Activation of the neutrophil respiratory burst by plasma from periodontitis patients is mediated by pro-inflammatory cytokines

Aim: To determine the effect of periodontitis patients' plasma on the neutrophil oxidative burst and the role of albumin, immunoglobulins (Igs) and cytokines. Materials and Methods: Plasma was collected from chronic periodontitis patients (n=11) and periodontally healthy controls (n=11) and used with/without depletion of albumin and Ig or antibody neutralization of IL-8, GM-CSF or IFN-a to prime/stimulate peripheral blood neutrophils, isolated from healthy volunteers. The respiratory burst was measured by lucigenin-dependent chemiluminescence. Plasma cytokine levels were determined by ELISA. Results: Plasmas from patients were significantly more effective in both directly stimulating neutrophil superoxide production and priming for subsequent formyl-met-leu-phe (fMLP)-stimulated superoxide production than plasmas from healthy controls (p<0.05). This difference was maintained after depletion of albumin and Ig. Plasma from patients contained higher mean levels of IL-8, GM-CSF and IFN-a. Individual neutralizing antibodies against IL-8, GM-CSF or IFN-a inhibited the direct stimulatory effect of patients' plasma, whereas the ability to prime for fMLP-stimulated superoxide production was only inhibited by neutralization of IFN-a. The stimulating and priming effects of control plasma were unaffected by antibody neutralization. Conclusions: This study demonstrates that plasma cytokines may have a role in inducing the hyperactive (IL-8, GM-CSF, IFN-a) and hyper-reactive (IFN-a) neutrophil phenotype seen in periodontitis patients.

Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 . - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 . - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. © 2013 Dias et al.

On the interpretation of synchronization in EEG hyperscanning studies:a cautionary note

EEG Hyperscanning is a method for studying two or more individuals simultaneously with the objective of elucidating how co-variations in their neural activity (i.e., hyperconnectivity) are influenced by their behavioral and social interactions. The aim of this study was to compare the performance of different hyper-connectivity measures using (i) simulated data, where the degree of coupling could be systematically manipulated, and (ii) individually recorded human EEG combined into pseudo-pairs of participants where no hyper-connections could exist. With simulated data we found that each of the most widely used measures of hyperconnectivity were biased and detected hyper-connections where none existed. With pseudo-pairs of human data we found spurious hyper-connections that arose because there were genuine similarities between the EEG recorded from different people independently but under the same experimental conditions. Specifically, there were systematic differences between experimental conditions in terms of the rhythmicity of the EEG that were common across participants. As any imbalance between experimental conditions in terms of stimulus presentation or movement may affect the rhythmicity of the EEG, this problem could apply in many hyperscanning contexts. Furthermore, as these spurious hyper-connections reflected real similarities between the EEGs, they were not Type-1 errors that could be overcome by some appropriate statistical control. However, some measures that have not previously been used in hyperconnectivity studies, notably the circular correlation co-efficient (CCorr), were less susceptible to detecting spurious hyper-connections of this type. The reason for this advantage in performance is discussed and the use of the CCorr as an alternative measure of hyperconnectivity is advocated. © 2013 Burgess.

Antenatal corticosteroids impact the inflammatory rather than the antiangiogenic profile of women with preeclampsia

Circulating antiangiogenic factors and proinflammatory cytokines are implicated in the pathogenesis of preeclampsia. This study was performed to test the hypothesis that steroids modify the balance of inflammatory and proangiogenic and antiangiogenic factors that potentially contribute to the patient’s evolving clinical state. Seventy singleton women, admitted for antenatal corticosteroid treatment, were enrolled prospectively. The study group consisted of 45 hypertensive women: chronic hypertension (n=6), severe preeclampsia (n=32), and superimposed preeclampsia (n=7). Normotensive women with shortened cervix (<2.5 cm) served as controls (n=25). Maternal blood samples of preeclampsia cases were obtained before steroids and then serially up until delivery. A clinical severity score was designed to clinically monitor disease progression. Serum levels of angiogenic factors (soluble fms-like tyrosine kinase-1 [sFlt-1], placental growth factor [PlGF], soluble endoglin [sEng]), endothelin-1 (ET-1), and proinflammatory markers (IL-6, C-reactive protein [CRP]) were assessed before and after steroids. Soluble IL-2 receptor (sIL-2R) and total immunoglobulins (IgG) were measured as markers of T- and B-cell activation, respectively. Steroid treatment coincided with a transient improvement in clinical manifestations of preeclampsia. A significant decrease in IL-6 and CRP was observed although levels of sIL-2R and IgG remained unchanged. Antenatal corticosteroids did not influence the levels of angiogenic factors but ET-1 levels registered a short-lived increase poststeroids. Although a reduction in specific inflammatory mediators in response to antenatal steroids may account for the transient improvement in clinical signs of preeclampsia, inflammation is unlikely to be the major contributor to severe preeclampsia or useful for therapeutic targeting.

On some Mixture Distributions

The aim of this paper is to establish some mixture distributions that arise in stochastic processes. Some basic functions associated with the probability mass function of the mixture distributions, such as k-th moments, characteristic function and factorial moments are computed. Further we obtain a three-term recurrence relation for each established mixture distribution.

Operational Rules for a Mixed Operator of the Erdélyi-Kober Type

2000 Mathematics Subject Classification: 26A33 (main), 44A40, 44A35, 33E30, 45J05, 45D05

Caputo Derivatives in Viscoelasticity: A Non-Linear Finite-Deformation Theory for Tissue

Mathematics Subject Classification: 26A33, 74B20, 74D10, 74L15

LDL-Lipids from patients with hypercholesterolaemia and Alzheimer's disease are inflammatory to microvascular endothelial cells:mitigation by statin intervention

Elevated LDL concentration in mid-life increases the risk of developing Alzheimer's disease (AD) in later life. Increased oxidative modification (oxLDL) and nitration is observed during dementia and hypercholesterolemia. We investigated the hypothesis that statin intervention in mid-life mitigates the inflammatory effects of oxLDL on the microvasculature. Human microvascular endothelial cells (HMVEC) were maintained on transwells to mimic the microvasculature and exposed to patient and control LDL. Blood was obtained from statin-naïve, normo- and hyperlipidaemic subjects, AD with vascular dementia (AD-plus) and AD subjects (n=10/group) at baseline. Only hyperlipidaemic subjects with normal cognitive function received 40mg simvastatin intervention/day for three months. Blood was re-analysed from normo- and hyper-lipidaemic subjects after three months. LDL isolated from statin-naïve hyperlipidaemic, AD and AD-plus subjects was more oxidised (agarose gel electrophoretic mobility, protein carbonyl content and 8-isoprostane F2α) compared to control subjects. Statin intervention decreased protein carbonyls (2.5±0.4 Vs 3.95±0.2nmol/mg; P<0.001) and 8-isoprostane F2α (30.4±4.0 pg/ml Vs 43.5±8.42 pg/ml; P<0.05). HMVEC treatment with LDL-lipids from hyperlipidaemic, AD and AD-plus subjects impaired endothelial tight junction expression and decreased total glutathione levels (AD; 18.61±1.3, AD-plus; 16.5±0.7nmol/mg protein) compared to untreated cells (23.8±1.2 vs nmol/mg protein). Basolateral IL-6 secretion was increased by LDL-lipids from hyperlipidaemic (78.4±1.9 pg/ml), AD (63.2±5.9 pg/ml) and AD-plus (80.8±0.9 pg/ml) groups compared to healthy subject lipids (18.6±3.6 pg/ml). LDL-Lipids isolated after statin intervention did not affect endothelial function. In summary, LDL-lipids from hypercholesterolaemic, AD and AD-plus patients are inflammatory to HMVEC. In vivo intervention with statins reduces the damaging effects of LDL-lipids on HMVEC.

Gain dependent pulse regimes transitions in a dissipative dispersion-managed fibre laser

For the first time, we demonstrate the possibility to switch between three distinct pulse regimes in a dissipative dispersion-managed (DM) fibre laser by solely controlling the gain saturation energy. Nonlinear Schrödinger equation based simulations show the transitions between hyper-Gaussian similaritons, parabolic similaritons, and dissipative solitons in the same laser cavity. It is also shown that such transitions exist in a wide dispersion range from all-normal to slightly net-normal dispersion. This work demonstrates that besides dispersion and filter managements gain saturation energy can be a new degree of freedom to manage pulse regimes in DM fibre lasers, which offers flexibility in designing ultrafast fibre lasers. Also, the result indicates that in contrast to conservative soliton lasers whose intensity profiles are unique, dissipative DM lasers show diversity in pulse shapes. The findings not only give a better understanding of pulse shaping mechanisms in mode-locked lasers, but also provide insight into dissipative systems.

Performance analysis of IEEE 802.11 cognitive radio ad hoc networks

IEEE 802.11 standard is the dominant technology for wireless local area networks (WLANs). In the last two decades, the Distributed coordination function (DCF) of IEEE 802.11 standard has become the one of the most important media access control (MAC) protocols for mobile ad hoc networks (MANETs). The DCF protocol can also be combined with cognitive radio, thus the IEEE 802.11 cognitive radio ad hoc networks (CRAHNs) come into being. There were several literatures which focus on the modeling of IEEE 802.11 CRAHNs, however, there is still no thorough and scalable analytical models for IEEE 802.11 CRAHNs whose cognitive node (i.e., secondary user, SU) has spectrum sensing and possible channel silence process before the MAC contention process. This paper develops a unified analytical model for IEEE 802.11 CRAHNs for comprehensive MAC layer queuing analysis. In the proposed model, the SUs are modeled by a hyper generalized 2D Markov chain model with an M/G/1/K model while the primary users (PUs) are modeled by a generalized 2D Markov chain and an M/G/1/K model. The performance evaluation results show that the quality-of-service (QoS) of both the PUs and SUs can be statistically guaranteed with the suitable settings of duration of channel sensing and silence phase in the case of under loading.

A seismic shift? An evaluation of the impact of new media on perceptions of freedom of expression and privacy

New media platforms have changed the media landscape forever, as they have altered our perceptions of the limits of communication, and reception of information. Platforms such as Facebook, Twitter and WhatsApp enable individuals to circumvent the traditional mass media, converging audience and producer to create millions of ‘citizen journalists’. This new breed of journalist uses these platforms as a way of, not only receiving news, but of instantaneously, and often spontaneously, expressing opinions and venting and sharing emotions, thoughts and feelings. They are liberated from cultural and physical restraints, such as time, space and location, and they are not constrained by factors that impact upon the traditional media, such as editorial control, owner or political bias or the pressures of generating commercial revenue. A consequence of the way in which these platforms have become ingrained within our social culture is that habits, conventions and social norms, that were once informal and transitory manifestations of social life, are now infused within their use. What were casual and ephemeral actions and/or acts of expression, such as conversing with friends or colleagues or swapping/displaying pictures, or exchanging thoughts that were once kept private, or maybe shared with a select few, have now become formalised and potentially permanent, on view for the world to see. Incidentally, ‘traditional’ journalists and media outlets are also utilising new media, as it allows them to react, and disseminate news, instantaneously, within a hyper-competitive marketplace. However, in a world where we are saturated, not only by citizen journalists, but by traditional media outlets, offering access to news and opinion twenty-four hours a day, via multiple new media platforms, there is increased pressure to ‘break’ news fast and first. This paper will argue that new media, and the culture and environment it has created, for citizen journalists, traditional journalists and the media generally, has altered our perceptions of the limits and boundaries of freedom of expression dramatically, and that the corollary to this seismic shift is the impact on the notion of privacy and private life. Consequently, this paper will examine what a reasonable expectation of privacy may now mean, in a new media world.

Inflation, currency substitution and dollarization: The case of Argentina

This dissertation discusses the relationship between inflation, currency substitution and dollarization that has taken place in Argentina for the past several decades.^ First, it is shown that when consumers are able to hold only domestic monetary balances (without capital mobility) an increase in the rate of inflation will produce a balance of payments deficit. We then look at the same issue but with heterogeneous consumers, this heterogeneity being generated by non-proportional lump-sum transfers.^ Second, we discussed some necessary assumptions related to currency substitution models and concluded that there was no a-priori conclusion on whether currencies should be assumed to be "cooperant" or "non-cooperant" in utility. That is to say, whether individuals held different currencies together or one instead of the other.^ Third, we went into discussing the issue of currency substitution as being a constraint on governments' inflationary objectives rather than a choice of those governments to avoid hyperinflations. We showed that imperfect substitutability between currencies does not "reduce the scope for rational (hyper)inflationary processes" as it had been previously argued. It will ultimately depend on the parametrization used and not on the intrinsic characteristics of imperfect substitutability between currencies.^ We further showed that in Argentina, individuals have been able to endogenize the money supply by holding foreign monetary balances. We argued that the decision to hold foreign monetary balances by individuals is always a second best due to the trade-off between holding foreign monetary balances and consumption. For some levels of income, consumption, and foreign inflation, individuals would prefer to hold domestic monetary balances rather than foreign ones.^ We then modeled the distinction between dollarization and currency substitution. We concluded that although dollarization is necessary for currency substitution to take place, the decision to use foreign monetary balances for transactions purposes is largely independent from the dollarization process.^ Finally, we concluded that Argentina should not fully dollarize its economy because dollarization is always a second best to using a domestic currency. Further, we argued that a fixed exchange system would be better than a flexible exchange rate or a "crawling-peg" system because of the characteristics of the political system and the possibilities of "mass praetorianism" to develop, which is intricately linked to "populist" solutions. ^

Exchange rate overvaluation under hyperinflation: The case of Peru

This dissertation examines the behavior of the exchange rate under two different scenarios. The first one is characterized by, relatively, low inflation or a situation where prices adjust sluggishly. The second is a high inflation economy where prices respond very rapidly even to unanticipated shocks. In the first one, following a monetary expansion, the exchange rate overshoots, i.e. the nominal exchange rate depreciates at a faster pace than the price level. Under high levels of inflation, prices change faster than the exchange rate so the exchange rate undershoots its long run equilibrium value.^ The standard work in this area, Dornbusch (1976), explains the overshooting process in the context of perfect capital mobility and sluggish adjustment in the goods market. A monetary expansion will make the exchange rate increase beyond its long run equilibrium value. This dissertation expands on Dornbusch's model and provides an analysis of the exchange rate under conditions of currency substitution and price flexibility, characteristics of the Peruvian economy during the hyper inflation process that took place at the end of the 1980's. The results of the modified Dornbusch model reveal that, given a monetary expansion, the change in the price level will be larger than the change in the exchange rate if prices react more than proportionally to the monetary shock.^ We will expect this over-reaction in circumstances of high inflation when the velocity of money is increasing very rapidly. Increasing velocity of money, gives rise to a higher relative price variability which in turn contributes to the appearance of new financial (and also non-financial) instruments that report a higher return than the exchange rate, causing people to switch their demand for foreign exchange to this new assets. In the context of currency substitution, economic agents hoard and use foreign exchange as a store of value. The big decline in output originated by hyper inflation induces people to sell this hoarded money to finance current expenses, increasing the supply of foreign exchange in the market. Both, the decrease in demand and the increase in supply reduce the price of foreign exchange i.e. the real exchange rate. The findings mentioned above are tested using Peruvian data for the period January 1985-July 1990, the results of the econometric estimation confirm our findings in the theoretical model. ^

Realization of Differentiated Quality of Service for Wideband Code Division Multiple Access Core Network

The development of 3G (the 3rd generation telecommunication) value-added services brings higher requirements of Quality of Service (QoS). Wideband Code Division Multiple Access (WCDMA) is one of three 3G standards, and enhancement of QoS for WCDMA Core Network (CN) becomes more and more important for users and carriers. The dissertation focuses on enhancement of QoS for WCDMA CN. The purpose is to realize the DiffServ (Differentiated Services) model of QoS for WCDMA CN. Based on the parallelism characteristic of Network Processors (NPs), the NP programming model is classified as Pool of Threads (POTs) and Hyper Task Chaining (HTC). In this study, an integrated programming model that combines both of the two models was designed. This model has highly efficient and flexible features, and also solves the problems of sharing conflicts and packet ordering. We used this model as the programming model to realize DiffServ QoS for WCDMA CN. ^ The realization mechanism of the DiffServ model mainly consists of buffer management, packet scheduling and packet classification algorithms based on NPs. First, we proposed an adaptive buffer management algorithm called Packet Adaptive Fair Dropping (PAFD), which takes into consideration of both fairness and throughput, and has smooth service curves. Then, an improved packet scheduling algorithm called Priority-based Weighted Fair Queuing (PWFQ) was introduced to ensure the fairness of packet scheduling and reduce queue time of data packets. At the same time, the delay and jitter are also maintained in a small range. Thirdly, a multi-dimensional packet classification algorithm called Classification Based on Network Processors (CBNPs) was designed. It effectively reduces the memory access and storage space, and provides less time and space complexity. ^ Lastly, an integrated hardware and software system of the DiffServ model of QoS for WCDMA CN was proposed. It was implemented on the NP IXP2400. According to the corresponding experiment results, the proposed system significantly enhanced QoS for WCDMA CN. It extensively improves consistent response time, display distortion and sound image synchronization, and thus increases network efficiency and saves network resource.^

Conceptualizing American power and security in a post -9/11 security context: Conflict, resistance, and global security, 2001–present

In a post-Cold War, post-9/11 world, the advent of US global supremacy resulted in the installation, perpetuation, and dissemination of an Absolutist Security Agenda (hereinafter, ASA). The US ASA explicitly and aggressively articulates and equates US national security interests with the security of all states in the international system, and replaced the bipolar, Cold War framework that defined international affairs from 1945-1992. Since the collapse of the USSR and the 11 September 2001 terrorist attacks, the US has unilaterally defined, implemented, and managed systemic security policy. The US ASA is indicative of a systemic category of knowledge (security) anchored in variegated conceptual and material components, such as morality, philosophy, and political rubrics. The US ASA is based on a logic that involves the following security components: (1) hyper militarization, (2) intimidation,(3) coercion, (4) criminalization, (5) panoptic surveillance, (6) plenary security measures, and (7) unabashed US interference in the domestic affairs of select states. Such interference has produced destabilizing tensions and conflicts that have, in turn, produced resistance, revolutions, proliferation, cults of personality, and militarization. This is the case because the US ASA rests on the notion that the international system of states is an extension, instrument of US power, rather than a system and/or society of states comprised of functionally sovereign entities. To analyze the US ASA, this study utilizes: (1) official government statements, legal doctrines, treaties, and policies pertaining to US foreign policy; (2) militarization rationales, budgets, and expenditures; and (3) case studies of rogue states. The data used in this study are drawn from information that is publicly available (academic journals, think-tank publications, government publications, and information provided by international organizations). The data supports the contention that global security is effectuated via a discrete set of hegemonic/imperialistic US values and interests, finding empirical expression in legal acts (USA Patriot ACT 2001) and the concept of rogue states. Rogue states, therefore, provide test cases to clarify the breadth, depth, and consequentialness of the US ASA in world affairs vis-à-vis the relationship between US security and global security.