Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Influence of Process Parameters on the Morphology of Spray‐Dried BaCl2 Powders

Spray‐drying is an effective method for producing powder aggregates with controlled size and morphology. Here, we report on a systematic study aimed at determining how spray‐drying parameters such as nozzle temperature, gas flow, salt concentration and solution feed rate, influence the characteristics of BaCl₂ granules prepared from aqueous solutions. We correlate the granule characteristics to these conditions through the use of processing maps and modeling. It is found that well‐dispersed, high density and spherical aggregates, which are favorable for subsequent powder compaction and sintering, can be obtained within a limited range of processing conditions.     

Sol–Gel-Prepared Pure and Lithium-Doped Hexacelsian Polymorphs: An Infrared, Raman, and Thermal Expansion Study of the β-Phase Stabilization by Frozen Short-Range Disorder

Monoclinic and hexagonal forms of celsians (BaAl₂Si₂O₈) were synthesized by hydrolysis–polycondensation of Si/Al alkoxide mixtures. Dilatometry, Raman scattering, IR absorption, and X-ray diffraction techniques were used to identify various hexacelsian phases and their conversion into the monoclinic phase as a function of thermal treatments and doping. Emphasis is given to the relationship between the shrinkage behavior and the static and dynamic short-range disorders in the XO₄ tetrahedra (X = Si/Al) arrangement. The α hexagonal phase exhibits a well-defined α–β_HT transition at about 300°C but a statically disorderedβ_SD form, which does not vary very much with temperature and is very similar to the β_HT form obtained below 300°C for some materials. This statically disordered phase is preferentially observed for fast-sintered lithium-free compositions and transforms gradually in the ordered form by annealing above 1100°C. Such stabilization of the high-temperature phase by the static disorder arising from the peculiar synthesis through alkoxide hydrolysis and the gel route, which freeze the dynamic disorder of gel-forming entities in a static disorder at the gelation step, is discussed in the light of previously observed cases. The thermal expansion behavior is very sensitive to the synthesis conditions, doping, and thermal treatments. The ordered α phase is more easily achieved with lithium-doped compositions, but lithium addition shifts the hexagonal-to-monoclinic phase transformation onset toward lower temperatures and promotes complete transformation with thermal annealing.     

Enzymatic hydrolysis of canola oil with hydrodynamic cavitation

A hydrodynamic cavitation system based on a venturi was used to test the effectiveness of cavitation for enhancing the enzymatic hydrolysis of canola oil using lipase from Candida rugosa. Cavitation led to the production of fine oil-in-water and water-in-oil emulsions with the enzyme in the water phase. Using venturi inlet pressures of up to 8 bar, the yield of fatty acids was only about 60% of the maximum possible. In contrast, a simple stirred batch reactor produced over 90% of the maximum possible yield with reaction rates equal to, or better than, those obtained in a cavitating system. It was concluded that cavitation inhibited the reaction in some way and is not effective for intensification of hydrolysis.     

Influence of the filler type on the rupture behavior of filled elastomers

This work is devoted to the rupture behavior of elastomers filled with carbon black (CB) or silica. Two elastomers have been studied: one which crystallizes under strain, natural rubber (NR), and another one which does not crystallize, styrene butadiene rubber (SBR). The study of the crack propagation of Single Edge Notched specimen (SENT) during stretching at different speeds focuses on the crack initiation and crack deviation phenomenon. This deviation is of main importance in the materials crack resistance as it leads to a large increase in the energy needed for rupture. The deviation in filled or unfilled NR is controlled by crystallization, which is a slow process. In unfilled SBR, deviation is controlled by polymer chain orientation, which is hindered by relaxation mechanisms. The introduction of fillers promotes strain amplification, and strain anisotropy in the crack tip region of the notched samples, and therefore crack deviation. In term of energy density at break of the SBR composites, the SBR filled with silica treated with a covering agent is the most efficient. Thus, a weak interface between the silica and SBR promotes better rupture properties. When comparing Silica and CB filled NR, the highest strain energy to rupture is also obtained with silica. This might be due to the weaker filler‐matrix interface for silica. Thus, these results evidence the kinetic aspect of the rupture, and of the mechanisms it involves: the polymer relaxation, the crystallization (for NR), and the filler‐matrix interaction and decohesion, all of them being strongly interrelated. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Endothelial Colony-Forming Cells Dysfunctions Are Associated with Arterial Hypertension in a Rat Model of Intrauterine Growth Restriction

Infants born after intrauterine growth restriction (IUGR) are at risk of developing arterial hypertension at adulthood. The endothelium plays a major role in the pathogenesis of hypertension. Endothelial colony-forming cells (ECFCs), critical circulating components of the endothelium, are involved in vasculo-and angiogenesis and in endothelium repair. We previously described impaired functionality of ECFCs in cord blood of low-birth-weight newborns. However, whether early ECFC alterations persist thereafter and could be associated with hypertension in individuals born after IUGR remains unknown. A rat model of IUGR was induced by a maternal low-protein diet during gestation versus a control (CTRL) diet. In six-month-old offspring, only IUGR males have increased systolic blood pressure (tail-cuff plethysmography) and microvascular rarefaction (immunofluorescence). ECFCs isolated from bone marrow of IUGR versus CTRL males displayed a decreased proportion of CD31+ versus CD146+ staining on CD45− cells, CD34 expression (flow cytometry, immunofluorescence), reduced proliferation (BrdU incorporation), and an impaired capacity to form capillary-like structures (Matrigel test), associated with an impaired angiogenic profile (immunofluorescence). These dysfunctions were associated with oxidative stress (increased superoxide anion levels (fluorescent dye), decreased superoxide dismutase protein expression, increased DNA damage (immunofluorescence), and stress-induced premature senescence (SIPS; increased beta-galactosidase activity, increased p16^INK4a, and decreased sirtuin-1 protein expression). This study demonstrated an impaired functionality of ECFCs at adulthood associated with arterial hypertension in individuals born after IUGR.     

Novel TTLL5 Variants Associated with Cone-Rod Dystrophy and Early-Onset Severe Retinal Dystrophy

Variants of the TTLL5 gene, which encodes tubulin tyrosine ligase-like family member five, are a rare cause of cone dystrophy (COD) or cone-rod dystrophy (CORD). To date, only a few TTLL5 patients have been clinically and genetically described. In this study, we report five patients harbouring biallelic variants of TTLL5. Four adult patients presented either COD or CORD with onset in the late teenage years. The youngest patient had a phenotype of early onset severe retinal dystrophy (EOSRD). Genetic analysis was performed by targeted next generation sequencing of gene panels and assessment of copy number variants (CNV). We identified eight variants, of which six were novel, including two large multiexon deletions in patients with COD or CORD, while the EOSRD patient harboured the novel homozygous p.(Trp640*) variant and three distinct USH2A variants, which might explain the observed rod involvement. Our study highlights the role of TTLL5 in COD/CORD and the importance of large deletions. These findings suggest that COD or CORD patients lacking variants in known genes may harbour CNVs to be discovered in TTLL5, previously undetected by classical sequencing methods. In addition, variable phenotypes in TTLL5-associated patients might be due to the presence of additional gene defects.     

An analytic method to predict the thermal map of cryosurgery iceballs in MR images

This paper presents a newly developed method to estimate, in magnetic resonance (MR) images, the temperatures reached within the volume of an iceball produced by a cryogenic probe. Building on the direct measurements of the MR signal intensity and its correlation with independent temperature variations at the phase transition from liquid to solid, the thermal information embedded in the images was accessed. The volume and diameter of the growing iceball were estimated from a time series of MR images. Using regressions over the volume in the time and thermal domains, this method predicted the cryogenic temperatures beyond the range of sensitivity of the MR signal itself. We present a validation of this method in samples of gelatin and ex vivo pig liver. Temperature predictions are shown to agree with independent thermosensor readings over a range extending from 20 degrees C down to -65 degrees C, with an average error of less than 6 degrees C.     

Did Frege Believe Frege's Principle?

In this essay I will consider two theses that are associated with Frege,and will investigate the extent to which Frege really believed them.Much of what I have to say will come as no surprise to scholars of thehistorical Frege. But Frege is not only a historical figure; he alsooccupies a site on the philosophical landscape that has allowed hisdoctrines to seep into the subconscious water table. And scholars in a widevariety of different scholarly establishments then sip from thesedoctrines. I believe that some Frege-interested philosophers at various ofthese establishments might find my conclusions surprising.Some of these philosophical establishments have arisen from an educationalmilieu in which Frege is associated with some specific doctrine at theexpense of not even being aware of other milieux where other specificdoctrines are given sole prominence. The two theses which I will discussillustrate this point. Each of them is called Frege's Principle, but byphilosophers from different milieux. By calling them milieux I do not want to convey the idea that they are each located at some specificsocio-politico-geographico-temporal location. Rather, it is a matter oftheir each being located at different places on the intellectuallandscape. For this reason one might (and I sometimes will) call them(interpretative) traditions.     

Verification of RANS solvers with manufactured solutions

This paper discusses code verification of Reynolds-Averaged Navier Stokes (RANS) solvers with the method of manufactured solutions (MMS). Examples of manufactured solutions (MSs) for a two-dimensional, steady, wall-bounded, incompressible, turbulent flow are presented including the specification of the turbulence quantities incorporated in several popular eddy-viscosity turbulence models. A wall-function approach for the MMS is also described. The flexiblity and usefulness of the MS is illustrated with calculations performed in three different exercises: the calculation of the flow field using the manufactured eddy-viscosity; the calculation of the eddy-viscosity using the manufactured velocity field; the calculation of the complete flow field coupling flow and turbulence variables. The results show that the numerical performance of the flow solvers is model dependent and that the solution of the complete problem may exhibit different orders of accuracy than in the exercises with no coupling between the flow and turbulence variables.