Cluster optimisation using Cgroups at a tier-2

The Linux kernel feature Control Groups (cgroups) has been used to gather metrics on the resource usage of single and eight-core ATLAS workloads. It has been used to study the effects on performance of a reduction in the amount of physical memory. The results were used to optimise cluster performance, and consequently increase cluster throughput by up to 10%

Topological effects at short antiferromagnetic Heisenberg chains

The manifestations of topological effects in finite antiferromagnetic Heisenberg chains is examined by density matrix renormalization group technique in this paper. We find that difference between integer and half-integer spin chains shows up in ground state energy per site when length of spin chain is longer than $\sim\xi$, where $\xi\sim\exp(\pi S)$ is a spin-spin correlation length, for spin magnitude S up to 5/2. For open chains with spin magnitudes $S=5/2$ to S=5, we verify that end states with fractional spin quantum numbers $S'$ exist and are visible even when the chain length is much smaller than the correlation length $\xi$. The end states manifest themselves in the structure of the low energy excitation spectrum.Comment: 4 pages, 6 figure

DLC1 SAM domain-binding peptides inhibit cancer cell growth and migration by inactivating RhoA

Deleted-in-liver cancer 1 (DLC1) exerts its tumor suppressive function mainly through the Rho-GTPase–activating protein (RhoGAP) domain. When activated, the domain promotes the hydrolysis of RhoA-GTP, leading to reduced cell migration. DLC1 is kept in an inactive state by an intramolecular interaction between its RhoGAP domain and the DLC1 sterile α motif (SAM) domain. We have shown previously that this autoinhibited state of DLC1 may be alleviated by tensin-3 (TNS3) or PTEN. We show here that the TNS3/PTEN-DLC1 interactions are mediated by the C2 domains of the former and the SAM domain of the latter. Intriguingly, the DLC1 SAM domain was capable of binding to specific peptide motifs within the C2 domains. Indeed, peptides containing the binding motifs were highly effective in blocking the C2-SAM domain-domain interaction. Importantly, when fused to the tat protein-transduction sequence and subsequently introduced into cells, the C2 peptides potently promoted the RhoGAP function in DLC1, leading to decreased RhoA activation and reduced tumor cell growth in soft agar and migration in response to growth factor stimulation. To facilitate the development of the C2 peptides as potential therapeutic agents, we created a cyclic version of the TNS3 C2 domain-derived peptide and showed that this peptide readily entered the MDA-MB-231 breast cancer cells and effectively inhibited their migration. Our work shows, for the first time, that the SAM domain is a peptide-binding module and establishes the framework on which to explore DLC1 SAM domain-binding peptides as potential therapeutic agents for cancer treatment

Dynamic interplay of two molecular switches enabled by the MEK1/2–ERK1/2 and IL-6–STAT3 signaling axes controls epithelial cell migration in response to growth factors

Cell migration is an essential physiological process, and aberrant migration of epithelial cells underlies many pathological conditions. However, the molecular mechanisms governing cell migration are not fully understood. We report here that growth factor–induced epithelial cell migration is critically dependent on the crosstalk of two molecular switches, namely phosphorylation switch (P-switch) and transcriptional switch (T-switch). P-switch refers to dynamic interactions of deleted in liver cancer 1 (DLC1) and PI3K with tensin-3 (TNS3), phosphatase and tensin homolog (PTEN), C-terminal tension, and vav guanine nucleotide exchange factor 2 (VAV2) that are dictated by mitogen-activated protein kinase kinase 1/2–extracellular signal–regulated protein kinase 1/2–dependent phosphorylation of TNS3, PTEN, and VAV2. Phosphorylation of TNS3 and PTEN on specific Thr residues led to the switch of DLC1–TNS3 and PI3K–PTEN complexes to DLC1–PTEN and PI3K–TNS3 complexes, whereas Ser phosphorylation of VAV2 promotes the transition of the PI3K–TNS3/PTEN complexes to PI3K–VAV2 complex. T-switch denotes an increase in C-terminal tension transcription/ expression regulated by both extracellular signal–regulated protein kinase 1/2 and signal transducer and activator of transcription 3 (STAT3) via interleukin-6–Janus kinase–STAT3 signaling pathway. We have found that, the P-switch is indispensable for both the initiation and continuation of cell migration induced by growth factors, whereas the T-switch is only required to sustain cell migration. The interplay of the two switches facilitated by the interleukin-6–Janus kinase–STAT3 pathway governs a sequence of dynamic protein–protein interactions for sustained cell migration. That a similar mechanism is employed by both normal and tumorigenic epithelial cells to drive their respective migration suggests that the P-switch and T-switch are general regulators of epithelial cell migration and potential therapeutic targets

NIP/DuoxA is essential for Drosophila embryonic development and regulates oxidative stress response

NIP/DuoxA, originally cloned as a protein capable of binding to the cell fate determinant Numb in Drosophila, was recently identified as a modulator of reactive oxygen species (ROS) production in mammalian systems. Despite biochemical and cellular studies that link NIP/DuoxA to the generation of ROS through the dual oxidase (Duox) enzyme, the in vivo function of NIP/DuoxA has not been characterized to date. Here we report a genetic and functional characterization of nip in Drosophila melanogaster. We show that nip is essential for Drosophila development as nip null mutants die at the 1st larval instar. Expression of UAS-nip, but not UAS-Duox, rescued the lethality. To understand the function of nip beyond the early larval stage, we generated GAL4 inducible UAS-RNAi transgenes. daG32-GAL4 driven, ubiquitous RNAi-mediated silencing of nip led to profound abnormality in pre-adult development, crinkled wing and markedly reduced lifespan at 29°C. Compared to wild type flies, da-GAL4 induced nip-RNAi transgenic flies exhibited significantly reduced ability to survive under oxidative stress and displayed impaired mitochondrial aconitase function. Our work provides in vivo evidence for a critical role for nip in the development and oxidative stress response in Drosophila

Surface loops in a single SH2 domain are capable of encoding the spectrum of specificity of the SH2 family

Src homology 2 (SH2) domains play an essential role in cellular signal transduction by binding to proteins phos-phorylated on Tyr residue. Although Tyr phosphorylation (pY) is a prerequisite for binding for essentially all SH2 domains characterized to date, different SH2 domains prefer specific sequence motifs C-terminal to the pY residue. Because all SH2 domains adopt the same structural fold, it is not well understood how different SH2 domains have acquired the ability to recognize distinct sequence motifs. We have shown previously that the EF and BG loops that connect the secondary structure elements on an SH2 domain dictate its specificity. In this study, we investigated if these surface loops could be engineered to encode diverse specificities. By characterizing a group of SH2 variants selected by different pY peptides from phage-displayed libraries, we show that the EF and BG loops of the Fyn SH2 domain can encode a wide spectrum of specificities, including all three major specificity classes (p 2, p 3 and p 4) of the SH2 domain family. Furthermore, we found that the specificity of a given variant correlates with the sequence feature of the bait peptide used for its isolation, suggesting that an SH2 domain may acquire specificity by co-evolving with its ligand. Intriguingly, we found that the SH2 variants can employ a variety of different mechanisms to confer the same specificity, suggesting the EF and BG loops are highly flexible and adaptable. Our work provides a plausible mechanism for the SH2 domain to acquire the wide spectrum of specificity observed in nature through loop variation with minimal disturbance to the SH2 fold. It is likely that similar mechanisms may have been employed by other modular interaction domains to generate diversity in specificity

Merging binary black holes formed through double-core evolution

Context. To date, various formation channels of merging events have been heavily explored with the detection of nearly 100 double black hole (BH) merger events reported by the LIGO-Virgo-KAGRA (LVK) Collaboration. In this paper, we systematically investigate an alternative formation scenario: binary BHs (BBHs) formed through double helium stars (hereafter, “double-core evolution channel”). In this scenario, two helium stars (He-rich stars) could be the outcome of the classical isolated binary evolution scenario with and without the common envelope (CE) phase (i.e., CE channel and stable mass transfer channel) or, alternatively, of massive close binaries evolving chemically homogeneously (i.e., CHE channel). Aims. We study the properties (i.e., the chirp masses and the effective spins) of BBHs formed through the double-core evolution and investigate the impact of different efficiencies of angular momentum transport within massive He-rich stars on double-core evolution. Methods. We performed detailed stellar structure and binary evolution calculations that take into account internal rotation and mass loss of He-rich stars as well as tidal interactions in binaries. We systematically studied the parameter space of initial binary He-rich stars, including the initial mass and metallicity of He-rich stars as well as initial orbital periods. Apart from direct core collapse with mass and angular momentum conserved, we also follow the framework in Batta & Ramirez-Ruiz (2019, ArXiv e-prints [arXiv:1904.04835]) to estimate the mass and spin of the resulting BHs. Results. We show that the radii of massive He-rich stars decrease as a function of time, which comes mainly from mass loss and mixing in high metallicity and from mixing in low metallicity. For double He-rich stars with equal masses in binaries, we find that tides start to be at work on the zero age helium main sequence (i.e., the time when a He-rich star starts to burn helium in the core, which is analogous to zero age main sequence for core hydrogen burning) for initial orbital periods not longer than 1.0 day, depending on the initial metallicities. In addition to the stellar mass-loss rate and tidal interactions in binaries, we find that the role of the angular momentum transport efficiency in determining the resulting BH spins becomes stronger when considering BH progenitors originated from a higher metal-metallicity environment. We highlight that the double-core evolution scenario does not always produce fast-spinning BBHs and compare the properties of the BBHs reported from the LVK with our modeling. Conclusions. After detailed binary calculations of double-core evolution, we have confirmed that the spin of the BH is not only determined by the interplay of the binary’s different initial conditions (metallicity, mass, and orbital period) but is also dependent on the angular momentum transport efficiency within its progenitor. We predict that with the sensitivity improvements to the LVK’s next observing run (O4), the sample of merging BBHs will contain more sources with positive but moderate (even high) χeff and part of the events will likely show to have been formed through the double-core evolution channel

The transcriptional repressor bs69 is a conserved target of the e1a proteins from several human adenovirus species

Early region 1A (E1A) is the first viral protein produced upon human adenovirus (HAdV) infection. This multifunctional protein transcriptionally activates other HAdV early genes and reprograms gene expression in host cells to support productive infection. E1A functions by interacting with key cellular regulatory proteins through short linear motifs (SLiMs). In this study, the molecular determinants of interaction between E1A and BS69, a cellular repressor that negatively regulates E1A transactivation, were systematically defined by mutagenesis experiments. We found that a minimal sequence comprised of MPNLVPEV, which contains a conserved PXLXP motif and spans residues 112–119 in HAdV-C5 E1A, was necessary and sufficient in binding to the myeloid, Nervy, and DEAF-1 (MYND) domain of BS69. Our study also identified residues P113 and L115 as critical for this interaction. Furthermore, the HAdV-C5 and-A12 E1A proteins from species C and A bound BS69, but those of HAdV-B3,-E4,-D9,-F40, and-G52 from species B, E, D, F, and G, respectively, did not. In addition, BS69 functioned as a repressor of E1A-mediated transactivation, but only for HAdV-C5 and HAdV-A12 E1A. Thus, the PXLXP motif present in a subset of HAdV E1A proteins confers interaction with BS69, which serves as a negative regulator of E1A mediated transcriptional activation

On the stability and uniqueness of the flow of a fluid through a porous medium

© 2016, The Author(s). In this short note, we study the stability of flows of a fluid through porous media that satisfies a generalization of Brinkman’s equation to include inertial effects. Such flows could have relevance to enhanced oil recovery and also to the flow of dense liquids through porous media. In any event, one cannot ignore the fact that flows through porous media are inherently unsteady, and thus, at least a part of the inertial term needs to be retained in many situations. We study the stability of the rest state and find it to be asymptotically stable. Next, we study the stability of a base flow and find that the flow is asymptotically stable, provided the base flow is sufficiently slow. Finally, we establish results concerning the uniqueness of the flow under appropriate conditions, and present some corresponding numerical results