Silicon-substrate microelectrode arrays for parallel recording ofneural activity in peripheral and cranial nerves

A new process for the fabrication of regeneration microelectrode arrays for peripheral and cranial nerve applications is presented. This type of array is implanted between the severed ends of nerves, the axons of which regenerate through via holes in the silicon and are thereafter held fixed with respect to the microelectrodes. The process described is designed for compatibility with industry-standard CMOS or BiCMOS processes (it does not involve high-temperature process steps nor heavily-doped etch-stop layers), and provides a thin membrane for the via holes, surrounded by a thick silicon supporting rim. Many basic questions remain regarding the optimum via hole and microelectrode geometries in terms of both biological and electrical performance of the implants, and therefore passive versions were fabricated as tools for addressing these issues in on-going work. Versions of the devices were implanted in the rat peroneal nerve and in the frog auditory nerve. In both cases, regeneration was verified histologically and it was observed that the regenerated nerves had reorganized into microfascicles containing both myelinated and unmyelinated axons and corresponding to the grid pattern of the via holes. These microelectrode arrays were shown to allow the recording of action potential signals in both the peripheral and cranial nerve settings, from several microelectrodes in parallel     

Optimizing one-shot learning with binary synapses

A network of excitatory synapses trained with a conservative version of Hebbian learning is used as a model for recognizing the familiarity of thousands of once-seen stimuli from those never seen before. Such networks were initially proposed for modeling memory retrieval (selective delay activity). We show that the same framework allows the incorporation of both familiarity recognition and memory retrieval, and estimate the network's capacity. In the case of binary neurons, we extend the analysis of Amit and Fusi (1994) to obtain capacity limits based on computations of signal-to-noise ratio of the field difference between selective and non-selective neurons of learned signals. We show that with fast learning (potentiation probability approximately 1), the most recently learned patterns can be retrieved in working memory (selective delay activity). A much higher number of once-seen learned patterns elicit a realistic familiarity signal in the presence of an external field. With potentiation probability much less than 1 (slow learning), memory retrieval disappears, whereas familiarity recognition capacity is maintained at a similarly high level. This analysis is corroborated in simulations. For analog neurons, where such analysis is more difficult, we simplify the capacity analysis by studying the excess number of potentiated synapses above the steady-state distribution. In this framework, we derive the optimal constraint between potentiation and depression probabilities that maximizes the capacity.     

Computations concerning Waring's problem for cubes

Waring's problem for cubes is investigated using numerical computations. The densities of number not representable as a sum of four and five cubes are computed in large intervals. Extrapolation of these data allows us to conjecture on the order of magnitude of last exceptions. The representability with four relative cubes and the validity of the theoretical asymptotic formula are investigated too. All the results reasonably confirm the conjecture that four relative cubes suffice to represent any integer and four nonnegative cubes suffice to represent any «large» integer.     

Perception of Host Plant Volatiles in Hyalesthes obsoletus: Behavior, Morphology, and Electrophysiology

The Palearctic planthopper Hyalesthes obsoletus is the natural vector of the grapevine yellow disease Bois noir. Grapevine is an occasional host plant of this polyphagous planthopper. To deepen our knowledge of the role of plant volatile organic compounds for H. obsoletus host plant searching, we carried out behavioral, morphological, and electrophysiological studies. We tested the attraction of H. obsoletus to nettle, field bindweed, hedge bindweed, chaste tree, and grapevine by using a Y-shaped olfactometer. The results showed a significant attraction of male H. obsoletus to chaste tree, and of the females to nettle. Male H. obsoletus were repelled by odor from hedge bindweed. Ultrastructural studies of the antennae showed at least two types of olfactory sensilla at the antennal pedicel: plaque organs and trichoid sensilla. Volatile organic compounds from nettle and chaste tree were collected, and the extracts were analyzed by coupling gas-chromatography to both mass-spectrometry and electroantennography. The volatile organic compounds that elicited electrophysiological responses in male and female antennae were identified. These findings are discussed with respect to behavior of H. obsoletus males and females in the field.     

ANP and BNP Exert Anti-Inflammatory Action via NPR-1/cGMP Axis by Interfering with Canonical,Non-Canonical,and Alternative Routes of Inflammasome Activation in Human THP1 Cells

Dysregulated inflammasome activation and interleukin (IL)-1β production are associated with several inflammatory disorders. Three different routes can lead to inflammasome activation: a canonical two-step, a non-canonical Caspase-4/5- and Gasdermin D-dependent, and an alternative Caspase-8-mediated pathway. Natriuretic Peptides (NPs), Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP), binding to Natriuretic Peptide Receptor-1 (NPR-1), signal by increasing cGMP (cyclic guanosine monophosphate) levels that, in turn, stimulate cGMP-dependent protein kinase-I (PKG-I). We previously demonstrated that, by counteracting inflammasome activation, NPs inhibit IL-1β secretion. Here we aimed to decipher the molecular mechanism underlying NPs effects on THP-1 cells stimulated with lipopolysaccharide (LPS) + ATP. Involvement of cGMP and PKG-I were assessed pre-treating THP-1 cells with the membrane-permeable analogue, 8-Br-cGMP, and the specific inhibitor KT-5823, respectively. We found that NPs, by activating NPR-1/cGMP/PKG-I axis, lead to phosphorylation of NLRP3 at Ser295 and to inflammasome platform disassembly. Moreover, by increasing intracellular cGMP levels and activating phosphodiesterases, NPs interfere with both Gasdermin D and Caspase-8 cleavage, indicating that they disturb non-canonical and alternative routes of inflammasome activation. These results showed that ANP and BNP anti-inflammatory and immunomodulatory actions may involve the inhibition of all the known routes of inflammasome activation. Thus, NPs might be proposed for the treatment of the plethora of diseases caused by a dysregulated inflammasome activation.     

Pollution's ambient problems and regularity of optimal cost function

We study pollution's ambient problems by using the optimal control theory applied to partial differential equations. We consider the problem to find the optimal way to eliminate pollution in the time, such that the concentration is close to a standard level which does not affect the ecological equilibrium when the source is pointwise. We consider a quadratic cost functional and we prove the existence and uniqueness of optimal control. We find a characterisation which makes possible the computing of optimal control. Additionally, we consider the problem moving the pointwise source. So, we define a function j(b) that associates to any point b ∈ Ω the optimal cost functional applied to the optimal control. We show that j is differentiable, provided that the controls are taken in a convenient subset of admissible functions satisfying the cone properties. We also find the point in Ω, for which the cost functional is minimum.     

Prognosis of myasthenia gravis: a retrospective study of 380 patients

The 9139 follow-up records of 438 myasthenia gravis (MG) patients were reviewed. Excluding those patients who were diagnosed 5 or more years after symptom onset (n = 37) and those who experienced only oculomotor symptoms throughout follow-up (n = 21), there were 380 patients. A survival analysis approach was used to assess the influence of prognostic factors on the following endpoints: (a) stable complete remission, (b) complete remission of at least 6 months and (c) pharmacological remission of at least 6 months. Early diagnosis was associated with a better prognosis with respect to all endpoints. Thymectomy also improved the prognosis but only for those patients without thymoma. Later MG onset was associated with a higher tendency to achieve pharmacological remission.     

Quantifying the relevance and stage of disease with the Tau image technique

Discusses a complementary diagnostic imaging technique based on infrared functional imaging. It is concluded that the Tau images obtained with our method provide a large amount of information. The method, in fact, correctly depicts the ill and symptomatic situation; moreover, it is able to identify the surface projection onto the skin of the damaged areas and, by means of the evaluated value of the Tau time, the stage of the disease. Additionally, it is possible to evaluate the evolution of the clinical situation following a rehabilitation therapy and to quantitatively compare the different Tau images recorded at different times.     

Analysis of jacking forces during microtunnelling in limestone

This paper is intended to describe an Italian case study of a microtunnelling project where the boring machine got stuck during jacking of a 760 mm pipe in a limestone formation. Reference is made to rock mass characterisation, including site investigations and laboratory tests. The machine’s performance is compared to prediction. To allow for a better understanding of the conditions which led to the unexpectedly high jacking forces, continuum and discontinuum numerical analyses have been used. These analyses are shown to be essential at the design stage, when dealing with microtunnelling in a rock mass, in order to obtain a good prediction of the jacking forces.