A bio-sourced molecule as carbon black coupling agent in rubber compounds with low hysteresis

The prime application of rubber composites is represented by tire compounds. To achieve the desired tire performances an equilibrium between dynamic rigidity and hysteresis must be acquired. Amorphous precipitated silica is the preferred reinforcing filler to have low energy dissipations and thus low fuel consumption. Indeed, silica is characterized by nano dimensions and by the possibility of establishing chemical bonds with rubber chains allowing the achievement of high hysteresis at low temperatures, to promote wet traction, and low hysteresis at medium-high temperatures, for low fuel consumption. Carbon black (CB) is the main filler for tire compounds, but it does not have functional groups able to promote chemical bonds with the rubber matrix, though it would be highly desirable. In this work, a pyrrole compound (PyC) containing a thiol group, and which can be synthesized starting from bio-based building blocks was used to functionalize CB by the socalled “pyrrole methodology”. The thiol group was expected to react with the sulphurbased crosslinking system and/or with rubber chains, thus forming strong bonds with the rubber matrix. Results The synthesis of the PyC and the functionalization reaction were characterized by high atom efficiency. A poly(styrene-co-butadiene) copolymer from anionic solution polymerization was used as the main rubber for the compound preparation. The crosslinked composite material filled with functionalized CB revealed substantial improvements with respect to the composite with pristine CB, in particular: high rigidity and low hysteresis at high temperature. Composite properties were even comparable to those of silica-based rubber composites. The formation of the expected rubber-filler chemical bond via the thiol group of the selected PyC was confirmed studying such functionalizing agent in a squalene-based model compound. The results here reported pave the way to CB-based rubber composites with a low environmental impact

Functional Characterisation of Alpha-Galactosidase A Mutations as a Basis for a New Classification System in Fabry Disease

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The study has been supported partially by an unrestricted scientific grant from Shire Human Genetic Therapies (Germany

Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model.

Parkinson's disease (PD) is characterized by the presence of α-synuclein aggregates known as Lewy bodies and Lewy neurites, whose formation is linked to disease development. The causal relation between α-synuclein aggregates and PD is not well understood. We generated a new transgenic mouse line (MI2) expressing human, aggregation-prone truncated 1-120 α-synuclein under the control of the tyrosine hydroxylase promoter. MI2 mice exhibit progressive aggregation of α-synuclein in dopaminergic neurons of the substantia nigra pars compacta and their striatal terminals. This is associated with a progressive reduction of striatal dopamine release, reduced striatal innervation and significant nigral dopaminergic nerve cell death starting from 6 and 12 months of age, respectively. In the MI2 mice, alterations in gait impairment can be detected by the DigiGait test from 9 months of age, while gross motor deficit was detected by rotarod test at 20 months of age when 50% of dopaminergic neurons in the substantia nigra pars compacta are lost. These changes were associated with an increase in the number and density of 20-500 nm α-synuclein species as shown by dSTORM. Treatment with the oligomer modulator anle138b, from 9 to 12 months of age, restored striatal dopamine release, prevented dopaminergic cell death and gait impairment. These effects were associated with a reduction of the inner density of large α-synuclein aggregates and an increase in dispersed small α-synuclein species as revealed by dSTORM. The MI2 mouse model recapitulates the progressive dopaminergic deficit observed in PD, showing that early synaptic dysfunction is associated to fine behavioral motor alterations, precedes dopaminergic axonal loss and neuronal death that become associated with a more consistent motor deficit upon reaching a certain threshold. Our data also provide new mechanistic insight for the effect of anle138b's function in vivo supporting that targeting α-synuclein aggregation is a promising therapeutic approach for PD

Faulting, basin formation and orogenic arcuation at the Dinaric–Hellenic junction (northern Albania and Kosovo)

The Dinaric–Hellenic mountain belt bends where two fault systems transect the orogen: (1) the dextral Shkoder-Peja Transfer Zone (SPTZ), active sometime between the Late Cretaceous and middle Eocene; (2) the Shkoder-Peja Normal Fault (SPNF), which accommodated NW–SE directed orogen-parallel extension. The SPTZ dextrally offsets the Dinaric–Hellenic nappes by ~ 75 km, a displacement attributed to reactivation of an Early Mesozoic rift transfer zone in the Adriatic margin during Paleogene subduction of the Pindos Ocean. This subduction involved an initial counter-clockwise rotation of the Hellenides with respect to the Dinarides around a pole at the NW end of the Budva–Krasta–Cukali–Pindos Basin. The SPNF overprints the SPTZ and is a composite structure comprising five fault segments: four of them (Cukali–Tropoja, Decani, Rožaje, Istog) were active under ductile-to-brittle conditions. They downthrow the West Vardar Ophiolite in the hanging wall. The Cukali–Tropoja and Decani segments exhume domes with anchizonal-to-greenschist-facies metamorphism in their footwalls. These structures formed during a first-phase of extension and clockwise rotation, whose Paleocene age is constrained by cross-cutting relationships. A second extensional phase was accommodated mainly by the fifth (Dukagjini) segment of the SPNF, a subsurface normal fault bordering syn-rift, mid-late Miocene clastic and lacustrine sediments in the Dukagjini Basin (DB) that are sealed by Plio-Pleistocene strata. This later phase involved subsidence of Neogene basins at the Dinaric–Hellenic junction coupled with accelerated clockwise oroclinal bending. The driving force for clockwise rotation is thought to be bending and rollback of the untorn part of the Adriatic slab beneath the Hellenides

Faulting, basin formation and orogenic arcuation at the Dinaric–Hellenic junction (northern Albania and Kosovo)

The Dinaric–Hellenic mountain belt bends where two fault systems transect the orogen: (1) the dextral Shkoder-Peja Transfer Zone (SPTZ), active sometime between the Late Cretaceous and middle Eocene; (2) the Shkoder-Peja Normal Fault (SPNF), which accommodated NW–SE directed orogen-parallel extension. The SPTZ dextrally offsets the Dinaric–Hellenic nappes by ~ 75 km, a displacement attributed to reactivation of an Early Mesozoic rift transfer zone in the Adriatic margin during Paleogene subduction of the Pindos Ocean. This subduction involved an initial counter-clockwise rotation of the Hellenides with respect to the Dinarides around a pole at the NW end of the Budva–Krasta–Cukali–Pindos Basin. The SPNF overprints the SPTZ and is a composite structure comprising five fault segments: four of them (Cukali–Tropoja, Decani, Rožaje, Istog) were active under ductile-to-brittle conditions. They downthrow the West Vardar Ophiolite in the hanging wall. The Cukali–Tropoja and Decani segments exhume domes with anchizonal-to-greenschist-facies metamorphism in their footwalls. These structures formed during a first-phase of extension and clockwise rotation, whose Paleocene age is constrained by cross-cutting relationships. A second extensional phase was accommodated mainly by the fifth (Dukagjini) segment of the SPNF, a subsurface normal fault bordering syn-rift, mid-late Miocene clastic and lacustrine sediments in the Dukagjini Basin (DB) that are sealed by Plio-Pleistocene strata. This later phase involved subsidence of Neogene basins at the Dinaric–Hellenic junction coupled with accelerated clockwise oroclinal bending. The driving force for clockwise rotation is thought to be bending and rollback of the untorn part of the Adriatic slab beneath the Hellenides

Automated Synthesis of Tableau Calculi

This paper presents a method for synthesising sound and complete tableau calculi. Given a specification of the formal semantics of a logic, the method generates a set of tableau inference rules that can then be used to reason within the logic. The method guarantees that the generated rules form a calculus which is sound and constructively complete. If the logic can be shown to admit finite filtration with respect to a well-defined first-order semantics then adding a general blocking mechanism provides a terminating tableau calculus. The process of generating tableau rules can be completely automated and produces, together with the blocking mechanism, an automated procedure for generating tableau decision procedures. For illustration we show the workability of the approach for a description logic with transitive roles and propositional intuitionistic logic.Comment: 32 page

An In Vitro Barrier Model of the Human Submandibular Salivary Gland Epithelium Based on a Single Cell Clone of Cell Line HTB-41: Establishment and Application for Biomarker Transport Studies

The blood–saliva barrier (BSB) consists of the sum of the epithelial cell layers of the oral mucosa and salivary glands. In vitro models of the BSB are inevitable to investigate and understand the transport of salivary biomarkers from blood to saliva. Up to now, standardized, cell line-based models of the epithelium of the submandibular salivary gland are still missing for this purpose. Therefore, we established epithelial barrier models of the submandibular gland derived from human cell line HTB-41 (A-253). Single clone isolation resulted in five different clones (B2, B4, B9, D3, and F11). Clones were compared to the parental cell line HTB-41 using measurements of the transepithelial electrical resistance (TEER), paracellular marker permeability assays and analysis of marker expression for acinar, ductal, and myoepithelial cells. Two clones (B9, D3) were characterized to be of acinar origin, one clone (F11) to be of myoepithelial origin and one isolation (B4) derived from two cells, to be presumably a mixture of acinar and ductal origin. Clone B2, presumably of ductal origin, showed a significantly higher paracellular barrier compared to other clones and parental HTB-41. The distinct molecular identity of clone B2 was confirmed by immunofluorescent staining, qPCR, and flow cytometry. Experiments with ferritin, a biomarker for iron storage, demonstrated the applicability of the selected model based on clone B2 for transport studies. In conclusion, five different clones originating from the submandibular gland cell line HTB-41 were successfully characterized and established as epithelial barrier models. Studies with the model based on the tightest clone B2 confirmed its suitability for transport studies in biomarker research