Discovery of TUG-770: a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing

Derivation of diagnostic models based on formalized process knowledge

© IFAC.Industrial systems are vulnerable to faults. Early and accurate detection and diagnosis in production systems can minimize down-time, increase the safety of the plant operation, and reduce manufacturing costs. Knowledge- and model-based approaches to automated fault detection and diagnosis have been demonstrated to be suitable for fault cause analysis within a broad range of industrial processes and research case studies. However, the implementation of these methods demands a complex and error-prone development phase, especially due to the extensive efforts required during the derivation of models and their respective validation. In an effort to reduce such modeling complexity, this paper presents a structured causal modeling approach to supporting the derivation of diagnostic models based on formalized process knowledge. The method described herein exploits the Formalized Process Description Guideline VDI/VDE 3682 to establish causal relations among key-process variables, develops an extension of the Signed Digraph model combined with the use of fuzzy set theory to allow more accurate causality descriptions, and proposes a representation of the resulting diagnostic model in CAEX/AutomationML targeting dynamic data access, portability, and seamless information exchange

Hypervelocity Impact of Composite Overwrap Pressure Vessels

There is a limited amount of hypervelocity impact (HVI) data on pressurized composite overwrapped pressure vessels (COPV). In recent years, NASA has performed HVI tests to characterize impact conditions resulting in either leak or burst of the COPVs representative of spacecraft hardware. This paper reports on the results of 40 tests that have been conducted on several types of COPV configurations, pressurized by inert gas to near the vessels rated maximum expected operating pressure (MEOP). These tests were used to better understand COPV response under HVI conditions and develop ballistic limit equations (BLE) related to these tests

Five New Species of Orchesella (Collembola: Entomobryidae)

This paper describes 5 species of the genus Orchesella (Collembola: Entomobryidae) new to science. The chaetotaxy of the abdomen as well as the antennal pin seta are used systematically for the first time in the taxonomy of the genus

Laser-induced rotation of iodine molecules in He-nanodroplets: revivals and breaking-free

Rotation of molecules embedded in He nanodroplets is explored by a combination of fs laser-induced alignment experiments and angulon quasiparticle theory. We demonstrate that at low fluence of the fs alignment pulse, the molecule and its solvation shell can be set into coherent collective rotation lasting long enough to form revivals. With increasing fluence, however, the revivals disappear -- instead, rotational dynamics as rapid as for an isolated molecule is observed during the first few picoseconds. Classical calculations trace this phenomenon to transient decoupling of the molecule from its He shell. Our results open novel opportunities for studying non-equilibrium solute-solvent dynamics and quantum thermalization.Comment: 6+7 pages; 4+1 figures; 1 tabl

Non-integrability of the mixmaster universe

We comment on an analysis by Contopoulos et al. which demonstrates that the governing six-dimensional Einstein equations for the mixmaster space-time metric pass the ARS or reduced Painlev\'{e} test. We note that this is the case irrespective of the value, $I$, of the generating Hamiltonian which is a constant of motion. For $I < 0$ we find numerous closed orbits with two unstable eigenvalues strongly indicating that there cannot exist two additional first integrals apart from the Hamiltonian and thus that the system, at least for this case, is very likely not integrable. In addition, we present numerical evidence that the average Lyapunov exponent nevertheless vanishes. The model is thus a very interesting example of a Hamiltonian dynamical system, which is likely non-integrable yet passes the reduced Painlev\'{e} test.Comment: 11 pages LaTeX in J.Phys.A style (ioplppt.sty) + 6 PostScript figures compressed and uuencoded with uufiles. Revised version to appear in J Phys.

Efficient full decay inversion of MRS data with a stretched-exponential approximation of the distribution

We present a new, efficient and accurate forward modelling and inversion scheme for magnetic resonance sounding (MRS) data. MRS, also called surface-nuclear magnetic resonance (surface-NMR), is the only non-invasive geophysical technique that directly detects free water in the subsurface. Based on the physical principle of NMR, protons of the water molecules in the subsurface are excited at a specific frequency, and the superposition of signals from all protons within the excited earth volume is measured to estimate the subsurface water content and other hydrological parameters. In this paper, a new inversion scheme is presented in which the entire data set is used, and multi-exponential behaviour of the NMR signal is approximated by the simple stretched-exponential approach. Compared to the mono-exponential interpretation of the decaying NMR signal, we introduce a single extra parameter, the stretching exponent, which helps describe the porosity in terms of a single relaxation time parameter, and helps to determine correct initial amplitude and relaxation time of the signal. Moreover, compared to a multi-exponential interpretation of the MRS data, the decay behaviour is approximated with considerably fewer parameters. The forward response is calculated in an efficient numerical manner in terms of magnetic field calculation, discretization and integration schemes, which allows fast computation while maintaining accuracy. A piecewise linear transmitter loop is considered for electromagnetic modelling of conductivities in the layered half-space providing electromagnetic modelling of arbitrary loop shapes. The decaying signal is integrated over time windows, called gates, which increases the signal-to-noise ratio, particularly at late times, and the data vector is described with a minimum number of samples, that is, gates. The accuracy of the forward response is investigated by comparing a MRS forward response with responses from three other approaches outlining significant differences between the three approaches. All together, a full MRS forward response is calculated in about 20 s and scales so that on 10 processors the calculation time is reduced to about 34 s. The proposed approach is examined through synthetic data and through a field example, which demonstrate the capability of the scheme. The results of the field example agree well the information from an in-site borehole

Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice.

Aging and injury are two major risk factors for osteoarthritis (OA). Yet, very little is known about how aging and injury interact and contribute to OA pathogenesis. In the present study, we examined age- and injury-related molecular changes in mouse knee joints that could contribute to OA. Using RNA-seq, first we profiled the knee joint transcriptome of 10-week-old, 62-week-old, and 95-week-old mice and found that the expression of several inflammatory-response related genes increased as a result of aging, whereas the expression of several genes involved in cartilage metabolism decreased with age. To determine how aging impacts post-traumatic arthritis (PTOA) development, the right knee joints of 10-week-old and 62-week-old mice were injured using a non-invasive tibial compression injury model and injury-induced structural and molecular changes were assessed. At six-week post-injury, 62-week-old mice displayed significantly more cartilage degeneration and osteophyte formation compared with young mice. Although both age groups elicited similar transcriptional responses to injury, 62-week-old mice had higher activation of inflammatory cytokines than 10-week-old mice, whereas cartilage/bone metabolism genes had higher expression in 10-week-old mice, suggesting that the differential expression of these genes might contribute to the differences in PTOA severity observed between these age groups

Gluon distributions in nucleons and pions at a low resolution scale

In this paper we study the gluon distribution functions in nucleons and pions at a low resolution $Q^2$ scale. This is an important issue since parton densities at low $Q^2$ have always been taken as an external input which is adjusted through DGLAP evolution to fit the experimental data at higher scales. Here, in the framework of a model recently developed, it is shown that the hypothetical cloud of {\it neutral} pions surrounding nucleons and pions appears to be responsible for the characteristic valence-like gluon distributions needed at the inital low scale. As an additional result, we get the remarkable prediction that neutral and charged pions have different intrinsic sea flavor contents.Comment: final version to appear in Phys. Rev. D. Discussion on several points enlarge

Multi-Shock Shield Performance at 15 MJ for Catalogued Debris

While orbital debris of ten centimeters or more are tracked and catalogued, the difficulty of finding and accurately accounting for forces acting on the objects near the ten centimeter threshold results in both uncertainty of their presence and location. These challenges result in difficult decisions for operators balancing potential costly operational approaches with system loss risk. In this paper, the assessment of the feasibility of protecting a spacecraft from this catalogued debris is described using numerical simulations and a test of a multi-shock shield system against a cylindrical projectile impacting normal to the surface with approximately 15 MJ of kinetic energy. The hypervelocity impact test has been conducted at the Arnold Engineering Development Complex (AEDC) with a 598 g projectile at 6.905 km/s on a NASA supplied multi-shock shield. The projectile used is a hollow aluminum and nylon cylinder with an outside diameter of 8.6 cm and length of 10.3 cm. Figure 1 illustrates the multi-shock shield test article, which consisted of five separate bumpers, four of which are fiberglass fabric and one of steel mesh, and two rear walls, each consisting of Kevlar fabric. The overall length of the test article was 2.65 m. The test article was a 5X scaled-up version of a smaller multi-shock shield previously tested using a 1.4 cm diameter aluminum projectile for an inflatable module project. The distances represented by S1 and S1/2 in the figure are 61 cm and 30.5 cm, respectively. Prior to the impact test, hydrodynamic simulations indicated that some enhancement to the standard multi-shock system is needed to address the effects of the cylindrical shape of the projectile. Based on the simulations, a steel mesh bumper has been added to the shield configuration to enhance the fragmentation of the projectile. The AEDC test occurred as planned, and the modified NASA multi-shock shield successfully stopped 598 g projectile using 85.6 kg/m(exp 2). The fifth bumper layer remained in tact, although it was torn free from its support structure and thrown into the first rear wall. The outer Kevlar layer of the first rear wall tore likely from the impact of the fifth bumper's support structure, but the back of the rear wall was intact. No damage occurred to the second rear wall, or to the witness plate behind the target