Saddle stresses for generic theories with a preferred acceleration scale

We show how scaling arguments may be used to generate templates for the tidal stresses around saddles for a vast class of MONDian theories {\it detached from their obligations as dark matter alternatives}. Such theories are to be seen simply as alternative theories of gravity with a preferred acceleration scale, and could be tested in the solar system by extending the LISA Pathfinder (LPF) mission. The constraints thus obtained may then be combined, if one wishes, with requirements arising from astrophysical and cosmological applications, but a clear separation of the issues is achieved. The central technical content of this paper is the derivation of a scaling prescription allowing complex numerical work to be bypassed in the generation of templates. We find that LPF could constrain very tightly the acceleration $a_0$ and the free parameter $\kappa$ present in these theories. As an application of our technique we also produce predictions for the moon saddle (for which a similar scaling argument is applicable) with the result that we recommend that it should be included in orbit design.Comment: Analysis of the lunar saddle added to version to appear in Physical Review

Comparative Molecular Transporter Efficiency of Cyclic Peptides Containing Tryptophan and Arginine Residues

Cyclic peptides containing tryptophan (W) and arginine (R) residues, [WR]5, [WR]6, [WR]7, [WR]8, and [WR]9, were synthesized through Fmoc solid-phase chemistry to compare their molecular transporter efficiency. The in vitro cytotoxicity of the peptides was evaluated using human leukemia carcinoma cell line (CCRF-CEM) and normal kidney cell line (LLC-PK1). [WR]6, [WR]7, [WR]8, and [WR]9 were not significantly cytotoxic to LLC-PK1cells at a concentration of 10 μM after 3 h incubation. Among all the peptides, [WR]9 was found to be a more efficient transporter than [WR]5, [WR]6, [WR]7, and [WR]8 in CCRF-CEM cells for delivery of a cell-impermeable fluorescence-labeled negatively charged phosphopeptide (F′-GpYEEI). [WR]9 (10 μM) improved the cellular uptake of F′-GpYEEI (2 μM) by 20-fold. The cellular uptake of a fluorescent conjugate of [WR]9, F′-[W9R8K], was increased in a concentration- and time-dependent pattern in CCRF-CEM cells. The uptake of F′-[W9R8K] was slightly reduced in CCRF-CEM cells in the presence of different endocytic inhibitors, such as nystatin, 5-(N-ethyl-N-isopropyl)amiloride, chlorpromazine, chloroquine, and methyl β-cyclodextrin. Furthermore, the uptake of F′-[W9R8K] was shown to be temperature-dependent and slightly adenosine 5′-triphosphate-dependent. The intracellular/cellular localization (in the nucleus and cytoplasm) of F′-[W9R8K] was confirmed by fluorescent microscopy in CCRF-CEM cells. These studies suggest that large cyclic peptides containing arginine and tryptophan can be used as a molecular transporter of specific compounds

State of Health Estimation of Lithium‐Ion Batteries in Electric Vehicles under Dynamic Load Conditions

Among numerous functions performed by the battery management system (BMS), online estimation of the state of health (SOH) is an essential and challenging task to be accomplished periodically. In electric vehicle (EV) applications, accurate SOH estimation minimizes failure risk and improves reliability by predicting battery health conditions. The challenge of accurate estimation of SOH is based on the uncertain dynamic operating condition of the EVs and the complex nonlinear electrochemical characteristics exhibited by the lithium‐ion battery. This paper presents an artificial neural network (ANN) classifier experimentally validated for the SOH estimation of lithium‐ion batteries. The ANN‐based classifier model is trained experimentally at room temperature under dynamic variable load conditions. Based on SOH characterization, the training is done using features such as the relative values of voltage, state of charge (SOC), state of energy (SOE) across a buffer, and the instantaneous states of SOC and SOE. At implementation, due to the slow dynamics of SOH, the algorithm is triggered on a large‐scale periodicity to extract these features into buffers. The features are then applied as input to the trained model for SOH estimation. The classifier is validated experimentally under dynamic varying load, constant load, and step load conditions. The model accuracies for validation data are 96.2%, 96.6%, and 93.8% for the respective load conditions. It is further demonstrated that the model can be applied on multiple cell types of similar specifications with an accuracy of about 96.7%. The performance of the model analyzed with the confusion matrices is consistent with the requirements of the automotive industry. The classifier was tested on a Texas F28379D microcontroller unit (MCU) board. The result shows that an average real‐time execution speed of 8.34 μs is possible with a negligible memory occupation

Simple generalizations of Anti-de Sitter space-time

We consider new cosmological solutions which generalize the cosmological patch of the Anti-de Sitter (AdS) space-time, allowing for fluids with equations of state such that $w\neq -1$. We use them to derive the associated full manifolds. We find that these solutions can all be embedded in flat five-dimensional space-time with $--+++$ signature, revealing deformed hyperboloids. The topology and causal-structure of these spaces is therefore unchanged, and closed time-like curves are identified, before a covering space is considered. However the structure of Killing vector fields is entirely different and so we may expect a different structure of Killing horizons in these solutions.Comment: 6 Pages, 5 Figures, Corrections and additions made for publication in Journal of Classical and Quantum Gravit

Cyclic Peptides as Protein Kinase Inhibitors: Structure–Activity Relationship and Molecular Modeling

Under-expression or overexpression of protein kinases has been shown to be associated with unregulated cell signal transduction in cancer cells. Therefore, there is major interest in designing protein kinase inhibitors as anticancer agents. We have previously reported [WR]5, a peptide containing alternative arginine (R) and tryptophan (W) residues as a non-competitive c-Src tyrosine kinase inhibitor. A number of larger cyclic peptides containing alternative hydrophobic and positively charged residues [WR]x (x = 6–9) and hybrid cyclic-linear peptides, [R6K]W6 and [R5K]W7, containing R and W residues were evaluated for their protein kinase inhibitory potency. Among all the peptides, cyclic peptide [WR]9 was found to be the most potent tyrosine kinase inhibitor. [WR]9 showed higher inhibitory activity (IC50 = 0.21 μM) than [WR]5, [WR]6, [WR]7, and [WR]8 with IC50 values of 0.81, 0.57, 0.35, and 0.33 μM, respectively, against c-Src kinase as determined by a radioactive assay using [γ-33P]ATP. Consistent with the result above, [WR]9 inhibited other protein kinases such as Abl kinase activity with an IC50 value of 0.35 μM, showing 2.2-fold higher inhibition than [WR]5 (IC50 = 0.79 μM). [WR]9 also inhibited PKCa kinase activity with an IC50 value of 2.86 μM, approximately threefold higher inhibition than [WR]5 (IC50 = 8.52 μM). A similar pattern was observed against Braf, c-Src, Cdk2/cyclin A1, and Lck. [WR]9 exhibited IC50 values of 9 is consistently more potent than other cyclic peptides with a smaller ring size and hybrid cyclic-linear peptides [R6K]W6 and [R5K]W7 against selected protein kinases. Thus, the presence of R and W residues in the ring, ring size, and the number of amino acids in the structure of the cyclic peptide were found to be critical in protein kinase inhibitory potency. We identified three putative binding pockets through automated blind docking of cyclic peptides [WR](5–9). The most populated pocket is located between the SH2, SH3, and N-lobe domains on the opposite side of the ATP binding site. The second putative pocket is formed by the same domains and located on the ATP binding site side of the protein. Finally, a third pocket was identified between the SH2 and SH3 domains. These results are consistent with the non-competitive nature of the inhibition displayed by these molecules. Molecular dynamics simulations of the protein–peptide complexes indicate that the presence of either [WR]5 or [WR]9 affects the plasticity of the protein and in particular the volume of the ATP binding site pocket in different ways. These results suggest that the second pocket is most likely the site where these peptides bind and offer a plausible rationale for the increased affinity of [WR]9

Association between adenovirus viral load and mortality in pediatric allo-hct recipients. the multinational advance study

This multivariable analysis from the AdVance multicenter observational study assessed adenovirus (AdV) viremia peak, duration, and overall AdV viral burden—measured as time-averaged area under the viremia curve over 16 weeks (AAUC0-16)—as predictors of all-cause mortality in pediatric allo-HCT recipients with AdV viremia. In the 6 months following allo-HCT, 241 patients had AdV viremia ≥ 1000 copies/ml. Among these, 18% (43/241) died within 6 months of first AdV ≥ 1000 copies/ml. Measures of AdV viral peak, duration, and overall burden of infection consistently correlate with all-cause mortality. In multivariable analyses, controlling for lymphocyte recovery, patients with AdV AAUC0-16 in the highest quartile had a hazard ratio of 11.1 versus the lowest quartile (confidence interval 5.3–23.6); for peak AdV viremia, the hazard ratio was 2.2 for the highest versus lowest quartile. Both the peak level and duration of AdV viremia were correlated with short-term mortality, independent of other known risk factors for AdV-related mortality, such as lymphocyte recovery. AdV AAUC0-16, which assesses both peak and duration of AdV viremia, is highly correlated with mortality under the current standard of care. New therapeutic agents that decrease AdV AAUC0-16 have the potential of reducing mortality in this at-risk patient population

The repetitive structure of DNA clamps: An overlooked protein tandem repeat

Structured tandem repeats proteins (STRPs) are a specific kind of tandem repeat proteins characterized by a modular and repetitive three-dimensional structure arrangement. The majority of STRPs adopt solenoid structures, but with the increasing availability of experimental structures and high-quality predicted structural models, more STRP folds can be characterized. Here, we describe “Box repeats”, an overlooked STRP fold present in the DNA sliding clamp processivity factors, which has eluded classification although structural data has been available since the late 1990s. Each Box repeat is a β⍺βββ module of about 60 residues, which forms a class V “beads-on-a-string” type STRP. The number of repeats present in processivity factors is organism dependent. Monomers of PCNA proteins in both Archaea and Eukarya have 4 repeats, while the monomers of bacterial beta-sliding clamps have 6 repeats. This new repeat fold has been added to the RepeatsDB database, which now provides structural annotation for 66 Box repeat proteins belonging to different organisms, including viruses