Predesign Considerations for the DC Link Voltage Level of the CENTRELINE Fuselage Fan Drive Unit

Electric propulsion (EP) systems offer considerably more degrees of freedom (DOFs) within the design process of aircraft compared to conventional aircraft engines. This requires large, computationally expensive design space explorations (DSE) with coupled models of the single components to incorporate interdependencies during optimization. The purpose of this paper is to exemplarily study these interdependencies of system key performance parameters (KPIs), e.g., system mass and efficiency, for a varying DC link voltage level of the power transmission system considering the example of the propulsion system of the CENTRELINE project, including an electric motor, a DC/AC inverter, and the DC power transmission cables. Each component is described by a physically derived, analytical model linking specific subdomains, e.g., electromagnetics, structural mechanics and thermal analysis, which are used for a coupled system model. This approach strongly enhances model accuracy and simultaneously keeps the computational effort at a low level. The results of the DSE reveal that the system KPIs improve for higher DC link voltage despite slightly inferior performance of motor and inverter as the mass of the DC power transmission cable has a major share for a an aircraft of the size as in the CENTRELINE project. Modeling of further components and implementation of optimization strategies will be part of future work

Sox9 Inhibits -Trcp-Mediated Protein Degradation To Promote Nuclear Gli1 Expression And Cancer Stem Cell Properties

The high mobility group box protein SOX9 and the GLI1 transcription factor play protumorigenic roles in pancreatic ductal adenocarcinoma (PDA). In Kras transgenic mice, each of these factors are crucial for the development of PDA precursor lesions. SOX9 transcription is directly regulated by GLI1, but how SOX9 functions downstream of GLI1 is unclear. We observed positive feedback, such that SOX9-deficient PDA cells have severely repressed levels of endogenous GLI1, attributed to loss of GLI1 protein stability. SOX9 associated with the F-box domain of the SKP1/CUL1/F-box (SCF) E3 ubiquitin ligase component, β-TrCP (also known as F-box/WD repeat-containing protein 1A), and suppressed its association with SKP1 and GLI1, a substrate of SCF-β-TrCP. SOX9 also tethered β-TrCP within the nucleus and promoted its degradation. SOX9 bound to β-TrCP through the SOX9 C-terminal PQA/S domain that mediates transcriptional activation. Suppression of β-TrCP in SOX9-deficient PDA cells restored GLI1 levels and promoted SOX9-dependent cancer stem cell properties. These studies identify SOX9–GLI1 positive feedback as a major determinant of GLI1 protein stability and implicate β-TrCP as a latent SOX9-bound tumor suppressor with the potential to degrade oncogenic proteins in tumor cells

The long noncoding RNA, treRNA, decreases DNA damage and is associated with poor response to chemotherapy in chronic lymphocytic leukemia.

The study of long noncoding RNAs (lncRNAs) is an emerging area of cancer research, in part due to their ability to serve as disease biomarkers. However, few studies have investigated lncRNAs in chronic lymphocytic leukemia (CLL). We have identified one particular lncRNA, treRNA, which is overexpressed in CLL B-cells. We measured transcript expression in 144 CLL patient samples and separated samples into high or low expression of treRNA relative to the overall median. We found that high expression of treRNA is significantly associated with shorter time to treatment. High treRNA also correlates with poor prognostic indicators such as unmutated IGHV and high ZAP70 protein expression. We validated these initial findings in samples collected in a clinical trial comparing the nucleoside analog fludarabine alone or in combination with the alkylating agent cyclophosphamide in untreated CLL samples collected prior to starting therapy (E2997). High expression of treRNA was independently prognostic for shorter progression free survival in patients receiving fludarabine plus cyclophosphamide. Given these results, in order to study the role of treRNA in DNA damage response we generated a model cell line system where treRNA was over-expressed in the human B-CLL cell line OSU-CLL. Relative to the vector control line, there was less cell death in OSU-CLL over-expressing treRNA after exposure to fludarabine and mafosfamide, due in part to a reduction in DNA damage. Therefore, we suggest that treRNA is a novel biomarker in CLL associated with aggressive disease and poor response to chemotherapy through enhanced protection against cytotoxic mediated DNA damage

Bounds for the ℓ‐torsion in class groups

We prove for each integer $\ell\geq 1$ an unconditional upper bound for the size of the $\ell$-torsion subgroup $Cl_K[\ell]$ of the class group of $K$, which holds for all but a zero density set of number fields $K$ of degree $d\in\{4,5\}$ (with the additional restriction in the case $d = 4$ that the field be non-$D_4$). For sufficiently large $\ell$ this improves recent results of Ellenberg, Matchett Wood, and Pierce, and is also stronger than the best currently known pointwise bounds under GRH. Conditional on GRH and on a weak conjecture on the distribution of number fields our bounds also hold for arbitrary degrees $d$.Comment: To appear in Bull. Lond. Math. So

Signatures in the Planck Regime

String theory suggests the existence of a minimum length scale. An exciting quantum mechanical implication of this feature is a modification of the uncertainty principle. In contrast to the conventional approach, this generalised uncertainty principle does not allow to resolve space time distances below the Planck length. In models with extra dimensions, which are also motivated by string theory, the Planck scale can be lowered to values accessible by ultra high energetic cosmic rays (UHECRs) and by future colliders, i.e. $M_f\approx$ 1 TeV. It is demonstrated that in this novel scenario, short distance physics below $1/M_f$ is completely cloaked by the uncertainty principle. Therefore, Planckian effects could be the final physics discovery at future colliders and in UHECRs. As an application, we predict the modifications to the $e^+e^- \to f^+f^-$ cross-sections.Comment: 14 pages, 4 figures, typos corrected, references adde

EL POBLADO DE LA EDAD DEL COBRE DE VALENCINA DE LA CONCEPCIÓN (SEVILLA): NUEVOS DATOS SOBRE SUS RECINTOS Y ESPACIOS DOMÉSTICOS. CAMPAÑA DE 2018

The second excavation campaign during 2018 in the northern sector of the site of Valencina de la Concepción has documented four Chalcolithic huts with an oval floor plan, semi-excavated in the subsoil, which should have adobe walls, of which the biggest one, UC 447/448, is 6 m long by 3 m wide. Moreover, the largest identified ditch, No. 10, was drilled, which has a V-section, 11 m wide in grid 4 and a maximum depth of 8,50 m according to the drillings made. The main occupation of the sector corresponds to the Middle Chalcolithic, although there are structures assignable to the Early Chalcolithic and more specific occupation of the early Bell-Beakers, Early- Middle Bronze Age and transition from the Late Bronze Age to the Early Iron Age. Otherwise, the geomagnetic surveys of 2018 have covered 14 ha and made it possible to identify a fifth possible enclosure with two parallel ditches, which at least are surrounding the North, Northwest and West sides of the settlement. La segunda campaña de excavación durante 2018 en el sector norte del yacimiento de Valencina de la Concepción ha documentado cuatro cabañas calcolíticas de planta oval, semi-excavadas en el subsuelo, que debían tener paredes de adobes, de las cuales, la de mayores dimensiones, UC 447/448, tiene 6 m de longitud por 3 m de ancho. Por otra parte, se sondeó el foso más grande identificado, el n.º 10, que presenta sección en V, 11 m de ancho en el corte 4 y 8,50 m de profundidad máxima según las perforaciones realizadas. La ocupación principal del sector corresponde al Calcolítico Medio, aunque hay estructuras asignables al Calcolítico Inicial y ocupación más puntual de inicios del Campaniforme, Bronce Antiguo-Medio y transición del Bronce Final al Hierro Inicial. Por otra parte, las prospecciones geomagnéticas de 2018 han abarcado 14 ha y permitido identificar un quinto posible recinto con dos fosos paralelos, los cuales al menos están rodeando el norte, noroeste y oeste del yacimiento.&nbsp

Shock waves in strongly coupled plasmas

Shock waves are supersonic disturbances propagating in a fluid and giving rise to dissipation and drag. Weak shocks, i.e., those of small amplitude, can be well described within the hydrodynamic approximation. On the other hand, strong shocks are discontinuous within hydrodynamics and therefore probe the microscopics of the theory. In this paper we consider the case of the strongly coupled N=4 plasma whose microscopic description, applicable for scales smaller than the inverse temperature, is given in terms of gravity in an asymptotically $AdS_5$ space. In the gravity approximation, weak and strong shocks should be described by smooth metrics with no discontinuities. For weak shocks we find the dual metric in a derivative expansion and for strong shocks we use linearized gravity to find the exponential tail that determines the width of the shock. In particular we find that, when the velocity of the fluid relative to the shock approaches the speed of light $v\to 1$ the penetration depth $\ell$ scales as $\ell\sim (1-v^2)^{1/4}$. We compare the results with second order hydrodynamics and the Israel-Stewart approximation. Although they all agree in the hydrodynamic regime of weak shocks, we show that there is not even qualitative agreement for strong shocks. For the gravity side, the existence of shock waves implies that there are disturbances of constant shape propagating on the horizon of the dual black holes.Comment: 47 pages, 8 figures; v2:typos corrected, references adde

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

Objective: Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods: In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results: More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions: The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse population of patients with active PsA, including anti-TNF-experienced PsA patients