior in the G2CT mice, respectively. Collectively, our data indicate that the striatum of the basal ganglia network integrates negative emotions and controls appropriate coping responses in which the bridging collateral connections in the GPe play a critical regulatory role.


'I have become whore through goodwill and libertine through virtue.' Orphaned and penniless at the age of twelve, the beautiful and devout Justine embarks upon her remarkable odyssey. Her steadfast faith and naive trust in trust in everyone she meets destine her from the outset for sexual exploitation and martyrdom. The unending catalogue of disasters that befall her, during which she is subject to any number of perverse practices, illustrate Sade's belief in the primacy of Nature over civilization. Virtue is no match for vice, and as criminality and violence triumph, Justine is doomed to suffer. Sade's writings have become a byword for transgression and obscenity, and the logical amorality of his philosophy still has the power to shock. By overturning social, religious, and political norms he puts under scrutiny conventional ideas of justice, power, life, and death. Justine is a ferocious physical and intellectual assault on absolute notions of good and evil, and as such, one of the earliest literary manifestos for atheism. ABOUT THE SERIES: For over 100 years Oxford World's Classics has made available the widest range of literature from around the globe. Each affordable volume reflects Oxford's commitment to scholarship, providing the most accurate text plus a wealth of other valuable features, including expert introductions by leading authorities, helpful notes to clarify the text, up-to-date bibliographies for further study, and much more.


Embolic stroke is a common complication in patients on ventricular assist devices in both adults and children. The reported incidence of strokes in children supported by VAD's varies from 7 to 38%. The rapid increase in recent years in the availability of both adult and pediatric VADs will likely add to the overall prevalence of strokes in patients being bridged to heart transplant. Strokes in this population can be lethal as they frequently necessitate withdrawal of the extracorporeal device support and withdrawal from the organ transplant waiting list. We present a case of a fully anti‐coagulated 29‐month‐old supported on a Berlin EXCOR LVAD (Berlin, Germany) with embolic stroke which was treated successfully with direct thrombolysis with recombinant tissue plasminogen activator. This is the first report which uses intra‐arterial thrombolytics while on a ventricular assist device in a pediatric patient.


In this paper, we analyze the impact of hardware impairments at relay node and source node (i.e. imperfect nodes) on network performance by evaluating outage probability based on the effective signal to noise and distortion ratio (SNDR). Especially, we propose energy harvesting protocol at the relay and source nodes, namely, power switching imperfect relay (PSIR) and power switching imperfect source (PSIS). Aiming to determine the performance of energy constrained network, we first derive closed-form expressions of the outage probability and then the throughput can be maximized in delay-limited transmission mode. The simulation results provide practical insights into the impacts of hardware impairments and power switching factors of the energy harvesting protocol on the performance of energy harvesting enabled two-way relaying network.


Youth film is a kind of film that is very popular all over the world, which has developed very fast in China in recent years. The audience, especially teenagers, set off a wave to watch this kind of movies. But after watching high box-office youth films screened in the last two or three years, we find that Chinese youth films have a tendency to be homogenous, and they have an obvious style different from that from the United States. Films can reflect culture, and youth culture is an important part of any culture. Consequently, it is extremely important to know what the differences between Chinese and American youth film are and why is that. We examine this problem from a specific angle—the youth image in youth films. Significant differences are found in this comparative study.


We analyze the connection between productivity, pollution abatement expenditures, and other measures of environmental regulation for plants in three industries (paper, oil, and steel). We examine data from 1979 to 1985, considering, both labor and total factor productivity, both levels and growth rates, and both annual measures and averages over the period. We find a strong connection between regulation and productivity when regulation is measured by compliance costs. More regulated plants have significantly lower productivity levels and slower productivity growth rates than less regulated plants. The magnitude of the impacts are larger than expected: a $1 increase in compliance costs appears to reduce TFP by the equivalent of $3 to $4. Thus, commonly used methods of calculating the impact of regulation on productivity are substantially underestimated. Other measures of regulation (compliance status, enforcement activity, and emissions) show much less consistent results. Higher enforcement, lower compliance, and higher emissions are generally associated with lower productivity levels and slower productivity growth, but the coefficients are rarely significant.


Context. NGC 3311, the central galaxy of the Hydra I cluster, shows signatures of recent infall of satellite galaxies from the cluster environment. Previous work has shown that the line-of-sight velocity dispersion of the stars and globular clusters in the extended halo of NGC 3311 rises up to the value of the cluster velocity dispersion. In the context of Jeans models, a massive dark halo with a large core is needed to explain this finding. However, position dependent long-slit measurements show that the kinematics are still not understood. Aims. We aim to find kinematic signatures of sub-structures in the extended halo of NGC 3311. Methods. We performed multi-object spectroscopic observations of the diffuse stellar halo of NGC 3311 using VLT/FORS2 in MXU mode to mimic a coarse "IFU". The slits of the outermost masks reach out to about 35 kpc of galactocentric distance. We use pPXF to extract the kinematic information of velocities, velocity dispersions and the high-order moments h3 and h4. Results. We find a homogeneous velocity field and velocity dispersion field within a radius of about 10 kpc. Beyond this radius, both the velocities and the velocity dispersion start to depend on azimuth angle and show a significant intrinsic scatter. The inner spheroid of NGC 3311 can be described as a slow rotator. Outside 10 kpc the cumulative angular momentum is rising, however, without showing an ordered rotation signal. If the radial dependence alone is considered, the velocity dispersion does not simply rise but fills an increasingly large range of dispersion values with two well defined envelopes. The lower envelope is about constant at 200 km s−1. The upper envelope rises smoothly, joining the velocity dispersion of the outer globular clusters and the cluster galaxies. We interpret this behaviour as the superposition of tracer populations with increasingly shallower radial distributions between the extremes of the inner stellar populations and the cluster galaxies. Simple Jeans models illustrate that a range of mass profiles can account for all observed velocity dispersions, including radial MOND models. Conclusions. The rising velocity dispersion of NGC 3311 apparently is a result of averaging over a range of velocity dispersions related to different tracer populations in the sense of different density profiles and anisotropies. Jeans models using one tracer population with a unique density profile are not able to explain the large range of the observed kinematics. Previous claims about the cored dark halo of NGC 3311 are therefore probably not valid. This may in general apply to central cluster galaxies with rising velocity dispersion profiles, where infall processes are important.


This article seeks to explore whether institutional solutions to antitrust enforcement problems can be transported from one jurisdiction to another. It does so by focusing on the effects of scarce enforcement resources (both financial and human) on optimal institutional design. The prevalence of this characteristic in small, developing and transition economies makes it an interesting and important subject to study. Accordingly, the following question is raised: if a country has a small institutional endowment, can it transplant the institutional structure of another jurisdiction with a large resource endowment and simply shrink it to fit its budget - like the shrinking of the house in Alice in Wonderland - or should it apply a different institutional structure? To answer this question, the article first analyzes the effects of a limited institutional endowment on the effective enforcement of antitrust law. It then analyzes the tools which have been employed or that can be employed to limit such negative effects, such as prioritizing and sharing. One of the more interesting solutions relates to the interplay between substantive rules and institutional structures: a combination of poorly equipped institutions with limited economic expertise and antitrust laws which require complex analysis of market conditions and their effect on welfare are apt to create erroneous decisions; thus, as this article argues, designing an efficient antitrust regime also involves the creation of a delicate balance between institutional conditions and substantive rules.


Oncogenesis is governed by genetic and epigenetic events that co-opt to malignant progression. The role of the microenvironment in tumorigenesis and maintenance is increasingly appreciated. Oxygen supply is one of the rate limiting microenvironmental factors. Like healthy cells, cancer cells rely on oxygen. Hypoxia is the condition in which the partial oxygen pressure has dropped to levels that are no longer sufficient to sustain normal cellular function. Hypoxic cells alter metabolism and growth rate and produce angiogenic factors. This ultimately promotes tumor progression. The hypoxia-inducible factor (HIF) transcription factors account for a major part of this response. The HIF transcription factor is a heterodimer composed of a constitutively expressed beta subunit and a hypoxia-regulated alpha subunit. There are three distinct alpha subunits, HIF-1alpha, -2alpha and -3alpha. At physiological oxygen tensions (normoxia), the alpha subunits are continuously degraded upon synthesis, which is dependent on the Von Hippel Lindau tumorsuppressor protein. In the absense of oxygen (hypoxia), the alpha subunits stabilize and constitute the HIF transcription factor after dimerisation with the beta subunit. The HIF trancription factor is involved in the regulation of genes involved in angiogenesis, energy metabolism, cell survival and metastasis. In multiple solid cancer types, expression of HIFalpha subunits has been associated with poor prognosis. Understanding the molecular pathways triggered by hypoxia will enhance insight into the pathological mechanism that underlies hypoxia-associated poor prognosis of cancer. This thesis addresses two main questions: i. how is HIF-1alpha regulated, and ii. how does hypoxia, and particularly HIFalpha overexpression, result in a poor prognosis? Studies concerning the first research question have provided insights into regulation of the HIF pathway and these are presented in this thesis. First of all, experiments in a cell culture model mimicking the serum- and oxygen-deprived microenvironment of solid cancers indicate a crosstalk between oncogenic pathways like the PI 3-kinase pathway and the HIF pathway. This was confirmed in specimen from breast cancer patients. Furthermore, genetic screening has resulted in the identification of multiple genes potentially involved in regulation of the HIF pathway. The second research question has been addressed in multiple chapters of this thesis. In endometrium cancer the HIF pathway induces expression of the cell cycle regulator p27. Subsequent induction of cell cycle arrest might promote hypoxic cancer cell survival. Importantly, this thesis describes the identification of TWIST1 as a HIF-2alpha target gene by genetic screening in the nematode C. elegans. The HIF pathway has been conserved in the evolution, which allows usage of these model organisms. The TWIST1 gene has previously been shown to be a key molecule in metastasis formation in breast cancer. Therefore, the expression profiles of TWIST1 in breast cancer and relation to promotor methylation are also presented. Hypoxic regulation of TWIST1 might explain the association between hypoxia and metastasis formation in human cancer. In addition to the novel results on hypoxic regulation of TWIST1, this thesis also includes a current review on the latest insights in HIF-mediated regulation of metastasis.


Rural space represents a definite element in the structural and functional transformations of Subcarpathian landscapes, analysed through their geodiversity, biodiversity, and cultural patrimony. The present analyse relieves historical and socio-economic land use changes, process, which determined a restructuring of rural landscapes, allowing a classification of environmental critical areas. Elements defining the rurality of the Subcarpathian landscapes between the Ramnicu Sarat and the Buzau valleys were evidenced and characterised in concordance with the new strategic directions of the European Council regarding rural development in 2007 – 2013 period, and with the national legislation in the field, for establishing protection, rehabilitation and valorization strategies for the Subcarpathian rural landscapes. The case study realised in the villages included in the Subcarpathian sector of the Slanic de Buzau valley relieved a spatial and temporal dynamics for the indices of human pressure through different landuses, allowing the establishment of artificial degrees of rural Subcarpathian landscapes. The data obtained from the CORINE Land Cover model, 1990 and 2006 editions, corroborated with the data rendered in agricultural registers and statistical data from NIS (National Institute of Statistics) relieve spatial dynamics of land-uses in the analysed area, and at the same time, there were identified the areas which induce important modifications in the landscapes structure and


Objectives: This article reports a cost-effectiveness analysis of targeted screening for abdominal aortic aneurysm (AAA). A major emphasis was on the estimation of distributions of costs and effectiveness. Methods: We performed a Monte Carlo simulation using C programming language in a PC environment. Data on survival and costs, and a majority of screening probabilities, were from our own empirical studies. Natural history data were based on the literature. Results: Each screened male gained 0.07 life-years at an incremental cost of FIM 3,300. The expected values differed from zero very significantly. For females, expected gains were 0.02 life-years at an incremental cost of FIM 1,100, which was not statistically significant. Cost-effectiveness ratios and their 95% confidence intervals were FIM 48,000 (27,000–121,000) and 54,000 (22,000–∞) for males and females, respectively. Sensitivity analysis revealed that the results for males were stable. Individual variation in life-year gains was high. Conclusions: Males seemed to benefit from targeted AAA screening, and the results were stable. As far as the cost-effectiveness ratio is considered acceptable, screening for males seemed to be justified. However, our assumptions about growth and rupture behavior of AAAs might be improved with further clinical and epidemiological studies. As a point estimate, females benefited in a similar manner, but the results were not statistically significant. The evidence of this study did not justify screening of females.


Due to its high coherence in transmission over a large distance in the ambient environment, the quantum optical system has been a prevailing platform for long-distance quantum communication, which was recently realized over a continental distance with a low earth orbit satellite and ground stations [102, 70]. However, the pure quantum optical system has so far shown weak interactions between photon and matter, which makes it inefficient in carrying out deterministic quantum gates for quantum repeater based scalable quantum network and quantum computing. On the other hand, superconducting quantum systems operating in the microwave domain with Josephson junction transmon qubits have proven to be capable of efficient deterministic quantum operations on quantum states [86, 87, 66]. Nevertheless, such architecture is prone to errors and decoherence due to cross-talk between microwave elements in a large-scale superconducting quantum circuit. Furthermore, superconducting systems, in general, also have large footprint (100s um) elements (resonators and superconducting quantum bits) [92, 60] that limit the ability to scale up a superconducting quantum system. Moreover, microwave quantum circuits require cooling to around 10 mK, making it unsuitable for communicating quantum information outside a dilution refrigerator (DF). Micro- and nano- acoustic elements have been extensively used in conventional integrated information processing systems due to their compactness and high coherence [97]. Acoustic systems in quantum engineering also have the advantage of being a platform for universal couplings between various quantum systems including spins, optical photons, and superconducting circuits. As it will be discussed in this thesis, elements critical to scalable optical quantum network and superconducting quantum circuit can be constructed relying on the cavity optomechanics and piezoelectric interactions. Optomechanical interaction is concerned with the light pressure coupling of cavity mechanical deformation to a strong optical field. This interaction has allowed the close to mechanical ground state cooling of mechanical resonators using laser and the ultra-sensitive displacement measurement that led to the detection of gravitational waves in the LIGO collaboration [125, 25]. Optomechanical crystals (OMCs) are lithographically patterned devices which contain a periodic structure that host bandgaps for both optical band electromagnetic waves and microwave band acoustic waves. A properly engineered defect in the crystal can confine and localize acoustic and electromagnetic modes of similar wavelengths into a small mode volume [17, 20, 21]. A strong optomechanical coupling, which can be achieved between such strongly confined co-localized optical and acoustic modes, can be used in engineering the quantum state of mechanical motion to realize useful quantum devices such as a high-coherence quantum memory [74] and an optomechanical high efficiency optical isolator for unidirectionally connecting distant optical cavities via an acoustic bus [37]. To strongly couple the mechanical degree of freedom with a superconducting quantum circuit, various methods can be used, ranging from electromechanic coupling (electric coupling to a mechanically compliant capacitor), magnetomechanical coupling (magnetic coupling to a vibrating SQUID loop), and piezoelectric coupling. The recent advent of quantum acoustics [23, 8, 9] was realized with the strong piezoelectric coupling between a superconducting transmon qubit and a high-coherence mechanical resonator. The engineered strong piezoacoustic coupling provides the possibility to carry out deterministic ultra-high fidelity two-qubit quantum gates on non-classical mechanical quantum states [52]. This ability together with the recent demonstration of ultra-long phonon lifetime mechanical resonators show the possibility of integrating the ultra-high quality mechanical resonator as a compact quantum memory element and even a new ultra-compact (10s um) quantum bit architecture for scalable superconducting quantum circuits. Furthermore, the strong piezoelectric coupling that can transduce quantum state in a superconducting circuit into mechanical wave also makes it possible to efficiently transduce a quantum state between a superconducting quantum circuit and a telecommunication band optical channel via a mechanical waveguide connected to an optomechanical crystal cavity.


A novel method for preparing a luminescent solar concentrator (LSC) with fluorescent aqueous layer sandwiched between two pieces of flat glass is developed. By this method, an aqueous layer concentrator with a size of 78×78×7 (mm) is fabricated. After coupled with silicon solar cell, the concentrator shows a power conversion efficiency of 3.9%, about 30% higher than that of the same sized laminated glass concentrator employing the same dyes. Furthermore, the measured efficiency almost reaches the calculated limit of the aqueous layer LSC. This kind of aqueous layer LSC offers a potential application in the building-integrated photovoltaics.


Determining the cost of volatile anesthetic agents is important to buffer the rising cost of healthcare by cost effective use of these drugs. Herein, this paper presented a cost analysis of sevoflurane and isoflurane with considering their effects on hemodynamic stability. In a randomized clinical trial, 52 ASA status I–II patients candidate for aortobifemoral bypass surgery were assigned to receive low-flow sevoflurane anesthesia (n = 26) or low-flow isoflurane (n = 26). Patients were monitored for assessment of hemodynamic parameters and the amount of gas consumption and costs for each patient was also recorded. The mean cost of consumed gas in sevoflurane group was 87807 ± 41261 Iranian rials (currency) and in isoflurane group was 144423 ± 69609 Iranian rials that was considerably higher in isoflurane group (p 100 mmHg) was obtained in 80.8% in sevoflurane group and 84.6% in isoflurane group after aortic clamping and also following removal of aortic clamp with no significant differences. Regarding changes in heart rate in sevoflurane and isoflurane groups, after removal of aortic clamp, the overall prevalence of bradycardia was higher in those who received isoflurane compared with another group (97.2% versus 26.8%), while sevoflurane group experienced normal sinus rhythm more than that observed in isoflurane group (30.8% versus 3.8%, p < 0.001). Considering both clinical safety and affordability, Sevoflurane is preferred to isoflurane as anesthetics for surgical patients.


This paper presents an approach for reducing the cognitive load for humans working in quality control (QC) for production processes that adhere to the 6σ -methodology. While 100% QC requires every part to be inspected, this task can be reduced when a human-in-the-loop QC process gets supported by an anomaly detection system that only presents those parts for manual inspection that have a significant likelihood of being defective. This approach shows good results when applied to image-based QC for metal textile products.


The article questions some scholarly assumptions about the famous anecdote on the meeting between Alexander and Diogenes the Cynic. While scholars have rightly placed the story within the topos of the opposition between wise man and king, its interest in the two figures amounts to more than generic exempla and its depiction of Alexander is not necessarily hostile. It seems probable that the original form was not a chreia; rather, later versions were extracted from an extended literary version of such an encounter. An early work satisfying these criteria is the Education of Alexander by Onesicritus, the pupil of Diogenes who accompanied Alexander on his Asian campaign.


The purpose of this research was to investigate the motivations and involvement of Chinese rock climbers. Rock climbing has experienced considerable growth in many regions of China over the last decade, yet there is little published research on this outdoor recreation user group. A questionnaire was distributed on-site in Yangshuo, China in 2010 (n=256). A profile of the respondents showed a male-dominated sample with mean age of 31 years and active in indoor and outdoor sports climbing. Factor analysis of motivational items resulted in five dimensions: stress release & escape, achievement, experience nature & develop knowledge, experience adventure, and interaction with peers. Results for the involvement items yielded three factors: attraction, risk consequence and sign. The involvement factors were positively influenced by several of the motivational factors. The findings provide baseline information in understanding more about rock climbers which will prompt theoretical research and provide practical applications for this growing outdoor activity in China


The development of Globalization in this century is far more interesting for so many academias. The main issue that becomes the area of debate is the impact of Globalization to the concept of Nation-State, territory and sovereignty (Wesphalian System). The group of skeptic thinker assume that globalization bring a negative impact to Nation-State, territory and sovereignty. In the other hand, those who put their faith in globalization argue that globalization is inevitable. Therefore, an action of reconfiguration is needed to control the shift of every aspect in the context of world politics. For the sake of this need, Nation-State needs to be strengthening in order to retain its existence and legitimation. The arguments of this paper tend to pro the second position as the staple of this paper. The nature of relationship between Globalization and Nation-State is continuous and dynamic. Therefore, reconfiguration is needed if we want to have a better understanding for the concept of Nation-State, territory, and sovereignty.


This review essay interrogates the theoretical underpinning of Mordechai Tamarkin's recent volume on the anti-Scab Act movement in the Cape Colony during the 1890s. Tamarkin views the opponents of the Scab Act of 1894 as victims of modernity. Since the Act's opponents were mainly Afrikaans-speaking trek farmers, he casts what could have been persuasively analysed as a class conflict between mutton and wool farmers as an ethnic conflict. As a result, his text focuses on isolating aspects of a supposed trek farmer ethnic character. A number of 'traditional' characteristics are ascribed to trek farmers that supposedly contrast with the hegemonic progressive worldview. On closer analysis, these characteristics are ill defined and cannot be sufficiently historicised. It is argued here that Tamarkin essentially took the trek farmers' assertions of the Scab Act's expected impact at face value. The result is a theoretically unsophisticated analysis of Afrikaner intra-ethnic conflict mainly affecting the Afrikaner Bond. Real historiographical gaps in the environmental and economic history of the Cape Colony are not addressed.


Discrete Element Modeling of a Vibratory Subsoiler J. van der Linde Department of Mechanical and Mechatronic Engineering, University of Stellenbosch, Private Bag X1, 7602 Matieland, South Africa. Thesis: MScEng (Mech) December 2007 Vibrating a tillage tool is an e ective way of reducing the draft force required to pull it through the soil. The degree of draft force reduction is dependent on the combination of operating parameters and soil conditions. It is thus necessary to optimize the vibratory implement for di erent conditions. Numerical modelling is more exible than experimental testing and analytical models, and less costly than experimental testing. The Discrete Element Method (DEM) was speci cally developed for granular materials such as soils and can be used to model a vibrating tillage tool for its design and optimization. The goal was thus to evaluate the ability of DEM to model a vibratory subsoiler and to investigate the cause of the draft force reduction. The DEM model was evaluated against data obtained from eld testing done with a full scale single tine vibratory subsoiler. Soil testing was also done for material characterization and for the calibration of DEM material properties. The subsoiler was simulated using a commercial code, PFC3D. The e ect on the simulation results of particle diameter, di erent bonding models and damping models was investigated. The nal simulations were evaluated against the experimental results in terms of the draft force and material behaviour. The cause of the draft force reduction due to vibration was also investigated with the aid of the DEM model. From the results it was concluded that DEM is able to model the vibratory subsoiler for its design and optimization. The DEM model also provided valuable insight into the cause of the draft force reduction such as the increased peak stresses due to vibration and the increase in particle kinetic energy.


This paper examines principles for properly computing prejudgment interest by examining the impact on different corporate constituencies. This paper concludes that prejudgment interest at a promisor's cost of funds can undercompensate promisees, by shifting value from the promisee's equityholders to its creditors through a forced investment that decreases the risk of the promisee's portfolio of assets.


Spectrophotometric method is described for the simultaneous determination of binary mixtures of eosin and erythrosine in pharmaceutical and food samples, without prior separation steps, using mean centering of ratio spectra. The method is based on the difference in the absorption spectra for the products of the reaction of eosin and erythrosine with Cr(VI) in the presence of CPB micellar media at pH 6.0. The method allows rapid and accurate determination of eosin and erythrosine. The results showed that the method was capable to simultaneous determination of 1.24-6.86 µg/mL and 1.47- 8.06 µg/mL each of eosin and erythrosine. The proposed method was successfully applied to the simultaneous determination of eosin and erythrosine in pharmaceutical and food samples.


Sexual jealousy is a basic emotion. Although it lacks a distinctive facial expression and is unlikely to solve problems of survival, it evolved because it solves adaptive problems of mating. Some adaptive functions are similar in men and women at one level of abstraction, such as warding off potential mate poachers and deterring relationship defection. Other functions are sexdifferentiated, such as increasing paternity probability for men and monopolizing a mate's economic commitments for women. Dozens of studies have documented sex-differentiated design features of jealousy: The relative upset about sexual and emotional aspects of infidelity; processing speed and memorial recall of sexual and emotional infidelity cues; physiological distress to sexual and emotional infidelity cues; qualities of same-sex rivals that evoke jealousy, such as superior job prospects versus greater physical attractiveness; triggers of mate retention tactics; jealous interrogations following the discovery of infidelity; and whether an infidelity produces forgiveness or breakup. Although showing all the hallmarks of evolved functionality, sexual jealousy also leads to tremendous destruction, from humiliation to homicide. By these scientific theoretical and empirical criteria, sexual jealousy is properly considered not only "basic" but also "one of the most


In this work we quantify the effects of surfactant transport on the deformation of a viscous drop under a DC electric field. We study how convective and diffusive transport of surfactants at drop surfaces influence the equilibrium and dynamic deformation of a leaky dielectric drop and a conducting drop. Focusing on the prolate drop shape (elongates along the electric field), we show the differences in equilibrium deformation and flow circulation between a leaky dielectric drop and a conducting drop. We quantify the drop electrodeformation via its dependence on the interior flow circulation and the dominant surfactant transport regime (characterized by the surface Péclet number Pe_{s}). For a leaky dielectric drop with dominant surfactant diffusion (Pe_{s}≪1), equator-to-pole (pole-to-equator) circulation yields smaller (larger) equilibrium deformation with increasing surfactant coverage, compared to a clean drop. However, when convection dominates (Pe_{s}≫1), the equilibrium drop deformation increases (decreases) with larger surfactant coverage for equator-to-pole (pole-to-equator) circulation. Larger equilibrium drop deformation is found for a leaky dielectric drop than a conducting drop when the interior flow is from equator to pole. For an interior flow from pole to equator, we identify cases where larger deformation is found for a conducting interior fluid. Finally, we study the effect of the surfactant transport on the dynamic evolution of drop shape. We found the drop undergoes an overshoot in the early deformation phase, before settling to its equilibrium shape-similar to the overshoot observed for unsteady Stokes flow.


The feeling of embodiment, i.e., experiencing the body as belonging to oneself and being able to integrate objects into one's bodily self-representation, is a key aspect of human self-consciousness and has been shown to importantly shape human cognition. An extension of such feelings toward robots has been argued as being crucial for assistive technologies aiming at restoring, extending, or simulating sensorimotor functions. Empirical and theoretical work illustrates the importance of sensory feedback for the feeling of embodiment and also immersion; we focus on the the perceptual level of touch and the role of tactile feedback in various assistive robotic devices. We critically review how different facets of tactile perception in humans, i.e., affective, social, and self-touch, might influence embodiment. This is particularly important as current assistive robotic devices – such as prostheses, orthoses, exoskeletons, and devices for teleoperation–often limit touch low-density and spatially constrained haptic feedback, i.e., the mere touch sensation linked to an action. Here, we analyze, discuss, and propose how and to what degree tactile feedback might increase the embodiment of certain robotic devices, e.g., prostheses, and the feeling of immersion in human-robot interaction, e.g., in teleoperation. Based on recent findings from cognitive psychology on interactive processes between touch and embodiment, we discuss technical solutions for specific applications, which might be used to enhance embodiment, and facilitate the study of how embodiment might alter human-robot interactions. We postulate that high-density and large surface sensing and stimulation are required to foster embodiment of such assistive devices.


Current differencing transconductance amplifier (CDTA) is receiving considerable attention as a building block for current-mode (CM) analog signal processing / signal generation. In this paper, new CDTA based lossless grounded and floating inductance simulation circuits have been proposed. The proposed grounded simulated inductance circuit employs two CDTAs and a single grounded capacitor whereas the floating simulated inductance circuit employs three CDTAs and a grounded capacitor. The circuit for grounded inductance does not require any realization conditions whereas in case of floating inductance only equality of two transconductances is needed (which can be easily maintained in practice by ensuring equal dc bias currents in the two transconductance amplifiers). Some sample results demonstrating the applications of the new simulated inductors using CMOS CDTAs have been given to confirm the workability of the new circuits.


The increased development and expansion of population in urbanize area in Malaysia have created a definite need to construct an inter-basin water transfer tunnel to fulfil the increase demand of water in the water scarcity region. As one of the main component in the inter basin raw water transfer tunnel project, the Kelau Dam had been designed to serve as a regulating dam in order to maintain a sufficient water level in the Kelau River for the water intake. The successful construction and operation of the dam over the full range of loading require a comprehensive evaluation of the dam designed before the construction proceeds. Thus, this study serves to investigate the factors that can cause instability of the earth-fill dam slope and to evaluate the earth-fill dam performance under main critical conditions by determining the factor of safety (FOS) of the dam conceptual design. Four main critical conditions considered in the analysis are end of construction, steady state, steady state with seismic loading and rapid drawdown conditions. This study began with detailed site characterization and investigation for the engineering information needed in the slope stability analysis. The dam slope stability analysis considering of the critical conditions were carried out using limit equilibrium method (LEM), shear strength reduction method together with seepage analysis using finite element method (FEM). It is found that FOS of rapid drawdown and steady state with seismic loading conditions are close to each other and have obvious lower value compare to steady state and end of construction conditions. The 2-D conceptual model of the earth-fill dam can be classified as stable under all critical loadings as the FOS are more than the minimum requirement specified by the design. Factors of safety computed by both LEM and FEM are close to each other where differences in percentage are less than 6 %. Based on the seepage qualitative and quantitative results analysis, piping failure at the toe of downstream slope is unlikely to occur due to systematic arrangement of filters and drains at internal surface of slope.


The ability of animals to disperse towards their original home range following displacement has been demonstrated in a number of species. However, little is known about the homing ability of three-spine sticklebacks (Gasterosteus aculeatus), an important model species in behavioural ecology. In addition, few studies have examined the role of social facilitation in relation to homing behaviour in fishes. We examined homing behaviour of sticklebacks displaced over distances of between 80 m and 160 m in land-drains with directional water flow. Fish were translocated from their original capture site, tagged and then released either in groups or solitarily. We performed recapture transects either one or two days later. Data provided by recaptured sticklebacks show that the fish dispersed in the direction of their original capture site. Although fish translocated downstream typically moved further than those translocated upstream, both dispersed towards their original capture site. There was no difference between fish released solitarily or in groups in their homing ability and indeed there was little evidence that fish translocated in groups remained together following their release. The homing ability of the fish was demonstrated by the finding that up to 80% of fish returned to their home ranges within two days of release over a distance equivalent to approximately 5000 body lengths of these small fish.


Introduction: Chronic Philadelphia chromosome-negative myeloproliferative neoplasm-associated myelofibrosis significantly impacts afflicted patients with cytopenia, splenomegaly, debilitating constitutional symptoms and decreased survival. Approval of the first Janus kinase 2 (JAK2) inhibitor therapy, ruxolitinib, has improved splenomegaly, symptomatic burden, survival and perhaps fibrosis in some treated patients; however, other patients remain symptomatic and are in need of alternate therapeutic strategies. Areas covered: A review of recent literature via PubMed and meeting abstracts has revealed many studies investigating new treatment approaches for chronic Philadelphia chromosome-negative myeloproliferative neoplasms. Multiple additional JAK2 inhibitors (fedratinib, pacritinib and momelotinib) are well into single agent development, as well as multiple combination approaches with ruxolitinib. Efforts to combine JAK2 inhibition with agents to improve cytopenia, marrow fibrosis, additional pathway inhibitors and even allogeneic transplant are planned or ongoing. Additionally, Phase III trials of immunomodulation with pomalidomide are ongoing. Expert opinion: This article discusses investigational therapies for the treatment of Philadelphia chromosome-negative myeloproliferative neoplasms, particularly those in Phase II clinical trials, employing new JAK2 inhibitors, novel multi-agent therapeutic approaches and innovative new drug targets. Additionally, the future era of Philadelphia chromosome-negative myeloproliferative neoplasms is addressed with potentially expanded niches for JAK2 inhibition.


While controversy swirls around the federal government's small business tax reform proposals, Ottawa has a significant opportunity to open a rich vein of wealth for Canada's charitable sector and simultaneously increase tax planning options for owners of private company shares and real estate, according to a report by the C.D. Howe Institute. In "No Need to Reinvent the Wheel: Promoting Donations of Private Company Shares and Real Estate," author Adam Aptowitzer recommends Ottawa extend favourable tax treatment to the donation of private company shares and real estate.


Recently methanol's use as a fuel is becoming more attractive. Firstly, because of the prices of NG (the main feedstock for methanol production) are now at record low. This has prompted consideration of other alternative energy sources that are not oil dependent. A second key issue has been growing global concern for environment and emphasis being placed on the use of fuels with lower SO2, NOx and particulates emissions. Methanol offers these advantages, being a derivative of natural gas which partly de-linked from oil, and is a clean burning fuel.In this manner full scale test of methanol firing at FT4C TWIN PAC 50 MWe GT designed by Pratt & Whitney was performed. The obtained results clearly show that with minor low cost fuel system retrofit methanol firing leads to significant NOx, SO2 and particulates emission reduction. NOx emissions were reduced by more than 75% and are equal 75 mg/dNm3 at 15%O2. It is less then required standard even with water injection operation mode (the standard is 86 mg/dNm3 at 15%O2 of NOx emission). SO2 emissions were reduced to zero with methanol firing. Particulate emissions vary from 1.3 to 1.6 mg/dNm3 at 15% O2 with methanol firing, while with LFO this parameter was 13–37 mg/dNm3 at 15% O2.However, it should be noted that methanol has a significantly lower calorific value, which is, for example, half of diesel oil and requires therefore some specific modification in gas turbine equipment. First, the existing fuel nozzles are too small for the higher volumetric methanol flow and should be replaced by high flow fuel nozzles. The existing fuel supplying pump should also be upgraded to the higher methanol flow. Modulating valve was also replaced due to the same reason.The paper first gives an overview of some of the key technical considerations of the gas turbine conversion from diesel oil to methanol firing, and results of long term operation of gas turbine fired by methanol.Based on the obtained results one may conclude that methanol is an attractive alternative fuel for meeting the energy needs of niche markets in an economic and environmentally sustainable manner, utilizing existing and/or new power generation units.Copyright © 2015 by ASME


Individuals within the aged population show an increased susceptibility to infection, implying a decline in immune function, a phenomenon known as immunosenescence. Paradoxically, an increase in autoimmune disease, such as rheumatoid arthritis, is also associated with ageing, therefore some aspects of the immune system appear to be inappropriately active in the elderly. The above evidence suggests inappropriate control of the immune system as we age. Macrophages, and their precursors monocytes, play a key role in control of the immune system. They play an important role in host defence in the form of phagocytosis, and also link the innate and adaptive immune system via antigen presentation. Macrophages also have a reparative role, as professional phagocytes of dead and dying cells. Clearance of apoptotic cells by macrophages has also been shown to directly influence immune responses in an anti-inflammatory manner. Inappropriate control of macrophage function with regards to dead cell clearance may contribute to pathology as we age. The aims of this study were to assess the impact of lipid treatment, as a model of the aged environment, on the ability of macrophages to interact with, and respond to, apoptotic cells. Using a series of in vitro cell models, responses of macrophages (normal and lipid-loaded) to apoptotic macrophages (normal and lipid-loaded) were investigated. Monocyte recruitment to apoptotic cells, a key process in resolving inflammation, was assessed in addition to cytokine responses. Data here shows, for the first time, that apoptotic macrophages (normal and lipid-loaded) induce inflammation in human monocyte-derived macrophages, a response that could drive inflammation in age-associated pathology e.g. atherosclerosis. Monoclonal antibody inhibition studies suggest the classical chemokine CX3CL1 may be involved in monocyte recruitment to apoptotic macrophages, but not apoptotic foam cells, therefore differential clearance strategies may be employed following lipid-loading. CD14, an important apoptotic cell tethering receptor, was not found to have a prominent role in this process, whilst the role for ICAM-3 remains unclear. Additionally, a small pilot study using macrophages from young ( 40) donors was undertaken. Preliminary data was gathered to assess the ability of primary human monocyte-derived macrophages, from young and mid-life donors, to interact with, and respond to, apoptotic cells. MO from mid-life individuals showed no significant differences in their ability to respond to immune modulation by apoptotic cells compared to MO from young donors. Larger cohorts would be required to investigate whether immune modulation of MO by apoptotic cells contribute to inflammatory pathology throughout ageing.


We study how inertia and personal experiences affect individual risk taking. Our research design relies on active portfolio decisions relating to inheritances to separate the effect of personal experiences from inertia, which otherwise would be observationally equivalent. Experience derives from investments in banks that defaulted following the financial crisis. We classify experiences into first-hand experiences, resulting from personal losses; second-hand experiences, from the losses of close family members; and third-hand experiences, from living in municipalities where banks defaulted. Our results demonstrate that experiences gained personally, aside from inertia or common shocks, explain substantial heterogeneity in individuals' risk taking.


Introduction University students have been at the forefront of social change since the end of World War II. They were among the first in the United States to use the Internet for communication, recreation, and file sharing, and the first to have regular broadband Internet access (The Chronicle of Higher Education, Almanac Issue 2001-2). Internet use first became widespread on university campuses in the 1990s, and in many ways the Internet is a direct outcome of university-based research. Yahoo, Napster, and many other Internet tools were created by university students, while the vast majority of university students are simply Internet users, as a group they can be considered pioneers. A survey carried out in USA (Rainie and Packel 2001) shows that the demographic profile of today's university students is not much changed over the past decade. One characteristic that sets them apart from past generations of university students is their degree of familiarity with the Internet. Most of the 18-year-old university first year students of today were born years after the personal computer was introduced to the public, and they are less aware of a "pre-Internet" world as they are of one in which the Internet also called the "Net" is central to their communication. A count put the number of Internet users in United States at over 104 million and everyday, 50 million Americans go online (Rainie and Packel 2001). Statistics show that Africa as a continent has recorded an Internet user growth of 171.4% between year 2000 - 2004, but accounts for only 1.5% of the world Internet usage. Asia is at the foremost with 32.0%, while North America and Europe has 28.1% and 27.9% respectively of the Internet users in the world (Fatoki, 2004). The Internet, sometimes called simply "the Net," is a worldwide system of computer networks--a network of networks in which users at any one computer can, if they have permission, get information from any other computer (and sometimes talk directly to users at other computers). It was conceived by the Advanced Research Projects Agency (ARPA) of the U.S. government in 1969 and was first known as the ARPANET. The original aim was to create a network that would allow users of a research computer at one university to be able to "talk to" research computers at other universities (The Internet Society, 2002). The Internet can now be accessed virtually anywhere by numerous means. Mobile phones, data cards, handheld game consoles and cellular routers allow users to connect to the Internet from anywhere there is a cellular network supporting that device's technology. Other Internet resources include email, www (World Wide Web), file sharing, streaming media, collaboration, remote access, voice telephony, webcams and so on. Studies done on the use of Internet resources among Nigerian students show that the use of computer and the Internet to aid their academic activities is gradually becoming acceptable but the students have not fully used these facilities (Ajuwon, 2003). Literature has shown that the use of Internet by students can be influenced by certain variables like demographic characteristics such as age, sex, marital status, educational qualification, computer skills, accessibility to computer and the Internet. In addition, Katz (1998) indicated that student attitudes such as self-image, social-image, self-confidence, locus of control, satisfaction, and motivation are those, which lay the foundation and contribute towards the willingness of students to use information and communication technology in learning. Basic personal computer skills are prerequisite to using the Internet, though in practice these skills are often acquired together, as the popularity of the Internet motivates many adults to use computers for the first time. Motor skills (learning to use a keyboard, learning to manipulate a mouse) and perceptual skills (learning to associate images and events on the computer screen with motor actions) form the most elementary substrate. …


The mixed-method study presented in this paper investigates the changes in direct and indirect intercultural contact and language-learning attitudes and effort of international students in the United Kingdom. Seventy international learners of English were asked to fill in a questionnaire three times during one academic year in an international foundation program. An additional 10 students and two of their English language tutors were interviewed at the end of their study period. We analysed variations in language-learning motivation as well as in the frequency and type of contact the learners experienced at three distinct points of time during the international study programme. The results indicate that whereas written and media contact increased in frequency during the academic year, the participants engaged in less frequent spoken contact at the end of the period investigated. The qualitative and quantitative data show that contact experiences, socio-environmental factors and learner internal variables have a dynamic impact on each other and they together can play an important role in the language-learning experiences of international students.


The power of today's tech giants has prompted calls for changes in antitrust law and policy which, for decades, has been exceedingly permissive in merger enforcement and in constraining dominant firm conduct. Economically, the fear is that the largest digital platforms are so dominant and its data advantage so substantial that competition is foreclosed, resulting in long term harm to consumers and to the economy. But the concerns extend beyond economics. Critics also worry that the large platforms' tremendous economic power poses risks of social and political harm and threatens our democracy. These concerns have prompted discussions of ways to reinvigorate Section 2 of the Sherman Act.

One of those suggestions is no-fault monopolization, a theory that dispenses with the conduct requirement of monopolization. Much of the appeal of no-fault monopolization, first considered in the late 1960s through the 1970s, is that it would sidestep the difficult "bad act" and "anticompetitive effects" requirements of Section 2, which are particularly difficult to prove in digital platform markets, for reasons that the Article addresses.

In this Article, I develop the reasons why no-fault monopolization would be inadvisable, though stronger Section 2 enforcement is long overdue. Rather than adopt an approach with uncertain results that might do more harm than good, I suggest more modest changes tailored to specific problems that could nevertheless reinvigorate Section 2. They include greater vigilance in identifying improper conduct, and seeking a steady widening of the scope of exclusionary conduct through bolder choice of cases, moving toward greater flexibility in the analysis of anticompetitive effects, and overcoming some of the skepticism surrounding the legitimacy and value of qualitative evidence, including intent evidence.


A COMPARISON OF TWO METHODS TO ARTICULATE A MAXILLARY CAST WITH LATERAL CEPHALOMETRY Laura H. Lux D.D.S Marquette University, 2014 The Kois Dento-Facial Analyzer, an arbitrary articulation system, is used by clinicians to articulate and evaluate clinical cases. There is, however, limited information for understanding how the Kois Dento-Facial Analyzer should be utilized. Dr. Kois and Dr. Lee originally patented the device in 2003 yet there is essentially no evidence-based research in the literature. The purpose of this study was to evaluate the outcomes of articulating the maxillary cast using the Kois Dento-Facial Analyzer in three-dimensions as compared to the position of the cast when using Panadent's Pana-Mount Facebow. Fifteen dried human skulls were used as test subjects. Maxillary diagnostic impressions were made on each skull as well as lateral cephalometric radiographs. Each diagnostic cast was articulated on a Panadent articulator according to the manufacturer's instructions by means of the Kois Dento-Facial Analyzer as well as the Pana-Mount facebow. Standardized photographs of each articulation were then taken from a lateral view. From the cephalometric radiograph, key landmarks and measurements were made including the distance from the condylar center to the incisal edge and the occlusal plane angle relative to Frankfort Horizontal Plane. From the photographs taken of each articulation, the distance from the articular centers to the incisal edge position was measured, as was the occlusal plane angle relative to Frankfort Horizontal Plane. Finally, the three-dimensional position of each articulation was located and compared by means of the Panadent CPI III device. Statistical analysis was completed for the data collected. From this study, the following conclusions were made: 1. The Kois Dento-Facial Analyzer articulates the maxillary cast in a position that is not statistically different to the Pana-Mount facebow when comparing the incisal edge position and occlusal plane angle relative to Frankfort Horizontal. 2. Both the Kois Dento-Facial Analyzer and the Pana-Mount facebow locate the maxillary incisal edge position in a significantly different position compared to the skull. 3. Both the Kois Dento-Facial Analyzer and the Pana-Mount facebow produce occlusal plane angles that are not significantly different than the angle on the skull. 4. The three dimensional location of the maxillary cast varies approximately 810 mm at the condyles.


The recommendation of additional shopping items that are potentially interesting for the customer has become a standard feature of modern online stores. In academia, research on recommender systems (RS) is mostly centered around approaches that rely on explicit item ratings and long-term user profiles. In practical environments, however, such rating information is often very sparse and for a large fraction of the users very little is known about their preferences. Furthermore, in particular when the shop offers products from a variety of categories, the decision of what should be recommended can strongly depend on the user's current short-term interests and the navigational context. In this paper, we report the results of an initial experimental analysis evaluating the predictive accuracy of different contextualized and non-contextualized recommendation strategies and discuss the question of appropriate experimental designs for such types of evaluations. To that purpose, we introduce a parameterizable protocol that supports session-specific accuracy measurements. Our analysis, which was based on log data obtained from a large online retailer for clothing and lifestyle products, shows that even a comparably simple contextual post-processing approach based on product features can leverage short-term user interests to increase the accuracy of the recommendations.


We report the discovery of diffuse far-infrared and far-ultraviolet emission projected near the interacting pair NGC 4435/4438, in the Virgo cluster. This feature spatially coincides with a well-known low surface-brightness optical plume, usually interpreted as tidal debris. If extragalactic, this stream would represent not only one of the clearest examples of intracluster dust, but also a rare case of intracluster molecular hydrogen and large-scale intracluster star formation. However, the ultraviolet, far-infrared, H i and CO emission as well as the dynamics of this feature are extremely unusual for tidal streams but are typical of Galactic cirrus clouds. In support to the cirrus scenario, we show that a strong spatial correlation between far-infrared and far-ultraviolet cirrus emission is observed across the centre of the Virgo cluster, over a scale of several degrees. This study demonstrates how dramatic Galactic cirrus contamination can be, even at optical and ultraviolet wavelengths and at high galactic latitudes. If ignored, the presence of diffuse light scattered by Galactic dust clouds could significantly bias our interpretation of low surface-brightness features and diffuse light observed around galaxies and in clusters of galaxies.


We report on the results of an experimental study based on the petrology of the Tissint meteorite, an olivine‐phyric shergottite that preserves evidence of an oxidation event during its petrogenesis. We find that oxidation occurring after olivine saturation modifies the Cr zoning profiles in experimental run products, and note that similar Cr‐depleted olivine profiles occur in the natural sample. We consider processes that could operate to modify Cr zoning profiles in experimentally produced olivine, and find that diffusion operates too slowly; furthermore, peritectic resorption of olivine, which occurs during oxidation, does not adequately shorten the diffusion length to account for the depletion. Fine‐grained (<10 μm) spinel grains are observed within olivine crystals exclusively in cooling rate experiments involving an oxidation step, suggesting that the mechanism causing modification of Cr zoning profiles in olivine is the oxidation‐induced exsolution of Cr‐spinel, consistent with observations of natural samples. A replicate experiment with V included in the composition shows that V is similarly affected. Known partitioning behavior suggests that Ni and Co should be similarly affected due to preferential partitioning into spinel. We consider implications of our observations for the interpretation of the petrogenetic histories of other olivine‐phyric shergottites, and provide a new petrographic tool for recognizing oxidation events in olivine‐phyric shergottites.


This paper presents the approach taken and the tools developed and advanced within the European research project CARE-W (Computer Aided REhabilitation of Water networks) for strategic rehabilitation investment planning as a complement to short-term performance monitoring and annual rehabilitation (rehab) budget allocation planning. In a first step, future rehab needs are quantified with a cohort-survival model from the present stock of assets taking into account the specific service lives of its components. Utility managers may choose in the short and medium range from many rehab options: doing more or less, sooner or later, on particular network components and with specific rehab technologies at lower or higher cost. So, in a second step, alternative medium-term rehab programs are specified and tested for their effects. The annual costs and benefits of these alternative rehab programs are forecast with the cohort-survival model beyond the rehab program period to capture the long-term effects of rehabilitating these long-lived assets. Advantages and disadvantages of alternative rehab programs are systematically compared to find out which one is most appropriate under local constraints. However, whereas the survival of network components can be forecast over very long periods with sufficient accuracy, many other characteristics of the water supply system that must be considered for finding the best network rehab strategy may take unforeseeable paths into the far future. Therefore, a scenario writing tool was developed allowing consistent scenarios for particular water utilities to be created and to test whether the alternative rehab programs are robust enough to meet all eventualities of the future. This approach is illustrated by a case study from East Germany.


Offshore wind farming is gaining increasing momentum in Germany. Given the wide range of other sea uses in the North Sea, the potential for contention is high. This study traces attitudes to offshore wind farming among local residents on the West coast of Schleswig-Holstein. It is an explorative, qualitative study which evaluates expected impacts based on a non-representative questionnaire survey in selected municipalities. Since landscape aesthetics play a particular role in determining the acceptance of wind farming on land, the study particularly focuses on the role of seascape values in determining acceptance of offshore wind farming. In order to establish the range of values carried by the sea, a new definition of 'seascape' is developed encompassing physical properties (forms), visual-aesthetic elements as well as the 'sea of the mind'. A cognitive belief framework is constructed to establish how opinions on offshore wind farming are formed. It includes basic human beliefs as the first order of cognition, followed by beliefs about nature, sea and West coast values and finally attitude to offshore wind farming. Qualitative links emerge between particular images of nature, nature ideologies and sea values; these in turn are linked to West coast values and with these offshore wind farming values. Results show the existence of four basic types indicative of trade-offs between offshore wind farming values and marine values at different stages of the cognitive belief framework: the 'conservationist type', the 'aesthetic type', the clean energy proponent', and the 'utilitarian type'. Strong existence value assigned to the marine environment, the belief that nature is fragile and the belief that offshore wind farming will damage the marine environment is likely to lead to a negative attitude to offshore wind farming. In contrast, strong moral convictions associated with offshore wind farming (such as strong beliefs in offshore wind farming) are likely to tip the balance in favour of offshore wind even if nature and sea values are also considered important. Ultimately, however, there is no simple yes or no to offshore wind farming as support or rejection is always the result of a complex internal process driven by subjective rationalities. Since circumstances change, the results described in this study must be interpreted as a snapshot in time. Nevertheless, the overall concept can readily be transferred to other settings and contexts. The benefit of the approach is that it leads to better understanding of the positions taken up by stakeholders, facilitating process of negotiation and debate.


Background The appropriate control of mitotic entry and exit is reliant on a series of interlocking signaling events that coordinately drive the biological processes required for accurate cell division. Overlaid onto these signals that promote orchestrated cell division are checkpoints that ensure appropriate mitotic spindle formation, a lack of DNA damage, kinetochore attachment, and that each daughter cell has the appropriate complement of DNA. We recently discovered that AMP-activated protein kinase (AMPK) modulates the G2/M phase of cell cycle progression in part through its suppression of mammalian target of rapamycin (mTOR) signaling. AMPK directly phosphorylates the critical mTOR binding partner raptor inhibiting mTORC1 (mTOR-raptor rapamycin sensitive mTOR kinase complex 1). As mTOR has been previously tied to mitotic control, we examined further how raptor may contribute to this process. Methodology/Principal Findings We have discovered that raptor becomes highly phosphorylated in cells in mitosis. Utilizing tandem mass spectrometry, we identified a number of novel phosphorylation sites in raptor, and using phospho-specific antibodies demonstrated that raptor becomes phosphorylated on phospho-serine/threonine-proline sites in mitosis. A combination of site-directed mutagenesis in a tagged raptor cDNA and analysis with a series of new phospho-specific antibodies generated against different sites in raptor revealed that Serine 696 and Threonine 706 represent two key sites in raptor phosphorylated in mitosis. We demonstrate that the mitotic cyclin-dependent kinase cdc2/CDK1 is the kinase responsible for phosphorylating these sites, and its mitotic partner Cyclin B efficiently coimmunoprecipitates with raptor in mitotic cells. Conclusions/Significance This study demonstrates that the key mTOR binding partner raptor is directly phosphorylated during mitosis by cdc2. This reinforces previous studies suggesting that mTOR activity is highly regulated and important for mitotic progression, and points to a direct modulation of the mTORC1 complex during mitosis.


M CASE is an approach to software development which emphasizes the use of operational models throughout the life cycle. Software development consists , therefore, in building, testing and reening models within a seamless process that leads the ana-lyst/developer from analysis to design and nally to the implementation of the system. M CASE is made up of two modeling languages, namely Protob and Quid (the former covering functional and behavioral issues, the latter addressing in-formational aspects), and a methodology for building the architecture of models. The paper also describes the simulation and animation of the models emphasizing the integration between the functional/behavioral part and the information one.


Introduction: The production of carbapenem enzyme is one of the most frequent mechanisms reported in cabapenem resistant Pseudomonas aeruginosa. Besides, a growing number of mobile colistin resistance (MCR) genes are threatening the renewed interest of colistin as a "last-resort" against carbapenem-resistant pathogens. Therefore, the detection of carbapenem-resistant and colistin-resistant phenotypes as well as preventing transmission of multi-resistant P. aeruginosa strains with genes coding for carbapenemase is extremely necessary.

Material and methods: Among 159 P. aeruginosa strains were collected 46 isolates, which is resistant or intermediated to meropenem. Modified carbapenem inactivation (mCIM) and colistin broth disk elution (CBDE) methods were used to identify carbapenemase-producing strains and colistin resistance. In addition, a multiplex real-time PCR technique was applied to investigate the frequency of emergence of carbapenem resistance genes.

Results: The results revealed that 25 strains (54.3%) were positive with mCIM test and none of them resistant to colistin by CBDE method. Number of strains carrying a gene blaIMP: 4 strains (16%), blaNDM: 2 strains (8%). Strains are carrying two genes: blaIMP + blaNDM: 10 strains (40%), blaVIM + blaNDM: 1 strain (4%), blaNDM + blaOXA-48: 1 strain (4%) and are carrying three genes blaIMP + blaNDM + blaOXA-48: 6 strains (24%), blaKPC + blaIMP + blaNDM: 1 strain (4%).

Conclusions: All mCIM positive P. aeruginosa were contained carbapenemase genes. Colistin still reserved a good effect to combine with other antibiotics in multi-resistant treatment. Hence, the classification of genes can help clinicians selected appropriate antibiotics so that more effective treatment for patients.


Iterative learning algorithms that approximate the solution of support vector machines (SVMs) have two potential advantages. First, they allow online and active learning. Second, for large data sets, computing the exact SVM solution may be too time-consuming, and an efficient approximation can be preferable. The powerful LASVM iteratively approaches the exact SVM solution using sequential minimal optimization (SMO). It allows efficient online and active learning. Here, this algorithm is considerably improved in speed and accuracy by replacing the working set selection in the SMO steps. A second-order working set selection strategy, which greedily aims at maximizing the progress in each single step, is incorporated.


In the present paper, seismic performance assessment of a typical low-rise unreinforced masonry (URM) building, which has been built in accordance with template designs in Albania, has been performed. For this purpose, one of the most widely used template designed URM building typology has been selected as a good representatives of residential building stock. This type shows some particular features, typical of the traditional construction techniques at that time which could be identified as the additional potential damage sources. The building was designed and constructed in 1960 and contains details which are typical of that construction period of the region. Material properties are assessed based upon experimental test results. Then, the buildings is modeled and analyzed as 3-D assembly of finite elements. The earthquake ground motion to be used in performance assessment is determined through probabilistic seismic hazard assessment. The seismic response of the buildings has been evaluated for various earthquake levels based on Eurocode 8 and FEMA 440 guidelines. Upon the evaluation of the obtained results here for the earthquake performance of this type of buildings, useful conclusions are drawn on the strength and nonlinear behavior of masonry subjected to earthquake actions.


This paper explores the topics of competition and coordination in trade dynamics in the People's Republic of China. Focusing on the rationality of trade cooperation rather than on the rationality of competition, facts and data will be presented; existing studies from international organizations will be discussed; and conclusions derived by them will be quoted. Although there is an increasing share of service in trade, only merchandise trade is studied here in order to limit the scope of this paper. This paper was prepared for the Latin America/Caribbean and Asia/Pacific Economics and Business Association (LAEBA)'s 4th Annual Meeting held in Lima, Peru, on June 17th, 2008.


Problem structuring methods (PSMs) have been developed within operational research (OR) to assist a set of actors to agree on a problem structure and make commitments to consequential action. Their characteristic feature is the use of a model to represent alternative versions of the problem of common interest, combined with facilitation to help actors make constructive mutual adjustments. Whilst most PSMs have traditionally been applied with actors confronting problems within organizations, others have also been applied with actors working between and across organisations to address a problem of common interest. This research will explore the significance of PSMs in collaborative contexts of this kind. The aim of this research is to investigate the possible roles of PSMs in assisting actors of an inter-organisational domain who engage in collaboration to address a problematique of common interest in order to reach joint agreements with respect to it. The hypothesis investigated in this research is that the analytical assistance provided by PSMs can be expected to contribute to a collaboration process principally through improving actors' sense-making of their problematique, and through providing structure to the product of this sense- making activity. The interpretation of our hypothesis is that PSMs generate this effect through improving the quality of dialogue between actors. This effect should tend to impact positively on the ownership of the commitments resulting from the dialogue, and on mutual accommodations in the power balance among actors. In order to articulate this hypothesis, it has been necessary to conduct some conceptual clarification to achieve a clear meaning for the terms 'shared meaning', 'power', and 'dialogue'. Building upon this conceptual clarification, a model of collaboration as a process has been developed, which identifies the factors, pre-requisites and processes involved in actors' ability to achieve the intended products of collaboration. This model provides the basis for identifying the possible effects of PSMs, and for evaluating their effectiveness. To explore our hypothesis and the adequacy of the conceptual model, a case study drawn from an action research project in the UK construction industry was carried out. This action research project was industry-academic collaboration aimed at contributing to build a high value construction environment, and its principal output was the development of a PSM-based methodology for construction project reviews. The case study reported in this thesis involved the application of this methodology in a multi-organizational construction partnership in the hotel business. This involved engagement in and observation of ongoing partnership activity of three construction project teams. Reasonably clear and positive effects from the application of the methodology were found in the dialogue between participants, consistent with the hypothesis. Additional positive effects in terms of achieving inter-organisational learning within the selected partnership were also identified. Overall the results of the case study are encouraging; however, as they result from the application of a particular PSM-based methodology, extrapolation to more general conclusions about the potential of PSMs for multi-organisational collaboration should be made with caution. Nevertheless, the results of this research suggest valuable potential avenues for further research. The case experience also was generally supportive of the conceptual model of the collaboration process, in that the activities and processes observed could be interpreted without difficulties within the model's framework. The model offers a means for further theoretical and empirical work aimed at confirming and enriching its structure and validity.


1. In the collembolan, Podura aquatica , transpiration through the cuticle is high at all relative humidities. Above 90% relative humidity, cuticular permeability is abnormally high but no adequate explanation of this can be given.

2. Transpiration through the cuticle is high at all temperatures and there is no evidence of a critical temperature over the range 17-29° C.

3. Abrasion increases the transpiration rate, and at least partial recovery occurs within the instar. Moulting fully restores the transpiration rate to the normal level.

4. The hydrofuge nature of the cuticle strongly suggests the presence of an orientated lipid monolayer on its surface. Strong wax solvents render the cuticle wettable, whereas treatment with water under reduced pressure does not.

5. Consideration of the fine structure suggests that the hydrofuge layer is discontinuous and that it occurs on the tips of the minor tubercles. This is compatible with an overall high transpiration rate.

6. The occurrence of hydrophil areas of cuticle is correlated with a smooth cuticular surface.

7. The biological effects of the hydrofuge and hydrophil areas in the life of the insect are discussed.