Inelastic J/ΨJ/\Psi Photoproduction off Nuclei: Gluon Enhancement or Double Color Exchange?

The nuclear enhancement observed in inelastic photoproduction of $J/\Psi$ should not be interpreted as evidence for an increased gluon density in nuclei. The nuclear suppression of the production rate due to initial and final state interactions is calculated and a novel two-step color exchange process is proposed, which is able to explain the data.Comment: Latex file, 23 pages including 5 Postscript figure

Radio Emission from Ultra-Cool Dwarfs

The 2001 discovery of radio emission from ultra-cool dwarfs (UCDs), the very low-mass stars and brown dwarfs with spectral types of ~M7 and later, revealed that these objects can generate and dissipate powerful magnetic fields. Radio observations provide unparalleled insight into UCD magnetism: detections extend to brown dwarfs with temperatures <1000 K, where no other observational probes are effective. The data reveal that UCDs can generate strong (kG) fields, sometimes with a stable dipolar structure; that they can produce and retain nonthermal plasmas with electron acceleration extending to MeV energies; and that they can drive auroral current systems resulting in significant atmospheric energy deposition and powerful, coherent radio bursts. Still to be understood are the underlying dynamo processes, the precise means by which particles are accelerated around these objects, the observed diversity of magnetic phenomenologies, and how all of these factors change as the mass of the central object approaches that of Jupiter. The answers to these questions are doubly important because UCDs are both potential exoplanet hosts, as in the TRAPPIST-1 system, and analogues of extrasolar giant planets themselves.Comment: 19 pages; submitted chapter to the Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag

Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells

The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al

Normal forms and internal regularization of nonlinear differential-algebraic control systems

In this article, we propose two normal forms for nonlinear differential-algebraic control systems (DACSs) under external feedback equivalence, using a notion called maximal controlled invariant submanifold. The two normal forms simplify the system structures and facilitate understanding the various roles of variables for nonlinear DACSs. Moreover, we study when a given nonlinear DACS is internally regularizable, that is, when there exists a state feedback transforming the DACS into a differential-algebraic equation (DAE) with internal regularity, the latter notion is closely related to the existence and uniqueness of solutions of DAEs. We also revise a commonly used method in DAE solution theory, called the geometric reduction method. We apply this method to DACSs and formulate it as an algorithm, which is used to construct maximal controlled invariant submanifolds and to find internal regularization feedbacks. Two examples of mechanical systems are used to illustrate the proposed normal forms and to show how to internally regularize DACSs

Multiple-length-scale elastic instability mimics parametric resonance of nonlinear oscillators

Spatially confined rigid membranes reorganize their morphology in response to the imposed constraints. A crumpled elastic sheet presents a complex pattern of random folds focusing the deformation energy while compressing a membrane resting on a soft foundation creates a regular pattern of sinusoidal wrinkles with a broad distribution of energy. Here, we study the energy distribution for highly confined membranes and show the emergence of a new morphological instability triggered by a period-doubling bifurcation. A periodic self-organized focalization of the deformation energy is observed provided an up-down symmetry breaking, induced by the intrinsic nonlinearity of the elasticity equations, occurs. The physical model, exhibiting an analogy with parametric resonance in nonlinear oscillator, is a new theoretical toolkit to understand the morphology of various confined systems, such as coated materials or living tissues, e.g., wrinkled skin, internal structure of lungs, internal elastica of an artery, brain convolutions or formation of fingerprints. Moreover, it opens the way to new kind of microfabrication design of multiperiodic or chaotic (aperiodic) surface topography via self-organization.Comment: Submitted for publicatio

Study of the Falling Friction Effect on Rolling Contact Parameters

[EN] The existence of a wheel rail friction coefficient that depends on the slip velocity has been associated in the literature with important railway problems like the curving squeal and certain corrugation problems in rails. Rolling contact models that take into account this effect were carried out through the so-called Exact Theories adopting an exact elastic model of the solids in contact, and Simplified Theories which assume simplified elastic models such as Winkler. The former ones, based on Kalker s Variational Theory, give rise to numerical problems; the latter ones need to adopt hypotheses that significantly deviate from actual conditions, leading to unrealistic solutions of the contact problem. In this paper, a methodology based on Kalker s Variational Theory is presented, in which a local slip velocity-dependent friction law is considered. A formulation to get steady-state conditions of rolling contact by means of regularisation of the Coulomb s law is proposed. The model allows establishing relationships in order to estimate the global properties (creepage velocities vs. total longitudinal forces) through local properties (local slip velocity vs. coefficient of friction) or vice versa. The proposed model shows a good agreement with experimental tests while solving the numerical problems previously mentioned.The authors acknowledge the financial contribution of the Spanish Ministry of Economy and Competitiveness through the Project TRA2013-45596-C2-1-R.Giner Navarro, J.; Baeza González, LM.; Vila Tortosa, MP.; Alonso Pazos, A. (2017). Study of the Falling Friction Effect on Rolling Contact Parameters. Tribology Letters. 65(1). https://doi.org/10.1007/s11249-016-0810-8S651Grassie, S.L., Elkins, J.A.: Rail corrugation on North American transit systems. Veh. Syst. Dyn. 28, 5–17 (1998)Hsu, S.S., Huang, Z., Iwnicki, S.D., Thompson, D.J., Jones, C.J.C., Xie, G., Allen, P.D.: Experimental and theoretical investigation of railway wheel squeal. Proc. Inst. Mech. Eng. F J. Rail Rapid Transit 221, 59–73 (2007)Kalker, J.J.: Three-Dimensional Elastic Bodies in Rolling Contact. Kluwer, Dordrecht (1990)Polach, O.: Influence of locomotive tractive effort on the forces between wheel and rail. Veh. Syst. Dyn. 35, 7–22 (2001)Giménez, J.G., Alonso, A., Gómez, E.: Introduction of a friction coefficient dependent on the slip in the FastSim algorithm. Veh. Syst. Dyn. 43, 233–244 (2005)Baeza, L., Vila, P., Roda, A., Fayos, J.: Prediction of corrugation in rails using a non-stationary wheel–rail contact model. Wear 265, 1156–1162 (2008)Vollebregt, E.A.H., Schuttelaars, H.M.: Quasi-static analysis of two-dimensional rolling contact with slip-velocity dependent friction. J. Sound Vib. 331, 2141–2155 (2012)Avlonitis, M., Kalaitzidou, K., Streator, J.: Investigation of friction statics and real contact area by means a modified OFC model. Tribol. Int. 69, 168–175 (2014)Berger, E.J., Mackin, T.J.: On the walking stick–slip problem. Tribol. Int. 75, 51–60 (2014)Alonso, A., Guiral, A., Baeza, B., Iwnicki, S.D.: Wheel–rail contact: experimental study of the creep forces–creepage relationships. Veh. Syst. Dyn. 52(S1), 469–487 (2014)Spiryagin, M., Polach, O., Cole, C.: Creep force modelling for rail traction vehicles based on the Fastsim algorithm. Veh. Syst. Dyn. 51, 1765–1783 (2013)Vollebregt, E.A.H.: Numerical modeling of measured railway creep versus creep-force curves with CONTACT. Wear 314, 87–95 (2014)Kalker, J.J.: On the Rolling Contact of Two Elastic Bodies in the Presence of Dry Friction. PhD Thesis, Technical University of Delft (Holland) (1967)Baeza, L., Fuenmayor, F.J., Carballeira, J., Roda, A.: Influence of the wheel–rail contact instationary process on contact parameters. J. Strain Anal. Eng. 42, 377–387 (2007)Le Rouzic, J., Le Bot, A., Perret-Liaudet, J., Guibert, M., Rusanov, A., Douminge, L., Bretagnol, F., Mazuyer, D.: Friction-induced vibration by Stribeck’s law: application to wiper blade squeal noise. Tribol. Lett. 49, 563–572 (2013)Rabinowicz, E.: The nature of the static and kinetic coefficients of friction. J. Appl. Phys. 22, 1373–1379 (1951)Carter, F.W.: On the action of locomotive driving wheel. Proc. R. Soc. Lon. Ser. A 112, 151–157 (1926)Kalker, J.J.: A fast algorithm for the simplified theory of rolling contact. Veh. Syst. Dyn. 11, 1–13 (1982

Impact of long-term elosulfase alfa treatment on respiratory function in patients with Morquio A syndrome

OBJECTIVE: To present long-term respiratory function outcomes from an open-label, multi-center, phase 3 extension study (MOR-005) of elosulfase alfa enzyme replacement therapy (ERT) in patients with Morquio A syndrome. METHODS: In part 1 of MOR-005, patients initially randomized to ERT in the 24-week pivotal study (MOR-004) remained on their regimen (2.0 mg/kg/week or every other week); placebo patients were re-randomized to one of the two regimens. During part 2, all patients received elosulfase alfa 2.0 mg/kg/week. Respiratory function was one of the efficacy endpoints evaluated in MOR-005. Change from MOR-004 baseline to 120 weeks of treatment for the combined population was determined and compared with results from untreated patients from a Morquio A natural history study (MorCAP). RESULTS: Maximum voluntary ventilation (MVV) improved up to week 72 and then stabilized; forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) increased continuously over 120 weeks. Mean increases in the modified per-protocol population was 9.2 % for FVC, 8.8 % for FEV1, and 6.1 % for MVV after 120 weeks. All patients ≤14 years showed respiratory improvements, presumably in part related to growth; however, these were greater in treated patients. For those >14 years, treated patients showed improvements, while deterioration occurred in untreated. Altogether, the improvements were significantly greater (P < 0.05) in treated patients. CONCLUSIONS: Long-term ERT is associated with sustained improvements in respiratory function in Morquio A. In younger patients (≤14 years), some improvement may be ascribed to growth. In older patients, other mechanisms, e.g., decreased glycosaminoglycan storage, are likely involved

Notch and MAML-1 Complexation Do Not Detectably Alter the DNA Binding Specificity of the Transcription Factor CSL

Canonical Notch signaling is initiated when ligand binding induces proteolytic release of the intracellular part of Notch (ICN) from the cell membrane. ICN then travels into the nucleus where it drives the assembly of a transcriptional activation complex containing the DNA-binding transcription factor CSL, ICN, and a specialized co-activator of the Mastermind family. A consensus DNA binding site motif for the CSL protein was previously defined using selection-based methods, but whether subsequent association of Notch and Mastermind-like proteins affects the DNA binding preferences of CSL has not previously been examined.Here, we utilized protein-binding microarrays (PBMs) to compare the binding site preferences of isolated CSL with the preferred binding sites of CSL when bound to the CSL-binding domains of all four different human Notch receptors. Measurements were taken both in the absence and in the presence of Mastermind-like-1 (MAML1). Our data show no detectable difference in the DNA binding site preferences of CSL before and after loading of Notch and MAML1 proteins.These findings support the conclusion that accrual of Notch and MAML1 promote transcriptional activation without dramatically altering the preferred sites of DNA binding, and illustrate the potential of PBMs to analyze the binding site preferences of multiprotein-DNA complexes

Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome

Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre-treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by ≥20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and -62.3 (1.8)% in the ITT and MPP populations, respectively. In the absence of a placebo group, significance of the sustained improvements could not be evaluated directly. However, to provide context for interpretation of results, comparisons were performed with untreated patients from a Morquio A natural history study. In contrast to the results of the extension study, the untreated patients experienced constant uKS levels and a gradual decline in endurance test results over a similar period of time. Differences from the untreated natural history study patients were significant for 6MWT, 3MSCT, and uKS outcomes for the cohort of patients receiving optimal dosing throughout the study and for all cohorts pooled together, for both ITT and MPP populations (P<0.05). Safety findings were consistent with those of the initial 24-week study, with no new safety signals identified