Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut

The largest mucosal surface in the body is in the gastrointestinal tract, a location that is heavily colonized by microbes that are normally harmless. A key mechanism required for maintaining a homeostatic balance between this microbial burden and the lymphocytes that densely populate the gastrointestinal tract is the production and transepithelial transport of poly-reactive IgA (ref. 1). Within the mucosal tissues, B cells respond to cytokines, sometimes in the absence of T-cell help, undergo class switch recombination of their immunoglobulin receptor to IgA, and differentiate to become plasma cells. However, IgA-secreting plasma cells probably have additional attributes that are needed for coping with the tremendous bacterial load in the gastrointestinal tract. Here we report that mouse IgA(+) plasma cells also produce the antimicrobial mediators tumour-necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), and express many molecules that are commonly associated with monocyte/granulocytic cell types. The development of iNOS-producing IgA(+) plasma cells can be recapitulated in vitro in the presence of gut stroma, and the acquisition of this multifunctional phenotype in vivo and in vitro relies on microbial co-stimulation. Deletion of TNF-α and iNOS in B-lineage cells resulted in a reduction in IgA production, altered diversification of the gut microbiota and poor clearance of a gut-tropic pathogen. These findings reveal a novel adaptation to maintaining homeostasis in the gut, and extend the repertoire of protective responses exhibited by some B-lineage cells.     

Functional exploration of the human spinal cord during voluntary movement and somatosensory stimulation

Demonstrations of the possibility of obtaining functional information from the spinal cord in humans using functional magnetic resonance imaging (fMRI) have been growing in number and sophistication, but the technique and the results that it provides are still perceived by the scientific community with a greater degree of scepticism than fMRI investigations of brain function. Here we review the literature on spinal fMRI in humans during voluntary movements and somatosensory stimulation. Particular attention is given to study design, acquisition and statistical analysis of the images, and to the agreement between the obtained results and existing knowledge regarding spinal cord anatomy and physiology.     

Diffusion-weighted MRI in the characterization of cystic pancreatic lesions: usefulness of ADC values

Purpose

To evaluate the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI) in the differentiation of cystic pancreatic lesions.

Materials and Methods

Institutional review board approval was obtained, and written informed consent was taken from all enrolled subjects. Fifty-four patients with cystic pancreatic lesions of at least 1 cm in diameter (range:10–96 mm) at ultrasonography and/or computed tomography and 10 normal subjects underwent MRI at 1.5 T. These subjects included thirty-four patients with intraductal papillary mucinous tumors (IPMTs), 10 with pseudocysts, 5 with serous cystoadenoma and 5 with mucinous cystoadenoma. The MR protocol included axial T1w and T2w sequences and coronal MR cholangiopancreatography images. DW-MRI was performed using a breath-hold single-shot echo-planar sequence with a b gradient factor value of 500 s/mm² in the three orthogonal axes. Apparent diffusion coefficient (ADC) was calculated for cerebrospinal fluid, normal pancreatic parenchyma, and for each focal pancreatic lesion. Imaging results were correlated with endoscopic retrograde cholangiopancreatography, endoscopic ultrasound-guided fine needle aspiration, surgery and/or imaging follow-up.

Results

Mean ADC value was 4.1×10⁻³ mm²/s for cerebrospinal fluid, 1.73×10⁻³ mm²/s for normal pancreatic parenchyma, 4.09×10⁻³ mm²/s for IPMT, 3.89×10⁻³ mm²/s for mucinous cystoadenoma, 3.65×10⁻³ mm²/s for serous cystoadenoma and 2.83×10⁻³ mm²/s for pseudocyst. Mean ADC values of each of the different types of pancreatic lesions were statistically different (P<.05).

Conclusion

DW-MRI may be helpful in the differential diagnosis of cystic pancreatic lesions.     

A ketogenic diet increases succinic dehydrogenase (SDH) activity and recovers age-related decrease in numeric density of SDH-positive mitochondria in cerebellar Purkinje cells of late-adult rats

Ketogenic diets (KDs) have been applied in the therapy of paediatric epilepsy for nearly a century. Recently, beneficial results have also been reported on metabolic disorders and neurodegeneration, designating aged individuals as possible recipients. However, KDs efficacy decrease after the suckling period, and very little is known about their impact on the aging brain. In the present study, the effect on the neuronal energetic supply of a KD containing 20% of medium chain triglycerides (MCT) was investigated in Purkinje cells of the cerebellar vermis of late-adult (19-month-old) rats. The animals were fed with the KD for 8 weeks, and succinic dehydrogenase (SDH) activity was cytochemically determined. The following parameters of SDH-positive mitochondria were evaluated by the use of a computer-assisted image analysis system connected to a transmission electron microscope: numeric density (Nv), average volume (V), volume density (Vv), and cytochemical precipitate area/mitochondrial area (R). Young, age-matched, and old animals fed with a standard chow were used as controls. We found significantly higher Nv in MCT-KD-fed rats vs. all the control groups, in young vs. late-adult and old controls, and in late-adult vs. old controls. V and Vv showed no significant differences among the groups. R was significantly higher in MCT-KD-fed rats vs. all the control animals, and in old vs. young and late-adult controls. Present data indicate that the ketogenic treatment counteracted age-related decrease in numeric density of SDH-positive mitochondria, and enhanced their metabolic efficiency. Given the central role of mitochondrial impairment in age-related physio-pathological changes of the brain, these findings may represent a starting point to examine novel potentialities for KDs.     

A comparison between different optimization criteria for tuned mass dampers design

Tuned mass sampers (TMDs) are widely used strategies for vibration control in many engineering applications, so that many TMD optimization criteria have been proposed till now. However, they normally consider only TMD stiffness and damping as design variables and assume that the tuned mass is a pre-selected value. In this work a more complete approach is proposed and then also TMD mass ratio is optimized. A standard single degree of freedom system is investigated to evaluate TMD protection efficiency in case of excitation at the support. More precisely, this model is used to develop two different optimizations criteria which minimize the main system displacement or the inertial acceleration. Different environmental conditions described by various characterizations of the input, here modelled by a stationary filtered stochastic process, are considered. Results show that all solutions obtained considering also the mass of the TMD as design variable are more efficient if compared with those obtained without it. However, in many cases these solutions are inappropriate because the optimal TMD mass is greater than real admissible values in practical technical applications for civil and mechanical engineering. Anyway, one can deduce that there are some interesting indications for applications in some actual contexts. In fact, the results show that there are some ranges of environmental parameters ranges where results attained by the displacement criterion are compatible with real applications requiring some percent of main system mass. Finally, the present research gives promising indications for complete TMD optimization application in emerging technical contexts, as micromechanical devices and nano resonant beams.     

Legendre spectral method for the fractional Bratu problem

In this paper, the Legendre spectral collocation method (LSCM) is applied for the solution of the fractional Bratu's equation. It shows the high accuracy and low computational cost of the LSCM compared with some other numerical methods. The fractional Bratu differential equation is transformed into a nonlinear system of algebraic equations for the unknown Legendre coefficients and solved with some spectral collocation methods. Some illustrative examples are also given to show the validity and applicability of this method, and the obtained results are compared with the existing studies to highlight its high efficiency and neglectable error.     

Modelling pedestrian dynamics into a metro station by thermostatted kinetic theory methods

This paper deals with the modelling of pedestrian dynamics at the entry of a metro station by means of the thermostatted kinetic theory framework. Specifically, the model depicts the time evolution of the pedestrian dynamics at the turnstiles under no panic conditions. The modelling of the microscopic interactions is based on the stochastic game theory and reflects the decision dynamics of the turnstiles pursued by pedestrians. A qualitative analysis is addressed to the equilibrium solutions by means of the classical stability theory of perturbations. Numerical simulations aim at showing the emerging behaviours captured by the model. In particular the model validation is obtained by performing a sensitivity analysis on the parameters and on the initial conditions. Further refinements and research perspective, including the modelling under panic conditions, are discussed in the last section of the paper.     

Small values of signed harmonic sums

For every $\tau \in \mathbb{R}$ and every integer N, let ${\mathfrak{m}}_N(\tau )$ be the minimum of the distance of τ from the sums ${\sum }_{n=1}^N{s}_n/n$, where $s_1,\dots ,s_n\in \{?1,+1\}$. We prove that ${\mathfrak{m}}_N(\tau )<\exp ?(?C{(\log ?N)}^2)$, for all sufficiently large positive integers N (depending on C and τ), where C is any positive constant less than $1/\log ?4$.     

RBFOpt: an open-source library for black-box optimization with costly function evaluations

We consider the problem of optimizing an unknown function given as an oracle over a mixed-integer box-constrained set. We assume that the oracle is expensive to evaluate, so that estimating partial derivatives by finite differences is impractical. In the literature, this is typically called a black-box optimization problem with costly evaluation. This paper describes the solution methodology implemented in the open-source library RBFOpt, available on COIN-OR. The algorithm is based on the Radial Basis Function method originally proposed by Gutmann (J Glob Optim 19:201–227, 2001.  https://doi.org/10.1023/A:1011255519438), which builds and iteratively refines a surrogate model of the unknown objective function. The two main methodological contributions of this paper are an approach to exploit a noisy but less expensive oracle to accelerate convergence to the optimum of the exact oracle, and the introduction of an automatic model selection phase during the optimization process. Numerical experiments show that RBFOpt is highly competitive on a test set of continuous and mixed-integer nonlinear unconstrained problems taken from the literature: it outperforms the open-source solvers included in our comparison by a large amount, and performs slightly better than a commercial solver. Our empirical evaluation provides insight on which parameterizations of the algorithm are the most effective in practice. The software reviewed as part of this submission was given the Digital Object Identifier (DOI)  https://doi.org/10.5281/zenodo.597767.     

Monotone thematic factorizations of matrix functions

We continue the study of the so-called thematic factorizations of admissible very badly approximable matrix functions. These factorizations were introduced by V.V. Peller and N.J. Young for studying superoptimal approximation by bounded analytic matrix functions. Even though thematic indices associated with a thematic factorization of an admissible very badly approximable matrix function are not uniquely determined by the function itself, R.B. Alexeev and V.V. Peller showed that the thematic indices of any monotone non-increasing thematic factorization of an admissible very badly approximable matrix function are uniquely determined. In this paper, we prove the existence of monotone non-decreasing thematic factorizations for admissible very badly approximable matrix functions. It is also shown that the thematic indices appearing in a monotone non-decreasing thematic factorization are not uniquely determined by the matrix function itself. Furthermore, we show that the monotone non-increasing thematic factorization gives rise to a great number of other thematic factorizations.