Differential Expression of Serum Extracellular Vesicle miRNAs in Multiple Sclerosis: Disease-Stage Specificity and Relevance to Pathophysiology

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Its first clinical presentation (clinically isolated syndrome, CIS) is often followed by the development of relapsing–remitting MS (RRMS). The periphery-to-CNS transmission of inflammatory molecules is a major pathophysiological pathway in MS. This could include signalling via extracellular vesicle (EV) microRNAs (miRNAs). In this study, we investigated the serum EV miRNome in CIS and RRMS patients and matched controls, with the aims to identify MS stage-specific differentially expressed miRNAs and investigate their biomarker potential and pathophysiological relevance. miRNA sequencing was conducted on serum EVs from CIS-remission, RRMS-relapse, and viral inflammatory CNS disorder patients, as well as from healthy and hospitalized controls. Differential expression analysis was conducted, followed by predictive power and target-pathway analysis. A moderate number of dysregulated serum EV miRNAs were identified in CIS-remission and RRMS-relapse patients, especially relative to healthy controls. Some of these miRNAs were also differentially expressed between the two MS stages and had biomarker potential for patient-control and CIS–RRMS separations. For the mRNA targets of the RRMS-relapse-specific EV miRNAs, biological processes inherent to MS pathophysiology were identified using in silico analysis. Study findings demonstrate that specific serum EV miRNAs have MS stage-specific biomarker potential and contribute to the identification of potential targets for novel, efficacious therapies.     

Structural Analysis of Human Serum Albumin in Complex with the Fibrate Drug Gemfibrozil

Gemfibrozil (GEM) is an orally administered lipid-regulating fibrate derivative drug sold under the brand name Lopid^®, among others. Since its approval in the early 80s, GEM has been largely applied to treat hypertriglyceridemia and other disorders of lipid metabolism. Though generally well tolerated, GEM can alter the distribution and the free, active concentration of some co-administered drugs, leading to adverse effects. Most of them appear to be related to the ability of GEM to bind with high affinity human serum albumin (HSA), the major drug-carrier protein in blood plasma. Here, we report the crystal structure of HSA in complex with GEM. Two binding sites have been identified, namely Sudlow’s binding sites I (FA7) and II (FA3–FA4). A comparison of the crystal structure of HSA in complex with GEM with those of other previously described HSA–drug complexes enabled us to appreciate the analogies and differences in their respective binding modes. The elucidation of the molecular interaction between GEM and HSA might offer the basis for the development of novel GEM derivatives that can be safely and synergistically co-administered with other drugs, enabling augmented therapeutic efficacies.     

Natural convection for in-vessel retention at prototypic Rayleigh numbers

The ACOPO experiment simulates natural convection heat transfer from volumetrically heated pools at a half-scale reactor lower head geometry (hemispherical). New data for internal Rayleigh numbers of up to 10¹⁶ are presented, correlated and discussed, in relation to other available correlations. These ACOPO results confirm a key component of the in-vessel retention severe accident management strategy for an AP600-like design, as recently established in DOE/ID-10460.     

Pattern Matching Machine implementation of a fast test for unique decipherability

A new fast implementation of the Sardinas-Patterson-Even test for unique decipherability is presented, based on the structure of a Pattern Matching Machine.     

Impact of waste cooking oil in biodiesel blends on particle size distributions from a city-car engine

Using biodiesel as a blending component in diesel engine has demonstrated to reduce hydrocarbon and particulate matter emissions. Literature showed that biodiesel type, engine architecture and test conditions deeply affect performance and emission characteristics. Among suitable biodiesel fuels, waste cooking oil (WCO) is considered very attractive due to the reduced environmental impact without sacrificing engine performance.This paper aims at investigating how mixing ratio of biodiesel from WCO and mineral diesel affects the particle size distributions of a current state of art small displacement diesel engine.Experimental tests have been performed on an up-to date light common rail diesel engine. Its complete operative field has been investigated. The results obtained show that the use of biodiesel blends from WCO reduces the total number of particles emitted from the engine with respect to the diesel fuel; the reduction is more evident as the percentage of biodiesel in the blend increases. The number of particles in WCO biodiesel soot with diameter smaller than 10 nm is reduced as compared to diesel fuel; the same trend is observed for diameters larger than 200 nm; comparable particle numbers were obtained in the ultrafine range (Dp < 100 nm).     

Chiral liquid crystal polymers

Summary Chiral glycidyl ethers containing biphenyl side groups have been synthesized starting from optically active isopropylidene glycidol. The anisotropic moiety can be bound to the oxirane ring either directly or through flexible spacers of varying length. Details relevant to the above reactions and to the reaction sequences adopted to get the corresponding glycidyl ethers are presented.     

Revisitation of the reaction between aniline and formaldehyde. VI. The accumulated amide ester function from Addition of Carboxylic Anhydrides to N-methyleneamines or their trimers

Some aliphatic carboxylic anhydrides gave excellent yields of the novel addition products to both aliphatic and aromatic N-methyleneimines, starting from their aliphatic and aromatic trimeric cyclic oligomers. A preliminary positive ion mass spectrometric study is here reported. They hydrolyze surprisingly faster than the corresponding acid amides, making necessary the intervention of a special mechanism. The reduction of the acetylamideester of cyclohexylmethyleneimine ( 3c ) with LiAlH₄ was also “abnormal”, as it yielded N-methyl-N-ethylcyclohexylamine in quantitative yield.