Integrity of the circadian time-keeping system in chronic fatigue syndrome

Chronic Fatigue Syndrome (CFS) is a debilitating condition in which severe, ongoing fatigue is the most prominent of a complex of somatic, psychological and neuropsychological symptoms. The aetiology of CFS remains uncertain and, to date, efforts to distinguish a clear pathophysiological profile for the disorder have been unsuccessful. Current evidence suggests that, rather than being a discrete disease entity with a single cause, CFS is a clinical condition resulting from the interaction of a number of pathophysiological factors, including acute infections, stress and psychiatric disorder. Recently, there has been some interest in the proposition that disordered circadian time-keeping may contribute to the development and/or course of the illness. The rationale for the investigation of circadian factors in CFS is based on the fact that disorders known to be associated with circadian dysregulation, such as jet lag and shiftwork related syndromes have a high degree of symptomatological overlap with CFS. Also, the presence of circadian disturbance could account, in part, for other phenomenological aspects of CFS, including the high rates of comorbid affective disturbance, and the reports of low-level immune dyregulation among sufferers. While several recent studies have produced some evidence of chronobiological dysregulation in CFS patients, much work remains before conclusions can be drawn about the presence, nature and clinical significance of circadian disturbance in CFS. This thesis describes a series of studies that were designed to systematically investigate: 1. whether CFS is associated with a state of circadian dysregulation, and 2. whether circadian dysregulation contributes significantly to the symptomatology of CFS. The first of the 5 studies reported here compared the circadian patterns of sleep-activity of CFS sufferers with those of healthy controls. Results indicated that CFS patients' sleep-activity cycles were significantly phase delayed compared to controls, and that some aspects of their circadian profiles of sleep-activity were related to some measures of sleep-disturbance and well-being. Studies 2 and 3 investigated the relationship between rhythms of sleep-wake and core temperature in CFS patients and healthy controls. The major finding from these studies was that sleep-wake and core temperature rhythms appear to be less effectively synchronised. Further evidence was collected that suggested that there was a relationship between circadian parameters and symptom measures in the CFS group. While this indicated that circadian dysregulation is linked in some way to the symptoms of CFS, assessment of the actual clinical significance of circadian disturbances required the use of a prospective methodology. The final two studies, therefore, report on a placebo-controlled trial of clinical interventions that were designed to restore circadian integrity to CFS patients, in order to see whether this would lead to a reduction in symptom number or severity. Results indicated that, although patients experienced improvements across a range of measures of symptoms and functional capacity, these were small in magnitude, of unlikely clinical significance, and no greater, in general, to improvements reported by patients who underwent placebo treatment. These results, along with those of the earlier studies, are discussed with respect to their implications regarding the presence and significance of circadian dysregulation. It is concluded that, while they provide evidence that CFS is associated with a degree of both internal and external circadian desynchrony, these findings suggest that circadian dysregulation is likely to be only a peripheral, contributor to the processes that generate and maintain the symptom complex. These findings are discussed with respect to how they contribute to our overall understanding of this multi-dimensional condition, and the implications they have for the continuing effort to investigate the causes and treatment of CFS.

Is the meander growth in the Brazil Current system off Southeast Brazil due to baroclinic instability?

Temporally-growing frontal meandering and occasional eddy-shedding is observed in the Brazil Current (BC) as it flows adjacent to the Brazilian Coast. No study of the dynamics of this phenomenon has been conducted to date in the region between 22 degrees S and 25 degrees S. Within this latitude range, the flow over the intermediate continental slope is marked by a current inversion at a depth that is associated with the Intermediate Western Boundary Current (IWBC). A time series analysis of 10-current-meter mooring data was used to describe a mean vertical profile for the BC-IWBC jet and a typical meander vertical structure. The latter was obtained by an empirical orthogonal function (EOF) analysis that showed a single mode explaining 82% of the total variance. This mode structure decayed sharply with depth, revealing that the meandering is much more vigorous within the BC domain than it is in the IWBC region. As the spectral analysis of the mode amplitude time series revealed no significant periods, we searched for dominant wavelengths. This search was done via a spatial EOF analysis on 51 thermal front patterns derived from digitized AVHRR images. Four modes were statistically significant at the 95% confidence level. Modes 3 and 4, which together explained 18% of the total variance, are associated with 266 and 338-km vorticity waves, respectively. With this new information derived from the data, the [Johns, W.E., 1988. One-dimensional baroclinically unstable waves on the Gulf Stream potential vorticity gradient near Cape Hatteras. Dyn. Atmos. Oceans 11, 323-350] one-dimensional quasi-geostrophic model was applied to the interpolated mean BC-IWBC jet. The results indicated that the BC system is indeed baroclinically unstable and that the wavelengths depicted in the thermal front analysis are associated with the most unstable waves produced by the model. Growth rates were about 0.06 (0.05) days(-1) for the 266-km (338-km) wave. Moreover, phase speeds for these waves were low compared to the surface BC velocity and may account for remarks in the literature about growing standing or stationary meanders off southeast Brazil. The theoretical vertical structure modes associated with these waves resembled very closely to the one obtained for the current-meter mooring EOF analysis. We interpret this agreement as a confirmation that baroclinic instability is an important mechanism in meander growth in the BC system. (C) 2008 Elsevier B.V. All rights reserved.

Azimuthal decorrelations and multiple parton interactions in gamma+2 jet and gamma+3 jet events in p(p)over-bar collisions at root s=1.96 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Evaluation of cutting patterns produced in primary teeth by an air-abrasion system

Objective: the aim of this in vitro study was to assess the effect of tip diameter, nozzle distance, and application time of an air-abrasion system for cavity preparation on the enamel of primary teeth. Method and materials: Forty exfoliated primary teeth were air abraded with a microabrasion machine used with a handpiece with an 80-degree-angle nozzle, 50-mum abrasive particle size, and 80-psi air pressure. The effects of 0.38- or 0.48-mm inner tip diameter, 2- or 5-mm distance from tip to tooth surface, and 15 or 30 seconds of application time on cutting efficiency were evaluated. Cutting width and depth were analyzed and measured from scanning electron micrographs. Results: Statistical analysis revealed that the width of the cuts was significantly greater when the tip distance was increased. Significantly deeper cavities were produced by a tip with a 0.48-mm inner diameter. The application time did not influence the cuts. Conclusion: the cutting patterns found in this study suggest that precise removal of enamel in primary teeth is best accomplished when a tip with a 0.38-mm inner diameter is used at a 2-mm distance.

Effect of handpiece tip design on the cutting efficiency of an air abrasion system

Purpose : the aim of this study was to evaluate the effect of nozzle angle and tip diameter on the cutting efficiency of an air abrasion system. Materials and Methods: Thirty-six extracted human third molars were air-abraded with the PrepStar microabrasion machine using a handpiece with either 80degrees or 45degrees nozzle angles with 0.38 or 0.48 nun tip orifice diameters. The following parameters were held constant: abrasive particle size (27 mum), air pressure (80 psi), distance (2 mm.) and duration (15 seconds). The cutting efficiency was compared using enamel, dentin and cementum substrates. Width and depth of the cutting patterns were analyzed and measured using scanning electron micrographs. Results: Statistical analysis using three-way ANOVA and Duncan's Multiple Range test revealed that the width of the cuts was significantly greater when the cavities were prepared using the 45degrees nozzle angle. Significantly deeper cavities were produced with the 80degrees nozzle angle. The tip orifice of the nozzle influenced the cutting efficiency in softer substrates, dentin and cementum. Precise removal of hard tissue is best accomplished using the 80degrees angle nozzle tips for all types of tooth surfaces, enamel, dentin and cementum.

Effect of collagenase ointment on a radiofrequency induced abrasive wound

• Aim: Radiofrequency is one of the methods used to treat wrinkles and skin lesions, but its application may result in an abrasive wound. The purpose of this study was to evaluate the effect of collagenase ointment on the epithelial healing of an abrasive wound induced by a radiofrequency system. • Methods: An abrasive wound was produced using radiofrequency at the dorsal midline of 30 guinea pigs, which were randomly divided into 2 groups: one group were treated with saline solution and the other group treated with collagenase ointment; both used twice daily. The animals were sacrificed at 1, 7, 15, 30 and 60 postoperative days. Macroscopic, histological and morphometric evaluations were performed and the results were submitted to statistical analysis. • Results: The animals treated with collagenase ointment presented accelerated healing process and less inflammatory cell infiltration than the saline solution treated animals from one to fifteen postoperative days. Morphometric evaluation showed a thicker epidermis and a thinner dermis layer in the saline solution group at one and seven postoperative days, but significant differences between both groups were not observed at thirty and sixty postoperative days. • Conclusion: According to our results the use of collagenase ointment may accelerate the healing process of a radiofrequency induced abrasive wound.

Influência do tipo de tratamento superficial na força adesiva do reparo com resina composta em materiais estéticos

Pós-graduação em Ciências Odontológicas - FOAR

Transfer of a cold atmospheric pressure plasma jet through a long flexible plastic tube

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Is the meander growth in the Brazil Current system off Southeast Brazil due to baroclinic instability?

Temporally-growing frontal meandering and occasional eddy-shedding is observed in the Brazil Current (BC) as it flows adjacent to the Brazilian Coast. No study of the dynamics of this phenomenon has been conducted to date in the region between 22 degrees S and 25 degrees S. Within this latitude range, the flow over the intermediate continental slope is marked by a current inversion at a depth that is associated with the Intermediate Western Boundary Current (IWBC). A time series analysis of 10-current-meter mooring data was used to describe a mean vertical profile for the BC-IWBC jet and a typical meander vertical structure. The latter was obtained by an empirical orthogonal function (EOF) analysis that showed a single mode explaining 82% of the total variance. This mode structure decayed sharply with depth, revealing that the meandering is much more vigorous within the BC domain than it is in the IWBC region. As the spectral analysis of the mode amplitude time series revealed no significant periods, we searched for dominant wavelengths. This search was done via a spatial EOF analysis on 51 thermal front patterns derived from digitized AVHRR images. Four modes were statistically significant at the 95% confidence level. Modes 3 and 4, which together explained 18% of the total variance, are associated with 266 and 338-km vorticity waves, respectively. With this new information derived from the data, the [Johns, W.E., 1988. One-dimensional baroclinically unstable waves on the Gulf Stream potential vorticity gradient near Cape Hatteras. Dyn. Atmos. Oceans 11, 323-350] one-dimensional quasi-geostrophic model was applied to the interpolated mean BC-IWBC jet. The results indicated that the BC system is indeed baroclinically unstable and that the wavelengths depicted in the thermal front analysis are associated with the most unstable waves produced by the model. Growth rates were about 0.06 (0.05) days(-1) for the 266-km (338-km) wave. Moreover, phase speeds for these waves were low compared to the surface BC velocity and may account for remarks in the literature about growing standing or stationary meanders off southeast Brazil. The theoretical vertical structure modes associated with these waves resembled very closely to the one obtained for the current-meter mooring EOF analysis. We interpret this agreement as a confirmation that baroclinic instability is an important mechanism in meander growth in the BC system. (C) 2008 Elsevier B.V. All rights reserved.

System size and energy dependence of near-side dihadron correlations

Two-particle azimuthal (Delta phi) and pseudorapidity (Delta eta) correlations using a trigger particle with large transverse momentum (p(T)) in d+Au, Cu+Cu, and Au+Au collisions at root s(NN) = 62.4 GeV and 200 GeV from the STAR experiment at the Relativistic Heavy Ion Collider are presented. The near-side correlation is separated into a jet-like component, narrow in both Delta phi and Delta eta, and the ridge, narrow in Delta phi but broad in Delta eta. Both components are studied as a function of collision centrality, and the jet-like correlation is studied as a function of the trigger and associated p(T). The behavior of the jet-like component is remarkably consistent for different collision systems, suggesting it is produced by fragmentation. The width of the jet-like correlation is found to increase with the system size. The ridge, previously observed in Au+Au collisions at root s(NN) = 200 GeV, is also found in Cu+Cu collisions and in collisions at root s(NN) = 62.4 GeV, but is found to be substantially smaller at root s(NN) = 62.4 GeV than at root s(NN) = 200 GeV for the same average number of participants (< N-part >). Measurements of the ridge are compared to models.

Forced Desynchronization of Activity Rhythms in a Model of Chronic Jet Lag in Mice

We studied locomotor activity rhythms of C57/Bl6 mice under a chronic jet lag (CJL) protocol (ChrA(6/2)), which consisted of 6-hour phase advances of the light-dark schedule (LD) every 2 days. Through periodogram analysis, we found 2 components of the activity rhythm: a short-period component (21.01 +/- 0.04 h) that was entrained by the LD schedule and a long-period component (24.68 +/- 0.26 h). We developed a mathematical model comprising 2 coupled circadian oscillators that was tested experimentally with different CJL schedules. Our simulations suggested that under CJL, the system behaves as if it were under a zeitgeber with a period determined by (24 -[phase shift size/days between shifts]). Desynchronization within the system arises according to whether this effective zeitgeber is inside or outside the range of entrainment of the oscillators. In this sense, ChrA(6/2) is interpreted as a (24 - 6/2 = 21 h) zeitgeber, and simulations predicted the behavior of mice under other CJL schedules with an effective 21-hour zeitgeber. Animals studied under an asymmetric T = 21 h zeitgeber (carried out by a 3-hour shortening of every dark phase) showed 2 activity components as observed under ChrA(6/2): an entrained short-period (21.01 +/- 0.03 h) and a long-period component (23.93 +/- 0.31 h). Internal desynchronization was lost when mice were subjected to 9-hour advances every 3 days, a possibility also contemplated by the simulations. Simulations also predicted that desynchronization should be less prevalent under delaying than under advancing CJL. Indeed, most mice subjected to 6-hour delay shifts every 2 days (an effective 27-hour zeitgeber) displayed a single entrained activity component (26.92 +/- 0.11 h). Our results demonstrate that the disruption provoked by CJL schedules is not dependent on the phase-shift magnitude or the frequency of the shifts separately but on the combination of both, through its ratio and additionally on their absolute values. In this study, we present a novel model of forced desynchronization in mice under a specific CJL schedule; in addition, our model provides theoretical tools for the evaluation of circadian disruption under CJL conditions that are currently used in circadian research.

Studies of pure rotational spectra of isolated molecules and molecular adducts using pulsed jet Fourier transform microwave (PJ-FTM) spectroscopy

This thesis focuses on studying molecular structure and internal dynamics by using pulsed jet Fourier transform microwave (PJ-FTMW) spectroscopy combined with theoretical calculations. Several kinds of interesting chemical problems are investigated by analyzing the MW spectra of the corresponding molecular systems. First, the general aspects of rotational spectroscopy are summarized, and then the basic theory on molecular rotation and experimental method are described briefly. ab initio and density function theory (DFT) calculations that used in this thesis to assist the assignment of rotational spectrum are also included. From chapter 3 to chapter 8, several molecular systems concerning different kind of general chemical problems are presented. In chapter 3, the conformation and internal motions of dimethyl sulfate are reported. The internal rotations of the two methyl groups split each rotational transition into several components line, allowing for the determination of accurate values of the V3 barrier height to internal rotation and of the orientation of the methyl groups with respect to the principal axis system. In chapter 4 and 5, the results concerning two kinds of carboxylic acid bi-molecules, formed via two strong hydrogen bonds, are presented. This kind of adduct is interesting also because a double proton transfer can easily take place, connecting either two equivalent or two non-equivalent molecular conformations. Chapter 6 concerns a medium strong hydrogen bonded molecular complex of alcohol with ether. The dimer of ethanol-dimethylether was chosen as the model system for this purpose. Chapter 7 focuses on weak halogen…H hydrogen bond interaction. The nature of O-H…F and C-H…Cl interaction has been discussed through analyzing the rotational spectra of CH3CHClF/H2O. In chapter 8, two molecular complexes concerning the halogen bond interaction are presented.

N-H center dot center dot center dot pi hydrogen-bonding and large-amplitude tipping vibrations in jet-cooled pyrrole-benzene

The N-H center dot center dot center dot pi hydrogen bond is an important intermolecular interaction in many biological systems. We have investigated the infrared (IR) and ultraviolet (UV) spectra of the supersonic-jet cooled complex of pyrrole with benzene and benzene-d(6) (Pyr center dot Bz, Pyr center dot Bz-d(6)). DFT-D density functional, SCS-MP2 and SCS-CC2 calculations predict a T-shaped and (almost) C(s) symmetric structure with an N-H center dot center dot center dot pi hydrogen bond to the benzene ring. The pyrrole is tipped by omega(S(0)) = +/- 13 degrees relative to the surface normal of Bz. The N center dot center dot center dot ring distance is 3.13 angstrom. In the S(1) excited state, SCS-CC2 calculations predict an increased tipping angle omega(S(1)) = +/- 21 degrees. The IR depletion spectra support the T-shaped geometry: The NH stretch is redshifted by -59 cm(-1), relative to the "free" NH stretch of pyrrole at 3531 cm(-1), indicating a moderately strong N-H center dot center dot center dot pi interaction. The interaction is weaker than in the (Pyr)(2) dimer, where the NH donor shift is -87 cm(-1) [Dauster et al., Phys. Chem. Chem. Phys., 2008, 10, 2827]. The IR C-H stretch frequencies and intensities of the Bz subunit are very similar to those of the acceptor in the (Bz)(2) dimer, confirming that Bz acts as the acceptor. While the S(1) <- S(0) electronic origin of Bz is forbidden and is not observable in the gas-phase, the UV spectrum of Pyr center dot Bz in the same region exhibits a weak 0(0)(0) band that is red-shifted by 58 cm(-1) relative to that of Bz (38 086 cm(-1)). The origin appears due to symmetry-breaking of the p-electron system of Bz by the asymmetric pyrrole NH center dot center dot center dot pi hydrogen bond. This contrasts with (Bz)(2), which does not exhibit a 0(0)(0) band. The Bz moiety in Pyr center dot Bz exhibits a 6a(0)(1) band at 0(0)(0) + 518 cm(-1) that is about 20x more intense than the origin band. The symmetry breaking by the NH center dot center dot center dot pi hydrogen bond splits the degeneracy of the v(6)(e(2g)) vibration, giving rise to 6a' and 6b' sub-bands that are spaced by similar to 6 cm(-1). Both the 0(0)(0) and 6(0)(1) bands of Pyr center dot Bz carry a progression in the low-frequency (10 cm(-1)) excited-state tipping vibration omega', in agreement with the change of the omega tipping angle predicted by SCS-MP2 and SCS-CC2 calculations.

Jet energy measurement with the ATLAS detector in proton-proton collisions at sqrt(s) = 7 TeV

The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of sqrt(s) = 7 TeV corresponding to an integrated luminosity of 38 inverse pb. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0.4 or R=0.6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pt > 20 GeV and pseudorapidities eta<4.5. The JES systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams. The JES uncertainty is less than 2.5% in the central calorimeter region (eta<0.8) for jets with 60 < pt < 800 GeV, and is maximally 14% for pt < 30 GeV in the most forward region 3.2jets with pt > 50 GeV after a dedicated correction for this effect. The JES is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pt, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pt jets recoiling against a high-pt jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, providing an improved jet energy resolution and a reduced flavour dependence of the jet response. The JES systematic uncertainty determined from a combination of in situ techniques are consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pt jets.

Jet energy measurement with the ATLAS detector in proton-proton collisions at sqrt(s) = 7 TeV

The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of sqrt(s) = 7 TeV corresponding to an integrated luminosity of 38 inverse pb. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0.4 or R=0.6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pt > 20 GeV and pseudorapidities eta<4.5. The JES systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams. The JES uncertainty is less than 2.5% in the central calorimeter region (eta<0.8) for jets with 60 < pt < 800 GeV, and is maximally 14% for pt < 30 GeV in the most forward region 3.2jets with pt > 50 GeV after a dedicated correction for this effect. The JES is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pt, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pt jets recoiling against a high-pt jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, providing an improved jet energy resolution and a reduced flavour dependence of the jet response. The JES systematic uncertainty determined from a combination of in situ techniques are consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pt jets.