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Differential reprogramming of somatic cell nuclei after transfer into mouse cleavage stage blastomeres

Mammalian somatic cell cloning requires factors specific to the oocyte for reprogramming to succeed. This does not exclude that reprogramming continues during the zygote and cleavage stages. The capacity or role of zygotic and cleavage stages to reprogram somatic cell nuclei is difficult to assess due to the limited development of somatic cell nuclei transplanted into cytoplasts of these stages. Alternatively, tetraploid embryos have been used to study reprogramming and can be assessed for their contribution to extra-embryonic lineages. When mouse cumulus cell nuclei transgenic for Oct4-green fluorescent protein (GFP) were injected into intact two- and four-cell stage blastomeres, manipulated embryos developed into blastocysts with expression of Oct4-GFP as observed in embryos produced by nuclear transfer into metaphase II oocytes. However, only the latter contributed to extra-embryonic tissues in day 10.5 conceptuses, with the exclusion of the somatic genome in cells originating from transfer into blastomeres already at 5.5 days post conception. Somatic nuclei transferred into cleavage stage blastomeres reinitiated expression of an embyronic-specific transgene, but lacked the extent of reprogramming required for contribution to postimplantation development, even when complemented by an embryonic genome.     

Nonisothermal thermophysical evaluation of polypropylene/natural rubber based TPEs: Effect of blend ratio and dynamic vulcanization

Ozawa macrokinetic model is applied to describe the nonisothermal melt crystallization process of polypropylene (PP), in natural rubber/polypropylene (NR/PP) thermoplastic elastomers (TPEs) as a function of blend ratio and dynamic vulcanization of the rubber phase. It was found that as cooling rate increases, the crystallization temperature T_c and half time for crystallization t_1/2 get diminished. Dynamic vulcanizates show a similar trend in crystallization as that of neat PP. Crystallization rate constant and Ozawa exponent were found out for different temperatures by linear regression method using Ozawa analysis. Ozawa exponent, n_O, showed variation in values when the conversion proceeded. For neat PP, the value of n_O changes from 1.4 (102°C) to 3 (112°C). The n_O values for NR/PP 50/50 blend were higher (e.g. 4.1 at 116°C). Crystallization rate constant K_O shows a maximum at 0.5 relative crystallinity. The highest crystallization rate constants were found for NR/PP 50/50 TPEs. The activation energy for the melt crystallization was found to vary with the degree of conversion, as well as with the concentration of NR in the TPEs. Finally, attempts have been made to correlate the crystallization process with morphology of the blend. POLYM. ENG. SCI., 2009. © 2009 Society of Plastics Engineers     

Short-term maternal psychological stress in the post-conception period in ewes affects fetal growth and gestation length

Fetal development can be influenced by maternal environment in the peri-conceptional period. This study investigated the effect of maternal feed intake and psychological stress within the first 6 days after conception on embryo development and fetal growth. Superovulated ewes (n=40) were artificially inseminated with semen from one ram. Ewes were then divided into four groups (n=10): group 1 (control) was fed at maintenance level, group 2 (high) at 2x maintenance, and group 3 (low) at 0.5x maintenance on days 2-6 after conception. Group 4 (stress) was fed at maintenance level and then an intense physical and psychological stress challenge was applied for 1 h only on days 2 and 3 after conception. Embryos were recovered at day 6. A total of 113 transferable grade embryos were transferred singly into synchronized untreated recipients, while the remaining embryos (n=165) were fixed and stained for cell counts. Post-conception maternal stress or feed intake did not alter the cell count or grade of day 6 embryos. Fetuses from the stress group had longer crown-rump lengths at day 30 and longer femur length at day 58. Fetuses from the stressed and high feed groups had greater abdominal circumferences at day 85. Subsequent birth weights were not significantly different. Ewes carrying lambs from the stress treatment had shorter gestation lengths. These results show that short-term perturbations of the post-conception maternal environment have measurable effects on fetal development and gestation length.     

Novel BQCA- and TBPB-Derived M1 Receptor Hybrid Ligands: Orthosteric Carbachol Differentially Regulates Partial Agonism

Recently, investigations of the complex mechanisms of allostery have led to a deeper understanding of G protein-coupled receptor (GPCR) activation and signaling processes. In this context, muscarinic acetylcholine receptors (mAChRs) are highly relevant due to their exemplary role in the study of allosteric modulation. In this work, we compare and discuss two sets of putatively dualsteric ligands, which were designed to connect carbachol to different types of allosteric ligands. We chose derivatives of TBPB [1-(1′-(2-tolyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one] as M₁-selective putative bitopic ligands, and derivatives of benzyl quinolone carboxylic acid (BQCA) as an M₁ positive allosteric modulator, varying the distance between the allosteric and orthosteric building blocks. Luciferase protein complementation assays demonstrated that linker length must be carefully chosen to yield either agonist or antagonist behavior. These findings may help to design biased signaling and/or different extents of efficacy.     

Optimization of rhein-loaded polymeric nanoparticles using a factorial design and evaluation of the cytotoxic and anti-inflammatory effects

The aim of the work was to develop rhein loaded polymeric nanoparticles (R-PNPs). Nanoparticles were prepared by three methods, solvent emulsion-evaporation, double emulsion, and nanoprecipitation, by means of experimental design. Additionally, the effects of the best formulation on in vitro cytotoxicity and inflammation were evaluated. The solvent emulsion-evaporation method presented the highest encapsulation efficiency of the three techniques (38.41%), as well as had a mean diameter of 189.33?nm and a polydispersity index of less than 0.1. Despite efforts to optimize the encapsulation of rhein, the drug release from nanoparticles was close to 50% during the first 5?min, followed by a continuous release within 60?min. It was observed that macrophages exposed to the highest concentration of R-PNPs showed cell viability about 80% and at the lowest nanoparticle concentrations was closed to 100%. IL-1β in cell culture supernatants was decreased in the presence of R-PNPs and TNFα concentrations were lower than the sensitivity of the assay. ROS production was only inhibited with R-PNPs at concentrations of 2.5 and 5?μM. In conclusion, the solvent emulsion-evaporation was the best method evaluated to obtain nanoparticles with the desired specifications. It was possible to assess R-PNPs with low cytotoxicity and anti-inflammatory properties showed by the inhibition of IL-1β production and a low decrease in ROS production.     

On optical data-guided optimal control simulations of human motion

Multibody System Dynamics - This work addresses the synergistic fusion of optimal control simulations and marker-based optical measurements of human motion. The latter is a widespread capturing...     

10 Years of research on debugging concurrent and multicore software: a systematic mapping study

Debugging—the process of identifying, localizing and fixing bugs—is a key activity in software development. Due to issues such as non-determinism and difficulties of reproducing failures, debugging concurrent software is significantly more challenging than debugging sequential software. A number of methods, models and tools for debugging concurrent and multicore software have been proposed, but the body of work partially lacks a common terminology and a more recent view of the problems to solve. This suggests the need for a classification, and an up-to-date comprehensive overview of the area. This paper presents the results of a systematic mapping study in the field of debugging of concurrent and multicore software in the last decade (2005–2014). The study is guided by two objectives: (1) to summarize the recent publication trends and (2) to clarify current research gaps in the field. Through a multi-stage selection process, we identified 145 relevant papers. Based on these, we summarize the publication trend in the field by showing distribution of publications with respect to year, publication venues, representation of academia and industry, and active research institutes. We also identify research gaps in the field based on attributes such as types of concurrency bugs, types of debugging processes, types of research and research contributions. The main observations from the study are that during the years 2005–2014: (1) there is no focal conference or venue to publish papers in this area; hence, a large variety of conferences and journal venues (90) are used to publish relevant papers in this area; (2) in terms of publication contribution, academia was more active in this area than industry; (3) most publications in the field address the data race bug; (4) bug identification is the most common stage of debugging addressed by articles in the period; (5) there are six types of research approaches found, with solution proposals being the most common one; and (6) the published papers essentially focus on four different types of contributions, with “methods” being the most common type. We can further conclude that there are still quite a number of aspects that are not sufficiently covered in the field, most notably including (1) exploring correction and fixing bugs in terms of debugging process; (2) order violation, suspension and starvation in terms of concurrency bugs; (3) validation and evaluation research in the matter of research type; (4) metric in terms of research contribution. It is clear that the concurrent, parallel and multicore software community needs broader studies in debugging. This systematic mapping study can help direct such efforts.