Synchronous Behavior of Two Coupled Electronic Neurons

We report on experimental studies of synchronization phenomena in a pair of analog electronic neurons (ENs). The ENs were designed to reproduce the observed membrane voltage oscillations of isolated biological neurons from the stomatogastric ganglion of the California spiny lobster Panulirus interruptus. The ENs are simple analog circuits which integrate four dimensional differential equations representing fast and slow subcellular mechanisms that produce the characteristic regular/chaotic spiking-bursting behavior of these cells. In this paper we study their dynamical behavior as we couple them in the same configurations as we have done for their counterpart biological neurons. The interconnections we use for these neural oscillators are both direct electrical connections and excitatory and inhibitory chemical connections: each realized by analog circuitry and suggested by biological examples. We provide here quantitative evidence that the ENs and the biological neurons behave similarly when coupled in the same manner. They each display well defined bifurcations in their mutual synchronization and regularization. We report briefly on an experiment on coupled biological neurons and four dimensional ENs which provides further ground for testing the validity of our numerical and electronic models of individual neural behavior. Our experiments as a whole present interesting new examples of regularization and synchronization in coupled nonlinear oscillators.Comment: 26 pages, 10 figure

Ebp1 expression in benign and malignant prostate

<p>Abstract</p> <p>Background</p> <p>ErbB3-binding protein 1 (Ebp1) is a member of the <it>PA2G4 </it>family of proliferation-regulated proteins that is expressed in multiple malignant and non-malignant cells. ErbB3 and other members of the EGFR family have been implicated in cancer progression, it however remains unknown whether Ebp1 participate in prostate cancer progression <it>in vivo</it>. Therefore, the present study examines Ebp1 expression in cancerous and non-cancerous prostates tissues. Ebp1 expression was also correlated to known Ebp1 regulated proteins (Androgen receptor (AR), Cyclin D1 & ErbB3) and the proliferation marker Ki67. Furthermore we evaluated whether Ebp1 expression correlated with biochemical recurrence (BCR) following radical prostatectomy.</p> <p>Methods</p> <p>The expression of Ebp1, AR, Cyclin D1, ErbB3 and Ki67 were evaluated by immunohistochemistry using three separate tissue micro-arrays containing normal prostate tissues, non-cancerous tissue adjacent to the primary tumor, hormone-sensitive and hormone-refractory cancerous tissues. Multivariate COX regression analysis was performed with four clinical parameters in order to correlate Ebp1 expression with PCa progression.</p> <p>Results</p> <p>The expression of Ebp1 significantly increased with the progression from normal to hormone sensitive and to hormone refractory PCa. Furthermore, we observed strong correlation between Ebp1 expression and the nuclear expression of AR, Cyclin D1 and ErbB3 in both normal adjacent and cancer tissues. The expression of AR, Cyclin D1 and ErbB3 in normal adjacent tissues correlated with PSA relapse, whereas Ebp1 on its own did not significantly predict PSA relapse. Finally, in a multivariate analysis with a base clinical model (Gleason, Pre-op PSA, surgical margins and P-stage) we identified the multi-marker combination of Ebp1+/Cyclin D1- as an independent predictor of PSA relapse with a hazard ratio of 4.79.</p> <p>Conclusion</p> <p>Although not related to disease recurrence, this is the first <it>in vivo </it>study to report that Ebp1 expression correlates with PCa progression.</p

Generalizations of Yang-Mills Theory with Nonlinear Constitutive Equations

We generalize classical Yang-Mills theory by extending nonlinear constitutive equations for Maxwell fields to non-Abelian gauge groups. Such theories may or may not be Lagrangian. We obtain conditions on the constitutive equations specifying the Lagrangian case, of which recently-discussed non-Abelian Born-Infeld theories are particular examples. Some models in our class possess nontrivial Galilean (c goes to infinity) limits; we determine when such limits exist, and obtain them explicitly.Comment: Submitted to the Proceedings of the 3rd Symposium on Quantum Theory and Symmetries (QTS3) 10-14 September 2003. Preprint 9 pages including reference

StdpC: a modern dynamic clamp

With the advancement of computer technology many novel uses of dynamic clamp have become possible. We have added new features to our dynamic clamp software StdpC (“Spike timing-dependent plasticity Clamp”) allowing such new applications while conserving the ease of use and installation of the popular earlier Dynclamp 2/4 package. Here, we introduce the new features of a waveform generator, freely programmable Hodgkin–Huxley conductances, learning synapses, graphic data displays, and a powerful scripting mechanism and discuss examples of experiments using these features. In the first example we built and ‘voltage clamped’ a conductance based model cell from a passive resistor–capacitor (RC) circuit using the dynamic clamp software to generate the voltage-dependent currents. In the second example we coupled our new spike generator through a burst detection/burst generation mechanism in a phase-dependent way to a neuron in a central pattern generator and dissected the subtle interaction between neurons, which seems to implement an information transfer through intraburst spike patterns. In the third example, making use of the new plasticity mechanism for simulated synapses, we analyzed the effect of spike timing-dependent plasticity (STDP) on synchronization revealing considerable enhancement of the entrainment of a post-synaptic neuron by a periodic spike train. These examples illustrate that with modern dynamic clamp software like StdpC, the dynamic clamp has developed beyond the mere introduction of artificial synapses or ionic conductances into neurons to a universal research tool, which might well become a standard instrument of modern electrophysiology

New PRSS1 and common CFTR mutations in a child with acute recurrent pancreatitis, could be considered an "Hereditary" form of pancreatitis ?

<p>Abstract</p> <p>Background</p> <p>acute recurrent pancreatitis is a complex multigenic disease, the diagnosis is even more difficult when this disease develops in a child.</p> <p>Case Presentation</p> <p>a 6-years old boy, hospitalized with epigastric pain radiating to the back showed high serum levels of serum amylase, lipase, CRP and erythrosedimentation rate. Several similar milder episodes of pain, followed by quick recovery and complete disappearance of symptoms were reported during the previous 13 months. The child was medically treated and after 7 days with normal clinic and laboratory tests was discharged with a hypolipidic diet. All the known aetiologic hypotheses were excluded by anamnestic investigation, clinical observation and biochemical evaluation, whereas, anatomic abnormality were excluded by a secretin stimulated magnetic resonance (MRI). At the last follow-up visit, (11 months later), the child showed a normal body weight and anthropometric profile, without further abdominal pain. Mutation screening for coding regions of <it>PRSS1, SPINK1, CFTR </it>and the new hereditary pancreatitis-associated chymotrypsin C (<it>CTRC</it>) genes showed a novel variation, c.541A > G (p.S181G), in the exon 4 of PRSS1 gene and the classical CF p.F508del mutation in the <it>CFTR. </it>Both mutations were present in his clinically normal mother and absent in the patient's father.</p> <p>Conclusions</p> <p>this report extend the spectrum of PRSS1 mutations, however, the absence of family history of pancreatitis leaves the present case without the hallmark of the hereditary origin of pancreatitis. At the present knowledge it can be only stated that the combined genotype CFTR (F508del)/PRSS1 (S181G) is associated to a mild phenotype of acute recurrent pancreatitis in this child without any further conclusion on its pathogenetic role or prediction on the course of the disease.</p

Understanding the ellagitannin extraction process from oak wood

[EN] The extractability of the main oak ellagitannins has been studied in five model solutions containing different types of oak chips (two sizes and different toasting degrees for each size). A new extraction kinetic model has been proposed from the quantitative experimental results obtained by means of HPLCeESI-MS/MS-multiple reaction monitoring method. The model considers an initial extraction (i.e., washing step) followed by a diffusion step, which involves two different processes that follow first-order kinetics at different rates. Differences in the extractability of the ellagitannins in the different model solutions have been observed and explained on the basis of the kinetic model here proposed

Removing krypton from xenon by cryogenic distillation to the ppq level

The XENON1T experiment aims for the direct detection of dark matter in a cryostat filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by radioactive decays inside the detector has to be sufficiently low. One major contributor is the $\beta$-emitter $^{85}$Kr which is an intrinsic contamination of the xenon. For the XENON1T experiment a concentration of natural krypton in xenon $\rm{^{nat}}$Kr/Xe < 200 ppq (parts per quadrillion, 1 ppq = 10$^{-15}$ mol/mol) is required. In this work, the design of a novel cryogenic distillation column using the common McCabe-Thiele approach is described. The system demonstrated a krypton reduction factor of 6.4$\cdot$10$^5$ with thermodynamic stability at process speeds above 3 kg/h. The resulting concentration of $\rm{^{nat}}$Kr/Xe < 26 ppq is the lowest ever achieved, almost one order of magnitude below the requirements for XENON1T and even sufficient for future dark matter experiments using liquid xenon, such as XENONnT and DARWIN

Expression and localisation of Akt-1, Akt-2 and Akt-3 correlate with clinical outcome of prostate cancer patients

We investigated the correlation between the expression and localisation of Akt-1, Akt-2, Akt-3, phospho-Akt proteins and the clinicopathological parameters in 63 prostate cancer specimens. More than 60% of cancerous tissues overexpressed Akt-1, Akt-2 or Akt-3. Cytoplasmic Akt-1 expression was correlated with a higher risk of postoperative prostate-specific antigen (PSA) recurrence and shorter PSA recurrence interval. Cytoplasmic Akt-2 did not show any significant correlation with clinicopathological parameters predicting outcomes. Cytoplasmic Akt-3 was associated with hormone-refractory disease progression and extracapsular invasion. Nuclear Akt-1 and Akt-2 expression were correlated with favourable outcome parameters such as absence of lymph node and perineural invasion. Kaplan–Meier analysis and Cox regression model also showed that Akt-1 and Akt-2, but not Akt-3 or phospho-Akt was associated with a significantly higher risk of PSA recurrence. In contrast, nuclear Akt-1 was significantly associated with a lower risk of PSA recurrence. Multivariate analysis revealed that clinical stage, Gleason score and the combined cytoplasmic nuclear Akt-1 marker in cancerous tissues were significant independent prognostic factors of PSA recurrence. This is the first report demonstrating in patients with prostate cancer and the particular role of Akt-1 isoform expression as a prognostic marker depending of its localisation

Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial – The NeuroMorfeo trial

<p>Abstract</p> <p>Background</p> <p>Many studies have attempted to determine the <it>"best" </it>anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA) with volatile-based neuroanaesthesia (VA) has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaestesiological strategy depends only on the anaesthetists' preferences or institutional policies.</p> <p>This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures.</p> <p>Methods/Design</p> <p>NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III) and Glasgow Coma Scale (GCS) equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil). The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score ≥ 9 (primary end-point). Two statistical comparisons have been planned:</p> <p>1) sevoflurane + fentanyl vs. propofol + remifentanil;</p> <p>2) sevoflurane + remifentanil vs. propofol + remifentanil.</p> <p>Secondary end-points include: an assessment of neurovegetative stress based on (a) measurement of urinary catecholamines and plasma and urinary cortisol and (b) estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded during anaesthesia; intraoperative adverse events; evaluation of surgical field; postoperative adverse events; patient's satisfaction and analysis of costs.</p> <p>411 patients will be recruited in 14 Italian centers during an 18-month period.</p> <p>Discussion</p> <p>We presented the development phase of this anaesthesiological on-going trial. The recruitment started December 4^th, 2007 and up to 4^th, December 2008, 314 patients have been enrolled.</p