Non-invasive RF built-in testing using on-chip temperature sensors

This poster shows how to efficiently observe high-frequency figures of merit in RF circuits by measuring DC temperature with CMOS-compatible built-in sensors.

Synchronous and baroceptor-sensitive oscillations in skin microcirculation: evidence for central autonomic control.

To determine whether skin blood flow is local or takes part in general regulatory mechanisms, we recorded laser-Doppler flowmetry (LDF; left and right index fingers), blood pressure, muscle sympathetic nerve activity (MSNA), R-R interval, and respiration in 10 healthy volunteers and 3 subjects after sympathectomy. We evaluated 1) the synchronism of LDF fluctuations in two index fingers, 2) the relationship with autonomically mediated fluctuations in other signals, and 3) the LDF ability to respond to arterial baroreflex stimulation (by neck suction at frequencies from 0.02 to 0.20 Hz), using spectral analysis (autoregressive uni- and bivariate, time-variant algorithms). Synchronous LDF fluctuations were observed in the index fingers of healthy subjects but not in sympathectomized patients. LDF fluctuations were coherent with those obtained for blood pressure, MSNA, and R-R interval. LDF fluctuations were leading blood pressure in the low-frequency (LF; 0.1 Hz) band and lagging in the respiratory, high-frequency (HF; approximately 0.25 Hz) band, suggesting passive "downstream" transmission only for HF and "upstream" transmission for LF from the microvessels. LDF fluctuations were responsive to sinusoidal neck suction up to 0.1 Hz, indicating response to sympathetic modulation. Skin blood flow thus reflects modifications determined by autonomic activity, detectable by frequency analysis of spontaneous fluctuations.

Periodic Solutions in Low-Dimensional Climatic Models

Classic climatic models use constitutive laws without any response time. A more realistic approach to the natural processes governing climate dynamics must introduce response time for heat and radiation fluxes. Extended irreversible thermodynamics (EIT) is a good thermodynamical framework for introducing nonclassical constitutive laws. In the present study EIT has been used to analyze a Budyko–Sellers one-dimensional energybalance model developed by G. R. North. The results present self-sustained periodic oscillations when the response time is greater than a critical value. The high-frequency (few kiloyears) damped and nondamped oscillations obtained can be related to abrupt climatic changes without any variation in the external forcing of the system

Subthalamic nucleus deep brain stimulation for Parkinson's disease : "Are we where we think we are ?

ABSTRACT High frequency electrical deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a worldwide recognized therapy for the motor symptoms of Parkinson's disease in fluctuating patients who are progressively disabled despite medical treatment adjustments. However, such improvements emerge despite a lack of understanding of either the precise role of STN in human motor control or the mechanism(s) of action of DBS. Through the question "are we where we think we are", this thesis is first dedicated to the control of the position of the preoperatively defined target and of the implanted electrodes on magnetic resonance imaging (MRI). This anatomical approach will provide a way to identify more precisely the structure(s) involved by electrical stimulation. Then, a study of the correlation existing between the position of the preoperative target and the position of the electrode is performed. In this part, a unique opportunity is given to identify factors that may affect these correlation results. Finally, the whole work represents a « quality assessment » of the crucial steps of STN DBS: first, the target and the implanted electrode localisation procedures that have been developed in collaboration with the Radiological department; second the implantation procedure that has been performed nowadays on more than 50 parkinsonian patients in the Neurosurgical department of the Centre Hospitalier Universitaire Vaudois in collaboration with the Neurological department. This work is especially addressed to the multidisciplinary medical team involved in the surgical treatment of movement disorders, including also neurophysiologists, neuropsychologists and psychiatrists. RESUME La stimulation électrique à haute fréquence du noyau sous-thalamique est à ce jour mondialement reconnue pour le traitement des symptômes moteurs de la maladie de Parkinson chez des patients sévèrement atteints et chez qui la réponse fluctuante au traitement médicamenteux ne peut être améliorée de façon satisfaisante. Cependant, les résultats observés surviennent malgré une compréhension approximative et controversée du rôle réel du noyau sous-thalamique dans le contrôle du mouvement volontaire aussi bien que des mécanismes d'action de la stimulation cérébrale profonde. A travers la question « sommes-nous où nous pensons être », cette thèse est tout d'abord consacrée à l'étude du contrôle de la position de la cible définie avant l'intervention et de la position des électrodes implantées sur l'imagerie par résonance magnétique (IRM). Cette approche anatomique permettra d'identifier plus précisément la (les) structure(s) influencées par la stimulation électrique. Ensuite, une étude de la corrélation existant entre la position de la cible préopératoire et la position des électrodes implantées est effectuée. Elle a pour but de mettre en évidence les facteurs influençant les résultats de cette corrélation. Enfin, le travail dans son ensemble est un « contrôle de qualité » des étapes cruciales de la stimulation du noyau sous-thalamique : premièrement, des méthodes de localisation de la cible et des électrodes implantées effectuées sur IRM, développées en collaboration avec le service de Radiologie ; deuxièmement, de la méthode d'implantation utilisée à ce jour chez plus de 50 patients dans le service de Neurochirurgie du Centre Hospitalier Universitaire Vaudois en collaboration avec le service de Neurologie. Ce travail s'adresse spécialement aux équipes médicales pluridisciplinaires impliquées dans le traitement chirurgical des mouvements anormaux, incluant également des neurophysiologistes, des neuropsychologues et des psychiatres.

VLA multifrequency observations of RSCVn binaries

We present multiepoch Very Large Array (VLA) observations at 1.4 GHz, 4.9 GHz, 8.5 GHz and 14.9 GHz for a sample of eight RS CVn binary systems. Circular polarization measurements of these systems are also reported. Most of the fluxes observed are consistent with incoherent emission from mildly relativistic electrons. Several systems show an increase of the degree of circular polarization with increasing frequency in the optically thin regime, in conflict with predictions by gyrosynchrotron models. We observed a reversal in the sense of circular polarization with increasing frequency in three non-eclipsing systems: EI Eri, DM Uma and HD 8358. We find clear evidence for coherent plasma emission at 1.4 GHz in the quiescent spectrum of HD 8358 during the helicity reversal. The degrees of polarization of the other two systems could also be accounted for by a coherent emission process. The observations of ER Vul revealed two U-shaped flux spectra at the highest frequencies. The U-shape of the spectra may be accounted for by an optically thin gyrosynchrotron source for the low frequency part whereas the high frequency part is dominated by a thermal emission component.

Role of CD8 in aberrant function of cytotoxic T lymphocytes.

Using H-2Kd-restricted photoprobe-specific cytotoxic T lymphocyte (CTL) clones, which permit assessment of T cell receptor (TCR)-ligand interactions by TCR photoaffinity labeling, we observed that the efficiency of antigen recognition by CTL was critically dependent on the half-life of TCR-ligand complexes. We show here that antigen recognition by CTL is essentially determined by the frequency of serial TCR engagement, except for very rapid dissociations, which resulted in aberrant TCR signaling and antagonism. Thus agonists that were efficiently recognized exhibited rapid TCR-ligand complex dissociation, and hence a high frequency of serial TCR engagement, whereas the opposite was true for weak agonists. Surprisingly, these differences were largely accounted for by the coreceptor CD8. While it was known that CD8 substantially decreases TCR-ligand complex dissociation, we observed in this study that this effect varied considerably among ligand variants, indicating that epitope modifications can alter the CD8 contribution to TCR-ligand binding, and hence the efficiency of antigen recognition by CTL.

Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. PATIENTS AND METHODS: We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy. RESULTS: Most patients (92%) had stage I-II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P = 0.0015), while BCL2 expression predicted a worse OS (P = 0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P = 0.03). CONCLUSIONS: WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpart.

Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.

Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.

The role of energy correlations on Coulomb suppression in ballistic conductors contacted to degenerate reservoirs

Coulomb suppression of shot noise in a ballistic diode connected to degenerate ideal contacts is analyzed in terms of the correlations taking place between current fluctuations due to carriers injected with different energies. By using Monte Carlo simulations we show that at low frequencies the origin of Coulomb suppression can be traced back to the negative correlations existing between electrons injected with an energy close to that of the potential barrier present in the diode active region and all other carriers injected with higher energies. Correlations between electrons with energy above the potential barrier with the rest of electrons are found to influence significantly the spectra at high frequency in the cutoff region.

The complete Raman spectrum of nanometric SnO2 particles

The complete Raman spectrum of SnO2 nanoparticles in presented and analyzed. In addition to the "classical" modes observed in the rutile structure, two other regions shown Raman activity for nanoparticles. The Raman bands in the low-frequency region are attributed to acoustic modes associated with the vibration of the individual nanoparticle as a whole. The high-frequency region is activated by surface disorder. A detailed analysis of these regions and the changes in the normal modes of SnO2 are presented as a function nanoparticle size.

Nonresponse to clozapine and ultrarapid CYP1A2 activity: clinical data and analysis of CYP1A2 gene.

Clozapine (CLO), an atypical antipsychotic, depends mainly on cytochrome P450 1A2 (CYP1A2) for its metabolic clearance. Four patients treated with CLO, who were smokers, were nonresponders and had low plasma levels while receiving usual doses. Their plasma levels to dose ratios of CLO (median; range, 0.34; 0.22 to 0.40 ng x day/mL x mg) were significantly lower than ratios calculated from another study with 29 patients (0.75; 0.22 to 2.83 ng x day/mL x mg; P < 0.01). These patients were confirmed as being CYP1A2 ultrarapid metabolizers by the caffeine phenotyping test (median systemic caffeine plasma clearance; range, 3.85; 3.33 to 4.17 mL/min/kg) when compared with previous studies (0.3 to 3.33 mL/min/kg). The sequencing of the entire CYP1A2 gene from genomic DNA of these patients suggests that the -164C > A mutation (CYP1A2*1F) in intron 1, which confers a high inducibility of CYP1A2 in smokers, is the most likely explanation for their ultrarapid CYP1A2 activity. A marked (2 patients) or a moderate (2 patients) improvement of the clinical state of the patients occurred after the increase of CLO blood levels above the therapeutic threshold by the increase of CLO doses to very high values (ie, up to 1400 mg/d) or by the introduction of fluvoxamine, a potent CYP1A2 inhibitor, at low dosage (50 to 100 mg/d). Due to the high frequency of smokers among patients with schizophrenia and to the high frequency of the -164C > A polymorphism, CYP1A2 genotyping could have important clinical implications for the treatment of patients with CLO.

Ex vivo characterization of allo-MHC-restricted T cells specific for a single MHC-peptide complex.

Alloreactive T cells are thought to be a potentially rich source of high-avidity T cells with therapeutic potential since tolerance to self-Ags is restricted to self-MHC recognition. Given the particularly high frequency of alloreactive T cells in the peripheral immune system, we used numerous MHC class I multimers to directly visualize and isolate viral and tumor Ag-specific alloreactive CD8 T cells. In fact, all but one specificities screened were undetectable in ex vivo labeling. In this study, we report the occurrence of CD8 T cells specifically labeled with allo-HLA-A*0201/Melan-A/MART-1(26-35) multimers at frequencies that are in the range of 10(-4) CD8 T cells and are thus detectable ex vivo by flow cytometry. We report the thymic generation and shaping of tumor Ag-specific, alloreactive T cells as well as their fate once seeded in the periphery. We show that these cells resemble their counterparts in HLA-A*0201-positive individuals, based on their structural and functional attributes.

Extreme times in financial markets.

We apply the theory of continuous time random walks (CTRWs) to study some aspects involving extreme events in financial time series. We focus our attention on the mean exit time (MET). We derive a general equation for this average and compare it with empirical results coming from high-frequency data of the U.S. dollar and Deutsche mark futures market. The empirical MET follows a quadratic law in the return length interval which is consistent with the CTRW formalism.

The transcription factor c-Maf controls touch receptor development and function.

The sense of touch relies on detection of mechanical stimuli by specialized mechanosensory neurons. The scarcity of molecular data has made it difficult to analyze development of mechanoreceptors and to define the basis of their diversity and function. We show that the transcription factor c-Maf/c-MAF is crucial for mechanosensory function in mice and humans. The development and function of several rapidly adapting mechanoreceptor types are disrupted in c-Maf mutant mice. In particular, Pacinian corpuscles, a type of mechanoreceptor specialized to detect high-frequency vibrations, are severely atrophied. In line with this, sensitivity to high-frequency vibration is reduced in humans carrying a dominant mutation in the c-MAF gene. Thus, our work identifies a key transcription factor specifying development and function of mechanoreceptors and their end organs.

Distribution of the transposable elements bilbo and gypsy in original and colonizing populations of Drosophila subobscura

Background: Transposable elements (TEs) constitute a substantial amount of all eukaryotic genomes. They induce an important proportion of deleterious mutations by insertion into genes or gene regulatory regions. However, their mutational capabilities are not always adverse but can contribute to the genetic diversity and evolution of organisms. Knowledge of their distribution and activity in the genomes of populations under different environmental and demographic regimes, is important to understand their role in species evolution. In this work we study the chromosomaldistribution of two TEs, gypsy and bilbo, in original and colonizing populations of Drosophilasubobscura to reveal the putative effect of colonization on their insertion profile.Results: Chromosomal frequency distribution of two TEs in one original and three colonizingpopulations of D. subobscura, is different. Whereas the original population shows a low insertionfrequency in most TE sites, colonizing populations have a mixture of high (frequency ¿ 10%) andlow insertion sites for both TEs. Most highly occupied sites are coincident among colonizingpopulations and some of them are correlated to chromosomal arrangements. Comparisons of TEcopy number between the X chromosome and autosomes show that gypsy occupancy seems to becontrolled by negative selection, but bilbo one does not. Conclusion: These results are in accordance that TEs in Drosophila subobscura colonizing populations are submitted to a founder effect followed by genetic drift as a consequence of colonization. This would explain the high insertion frequencies of bilbo and gypsy in coincident sites of colonizing populations. High occupancy sites would represent insertion events prior to colonization. Sites of low frequency would be insertions that occurred after colonization and/orcopies from the original population whose frequency is decreasing in colonizing populations. Thiswork is a pioneer attempt to explain the chromosomal distribution of TEs in a colonizing specieswith high inversion polymorphism to reveal the putative effect of arrangements in TE insertionprofiles. In general no associations between arrangements and TE have been found, except in a fewcases where the association is very strong. Alternatively, founder drift effects, seem to play aleading role in TE genome distribution in colonizing populations.