Effects of Aedes aegypti salivary components on dendritic cell and lymphocyte biology

Abstract Background Saliva is a key element of interaction between hematophagous mosquitoes and their vertebrate hosts. In addition to allowing a successful blood meal by neutralizing or delaying hemostatic responses, the salivary cocktail is also able to modulate the effector mechanisms of host immune responses facilitating, in turn, the transmission of several types of microorganisms. Understanding how the mosquito uses its salivary components to circumvent host immunity might help to clarify the mechanisms of transmission of such pathogens and disease establishment. Methods Flow cytometry was used to evaluate if increasing concentrations of A. aegypti salivary gland extract (SGE) affects bone marrow-derived DC differentiation and maturation. Lymphocyte proliferation in the presence of SGE was estimated by a colorimetric assay. Western blot and Annexin V staining assays were used to assess apoptosis in these cells. Naïve and memory cells from mosquito-bite exposed mice or OVA-immunized mice and their respective controls were analyzed by flow cytometry. Results Concentration-response curves were employed to evaluate A. aegypti SGE effects on DC and lymphocyte biology. DCs differentiation from bone marrow precursors, their maturation and function were not directly affected by A. aegypti SGE (concentrations ranging from 2.5 to 40 μg/mL). On the other hand, lymphocytes were very sensitive to the salivary components and died in the presence of A. aegypti SGE, even at concentrations as low as 0.1 μg/mL. In addition, A. aegypti SGE was shown to induce apoptosis in all lymphocyte populations evaluated (CD4+ and CD8+ T cells, and B cells) through a mechanism involving caspase-3 and caspase-8, but not Bim. By using different approaches to generate memory cells, we were able to verify that these cells are resistant to SGE effects. Conclusion Our results show that lymphocytes, and not DCs, are the primary target of A. aegypti salivary components. In the presence of A. aegypti SGE, naïve lymphocyte populations die by apoptosis in a caspase-3- and caspase-8-dependent pathway, while memory cells are selectively more resistant to its effects. The present work contributes to elucidate the activities of A. aegypti salivary molecules on the antigen presenting cell-lymphocyte axis and in the biology of these cells.

What drives the seasonality of photosynthesis across the Amazon basin? A cross-site analysis of eddy flux tower measurements from the Brasil flux network

We investigated the seasonal patterns of Amazonian forest photosynthetic activity, and the effects thereon of variations in climate and land-use, by integrating data from a network of ground-based eddy flux towers in Brazil established as part of the ‘Large-Scale Biosphere Atmosphere Experiment in Amazonia’ project. We found that degree of water limitation, as indicated by the seasonality of the ratio of sensible to latent heat flux (Bowen ratio) predicts seasonal patterns of photosynthesis. In equatorial Amazonian forests (5◦ N–5◦ S), water limitation is absent, and photosynthetic fluxes (or gross ecosystem productivity, GEP) exhibit high or increasing levels of photosynthetic activity as the dry season progresses, likely a consequence of allocation to growth of new leaves. In contrast, forests along the southern flank of the Amazon, pastures converted from forest, and mixed forest-grass savanna, exhibit dry-season declines in GEP, consistent with increasing degrees of water limitation. Although previous work showed tropical ecosystem evapotranspiration (ET) is driven by incoming radiation, GEP observations reported here surprisingly show no or negative relationships with photosynthetically active radiation (PAR). Instead, GEP fluxes largely followed the phenology of canopy photosynthetic capacity (Pc), with only deviations from this primary pattern driven by variations in PAR. Estimates of leaf flush at three

Very Long Baseline Interferometry in Italy Wide-field VLBI imaging and astrometry and prospects for an Italian VLBI network including the Sardinia Radio Telescope

In this thesis the use of widefield imaging techniques and VLBI observations with a limited number of antennas are explored. I present techniques to efficiently and accurately image extremely large UV datasets. Very large VLBI datasets must be reduced into multiple, smaller datasets if today’s imaging algorithms are to be used to image them. I present a procedure for accurately shifting the phase centre of a visibility dataset. This procedure has been thoroughly tested and found to be almost two orders of magnitude more accurate than existing techniques. Errors have been found at the level of one part in 1.1 million. These are unlikely to be measurable except in the very largest UV datasets. Results of a four-station VLBI observation of a field containing multiple sources are presented. A 13 gigapixel image was constructed to search for sources across the entire primary beam of the array by generating over 700 smaller UV datasets. The source 1320+299A was detected and its astrometric position with respect to the calibrator J1329+3154 is presented. Various techniques for phase calibration and imaging across this field are explored including using the detected source as an in-beam calibrator and peeling of distant confusing sources from VLBI visibility datasets. A range of issues pertaining to wide-field VLBI have been explored including; parameterising the wide-field performance of VLBI arrays; estimating the sensitivity across the primary beam both for homogeneous and heterogeneous arrays; applying techniques such as mosaicing and primary beam correction to VLBI observations; quantifying the effects of time-average and bandwidth smearing; and calibration and imaging of wide-field VLBI datasets. The performance of a computer cluster at the Istituto di Radioastronomia in Bologna has been characterised with regard to its ability to correlate using the DiFX software correlator. Using existing software it was possible to characterise the network speed particularly for MPI applications. The capabilities of the DiFX software correlator, running on this cluster, were measured for a range of observation parameters and were shown to be commensurate with the generic performance parameters measured. The feasibility of an Italian VLBI array has been explored, with discussion of the infrastructure required, the performance of such an array, possible collaborations, and science which could be achieved. Results from a 22 GHz calibrator survey are also presented. 21 out of 33 sources were detected on a single baseline between two Italian antennas (Medicina to Noto). The results and discussions presented in this thesis suggest that wide-field VLBI is a technique whose time has finally come. Prospects for exciting new science are discussed in the final chapter.

Numerical coupling of thermal-electric network models and energy-transport equations including optoelectronic semiconductor devices

In this work the numerical coupling of thermal and electric network models with model equations for optoelectronic semiconductor devices is presented. Modified nodal analysis (MNA) is applied to model electric networks. Thermal effects are modeled by an accompanying thermal network. Semiconductor devices are modeled by the energy-transport model, that allows for thermal effects. The energy-transport model is expandend to a model for optoelectronic semiconductor devices. The temperature of the crystal lattice of the semiconductor devices is modeled by the heat flow eqaution. The corresponding heat source term is derived under thermodynamical and phenomenological considerations of energy fluxes. The energy-transport model is coupled directly into the network equations and the heat flow equation for the lattice temperature is coupled directly into the accompanying thermal network. The coupled thermal-electric network-device model results in a system of partial differential-algebraic equations (PDAE). Numerical examples are presented for the coupling of network- and one-dimensional semiconductor equations. Hybridized mixed finite elements are applied for the space discretization of the semiconductor equations. Backward difference formluas are applied for time discretization. Thus, positivity of charge carrier densities and continuity of the current density is guaranteed even for the coupled model.

Flash floods and their effects on the development in El-Qaá plain area in South Sinai, Egypt

The arid regions are dominated to a much larger degree than humid regions by major catastrophic events. Although most of Egypt lies within the great hot desert belt; it experiences especially in the north some torrential rainfall, which causes flash floods all over Sinai Peninsula. Flash floods in hot deserts are characterized by high velocity and low duration with a sharp discharge peak. Large sediment loads may be carried by floods threatening fields and settlements in the wadis and even people who are living there. The extreme spottiness of rare heavy rainfall, well known to desert people everywhere, precludes any efficient forecasting. Thus, although the limitation of data still reflects pre-satellite methods, chances of developing a warning system for floods in the desert seem remote. The relatively short flood-to-peak interval, a characteristic of desert floods, presents an additional impediment to the efficient use of warning systems. The present thesis contains introduction and five chapters, chapter one points out the physical settings of the study area. There are the geological settings such as outcrop lithology of the study area and the deposits. The alluvial deposits of Wadi Moreikh had been analyzed using OSL dating to know deposits and palaeoclimatic conditions. The chapter points out as well the stratigraphy and the structure geology containing main faults and folds. In addition, it manifests the pesent climate conditions such as temperature, humidity, wind and evaporation. Besides, it presents type of soils and natural vegetation cover of the study area using unsupervised classification for ETM+ images. Chapter two points out the morphometric analysis of the main basins and their drainage network in the study area. It is divided into three parts: The first part manifests the morphometric analysis of the drainage networks which had been extracted from two main sources, topographic maps and DEM images. Basins and drainage networks are considered as major influencing factors on the flash floods; Most of elements were studied which affect the network such as stream order, bifurcation ratio, stream lengths, stream frequency, drainage density, and drainage patterns. The second part of this chapter shows the morphometric analysis of basins such as area, dimensions, shape and surface. Whereas, the third part points the morphometric analysis of alluvial fans which form most of El-Qaá plain. Chapter three manifests the surface runoff through rainfall and losses analysis. The main subject in this chapter is rainfall which has been studied in detail; it is the main reason for runoff. Therefore, all rainfall characteristics are regarded here such as rainfall types, distribution, rainfall intensity, duration, frequency, and the relationship between rainfall and runoff. While the second part of this chapter concerns with water losses estimation by evaporation and infiltration which are together the main losses with direct effect on the high of runoff. Finally, chapter three points out the factors influencing desert runoff and runoff generation mechanism. Chapter four is concerned with assessment of flood hazard, it is important to estimate runoff and tocreate a map of affected areas. Therefore, the chapter consists of four main parts; first part manifests the runoff estimation, the different methods to estimate runoff and its variables such as runoff coefficient lag time, time of concentration, runoff volume, and frequency analysis of flash flood. While the second part points out the extreme event analysis. The third part shows the map of affected areas for every basin and the flash floods degrees. In this point, it has been depending on the DEM to extract the drainage networks and to determine the main streams which are normally more dangerous than others. Finally, part four presets the risk zone map of total study area which is of high inerest for planning activities. Chapter five as the last chapter concerns with flash flood Hazard mitigation. It consists of three main parts. First flood prediction and the method which can be used to predict and forecast the flood. The second part aims to determine the best methods which can be helpful to mitigate flood hazard in the arid zone and especially the study area. Whereas, the third part points out the development perspective for the study area indicating the suitable places in El-Qaá plain for using in economic activities.

An Input-Process-Output Approach to Interorganizational Teams: The Influence of Work Group Diversity, Trust and Shared Leadership on Communication Network and Team Outputs.

The market’s challenges bring firms to collaborate with other organizations in order to create Joint Ventures, Alliances and Consortia that are defined as “Interorganizational Networks” (IONs) (Provan, Fish and Sydow; 2007). Some of these IONs are managed through a shared partecipant governance (Provan and Kenis, 2008): a team composed by entrepreneurs and/or directors of each firm of an ION. The research is focused on these kind of management teams and it is based on an input-process-output model: some input variables (work group’s diversity, intra-team's friendship network density) have a direct influence on the process (team identification, shared leadership, interorganizational trust, team trust and intra-team's communication network density), which influence some team outputs, individual innovation behaviors and team effectiveness (team performance, work group satisfaction and ION affective commitment). Data was collected on a sample of 101 entrepreneurs grouped in 28 ION’s government teams and the research hypotheses are tested trough the path analysis and the multilevel models. As expected trust in team and shared leadership are positively and directly related to team effectiveness while team identification and interorganizational trust are indirectly related to the team outputs. The friendship network density among the team’s members has got positive effects on the trust in team and on the communication network density, and also, through the communication network density it improves the level of the teammates ION affective commitment. The shared leadership and its effects on the team effectiveness are fostered from higher level of team identification and weakened from higher level of work group diversity, specifically gender diversity. Finally, the communication network density and shared leadership at the individual level are related to the frequency of individual innovative behaviors. The dissertation’s results give a wider and more precise indication about the management of interfirm network through “shared” form of governance.

Modulation of network excitability and epileptiform activity in the hippocampus of immature rats by the activation of GlyRs

Epileptic seizures are the manifestations of epilepsy, which is a major neurological disorder and occurs with a high incidence during early childhood. A fundamental mechanism underlying epileptic seizures is loss of balance between neural excitation and inhibition toward overexcitation. Glycine receptor (GlyR) is ionotropic neurotransmitter receptor that upon binding of glycine opens an anion pore and mediates in the adult nervous system a consistent inhibitory action. While previously it was assumed that GlyRs mediate inhibition mainly in the brain stem and spinal cord, recent studies reported the abundant expression of GlyRs throughout the brain, in particular during neuronal development. But no information is available regarding whether activation of GlyRs modulates neural network excitability and epileptiform activities in the immature central nervous system (CNS). Therefore the study in this thesis addresses the role of GlyRs in the modulation of neuronal excitability and epileptiform activity in the immature rat brain. By using in vitro intact corticohippocampal formation (CHF) of rats at postnatal days 4-7 and electrophysiological methods, a series of pharmacological examinations reveal that GlyRs are directly implicated in the control of hippocampal excitation levels at this age. In this thesis I am able to show that GlyRs are functionally expressed in the immature hippocampus and exhibit the classical pharmacology of GlyR, which can be activated by both glycine and the presumed endogenous agonist taurine. This study also reveals that high concentration of taurine is anticonvulsive, but lower concentration of taurine is proconvulsive. A substantial fraction of both the pro- and anticonvulsive effects of taurine is mediated via GlyRs, although activation of GABAA receptors also considerably contributes to the taurine effects. Similarly, glycine exerts both pro- and anticonvulsive effects at low and high concentrations, respectively. The proconvulsive effects of taurine and glycine depend on NKCC1-mediated Cl- accumulation, as bath application of NKCC1 inhibitor bumetanide completely abolishes proconvulsive effects of low taurine and glycine concentrations. Inhibition of GlyRs with low concentration of strychnine triggers epileptiform activity in the CA3 region of immature CHF, indicating that intrinsically an inhibitory action of GlyRs overwhelms its depolarizing action in the immature hippocampus. Additionally, my study indicates that blocking taurine transporters to accumulate endogenous taurine reduces epileptiform activity via activation of GABAA receptors, but not GlyRs, while blocking glycine transporters has no observable effect on epileptiform activity. From the main results of this study it can be concluded that in the immature rat hippocampus, activation of GlyRs mediates both pro- and anticonvulsive effects, but that a persistent activation of GlyRs is required to prevent intrinic neuronal overexcitability. In summary, this study uncovers an important role of GlyRs in the modulation of neuronal excitability and epileptiform activity in the immature rat hippocampus, and indicates that glycinergic system can potentially be a new therapeutic target against epileptic seizures of children.

Botanical drugs, synergy, and network pharmacology: forth and back to intelligent mixtures

For centuries the science of pharmacognosy has dominated rational drug development until it was gradually substituted by target-based drug discovery in the last fifty years. Pharmacognosy stems from the different systems of traditional herbal medicine and its "reverse pharmacology" approach has led to the discovery of numerous pharmacologically active molecules and drug leads for humankind. But do botanical drugs also provide effective mixtures? Nature has evolved distinct strategies to modulate biological processes, either by selectively targeting biological macromolecules or by creating molecular promiscuity or polypharmacology (one molecule binds to different targets). Widely claimed to be superior over monosubstances, mixtures of bioactive compounds in botanical drugs allegedly exert synergistic therapeutic effects. Despite evolutionary clues to molecular synergism in nature, sound experimental data are still widely lacking to support this assumption. In this short review, the emerging concept of network pharmacology is highlighted, and the importance of studying ligand-target networks for botanical drugs is emphasized. Furthermore, problems associated with studying mixtures of molecules with distinctly different pharmacodynamic properties are addressed. It is concluded that a better understanding of the polypharmacology and potential network pharmacology of botanical drugs is fundamental in the ongoing rationalization of phytotherapy.

Individual and population level effects of partner notification for Chlamydia trachomatis

Partner notification (PN or contact tracing) is an important aspect of treating bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis. It facilitates the identification of new infected cases that can be treated through individual case management. PN also acts indirectly by limiting onward transmission in the general population. However, the impact of PN, both at the level of individuals and the population, remains unclear. Since it is difficult to study the effects of PN empirically, mathematical and computational models are useful tools for investigating its potential as a public health intervention. To this end, we developed an individual-based modeling framework called Rstisim. It allows the implementation of different models of STI transmission with various levels of complexity and the reconstruction of the complete dynamic sexual partnership network over any time period. A key feature of this framework is that we can trace an individual's partnership history in detail and investigate the outcome of different PN strategies for C. trachomatis. For individual case management, the results suggest that notifying three or more partners from the preceding 18 months yields substantial numbers of new cases. In contrast, the successful treatment of current partners is most important for preventing re-infection of index cases and reducing further transmission of C. trachomatis at the population level. The findings of this study demonstrate the difference between individual and population level outcomes of public health interventions for STIs.

Effects Of Perceived Financial Accessibility Of Colleges And Universities On Studentsâ¿ Assesment Of Institutional Desirability

This study focused on the effects of socioeconomic exclusivity indicators on college students¿ attitudes toward a hypothetical private liberal arts university. Students enrolled in two undergraduate courses in Education at an elite private liberal arts university in the northeast were randomly presented with one of three versions of an admissions brochure describing a fictitious university. The three versions of the brochure varied in their portrayals of the institution¿s financial exclusivity, ranging from high exclusivity to low exclusivity. Each student was asked to review the brochure and respond to a questionnaire, containing items pertaining to the overall desirability of the institution, as well as its student culture, academic program, campus traditions, and alumni network. Based on Thorstein Veblen¿s theory of the leisure class and Pierre Bourdieu¿s theory of social reproduction, it was hypothesized that students would judge the institution most favorably in all areas under the high exclusivity condition and least favorably under the low exclusivity condition. It was further hypothesized that differences in students¿ ratings of institutional desirability would be mediated by their own financial aid statuses. Results of a two-way multivariate analysis of variance (MANOVA) revealed significant (p < .05) interactive effects of institutional exclusivity and student aid status on the perceived desirability of the academic program and campus traditions of the institution. While recipients of need-based financial aid tended to rate more socioeconomically exclusive institutions more favorably on these two variables, those who were not receiving need-based financial aid tended to rate such institutions less favorably. Implications of the findings for student affairs practice are discussed and recommendations for further research are presented.

Postural effects on interstitial fluid pressure in humans

BACKGROUND: Direct assessment of the effect of postural changes on interstitial fluid pressure (IFP) in the human skin under physiological conditions is important for the understanding of mechanisms involved in diseases resulting in lower limb edema. Previous techniques to measure IFP had limitations of being invasive, and acute measurements were not possible. Here we describe the effect of postural changes on IFP in the skin of the foot using the minimally invasive servonulling technique. RESULTS: Measurements were performed in 12 healthy subjects. IFP (means +/- SD) was significantly higher in the sitting (5.1 +/- 2.9 mm Hg) than in the supine position (-0.3 +/- 3.6 mm Hg, p = 0.04) when measured in the sitting position first. The difference between the sitting and the supine position was not significant when measurements were taken in the supine position first [from 1.0 +/- 4.3 (supine) to 3.6 +/- 6.7 mm Hg (sitting), p = 0.46]. Spontaneous low-frequency pressure fluctuations occurred in 58% of the recordings during sitting, which was almost twice as frequent as in the supine position (33%; p = 0.001), while no effects on lymphatic capillary network extension were observed (p = 0.12). CONCLUSION: Using the servonulling micropressure system, postural effects on IFP can be directly assessed. IFP is higher in the sitting position, but differences are influenced by the time in the upright position.

Arteriolar vasoconstrictive response: comparing the effects of arginine vasopressin and norepinephrine

INTRODUCTION: This study was designed to examine differences in the arteriolar vasoconstrictive response between arginine vasopressin (AVP) and norepinephrine (NE) on the microcirculatory level in the hamster window chamber model in unanesthetized, normotonic hamsters using intravital microscopy. It is known from patients with advanced vasodilatory shock that AVP exerts strong additional vasoconstriction when incremental dosage increases of NE have no further effect on mean arterial blood pressure (MAP). METHODS: In a prospective controlled experimental study, eleven awake, male golden Syrian hamsters were instrumented with a viewing window inserted into the dorsal skinfold. NE (2 microg/kg/minute) and AVP (0.0001 IU/kg/minute, equivalent to 4 IU/h in a 70 kg patient) were continuously infused to achieve a similar increase in MAP. According to their position within the arteriolar network, arterioles were grouped into five types: A0 (branch off small artery) to A4 (branch off A3 arteriole). RESULTS: Reduction of arteriolar diameter (NE, -31 +/- 12% versus AVP, -49 +/- 7%; p = 0.002), cross sectional area (NE, -49 +/- 17% versus AVP, -73 +/- 7%; p = 0.002), and arteriolar blood flow (NE, -62 +/- 13% versus AVP, -80 +/- 6%; p = 0.004) in A0 arterioles was significantly more pronounced in AVP animals. There was no difference in red blood cell velocities in A0 arterioles between groups. The reduction of diameter, cross sectional area, red blood cell velocity, and arteriolar blood flow in A1 to A4 arterioles was comparable in AVP and NE animals. CONCLUSION: Within the microvascular network, AVP exerted significantly stronger vasoconstriction on large A0 arterioles than NE under physiological conditions. This observation may partly explain why AVP is such a potent vasopressor hormone and can increase systemic vascular resistance even in advanced vasodilatory shock unresponsive to increases in standard catecholamine therapy.

Diesel spray mixing limited vaporization with non-ideal and multi-component fuel thermophysical property effects

Internal combustion engines are, and will continue to be, a primary mode of power generation for ground transportation. Challenges exist in meeting fuel consumption regulations and emission standards while upholding performance, as fuel prices rise, and resource depletion and environmental impacts are of increasing concern. Diesel engines are advantageous due to their inherent efficiency advantage over spark ignition engines; however, their NOx and soot emissions can be difficult to control and reduce due to an inherent tradeoff. Diesel combustion is spray and mixing controlled providing an intrinsic link between spray and emissions, motivating detailed, fundamental studies on spray, vaporization, mixing, and combustion characteristics under engine relevant conditions. An optical combustion vessel facility has been developed at Michigan Technological University for these studies, with detailed tests and analysis being conducted. In this combustion vessel facility a preburn procedure for thermodynamic state generation is used, and validated using chemical kinetics modeling both for the MTU vessel, and institutions comprising the Engine Combustion Network international collaborative research initiative. It is shown that minor species produced are representative of modern diesel engines running exhaust gas recirculation and do not impact the autoignition of n-heptane. Diesel spray testing of a high-pressure (2000 bar) multi-hole injector is undertaken including non-vaporizing, vaporizing, and combusting tests, with sprays characterized using Mie back scatter imaging diagnostics. Liquid phase spray parameter trends agree with literature. Fluctuations in liquid length about a quasi-steady value are quantified, along with plume to plume variations. Hypotheses are developed for their causes including fuel pressure fluctuations, nozzle cavitation, internal injector flow and geometry, chamber temperature gradients, and turbulence. These are explored using a mixing limited vaporization model with an equation of state approach for thermopyhysical properties. This model is also applied to single and multi-component surrogates. Results include the development of the combustion research facility and validated thermodynamic state generation procedure. The developed equation of state approach provides application for improving surrogate fuels, both single and multi-component, in terms of diesel spray liquid length, with knowledge of only critical fuel properties. Experimental studies are coupled with modeling incorporating improved thermodynamic non-ideal gas and fuel

BOLD correlates of EEG alpha phase-locking and the fMRI default mode network

Phase locking or synchronization of brain areas is a key concept of information processing in the brain. Synchronous oscillations have been observed and investigated extensively in EEG during the past decades. EEG oscillations occur over a wide frequency range. In EEG, a prominent type of oscillations is alpha-band activity, present typically when a subject is awake, but at rest with closed eyes. The spectral power of alpha rhythms has recently been investigated in simultaneous EEG/fMRI recordings, establishing a wide-range cortico-thalamic network. However, spectral power and synchronization are different measures and little is known about the correlations between BOLD effects and EEG synchronization. Interestingly, the fMRI BOLD signal also displays synchronous oscillations across different brain regions. These oscillations delineate so-called resting state networks (RSNs) that resemble the correlation patterns of simultaneous EEG/fMRI recordings. However, the nature of these BOLD oscillations and their relations to EEG activity is still poorly understood. One hypothesis is that the subunits constituting a specific RSN may be coordinated by different EEG rhythms. In this study we report on evidence for this hypothesis. The BOLD correlates of global EEG synchronization (GFS) in the alpha frequency band are located in brain areas involved in specific RSNs, e.g. the 'default mode network'. Furthermore, our results confirm the hypothesis that specific RSNs are organized by long-range synchronization at least in the alpha frequency band. Finally, we could localize specific areas where the GFS BOLD correlates and the associated RSN overlap. Thus, we claim that not only the spectral dynamics of EEG are important, but also their spatio-temporal organization.