Orbital Magnetism of 2D Chaotic Lattices

We study the orbital magnetism of 2D lattices with chaotic motion of electrons withing a primitive cell. Using the temperature diagrammatic technique we evaluate the averaged value and rms fluctuation of magnetic response in the diffusive regime withing the model of non-interacting electrons. The fluctuations of magnetic susceptibility turn out to be large and at low temperature can be of the order of $\chi_{L} (k_{F}l)^{3/2}$, where $k_{F}$ is the Fermi wavevector, $l$ is the mean free path, and $\chi_{L}$ is the Landau susceptibility. In the certain region of magnetic fields the paramagnetic contribution to the averaged response is field independent and larger than the absolute value of Landau response.Comment: 6 pages, Latex file, figures available upon reques

Process-based classification of Mediterranean cyclones using potential vorticity

This is the final version. Available on open access from Copernicus Publications via the DOI in this recordCode availability:The code for the SOM classification algorithm is openly available at https://www.mathworks.com/help/deeplearning/gs/cluster-data-with-a-self-organizingmap.html (last access: 29 January 2024).Data availability: The composite cyclone tracks with the resulting cluster attribution are available in the supplementary assets of this paper. The track labels correspond to the composite cyclone track dataset at confidence level 5, made available as a Supplement by Flaounas et al. (2023) (“TRACKS_CL5.dat”).Mediterranean cyclones (MCs) govern extreme weather events across the Euro-African Basin, affecting the lives of hundreds of millions. Despite many studies addressing MCs in the last few decades, their correct simulation and prediction remain a significant challenge to the present day, which may be attributed to the large variability among MCs. Past classifications of MCs are primarily based on geographical and/or seasonal separations; however, here we focus on cyclone genesis and deepening mechanisms. A variety of processes combine to govern MC genesis and evolution, including adiabatic and diabatic processes, topographic influences, land-sea contrasts, and local temperature anomalies. As each process bears a distinct signature on the potential vorticity (PV) field, a PV approach is used to distinguish among different "types"of MCs. Here, a combined cyclone-tracking algorithm is used to detect 3190 Mediterranean cyclone tracks in ECMWF ERA5 from 1979-2020. Cyclone-centered, upper-level isentropic PV structures in the peak time of each cyclone track are classified using a self-organizing map (SOM). The SOM analysis reveals nine classes of Mediterranean cyclones, with distinct Rossby-wave-breaking patterns, discernible in corresponding PV structures. Although classified by upper-level PV structures, each class shows different contributions of lower-tropospheric PV and flow structures down to the surface. Unique cyclone life cycle characteristics, associated hazards (precipitation, winds, and temperature anomalies), and long-term trends, as well as synoptic, thermal, dynamical, seasonal, and geographical features of each cyclone class, indicate dominant processes in their evolution. Among others, the classification reveals the importance of topographically induced Rossby wave breaking to the generation of the most extreme Mediterranean cyclones. These results enhance our understanding of MC predictability by linking the large-scale Rossby wave formations and life cycles to coherent classes of under-predicted cyclone aspects.de Botton Center for Marine ScienceIsraeli Council for Higher Education (CHE)Weizmann Data Science Research CenterWeizmann Institute Sustainability and Energy Research Initiative (SAERI

Effect of promoter architecture on the cell-to-cell variability in gene expression

According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect noise in gene expression in a systematic rather than case-by-case fashion. In this article, we make such a systematic investigation, based on a simple microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcription product from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte

Eastern philosophies of education : Buddhist, Hindu, Daoist, and Confucian readings of Plato’s cave

This chapter provides readers with an understanding of some basic principles of selected Eastern traditions and their relation to philosophy of education. The attempt to characterize such diverse traditions and understandings of education raises numerous hermeneutical issues which can only be addressed through a pedagogical reduction as a vehicle for understanding. In this case, we have employed Plato’s cave allegory as that methodological and pedagogical vehicle. We explore aspects of the ontology, epistemology, and ethics of Buddhist, Hindu (focused on classical yoga), Daoist, and Confucian traditions, interpreting elements from Plato’s allegory in order to throw light onto the educational ideas and implications of those Eastern traditions

Different Patterns of Inappropriate Antimicrobial Use in Surgical and Medical Units at a Tertiary Care Hospital in Switzerland: A Prevalence Survey

Audits of individual patient care provide important data to identify local problems in antimicrobial prescription practice. In our study, antimicrobial prescriptions without indication, and divergence from institutional guidelines were frequent errors. Based on these results, we will tailor education, amend institutional guidelines and further develop the infectious diseases consultation service

GTP binding and intramolecular regulation by the ROC domain of Death Associated Protein Kinase 1

The ROCO proteins are a family of large, multidomain proteins characterised by the presence of a Ras of complex proteins (ROC) domain followed by a COR, or C-terminal of ROC, domain. It has previously been shown that the ROC domain of the human ROCO protein Leucine Rich Repeat Kinase 2 (LRRK2) controls its kinase activity. Here, the ability of the ROC domain of another human ROCO protein, Death Associated Protein Kinase 1 (DAPK1), to bind GTP and control its kinase activity has been evaluated. In contrast to LRRK2, loss of GTP binding by DAPK1 does not result in loss of kinase activity, instead acting to modulate this activity. These data highlight the ROC domain of DAPK1 as a target for modifiers of this proteins function, and casts light on the role of ROC domains as intramolecular regulators in complex proteins with implications for a broad range of human diseases

Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis

Vα24-invariant natural killer T (NKT) cells have shown potent anti-tumor properties in murine tumor models and have been linked to favorable outcomes in patients with cancer. However, low numbers of these cells in humans have hindered their clinical applications. Here we report interim results from all three patients enrolled on dose level 1 in a phase 1 dose-escalation trial of autologous NKT cells engineered to co-express a GD2-specific chimeric antigen receptor (CAR) with interleukin-15 in children with relapsed or resistant neuroblastoma (NCT03294954). Primary and secondary objectives were to assess safety and anti-tumor responses, respectively, with immune response evaluation as an additional objective. We ex vivo expanded highly pure NKT cells (mean ± s.d., 94.7 ± 3.8%) and treated patients with 3 × 106 CAR-NKT cells per square meter of body surface area after lymphodepleting conditioning with cyclophosphamide/fludarabine (Cy/Flu). Cy/Flu conditioning was the probable cause for grade 3–4 hematologic adverse events, as they occurred before CAR-NKT cell infusion, and no dose-limiting toxicities were observed. CAR-NKT cells expanded in vivo, localized to tumors and, in one patient, induced an objective response with regression of bone metastatic lesions. These initial results suggest that CAR-NKT cells can be expanded to clinical scale and safely applied to treat patients with cancer

Motion Planning via Manifold Samples

We present a general and modular algorithmic framework for path planning of robots. Our framework combines geometric methods for exact and complete analysis of low-dimensional configuration spaces, together with practical, considerably simpler sampling-based approaches that are appropriate for higher dimensions. In order to facilitate the transfer of advanced geometric algorithms into practical use, we suggest taking samples that are entire low-dimensional manifolds of the configuration space that capture the connectivity of the configuration space much better than isolated point samples. Geometric algorithms for analysis of low-dimensional manifolds then provide powerful primitive operations. The modular design of the framework enables independent optimization of each modular component. Indeed, we have developed, implemented and optimized a primitive operation for complete and exact combinatorial analysis of a certain set of manifolds, using arrangements of curves of rational functions and concepts of generic programming. This in turn enabled us to implement our framework for the concrete case of a polygonal robot translating and rotating amidst polygonal obstacles. We demonstrate that the integration of several carefully engineered components leads to significant speedup over the popular PRM sampling-based algorithm, which represents the more simplistic approach that is prevalent in practice. We foresee possible extensions of our framework to solving high-dimensional problems beyond motion planning.Comment: 18 page

A Soluble Acetylcholinesterase Provides Chemical Defense against Xenobiotics in the Pinewood Nematode

The pinewood nematode genome encodes at least three distinct acetylcholinesterases (AChEs). To understand physiological roles of the three pinewood nematode AChEs (BxACE-1, BxACE-2, and BxACE-3), BxACE-3 in particular, their tissue distribution and inhibition profiles were investigated. Immunohistochemistry revealed that BxACE-1 and BxACE-2 were distributed in neuronal tissues. In contrast, BxACE-3 was detected from some specific tissues and extracted without the aid of detergent, suggesting its soluble nature unlike BxACE-1 and BxACE-2. When present together, BxAChE3 significantly reduced the inhibition of BxACE-1 and BxACE-2 by cholinesterase inhibitors. Knockdown of BxACE-3 by RNA interference significantly increased the toxicity of three nematicidal compounds, supporting the protective role of BxACE-3 against chemicals. In summary, BxACE-3 appears to have a non-neuronal function of chemical defense whereas both BxACE-1 and BxACE-2 have classical neuronal function of synaptic transmission

DNA methylation and histone deacetylation associated with silencing DAP kinase gene expression in colorectal and gastric cancers

Death-associated protein kinase is a positive regulator of programmed cell death induced by interferon γ. To investigate the role of epigenetic inactivation of death-associated protein kinase in gastrointestinal cancer, we examined the methylation status of the 5′ CpG island of the death-associated protein kinase gene. Methylation of the 5′ CpG island was detected in 3 of 9 colorectal and 3 of 17 gastric cancer cell lines, while among primary tumours, it was detected in 4 of 28 (14%) colorectal and 4 of 27 (15%) gastric cancers. By contrast, methylation of the edge of the CpG island was detected in virtually every sample examined. Death-associated protein kinase expression was diminished in four cell lines that showed dense methylation of the 5′ CpG island, and treatment with 5-aza-2′-deoxycitidine, a methyltransferase inhibitor, restored gene expression. Acetylation of histones H3 and H4 in the 5′ region of the gene was assessed by chromatin immunoprecipitation and was found to correlate directly with gene expression and inversely with DNA methylation. Thus, aberrant DNA methylation and histone deacetylation of the 5′ CpG island, but not the edge of the CpG island, appears to play a key role in silencing death-associated protein kinase expression in gastrointestinal malignancies