Time localized tilted beams in nearly-degenerate laser cavities.

We show that nearly-degenerate Vertical External-Cavity Surface-Emitting Lasers may emit a set of tilted beams of individually addressable mode-locked pulses. These time localized beams feature a Gaussian profile and they are emitted in pairs with opposite transverse k-vector. Because they are phase locked, their interference leads to a non homothetic pattern in the near-field emission of the laser. In the simplest situation, when a single pair is emitted, this is a stripe pattern. Our analysis discloses the role of third order (spherical) aberrations of the cavity in stabilizing this spatio-temporal mode-locked regime and in selecting the value of the transverse k-vector.

Machine learning applied to ambulatory blood pressure monitoring: a new tool to diagnose autonomic failure?

BACKGROUND: Autonomic failure (AF) complicates Parkinson's disease (PD) in one-third of cases, resulting in complex blood pressure (BP) abnormalities. While autonomic testing represents the diagnostic gold standard for AF, accessibility to this examination remains limited to a few tertiary referral centers. OBJECTIVE: The present study sought to investigate the accuracy of a machine learning algorithm applied to 24-h ambulatory BP monitoring (ABPM) as a tool to facilitate the diagnosis of AF in patients with PD. METHODS: Consecutive PD patients naïve to vasoactive medications underwent 24 h-ABPM and autonomic testing. The diagnostic accuracy of a Linear Discriminant Analysis (LDA) model exploiting ABPM parameters was compared to autonomic testing (as per a modified version of the Composite Autonomic Symptom Score not including the sudomotor score) in the diagnosis of AF. RESULTS: The study population consisted of n = 80 PD patients (33% female) with a mean age of 64 ± 10 years old and disease duration of 6.2 ± 4 years. The prevalence of AF at the autonomic testing was 36%. The LDA model showed 91.3% accuracy (98.0% specificity, 79.3% sensitivity) in predicting AF, significantly higher than any of the ABPM variables considered individually (hypotensive episodes = 82%; reverse dipping = 79%; awakening hypotension = 74%). CONCLUSION: LDA model based on 24-h ABPM parameters can effectively predict AF, allowing greater accessibility to an accurate and easy to administer test for AF. Potential applications range from systematic AF screening to monitoring and treating blood pressure dysregulation caused by PD and other neurodegenerative disorders.

Screening indexes for cardiovascular autonomic failure in Parkinson's disease.

Autonomic failure (AF) is a common source of orthostatic hypotension (OH) in Parkinson's disease (PD). The diagnosis of AF is difficult on clinical grounds alone. We used autonomic testing and 24-h BP monitoring (ABPM) in 122 PD patients to evaluate the diagnostic accuracy of AF by (1) the reduced heart rate increase to fall in blood pressure (BP) ratio (ΔHR/ΔSBP), (2) reverse dipping (RD), and (3) increased diurnal systolic BP standard deviation (SD-SBP). Among patients with OH, ΔHR/ΔSBP yielded the best accuracy (85%), with excellent sensitivity (92%) and acceptable specificity (67%). RD and, to a lesser extent, SD-SBP had high specificity (93% and 73%, respectively) but low sensitivity, resulting in overall moderate accuracy (66% and 55%, respectively). In patients with OH, the addition of ABPM indexes to ΔHR/ΔSBP did not result in a significant improvement of accuracy. In patients without OH, RD and SD-SBP may be useful showing an accuracy of 72% and 81%, respectively, with high negative predictive value when both RD and increased SD-SBP are absent. The integration of bedside (∆HR/∆SBP) and ABPM-derived indexes can assist the clinician in screening PD patients for AF and guide referral to autonomic testing.

Manipulation of temporal localized structures in a vertical external-cavity surface-emitting laser with optical feedback.

We analyze the effect of optical feedback on the dynamics of an external-cavity passively mode-locked surface-emitting laser operating in the regime of temporal localized structures. Depending on the ratio between the cavity round trip time and the feedback delay, we show experimentally that feedback acts as a solution selector that either reinforces or hinders the appearance of one of the multistable harmonic arrangements of pulses. Our theoretical analysis reproduces well the experiment and allows us to evidence asymmetrical resonance tongues due to the parity symmetry-breaking induced by gain depletion.

Testing Critical Slowing Down as a Bifurcation Indicator in a Low-Dissipation Dynamical System.

We study a two-dimensional low-dissipation nonautonomous dynamical system, with a control parameter that is swept linearly in time across a transcritical bifurcation. We investigate the relaxation time of a perturbation applied to a variable of the system and we show that critical slowing down may occur at a parameter value well above the bifurcation point. We test experimentally the occurrence of critical slowing down by applying a perturbation to the accessible control parameter and we find that this perturbation leaves the system behavior unaltered, thus providing no useful information on the occurrence of critical slowing down. The theoretical analysis reveals the reasons why these tests fail in predicting an incoming bifurcation.

Third Order Dispersion in Time-Delayed Systems.

Time-delayed dynamical systems materialize in situations where distant, pointwise, nonlinear nodes exchange information that propagates at a finite speed. However, they are considered devoid of dispersive effects, which are known to play a leading role in pattern formation and wave dynamics. We show how dispersion may appear naturally in delayed systems and we exemplify our result by studying theoretically and experimentally the influence of third order dispersion in a system composed of coupled optical microcavities. Dispersion-induced pulse satellites emerge asymmetrically and destabilize the mode-locking regime.

Temporal localized structures in mode-locked vertical external-cavity surface-emitting lasers.

Temporal localized states (TLSs) are individually addressable structures traveling in optical resonators. They can be used to obtain bits of information and generate frequency combs with tunable spectral density. We show that a pair of specially designed nonlinear mirrors, a 1/2 vertical-cavity surface-emitting laser and a semiconductor saturable absorber, coupled in self-imaging conditions, can lead to the generation of such TLSs. Our results indicate how a conventional passive mode-locking scheme can be adapted to provide a robust and simple system emitting TLSs and paves the way towards the observation of three dimensional confined states, the so-called light bullets.

Nonlocality Induces Chains of Nested Dissipative Solitons.

Dissipative solitons often behave as quasiparticles, and they may form molecules characterized by well-defined bond distances. We show that pointwise nonlocality may lead to a new kind of molecule where bonds are not rigid. The elements of this molecule can shift mutually one with respect to the others while remaining linked together, in a manner similar to interlaced rings in a chain. We report experimental observations of these chains of nested dissipative solitons in a time-delayed laser system.

Attenuation of diet-induced obesity and induction of white fat browning with a chemical inhibitor of histone deacetylases.

BACKGROUND/OBJECTIVES: In the last decade, a strict link between epigenetics and metabolism has been demonstrated. Histone deacetylases (HDACs) have emerged as key epigenetic regulators involved in metabolic homeostasis in normal and pathologic conditions. Here we investigated the effect of the class I HDAC inhibitor MS-275 in a model of obesity induced by a high-fat diet (HFD). METHODS: C57BL6/J male mice were fed HFD for 17 weeks and then randomized in two groups, treated intraperitoneally with vehicle dimethylsulfoxide (DMSO) or with the class I selective HDAC inhibitor MS-275 every other day for 22 days. Glucose tolerance test and measurement of body temperature during cold exposure were performed. Adipose tissues and liver were phenotypically characterized through histological analysis. Gene and protein expression analysis of brown and white adipose tissues (WATs) were performed. RESULTS: MS-275 treated mice showed 10% reduction of body weight, lower adipocyte size and improved glucose tolerance. Inhibition of class I HDAC determined reduction of adipocyte size and of fat mass, paralleled by higher expression of adipose functionality markers and by increased rate of lipolysis and fatty acid ß-oxidation. MS-275 also promoted thermogenic capacity, related to 'browning' of visceral and subcutaneous WAT, showing increased expression of uncoupling protein 1. In brown adipose tissue, we observed limited effects on gene expression and only reduction of brown adipocyte size. CONCLUSIONS: This study provides evidence that class I HDAC inhibition stimulated functionality and oxidative potential of adipose tissue, improving glucose tolerance and ameliorating the metabolic profile in diet-induced obese mice.

Dynamics of Localized Structures in Systems with Broken Parity Symmetry.

A great variety of nonlinear dissipative systems are known to host structures having a correlation range much shorter than the size of the system. The dynamics of these localized structures (LSs) has been investigated so far in situations featuring parity symmetry. In this Letter we extend this analysis to systems lacking this property. We show that the LS drifting speed in a parameter varying landscape is not simply proportional to the parameter gradient, as found in parity preserving situations. The symmetry breaking implies a new contribution to the velocity field which is a function of the parameter value, thus leading to a new paradigm for LSs manipulation. We illustrate this general concept by studying the trajectories of the LSs found in a passively mode-locked laser operated in the localization regime. Moreover, the lack of parity affects significantly LSs interactions which are governed by asymmetrical repulsive forces.

Response of laser-localized structures to external perturbations in coupled semiconductor microcavities.

Laser-localized structures have been observed in several experiments based on broad-area semiconductor lasers. They appear as bounded regions of laser light emission which can exist independently of each other and are expected to be commuted via external optical perturbations. In this work, we perform a statistical analysis of time-resolved commutation experiments in a system of coupled lasers and show the role of wavelength, polarization and pulse energy in the switching process. Furthermore, we also analyse the response of the system outside of the stability region of laser-localized states in search of an excitable response. We observe not only a threshold separating two types of responses, but also a strong variability in the system's trajectory when returning to the initial stable fixed point.

How lasing localized structures evolve out of passive mode locking.

We investigate the relationship between passive mode locking and the formation of time-localized structures in the output intensity of a laser. We show how the mode-locked pulses transform into lasing localized structures, allowing for individual addressing and arbitrary low repetition rates. Our analysis reveals that this occurs when (i) the cavity round-trip is much larger than the slowest medium time scale, namely the gain recovery time, and (ii) the mode-locked solution coexists with the zero intensity (off) solution. These conditions enable the coexistence of a large quantity of stable solutions, each of them being characterized by a different number of pulses per round-trip and with different arrangements. Then, each mode-locked pulse becomes localized, i.e., individually addressable.

Control of excitable pulses in an injection-locked semiconductor laser.

In spite of numerous theoretical and experimental reports of excitability in lasers with injected signal based on the locking-unlocking transition, the response of the system to controlled external perturbations (which is at the basis of the definition of excitable systems) has not been experimentally studied yet. In the following, we analyze the response of an injection-locked semiconductor laser to different external perturbations. We demonstrate the existence of a perturbation threshold beyond which the response of the system is independent of the strength of the stimulation and, thus, demonstrate its excitable character. We show that optically perturbing such an excitable system via the control of the phase of the injection beam can be useful for optical pulse generation.

Drift-induced excitable localized states.

Excitable localized states, spatial structures which possess both the features of temporal excitable pulses and of transverse cavity solitons, have been theoretically predicted in model systems as single pulses of light localized in space with a finite and deterministic duration. We study experimentally the nucleation of laser localized structures on a device defect and its motion along a spatial gradient. We demonstrate that in the reference frame of the drifting localized structure, the resulting dynamics presents the typical features of excitable systems. In particular, for specific parameter values, we observe that the nucleation of laser localized structures is triggered by noise, while the drift of the localized structure up to a spatial region where it vanishes provides the deterministic orbit which brings the system back to its initial rest state. The control of such structures may open the way to novel applications of localized structures beyond that of simple stationary bits.

Synthesis, characterization and biological evaluation of ureidofibrate-like derivatives endowed with peroxisome proliferator-activated receptor activity.

A series of ureidofibrate-like derivatives was prepared and assayed for their PPAR functional activity. A calorimetric approach was used to characterize PPARγ-ligand interactions, and docking experiments and X-ray studies were performed to explain the observed potency and efficacy. R-1 and S-1 were selected to evaluate several aspects of their biological activity. In an adipogenic assay, both enantiomers increased the expression of PPARγ target genes and promoted the differentiation of 3T3-L1 fibroblasts to adipocytes. In vivo administration of these compounds to insulin resistant C57Bl/6J mice fed a high fat diet reduced visceral fat content and body weight. Examination of different metabolic parameters showed that R-1 and S-1 are insulin sensitizers. Notably, they also enhanced the expression of hepatic PPARα target genes indicating that their in vivo effects stemmed from an activation of both PPARα and γ. Finally, the capability of R-1 and S-1 to inhibit cellular proliferation in colon cancer cell lines was also evaluated.

Bistable and addressable localized vortices in semiconductor lasers.

We demonstrate experimentally that localized emission states in coupled broad-area semiconductor lasers can carry a finite orbital angular momentum. The resulting structures therefore possess the chirality of optical vortices together with the properties of localized structures in dissipative systems, namely, the coexistence with a low intensity homogeneous emission and the mutual independence. These results open the way to the realization of arrays of optically addressable and bistable chiral laser pixels.

Microresonator defects as sources of drifting cavity solitons.

Cavity solitons (CS) are localized structures appearing as single intensity peaks in the homogeneous background of the field emitted by a nonlinear (micro)resonator. In real devices, their position is strongly influenced by the presence of defects in the device structure. In this Letter we show that the interplay between these defects and a phase gradient in the driving field induces the spontaneous formation of a regular sequence of CSs moving in the gradient direction. Hence, defects behave as a device built-in CS source, where the CS generation rate can be set by controlling the system parameters.

Cavity soliton laser based on mutually coupled semiconductor microresonators.

We report on experimental observation of localized structures in two mutually coupled broad-area semiconductor resonators, one of which acts as a saturable absorber. These structures coexist with a dark homogeneous background and they have the same properties as cavity solitons without requiring the presence of a driving beam into the system. They can be switched individually on and off by means of a local addressing beam.

[Tetanus vaccination and antibody tritation: compulsory vaccination at work and the role of the occupational medicine in the induction of protective effects in the population in general]. / La vaccinazione antitetanica e titolazione anticorpale: obbligo vaccinale in ambito professionale e ruolo del medico competente nell'induzione di effetti protettivi nella popolazione generale.

In Italy in the last ten years tetanus incidence has been considerably decreased. It is a result first of the application of national laws that make compulsory the tetanus vaccine for some workers' group and for the population in general, and on the other hand for the working class as a consequence of D.Lgs 626/94. It was carried out by the U.O.O.M.L. of Garbagnate an activity of sanitary surveillance towards the working class with a tetanus biological risk (i.g. builder, metalworker, cleaning staff policemen, health visitors, cooks, etc.). During this activity it was considered the possibility of a tetanus vaccine cycle for those people that couldn't provide any certification about previous tetanus vaccine. The justification for this propose is to reduce the risk of side effects due to iperimmunization in case of close vaccinations and the safety and low cost of the tritation test of antibody anti-tetanus toxin method. Therefore it was decided to determine the personal condition of tetanus immunization for all those people without a valid certification. It resulted that 38% of people subject to sanitary surveillance were not protected and 55 years people resulted to be the group with highest risk. This result was also confirmed by the Ministry of Health that considers older population the highest risk group. It becomes clear that the vaccination for working purposes protects the population in general too. In conclusion we firmly think the procedure we followed completely accomplish the general principle of healthcare for infectious risk on the application of the tit. VIII of D.Lgs. 626/94.

Prenatal diagnosis of a de novo complex chromosome rearrangement (CCR) mediated by six breakpoints, and a review of 20 prenatally ascertained CCRs.

OBJECTIVES: To describe the cytogenetic and FISH characterization of a prenatally diagnosed de novo complex chromosome rearrangement (CCR), showing the involvement of four chromosomes and six breakpoints, and review the literature concerning prenatally detected CCRs in order to obtain insights into addressing karyotype-phenotype correlations in prenatal genetic counseling. METHODS: Conventional protocols were used to set up cultures and chromosome preparations. Commercial and homemade probes were used for the FISH analyses. RESULTS: An apparently balanced de novo t(4;10;20) was prenatally identified by means of cytogenetic analysis. FISH revealed a rearrangement mediated by six breakpoints and the insertion of chromosome 8 material within the 4q region. The pregnancy was interrupted. The fetus showed malformations and anomalous cortical neuron migration. The assembled list of 20 prenatally detected CCRs points to the preferential involvement of chromosomes 4, 6 and 14. The involvement of chromosome 20 is described here for the first time. CONCLUSIONS: FISH analysis is essential for the accurate definition of a complex rearrangement. Phenotype description of fetuses carrying CCRs investigated by means of molecular cytogenetic techniques may contribute to improving and personalizing genetic counseling in prenatal diagnosis.