Short communication: refinement of genetic regions associated with Mycobacterium avium subspecies paratuberculosis tissue infection and tolerance to Johne's disease

Johne's disease is a highly transmissible bacterial disease caused by Mycobacterium avium ssp. paratuberculosis (MAP). The objective of this study was to refine the locus associated with MAP tissue infection and the locus associated with tolerance to Johne's disease. Using a genome-wide association analysis, single nucleotide polymorphisms associated with MAP tissue infection and tolerance to Johne's disease on Bos taurus autosome (BTA)3 and BTA15, respectively, have previously been identified. A 235-kb region on BTA3 was evaluated with 42 single nucleotide polymorphisms, and a 193-kb region on BTA15 was evaluated with 54 single nucleotide polymorphisms in a group of 209 Holstein cows. Using a single marker association analysis and haplotype tests, we refined a region of 10.6 kb on BTA3 as being associated with MAP tissue infection and a region of 6.5 kb on BTA15 as being associated with tolerance to Johne's disease.     

Human iPSC-Derived 2D and 3D Platforms for Rapidly Assessing Developmental,Functional, and Terminal Toxicities in Neural Cells

With increasing global health threats has come an urgent need to rapidly develop and deploy safe and effective therapies. A common practice to fast track clinical adoption of compounds for new indications is to repurpose already approved therapeutics; however, many compounds considered safe to a specific application or population may elicit undesirable side effects when the dosage, usage directives, and/or clinical context are changed. For example, progenitor and developing cells may have different susceptibilities than mature dormant cells, which may yet be different than mature active cells. Thus, in vitro test systems should reflect the cellular context of the native cell: developing, nascent, or functionally active. To that end, we have developed high-throughput, two- and three-dimensional human induced pluripotent stem cell (hiPSC)-derived neural screening platforms that reflect different neurodevelopmental stages. As a proof of concept, we implemented this in vitro human system to swiftly identify the potential neurotoxicity profiles of 29 therapeutic compounds that could be repurposed as anti-virals. Interestingly, many compounds displayed high toxicity on early-stage neural tissues but not on later stages. Compounds with the safest overall viability profiles were further evaluated for functional assessment in a high-throughput calcium flux assay. Of the 29 drugs tested, only four did not modulate or have other potentially toxic effects on the developing or mature neurospheroids across all the tested dosages. These results highlight the importance of employing human neural cultures at different stages of development to fully understand the neurotoxicity profile of potential therapeutics across normal ontogeny.     

Myogenic Potential of Extracellular Matrix Derived from Decellularized Bovine Pericardium

Skeletal muscles represent 40% of body mass and its native regenerative capacity can be permanently lost after a traumatic injury, congenital diseases, or tumor ablation. The absence of physiological regeneration can hinder muscle repair preventing normal muscle tissue functions. To date, tissue engineering (TE) represents one promising option for treating muscle injuries and wasting. In particular, hydrogels derived from the decellularized extracellular matrix (dECM) are widely investigated in tissue engineering applications thanks to their essential role in guiding muscle regeneration. In this work, the myogenic potential of dECM substrate, obtained from decellularized bovine pericardium (Tissuegraft Srl), was evaluated in vitro using C2C12 murine muscle cells. To assess myotubes formation, the width, length, and fusion indexes were measured during the differentiation time course. Additionally, the ability of dECM to support myogenesis was assessed by measuring the expression of specific myogenic markers: α-smooth muscle actin (α-sma), myogenin, and myosin heavy chain (MHC). The results obtained suggest that the dECM niche was able to support and enhance the myogenic potential of C2C12 cells in comparison of those grown on a plastic standard surface. Thus, the use of extracellular matrix proteins, as biomaterial supports, could represent a promising therapeutic strategy for skeletal muscle tissue engineering.     

Contention-TDMA protocol: performance evaluation

A hybrid access protocol known, as contention time-division multiple access (C-TDMA), is presented and analyzed in a radio cellular multiuser system scenario. C-TDMA shows some features of contention-based (slotted-ALOHA) and reservation-based (packet reservation multiple access, PRMA) protocols. It has been recommended for use in the uplink of future European multimedia distribution systems. A simple Markov model is proposed to describe C-TDMA behavior. A complete statistical analysis of the model has been made in order to evaluate the performance of the protocol. However, due to the long computation time required in the presence of a large number of users, a simpler approach known as equilibrium point analysis (EPA) is used. Moreover, on the basis of the EPA analysis and the C-TDMA design parameters, a fast algorithm has been developed to improve the achievable throughput of C-TDMA. Results in terms of throughput and delay under variable traffic conditions indicate that C-TDMA is able to grant optimum throughput/delay figures for typical multiuser systems. Moreover, for a digital speech scenario, a performance comparison with PRMA demonstrates that C-TDMA yields equivalent performance to PRMA in terms of number of users supported by the system with a limited packet dropping rate     

Sulle regioni di confidenza per i parametri dei modelli non lineari. I

Sommario Nell'ambito della ricerca sperimentale si presenta il problema di stimare i parametri di un modello interpretativo teorico che ne dipende in modo non lineare. In concreto però, come per il caso lineare, le stime puntuali, ottenute tipicamente secondo il principio dei minimi quadrati, possono avere, in sè, scarso rilievo per la variabilità ad esse inerente a causa dell'errore sperimentale e vengono impiegate per la determinazione di insiemi di valori che hanno una prefissata probabilità di comprendere quelli degli incogniti parametri in studio (regioni di confidenza). Nel presente studio si propone un miglioramento, in modo da tener conto della ?curvatura?, del metodo di uso corrente, che fa ricorso alla ?linearizzazione locale? del modello per ottenere regioni di confidenza approssimate. La teoria qui proposta si basa: 1) sull'interpretazione di un modello non lineare ink (k>1) parametri come una varietà riemannianaV _(k) immersa in uno spazio euclideoS _(n) di dimensioni pari al numeron(n>k+1) delle osservazioni; 2) sulla sua identificazione con unaipersuperficie, che sotto particolari condizioni, meglio approssimaV _(k) , per quanto riguarda la curvatura globale media, nell'intorno del punto corrispondente alle stime dei parametri. Si propongono due tipi di regioni di confidenza, uno generale ed uno sotto l'ipotesi che laipersuperficie approssimante sia convessa. La teoria proposta si lascia agevolmente formalizzare in una procedura di calcolo automatico di cui si indicano gli elementi costitutivi e si illustra l'applicazione ad un modello di cinetica chimica.

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Abtract In the experimental research we are often confronted with theoreitcal models which are non-linear in the parameter. As in the linear case, point estimates of the latter, typically obtained by the method of least squares, can result of little interest by themselves, because of the random variability inherent to them and they are rather taken as a basis for constructing sets with assigned probability of containing the ?true? unknown values of the parameters (confidence regions). In the former context an improvement of the current procedure, by which confidence regions are determined through ?local linearization? of the response functions, is proposed, in order to take the ?curvature? of the model into consideration. The theory developed in this paper is based: 1) on the identification of a non-linear model ink (k>1) parameters with a Riemann space imbedded in an euclideann dimensional spaceS _(n) , withn (n>k+1) equal to the number of observations; 2) on an approximation ofV _(k) by asurface of aS _(k+1), which is the best, in a particular class, insofar, as its ?mean curvature? is the nearest to that ofV _(k) in the point corresponding to the least squares estimates of the parameters. Two types of confidence regions are then obtained: the one more general, the other under the hypothesis that the approximatingsurface is convex. The former theoretical results can be easily formalized into a computer programme, the leading elements of which are presented in the paper together with an application of it to a model arising in the study of a chemical mechanism.

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Uno stralcio dell'artioolo è stato presentato come comunicazione alla Sessione Metodologica dello VIII Convegno Nazionale dell'Associazione Italiana per il Controllo della Qualità (Napoli 10-11-5-1973).     

Integral bread development with soybean, chia, linseed, and folic acid as a functional food for women

Six bread formulations were developed, using different proportions of whole-wheat flour, chia seeds and flaxseed flour. All of our formulations were added with folic acid. Sensorial and texture evaluations were performed, showing good acceptance of the products. Proximal chemical analysis was carried out; in addition, the following parameters were determined: calcium, phosphorus, total dietary fiber, folic acid, water hydration capacity, Glucose Dialysis Retardation Index (GDRI) and fatty acids. The results obtained showed higher protein levels in the developed breads (23.23-30.24 (g/100g dry matter) as compared to a control (21.00% of proteins in bread elaborated without chia or flaxseed). Furthermore, the breads contained 10.07-12.15 of lipids (g/100g dry matter) (linoleic acid: 2.43-4.05%; linolenic acid: 1.12-4.46 %; oleic acid: 2.93-6.13 %), GDRI values were between 89.1 and 98.1 % and folic acid was in the range 699.44 - 991.3 (microg/100g dry matter). The same parameters were determined in the chia seed and in the flaxseed flour. It was concluded that; due to their high levels of protein, insaturated fatty acids (omega-3 and omega-6), dietary fiber and folic acid, these breads have a high nutritional value, so they could have special benefits for woman.     

Synthesis and characterization of metal oxide multilayers obtained via MOCVD as protective coatings of graphite against oxidation

Zirconia (ZrO₂) titania (TiO₂) and alumina (Al₂O₃) thin films were deposited on a graphite substrate both in mono- and in multi-layer systems, using the metal organic chemical vapor deposition technique, to test their practical qualities as protective coatings against oxidation at high temperatures. The depositions were performed using a hot wall reactor at reduced pressure (0.6 Torr) in the temperature range 350–500 °C, using, as precursors, (η⁵-C₅H₅)₂Zr(CH₂C(CH₃)₃)₂, Ti(OCH(CH₃)₂)₄, and (CH₃CH₂)₂Al(OCCH₃CHCCH₃O), respectively. Surface and topographical analysis of the deposits using X-ray photoelectron spectroscopy, X-ray diffraction and scanning electron microscopy techniques as well as thermogravimetric measurements (TG and DTA) in an oxygen flux of mono- and multi-layer systems are reported and examined.     

Cationic Carboxylato Complexes of Dirhodium(II) with Oxo Thioethers: Catalysts for Silane Alcoholysis under Homogeneous and Liquid‐Liquid Biphasic Conditions

A set of cationic dirhodium(II) complexes with oxo thioethers was prepared and employed as catalysts for the silane alcoholysis reaction. The complexes were found to be highly active under homogeneous conditions, both in the absence and in the presence of a solvent, including coordinating solvents such as N,N‐dimethylformamide; the catalysts could be conveniently employed in concentrations as low as 0.01 mol %, and a maximum TON of 30000 was recorded after 24 h. The same catalysts were also employed under liquid‐liquid biphasic conditions with an ionic liquid as the catalyst‐containing phase: comparable catalytic activity was observed under these conditions, and the catalyst‐containing phase could be recovered and recycled. A chiral cationic dirhodium(II) complex was also prepared in the frame of this work; kinetic resolution of a racemic alcohol was attempted with this catalyst, unfortunately without success.     

Analysis of the impact of process variations on clock skew

In this paper, we analyze the impact of process variations on the clock skew of VLSI circuits designed in deep submicrometer technologies. With smaller feature size, the utilization of a dense buffering scheme has been proposed in order to realize efficient and noise-immune clock distribution networks. However, the local variance of MOSFET electrical parameters, such as V_T and I_DSS, increases with scaling of device dimensions, thus causing large intradie variability of the timing properties of clock buffers. As a consequence, we expect process variations to be a significant source of clock skew in deep submicrometer technologies. In order to accurately verify this hypothesis, we applied advanced statistical simulation techniques and accurate mismatch measurement data in order to thoroughly characterize the impact of intradie variations on industrial clock distribution networks. The comparison with Monte Carlo simulations performed by neglecting the effect of mismatch confirmed that local device variations play a crucial role in the design and sizing of the clock distribution network