Volume-preserving normal forms of Hopf-zero singularity

A practical method is described for computing the unique generator of the algebra of first integrals associated with a large class of Hopf-zero singularity. The set of all volume-preserving classical normal forms of this singularity is introduced via a Lie algebra description. This is a maximal vector space of classical normal forms with first integral; this is whence our approach works. Systems with a non-zero condition on their quadratic parts are considered. The algebra of all first integrals for any such system has a unique (modulo scalar multiplication) generator. The infinite level volume-preserving parametric normal forms of any non-degenerate perturbation within the Lie algebra of any such system is computed, where it can have rich dynamics. The associated unique generator of the algebra of first integrals are derived. The symmetry group of the infinite level normal forms are also discussed. Some necessary formulas are derived and applied to appropriately modified R\"{o}ssler and generalized Kuramoto--Sivashinsky equations to demonstrate the applicability of our theoretical results. An approach (introduced by Iooss and Lombardi) is applied to find an optimal truncation for the first level normal forms of these examples with exponentially small remainders. The numerically suggested radius of convergence (for the first integral) associated with a hypernormalization step is discussed for the truncated first level normal forms of the examples. This is achieved by an efficient implementation of the results using Maple

Nucleotide Polymorphisms in the Canine Noggin Gene and Their Distribution Among Dog (Canis lupus familiaris) Breeds

Noggin (NOG) is an important regulator for the signaling of bone morphogenetic proteins. In this study, we sequenced the complete coding sequence of the canine NOG gene and characterized the nucleotide polymorphisms. The sequence length varied from 717 to 729 bp, depending on the number of a 6-bp tandem repeat unit (GGCGCG), an insertion that has not been observed in other mammalian NOG genes investigated to date. It results in extensions of (Gly–Ala)3–5 in the putative NOG protein. To survey the distribution of these tandem repeat polymorphisms, we analyzed 126 individuals in seven dog breeds. We identified only three alleles: (GGCGCG)3, (GGCGCG)4, and (GGCGCG)5. Although the allele frequencies were remarkably different among the breeds, the three alleles were present in all seven of the breeds and did not show any deviation from Hardy–Weinberg equilibrium

Características tecnológicas de almidones de dos variedades de batatas (Ipomoea batatas [L.] Lam) infectadas con «encrespamiento amarillo»

El cultivo de batata se ve limitado por virosis y un complejo de siete virus, «encrespamiento amarillo» (EA), de alta incidencia en Argentina, provoca significativas disminuciones de rendimiento y calidad. En un ensayo experimental, con variedades Arapey INIA y Beauregard (sanas y enfermas con EA), se estimaron componentes de rendimiento (principalmente peso: PRC y número: NRC de raíces comerciales), rendimiento y característicastecnológicas de almidón como gelatinización y retrogradación (calorimetría diferencial de barrido) y viscosidad aparente de las pastas (analizador de viscosidad). Se analizó el comportamiento reológico de los geles de almidón, mediante resistencia a la compresión con analizador de textura, y se determinó distribución de tamaño de partícula. NRC y PRC fueron significativamente menores en plantas enfermas respecto a sanas (mermas de 81% para NRC en ambas variedades y 87% y 85,5% para PRC, en Beauregard y Arapey, respectivamente). EA no afectó al rendimiento de almidón, sin diferencias entre raíces sanas y enfermas de ambas variedades, aunque Arapey (9,00-10,05%) superó a Beauregard (6,23-8,06%). La entalpía de gelatinización del almidón resultó significativamente mayor en plantas enfermas de Beauregard que en sanas, sin diferencias en la temperatura de inicio de gelatinización entre ambos tratamientos, contrariamente a lo que sucedió en Arapey. El pico de viscosidad y la viscosidad final de los almidones fueron similares en plantas sanas y enfermas de ambas variedades, igual que la resistencia a la compresión de geles elaborados con almidones provenientes de plantas sanas y enfermas de ambos genotipos. Todas las muestras tuvieron una sola población de tamaño de partícula de almidón (rango: 5 -25 μm con pico cercano a 15 μm). En definitiva, EA no afectó la calidad tecnológica del almidón. Sin embargo, la disminución significativa de producción de raíces comerciales en plantas enfermas conllevó relevante reducción de la cantidad total de almidón por planta

The first biosimilar approved for the treatment of osteoporosis

To demonstrate the clinical comparability between RGB-10 (a biosimilar teriparatide) and the originator, a comparative pharmacokinetic trial was conducted. The study was successful in establishing bioequivalence. Marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency in 2017.Teriparatide, the first bone anabolic agent, is the biologically active fragment of human parathyroid hormone. The imminent patent expiry of the originator will open the door for biosimilars to enter the osteology market, thereby improving access to a highly effective, yet prohibitively expensive therapy.Subsequent to establishing comparability on the quality and non-clinical levels between RGB-10, a biosimilar teriparatide, and its reference product (Forsteo®), a randomised, double-blind, 2-way cross-over comparative study (duration: four days) was conducted in 54 healthy women (ages: 18 to 55 years) to demonstrate the pharmacokinetic/pharmacodynamic (PK/PD) equivalence and comparable safety of these products. Extents of exposure (AUC0-tlast) and peak exposure (Cmax), as measured by means of ELISA, were evaluated as co-primary PK endpoints, and serum calcium levels, as measured using standard automated techniques, were assessed for PD effects. Safety was monitored throughout the study.The 94.12% CIs for the ratio of the test to the reference treatments, used due to the two-stage design (85.20-98.60% and 85.51-99.52% for AUC0-tlast and Cmax, respectively), fell within the 80.00-125.00% acceptance range. The calcium PD parameters were essentially identical with geometric mean ratios (GMRs) of 99.93% and 99.87% for AUC and Cmax, respectively. Analysis of the safety data did not reveal any differences between RGB-10 and its reference.Based on the high level of similarity in the preclinical data and the results of this clinical study, marketing authorisation for RGB-10 (Terrosa®) was granted by the European Medicines Agency (EMA) in 2017

Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures

The basic mechanisms by which strontium ranelate acts on bone are still unclear. We show that an important action of strontium salts is to block calcification in cultures of osteoblasts, the bone-forming cells. These results suggest that strontium treatment could have previously overlooked effects on bone

TEM analysis of apatite surface layers observed on zinc based glass polyalkenoate cements

peer-reviewedGlass polyalkenoate cements (GPCs) are acid base cements formed by the reaction of an aqueous solution of polyalkenoic acid, usually polyacrylic acid (PAA) with an acid degradable aluminosilicate glass. The result of the reaction is cement consisting of reacted and unreacted glass particles embedded in a polysalt matrix. In addition to these conventional GPCs, aluminium free glass polyalkenoate cements based on zinc silicate glasses (Zn-GPCs) exhibit significant potential as bone cements for several reasons. Primarily, they are formulated without the inclusion of aluminium (Al) [1] in the glass phase and thus eliminate clinical complications arising from the release of the Al3+ ion from the cement in vivo. Such complications have, in the past, included aluminium induced encephalopathy [2-5] and defective mineralisation of cancellous bone [6]. Secondly, Zn-GPCs set without a significant evolution of heat, when compared with commercial bone cements such as Spineplex ® (Stryker, Limerick, Ireland). Finally, these materials can be tailored to release clinically beneficial ions into surrounding tissues [7]. In addition to Zn, these cements have been synthesized to contain strontium (Sr) [8, 9]. Both Sr and Zn inhibit osteoclastic turnover and promote osteoblastic turnover, resulting in increased bone strength and decreased fracture risk [10-14].Acceptedpeer-reviewe

Serum IGF-1 Affects Skeletal Acquisition in a Temporal and Compartment-Specific Manner

Insulin-like growth factor-1 (IGF-1) plays a critical role in the development of the growing skeleton by establishing both longitudinal and transverse bone accrual. IGF-1 has also been implicated in the maintenance of bone mass during late adulthood and aging, as decreases in serum IGF-1 levels appear to correlate with decreases in bone mineral density (BMD). Although informative, mouse models to date have been unable to separate the temporal effects of IGF-1 depletion on skeletal development. To address this problem, we performed a skeletal characterization of the inducible LID mouse (iLID), in which serum IGF-1 levels are depleted at selected ages. We found that depletion of serum IGF-1 in male iLID mice prior to adulthood (4 weeks) decreased trabecular bone architecture and significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th) by 16 weeks (adulthood). Likewise, depletion of serum IGF-1 in iLID males at 8 weeks of age, resulted in significantly reduced transverse cortical bone properties (Ct.Ar, Ct.Th) by 32 weeks (late adulthood), but had no effect on trabecular bone architecture. In contrast, depletion of serum IGF-1 after peak bone acquisition (at 16 weeks) resulted in enhancement of trabecular bone architecture, but no significant changes in cortical bone properties by 32 weeks as compared to controls. These results indicate that while serum IGF-1 is essential for bone accrual during the postnatal growth phase, depletion of IGF-1 after peak bone acquisition (16 weeks) is compartment-specific and does not have a detrimental effect on cortical bone mass in the older adult mouse

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass