On the equivalence of Eulerian and Lagrangian variables for the two-component Camassa-Holm system

The Camassa-Holm equation and its two-component Camassa-Holm system generalization both experience wave breaking in finite time. To analyze this, and to obtain solutions past wave breaking, it is common to reformulate the original equation given in Eulerian coordinates, into a system of ordinary differential equations in Lagrangian coordinates. It is of considerable interest to study the stability of solutions and how this is manifested in Eulerian and Lagrangian variables. We identify criteria of convergence, such that convergence in Eulerian coordinates is equivalent to convergence in Lagrangian coordinates. In addition, we show how one can approximate global conservative solutions of the scalar Camassa-Holm equation by smooth solutions of the two-component Camassa-Holm system that do not experience wave breaking

Targeting GATA4 for cardiac repair

Various strategies have been applied to replace the loss of cardiomyocytes in order to restore reduced cardiac function and prevent the progression of heart disease. Intensive research efforts in the field of cellular reprogramming and cell transplantation may eventually lead to efficient in vivo applications for the treatment of cardiac injuries, representing a novel treatment strategy for regenerative medicine. Modulation of cardiac transcription factor (TF) networks by chemical entities represents another viable option for therapeutic interventions. Comprehensive screening projects have revealed a number of molecular entities acting on molecular pathways highly critical for cellular lineage commitment and differentiation, including compounds targeting Wnt- and transforming growth factor beta (TGF beta)-signaling. Furthermore, previous studies have demonstrated that GATA4 and NKX2-5 are essential TFs in gene regulation of cardiac development and hypertrophy. For example, both of these TFs are required to fully activate mechanical stretch-responsive genes such as atrial natriuretic peptide and brain natriuretic peptide (BNP). We have previously reported that the compound 3i-1000 efficiently inhibited the synergy of the GATA4-NKX2-5 interaction. Cellular effects of 3i-1000 have been further characterized in a number of confirmatory in vitro bioassays, including rat cardiac myocytes and animal models of ischemic injury and angiotensin II-induced pressure overload, suggesting the potential for small molecule-induced cardioprotection.Peer reviewe

Two-Photon Doppler cooling of alkaline-earth-metal and ytterbium atoms

A new possibility of laser cooling of alkaline-earth-metal and Ytterbium atoms using a two-photon transition is analyzed. We consider a $^{1}S_{0}$ - $^{1}S_{0}$ transition, with excitation in near resonance with the $^{1}P_{1}$ level. This greatly increases the two-photon transition rate, allowing an effective transfer of momentum. The experimental implementation of this technique is discussed and we show that for Calcium, for example, two-photon cooling can be used to achieve a Doppler limit of 123 microKelvin. The efficiency of this cooling scheme and the main loss mechanisms are analyzed.Comment: 7 pages, 5 figure

Application of high-throughput sequencing for studying genomic variations in congenital heart disease

Congenital heart diseases (CHD) represent the most common birth defect in human. The majority of cases are caused by a combination of complex genetic alterations and environmental influences. In the past, many disease-causing mutations have been identified; however, there is still a large proportion of cardiac malformations with unknown precise origin. High-throughput sequencing technologies established during the last years offer novel opportunities to further study the genetic background underlying the disease. In this review, we provide a roadmap for designing and analyzing high-throughput sequencing studies focused on CHD, but also with general applicability to other complex diseases. The three main next-generation sequencing (NGS) platforms including their particular advantages and disadvantages are presented. To identify potentially disease-related genomic variations and genes, different filtering steps and gene prioritization strategies are discussed. In addition, available control datasets based on NGS are summarized. Finally, we provide an overview of current studies already using NGS technologies and showing that these techniques will help to further unravel the complex genetics underlying CHD

Magnetic trapping of metastable 3P2^3P_2 atomic strontium

We report the magnetic trapping of metastable $^3P_2$ atomic strontium. Atoms are cooled in a magneto-optical trap (MOT) operating on the dipole allowed $^1S_0-^1P_1$ transition at 461 nm. Decay via $^1P_1\to {^1D_2}\to {^3P_2}$ continuously loads a magnetic trap formed by the quadrupole magnetic field of the MOT. Over $10^8$ atoms at a density of $8 \times 10^9$ cm$^{-3}$ and temperature of 1 mK are trapped. The atom temperature is significantly lower than what would be expected from the kinetic and potential energy of atoms as they are transferred from the MOT. This suggests that thermalization and evaporative cooling are occurring in the magnetic trap.Comment: This paper has been accepted by PR

Loss of the mammal-specific tectorial membrane component CEA cell adhesion molecule 16 (CEACAM16) leads to hearing impairment at low and high frequencies

The vertebrate-restricted carcinoembryonic antigen gene family evolves extremely rapidly. Among their widely expressed members, the mammal-specific, secreted CEACAM16 is exceptionally well conserved and specifically expressed in the inner ear. To elucidate a potential auditory function we inactivated murine Ceacam16 by homologous recombination. In young Ceacam16-/- mice the hearing threshold for frequencies below 10 kHz and above 22 kHz was raised. This hearing impairment progressed with age. A similar phenotype is observed in hearing-impaired members of Family 1070 with non-syndromic autosomal dominant hearing loss (DFNA4) who carry a missense mutation in CEACAM16. CEACAM16 was found in interdental and Deiters cells and was deposited in the tectorial membrane of the cochlea between postnatal day 12 and 15, when hearing starts in mice. In cochlear sections of Ceacam16-/- mice tectorial membranes were significantly more often stretched out as compared to wild-type mice where they were mostly contracted and detached from the outer hair cells. Homotypic cell sorting observed after ectopic cell surface expression of the carboxy-terminal immunoglobulin variable-like N2 domain of CEACAM16 indicated that CEACAM16 can interact in trans. Furthermore, Western blot analyses of membrane-bound CEACAM16 under reducing and non-reducing conditions demonstrated oligomerization via unpaired cysteines. Taken together, CEACAM16 probably can form higher order structures with other tectorial membrane proteins such as α-tectorin and β-tectorin and influences the physical properties of the tectorial membrane. Evolution of CEACAM16 might have been an important step for the specialization of the mammalian cochlea allowing hearing over an extended frequency range

Ehlers-Danlos syndromes: state of the art on clinical practice guidelines.

Objective To report the effort of the European Reference Network for Rare and Complex CONnective tissue and musculoskeletal diseases NETwork working group on Ehlers-Danlos syndromes (EDS) and related disorders to assess current available clinical practice guidelines (CPGs) specifically addressed to EDS, in order to identify potential clinician and patient unmet needs. Methods Systematic literature search in PUBMED and EMBASE based on controlled terms (MeSH and Emtree) and keywords of the disease and publication type (CPGs). All the published articles were revised in order to identify existing CPGs on diagnosis, monitoring and treatment of EDS. Results Literature revision detected the absence of papers reporting good quality CPGs to optimise EDS patient care. The current evidence-based literature regarding clinical guidelines for the EDS was limited in size and quality, and there is insufficient research exploring the clinical features and interventions, and clinical decision-making are currently based on theoretical and limited research evidences. Conclusions Many clinician and patient unmet needs have been identifie

Long-Time Asymptotics of Perturbed Finite-Gap Korteweg-de Vries Solutions

We apply the method of nonlinear steepest descent to compute the long-time asymptotics of solutions of the Korteweg--de Vries equation which are decaying perturbations of a quasi-periodic finite-gap background solution. We compute a nonlinear dispersion relation and show that the $x/t$ plane splits into $g+1$ soliton regions which are interlaced by $g+1$ oscillatory regions, where $g+1$ is the number of spectral gaps. In the soliton regions the solution is asymptotically given by a number of solitons travelling on top of finite-gap solutions which are in the same isospectral class as the background solution. In the oscillatory region the solution can be described by a modulated finite-gap solution plus a decaying dispersive tail. The modulation is given by phase transition on the isospectral torus and is, together with the dispersive tail, explicitly characterized in terms of Abelian integrals on the underlying hyperelliptic curve.Comment: 45 pages. arXiv admin note: substantial text overlap with arXiv:0705.034

Fast analysis of antibody-derived therapeutics by automated multidimensional liquid chromatography - mass spectrometry

Characterization of post-translational modifications (PTMs) of therapeutic antibodies is commonly performed by bottom-up approaches, involving sample preparation and peptide analysis by liquid chromatography-mass spectrometry (LC-MS). Conventional sample preparation requires extensive hands-on time and can increase the risk of inducing artificial modifications as many off-line steps - denaturation, disulfide-reduction, alkylation and tryptic digestion - are performed. In this study, we developed an on-line multidimensional (mD)-LC-MS bottom-up approach for fast sample preparation and analysis of (formulated) monoclonal antibodies and antibody-derived therapeutics. This approach allows on-column reduction, tryptic digestion and subsequent peptide analysis by RP-MS. Optimization of the 1D -and 2D flow and temperature improved the trapping of small polar peptides during on-line peptide mapping analysis. These adaptations increased the sequence coverage (95-98% versus 86-94% for off-line approaches) and allowed identification of various PTMs (i.e. deamidation of asparagine, methionine oxidation and lysine glycation) within a single analysis. This workflow enables a fast (<2 h) characterization of antibody heterogeneities within a single run and a low amount of protein (10 mu g). Importantly, the new mD-LC-MS bottom-up method was able to detect the polar, fast-eluting peptides: Fc oxidation at Hc-Met-252 and the Fc N-glycosylation at Hc-Asn-297, which can be challenging using mD-LC-MS. Moreover, the method showed good comparability across the different measurements (RSD of retention time in the range of 0.2-1.8% for polar peptides). The LC system was controlled by only a standard commercial software package which makes implementation for fast characterization of quality attributes relatively easy. (C) 2021 The Author(s). Published by Elsevier B.V.Proteomic

Application of stochastic programming to reduce uncertainties in quality-based supply planning of slaughterhouses

To match products of different quality with end market preferences under supply uncertainty, it is crucial to integrate product quality information in logistics decision making. We present a case of this integration in a meat processing company that faces uncertainty in delivered livestock quality. We develop a stochastic programming model that exploits historical product quality delivery data to produce slaughterhouse allocation plans with reduced levels of uncertainty in received livestock quality. The allocation plans generated by this model fulfil demand for multiple quality features at separate slaughterhouses under prescribed service levels while minimizing transportation costs. We test the model on real world problem instances generated from a data set provided by an industrial partner. Results show that historical farmer delivery data can be used to reduce uncertainty in quality of animals to be delivered to slaughterhouses