Exotic polarizations of D2 branes and oblique vacua of (S)YM2+1_{2+1}

We investigate the oblique vacua in the perturbed 2+1 dimensional gauge theory living on D2 branes. The string theory dual of these vacua is expected to correspond to polarizations of the D2 branes into NS5 branes with D4 brane charge. We perturb the gauge theory by adding fermions masses. In the nonsupersymmetric case, we also consider the effect of slight variations of the masses of the scalars. For certain ranges of scalar masses we find oblique vacua. We show that D4 charge is an essential ingredient in understanding D2 -> NS5 polarizations. We find that some of the polarization states which appear as metastable vacua when D4 charge is not considered are in fact unstable. They decay by acquiring D4 charge, tilting and shrinking to zero size.Comment: 15 pages, 3 figures, LaTe

Readthrough of nonsense mutations in Rett syndrome: evaluation of novel aminoglycosides and generation of a new mouse model

Thirty-five percent of patients with Rett syndrome carry nonsense mutations in the MECP2 gene. We have recently shown in transfected HeLa cells that readthrough of nonsense mutations in the MECP2 gene can be achieved by treatment with gentamicin and geneticin. This study was performed to test if readthrough can also be achieved in cells endogenously expressing mutant MeCP2 and to evaluate potentially more effective readthrough compounds. A mouse model was generated carrying the R168X mutation in the MECP2 gene. Transfected HeLa cells expressing mutated MeCP2 fusion proteins and mouse ear fibroblasts isolated from the new mouse model were treated with gentamicin and the novel aminoglycosides NB30, NB54, and NB84. The localization of the readthrough product was tested by immunofluorescence. Readthrough of the R168X mutation in mouse ear fibroblasts using gentamicin was detected but at lower level than in HeLa cells. As expected, the readthrough product, full-length Mecp2 protein, was located in the nucleus. NB54 and NB84 induced readthrough more effectively than gentamicin, while NB30 was less effective. Readthrough of nonsense mutations can be achieved not only in transfected HeLa cells but also in fibroblasts of the newly generated Mecp2R168X mouse model. NB54 and NB84 were more effective than gentamicin and are therefore promising candidates for readthrough therapy in Rett syndrome patients

Perioperative changes in intraabdominal pressure during abdominoplasty

A prospective clinical study of aesthetic abdominoplasty effect on perioperative changes in intraabdominal pressure was performed in 50 patients. The changes in intraabdominal pressure intraoperatively and postoperatively were examined. Abdominoplasty was found to be associated with an increase of intraabdominal pressure with the development of intraabdominal hypertension in some cases. To predict the likelihood of intraabdominal hypertension postoperatively one should use the criterion of absolute increase in the peak airway pressure over 4 cm H20 during intraoperative ventillation.Проспективное клиническое исследование по изучению влияния абдоминопластики, выполненной по эстетическим показаниям, на изменение параметров внутрибрюшного давления проведено у 50 пациентов. Изучено изменение величины внутрибрюшного давления на этапах операции и в послеоперационном периоде. Установлено, что абдоминопластика сопровождается ростом внутрибрюшного давления с развитием в ряде случаев интраабдоминальной гипертензии. Для прогнозирования вероятности развития интраабдоминальной гипертензии в послеоперационном периоде следует использовать критерий абсолютного прироста пикового давления в дыхательных путях более 4 см вод.ст. при ИВЛ на этапах операции

Algorithm of preoperative examination of breast surgery patients

The review of breast augmentation complications revealed a direct correlation between postoperative complications and elevated prolactin and thyroid-stimulating hormone levels, and the presence of autoimmune thyroiditis. An algorithm of preoperative examination of breast surgery patients has been developed, which allowed us to identify groups of patients at risk and to reduce early and late complication rates of breast augmentation.Анализ осложнений после протезирования молочных желез выявил прямую зависимость послеоперационных осложнений с повышенным уровнем пролактина и тиреотропного гормона, наличием аутоиммунного тиреоидита. Разработан алгоритм обследования пациенток на догоспитальном этапе перед маммопластикой, что позволило формировать группы риска и снизить процент ранних и поздних осложнений после протезирования молочных желез

Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable

miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

Expression of excess receptors and negative feedback control of signal pathways are required for rapid activation and prompt cessation of signal transduction

Cellular signal transduction is initiated by the binding of extracellular ligands to membrane receptors. Receptors are often expressed in excess, and cells are activated when a small number of receptors bind ligands. Intracellular signal proteins are act

A Model for the Ultrastructure of Bone Based on Electron Microscopy of Ion-Milled Sections

The relationship between the mineral component of bone and associated collagen has been a matter of continued dispute. We use transmission electron microscopy (TEM) of cryogenically ion milled sections of fully-mineralized cortical bone to study the spatial and topological relationship between mineral and collagen. We observe that hydroxyapatite (HA) occurs largely as elongated plate-like structures which are external to and oriented parallel to the collagen fibrils. Dark field images suggest that the structures (“mineral structures”) are polycrystalline. They are approximately 5 nm thick, 70 nm wide and several hundred nm long. Using energy-dispersive X-ray analysis we show that approximately 70% of the HA occurs as mineral structures external to the fibrils. The remainder is found constrained to the gap zones. Comparative studies of other species suggest that this structural motif is ubiquitous in all vertebrates

Intermolecular channels direct crystal orientation in mineralized collagen

The mineralized collagen fibril is the basic building block of bone, and is commonly pictured as a parallel array of ultrathin carbonated hydroxyapatite (HAp) platelets distributed throughout the collagen. This orientation is often attributed to an epitaxial relationship between the HAp and collagen molecules inside 2D voids within the fibril. Although recent studies have questioned this model, the structural relationship between the collagen matrix and HAp, and the mechanisms by which collagen directs mineralization remain unclear. Here, we use XRD to reveal that the voids in the collagen are in fact cylindrical pores with diameters of ~2 nm, while electron microscopy shows that the HAp crystals in bone are only uniaxially oriented with respect to the collagen. From in vitro mineralization studies with HAp, CaCO3 and γ-FeOOH we conclude that confinement within these pores, together with the anisotropic growth of HAp, dictates the orientation of HAp crystals within the collagen fibril

Algorithm Portfolios for Noisy Optimization: Compare Solvers Early

International audienceNoisy optimization is the optimization of objective functions corrupted by noise. A portfolio of algorithms is a set of algorithms equipped with an algorithm selection tool for distributing the compu- tational power among them. We study portfolios of noisy optimization solvers, show that different settings lead to dramatically different perfor- mances, obtain mathematically proved adaptivity by an ad hoc selection algorithm dedicated to noisy optimization. A somehow surprising result is that it is better to compare solvers with some lag; i.e., recommend the current recommendation of the best solver, selected from a comparison based on their recommendations earlier in the run