A hydrothermal route for production of dense, nanostructured Y-TZP

Y-TZP powders were prepared either by calcination in air or crystallization under hydrothermal conditions of a hydrous gel, obtained by coprecipitation. Differences in powder properties, green compact structure and sinterability were examined. Crystallization under hydrothermal conditions occurs at temperatures as low as 190°C in the presence of ammonia. The hydrothermally treated powders are composed of soft agglomerates, that collapse under very low pressures, resulting in green bodies with high densities and small pore radii. The sinterability is greatly improved by the hydrothermal treatment and allowed the production of dense, nanostructured Y-TZP by free sintering at 1050°C

Characterization of Grain Boundaries in Superplastically Deformed Y-TZP Ceramics

The effects of compressive deformation on the grain boundary characteristics of fine-grained Y-TZP have been investigated using surface spectroscopy, impedance analysis, and transmission electron microscopy. After sintering at low temperature (1150°C), the grain boundaries are covered by an ultrathin (1nm) yttrium-rich amorphous film. After deformation at 1200°–1300°C under low stress, some grain boundaries are no longer covered by the amorphous film. Yttrium segregation seems to occur only at wetted grain boundaries. Evidence has been found that the extent of dewetting increases with increasing applied stress

Plasticity of nanocrystalline zirconia ceramics and composites

The deformation strain rate of nanocrystalline Y-TZP shows an increase by a factor 4 if the grain size decreases from 200 to 100 nm. Real superplastic deformation (strain rate > 10−4 s−1) is observed in these materials at relative low temperature (1100–1200 °C). Grain-boundary analysis indicates (partial) removal of an ultra-thin (1 nm), yttrium-rich grain boundary layer after deformation.\ud \ud Uniaxial pressure-assisted sintering techniques (=sinter-forging) provide the opportunity of large shear strains during densification. Sinter-forging experiments on zirconia-toughened alumina (15 wt% ZrO2/85 wt% Al2O3) resulted in a dense composite within 15 min at 1400 °C and 40 MPa, with effective shear strains up to 100%. Sinter-forging of Y-TZP and ZTA gives an increase in strength, reliability and fracture toughness. These improvements are caused by the large shear strains that result from the removal of processing flaws. Also, the number of microcraks at the grain boundaries and the interatomic spacing between the grains are reduced by the forging techniques, resulting in a strengthening of the grain boundaries if compared with pressureless sintering. K1C values of 10 MPa√m are obtained for Y-TZP, while no classical stress-induced phase transformation toughening is observed. Sinter-forged ZTA samples showed a better wear resistance than free sintered ones.\u

The effect of ceria co-doping on chemical stability and fracture toughness of Y-TZP

The fracture toughness and ageing resistance of yttria, ceria-stabilized tetragonal zirconia polycrystals (Y, Ce-TZP) were evaluated as a function of grain size and ceria content. Very fine grained, fully dense materials could be produced by sinter forging at relatively low temperatures (1150–1200 °C). The ageing resistance in hot water (185 °C) of 2 mol% Y2O3-stabilized TZP is strongly enhanced by alloying with ceria. The ceria content necessary to avoid degradation completely, decreases with grain size. The toughness of fully dense Y, Ce-TZP is 7–9 MPa m1/2 for grain sizes down to 0.2 mgrm. No or very little transformation took place during fracturing and no clear variation with grain size was observed for the toughness at grain sizes up to 0.8 mgrm. Reversible transformation and crack deflection may explain the observed toughness values

Detained introns are a novel, widespread class of post-transcriptionally spliced introns

Deep sequencing of embryonic stem cell RNA revealed many specific internal introns that are significantly more abundant than the other introns within polyadenylated transcripts; we classified these as “detained” introns (DIs). We identified thousands of DIs, many of which are evolutionarily conserved, in human and mouse cell lines as well as the adult mouse liver. DIs can have half-lives of over an hour yet remain in the nucleus and are not subject to nonsense-mediated decay (NMD). Drug inhibition of Clk, a stress-responsive kinase, triggered rapid splicing changes for a specific subset of DIs; half showed increased splicing, and half showed increased intron detention, altering transcript pools of >300 genes. Srsf4, which undergoes a dramatic phosphorylation shift in response to Clk kinase inhibition, regulates the splicing of some DIs, particularly in genes encoding RNA processing and splicing factors. The splicing of some DIs—including those in Mdm4, a negative regulator of p53—was also altered following DNA damage. After 4 h of Clk inhibition, the expression of >400 genes changed significantly, and almost one-third of these are p53 transcriptional targets. These data suggest a widespread mechanism by which the rate of splicing of DIs contributes to the level of gene expression.National Institutes of Health (U.S.) (Grant R01 GM34277-23)American Cancer Society (Novartis Institutes of Biomedical Research Postdoctoral Research Fellowship)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051

Rbfox2 controls autoregulation in RNA-binding protein networks

The tight regulation of splicing networks is critical for organismal development. To maintain robust splicing patterns, many splicing factors autoregulate their expression through alternative splicing-coupled nonsense-mediated decay (AS-NMD). However, as negative autoregulation results in a self-limiting window of splicing factor expression, it is unknown how variations in steady-state protein levels can arise in different physiological contexts. Here, we demonstrate that Rbfox2 cross-regulates AS-NMD events within RNA-binding proteins to alter their expression. Using individual nucleotide-resolution cross-linking immunoprecipitation coupled to high-throughput sequencing (iCLIP) and mRNA sequencing, we identified >200 AS-NMD splicing events that are bound by Rbfox2 in mouse embryonic stem cells. These “silent” events are characterized by minimal apparent splicing changes but appreciable changes in gene expression upon Rbfox2 knockdown due to degradation of the NMD-inducing isoform. Nearly 70 of these AS-NMD events fall within genes encoding RNA-binding proteins, many of which are autoregulated. As with the coding splicing events that we found to be regulated by Rbfox2, silent splicing events are evolutionarily conserved and frequently contain the Rbfox2 consensus UGCAUG. Our findings uncover an unexpectedly broad and multilayer regulatory network controlled by Rbfox2 and offer an explanation for how autoregulatory splicing networks are tuned.United States. Public Health Service (RO1-GM34277)National Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant CA112967)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)David H. Koch Graduate Fellowshi

Proteomic identification of antibodies

Methods and compositions for identification of candidate antigen-specific variable regions as well as generation of antibodies or antigen-binding fragments that could have desired antigen specificity are provided. For example, in certain aspects, methods for determining amino acid sequences of serum antibody CDR3 and abundancy levels are described. In some aspects, methods for determining nucleic acid sequences of antibody variable region sequences and the frequency thereof in biological samples are provided. Furthermore, the invention provides methods for identification and generation of antibodies or antigen-binding fragments that comprise highly-represented CDR domains.Board of Regents, University of Texas Syste

A prosodic perspective on the assignment of tonal melodies to Arabic loanwords in Bambara

There is a rich descriptive history on Bambara tonology in the published literature (e.g. Bird 1966; Courtenay 1974; Creissels 1978, 1988, 1992; Diarra 1976; Dumestre 1987; Dwyer 1976). Despite the existence of several seminal works on the subject, certain details of the language’s tonal system remain unclear. Scholars have developed deep knowledge about the lexical and grammatical functions of Bambara tone, yet the dependency of tones and tonal processes on prosodic structure has only more recently been explored in detail (Green 2013, 2015; Leben 2002, 2003; Weidman and Rose 2006; Vydrine 2002, 2010). In this paper, we aim to contribute to this ongoing trend by considering a role played by prosodic structure in one particular set of Arabic borrowings for which the assignment of tonal melodies differs from that found in words of non-Arabic origin. We explore possible explanations for this divergence that relate to contemporary scholarship on the properties of Bambara’s prosodic structure. Our point of view on this subject differs from earlier analyses (e.g., Dumestre 1987) in that we propose that prosodic structure plays an important role in the assignment of Bambara tonal melodies. Finally, we relate our findings to a taxonomic model of loanword prosody in Davis et al. (2012) and consider the bearing that our findings may have on the typology of Bambara prosodic structure alongside other Mande languages.Il existe une riche histoire descriptive sur la tonologie du bambara dans la littérature publiée (par exemple Bird 1966, Courtenay 1974, Creissels 1978, 1988, 1992, Diarra 1976, Dumestre 1987, Dwyer 1976). Malgré l'existence de plusieurs travaux séminaires sur ce sujet, certains détails du système tonal de la langue demeurent obscurs. Les chercheurs ont développé une connaissance approfondie des fonctions lexicales et grammaticales du ton en bambara, mais la dépendance des tonalités et des processus tonals sur la structure prosodique n'a été étudiée que plus récemment (Green 2013, 2015, Weiden et Rose, 2006; Vydrine 2002, 2010). Dans cet article, nous cherchons à contribuer à cette tendance en considérant le rôle joué par la structure prosodique dans un ensemble particulier d'emprunts arabes pour lesquels l'attribution de mélodies tonales diffère de celle trouvée dans des mots d'origine non arabe. Nous explorons les explications possibles de cette divergence qui se rapportent à l'érudition contemporaine sur les propriétés de la structure prosodique du bambara. Notre point de vue sur ce sujet diffère des analyses antérieures (par exemple, Dumestre 1987) en ce que nous proposons que la structure prosodique joue un rôle important dans l'attribution de mélodies tonales en bambara. Enfin, nous relions nos découvertes à un modèle taxonomique de prosodie d’emprunts dans Davis et al. (2012) et considérons la portée que nos résultats peuvent avoir sur la typologie de la structure prosodique du bambara aux côtés d’autres langues mandées.Описанию тонологии бамана посвящена богатая литература (в частности, Bird 1966; Courtenay 1974; Creissels 1978, 1988, 1992; Diarra 1976; Dumestre 1987; Dwyer 1976). Имеющиеся публикации освещают ключевые вопросы в этой области, однако некоторые детали баманской тонологии всё же остаются неясными. Исследователи уделили много внимания лексическим и грамматическим функциям баманского тона, однако зависимость тонов и тональных процессов от просодической структуры была рассмотрена в деталях лишь недавно (Green 2013, 2015; Leben 2002, 2003; Weidman and Rose 2006; Vydrine 2002, 2010). Эта статья имеет целью укрепить это направление, проанализировав роль просодической структуры на конкретной выборке, а именно, на арабских заимствованиях, приписывание которым тоновых контуров подчиняется особым правилам. Рассматриваются различные объяснения таких различий, связанных с современными взглядами на особенности просодической структуры бамана. Наша точка зрения по этому вопросу отличается от позиций предшественников (см., в частности, Dumestre 1987), поскольку мы считаем, что в языке бамана просодическая структура играет важную роль в приписывании тональных контуров. Наконец, мы связываем наши результаты с таксономической моделью просодии заимствований в (Davis et al. 2012) и высказываем предположения о последствиях, которые эти результаты могут иметь для тонологии баманской просодической структуры, а также таковой в других языках манде

A map of human protein interactions derived from co-expression of human mRNAs and their orthologs

The human protein interaction network will offer global insights into the molecular organization of cells and provide a framework for modeling human disease, but the network's large scale demands new approaches. We report a set of 7000 physical associations among human proteins inferred from indirect evidence: the comparison of human mRNA co-expression patterns with those of orthologous genes in five other eukaryotes, which we demonstrate identifies proteins in the same physical complexes. To evaluate the accuracy of the predicted physical associations, we apply quantitative mass spectrometry shotgun proteomics to measure elution profiles of 3013 human proteins during native biochemical fractionation, demonstrating systematically that putative interaction partners tend to co-sediment. We further validate uncharacterized proteins implicated by the associations in ribosome biogenesis, including WBSCR20C, associated with Williams–Beuren syndrome. This meta-analysis therefore exploits non-protein-based data, but successfully predicts associations, including 5589 novel human physical protein associations, with measured accuracies of 54±10%, comparable to direct large-scale interaction assays. The new associations' derivation from conserved in vivo phenomena argues strongly for their biological relevance

Enter exitrons

Staiger D, Simpson GG. Enter exitrons. Genome Biology. 2015;16(1): 136.Exitrons are exon-like introns located within protein-coding exons. Removal or retention of exitrons through alternative splicing increases proteome complexity and thus adds to phenotypic diversity