Anomaly detection in virtual machine logs against irrelevant attribute interference.

Virtual machine logs are generated in large quantities. Virtual machine logs may contain some abnormal logs that indicate security risks or system failures of the virtual machine platform. Therefore, using unsupervised anomaly detection methods to identify abnormal logs is a meaningful task.

Nanobody-assisted nanoluciferase fragment complementation for in situ measurement and visualization of endogenous protein-protein interaction.

Here, we developed nanobody-assisted nanoluciferase fragment complementation for in situ measurement and visualization of endogenous protein-protein interaction (NanaPPI). When an interaction occurs, primary antibodies for two proteins bring the proximity of secondary nanobody-fused small/large fragment to reassemble into an intact NanoLuc variant, thus transforming interaction events to luminescent signals in situ with high sensitivity. Compared to proximity ligation assay, NanaPPI has a similar signal-to-background ratio, but it is more convenient with faster procedures, easier readout and lower cost.

Nonionic Water-Soluble Oligo(ethylene glycol)-Modified Polypeptides with a β-Sheet Conformation.

The secondary structures of polypeptides, such as an α-helix and a β-sheet, often impart specific properties and functions, making the regulation of their secondary structures of great significance. Particularly, water-soluble polypeptides bearing a β-sheet conformation are rare and challenging to achieve. Here, a series of oligo(ethylene glycol)-modified lysine -carboxylic anhydrides (K-NCA, where = 1-3) and the corresponding polymers K are synthesized, with urethane bonds as the linker between the side-chain EG and lysine.

Hydration processes of barium chloride: Size-selected anion photoelectron spectroscopy and theoretical calculations of BaCl-water clusters.

In order to understand the hydration processes of BaCl, we investigated BaCl(HO) (n = 0-5) clusters using size-selected anion photoelectron spectroscopy and theoretical calculations. The structures of neutral BaCl(HO) clusters up to n = 8 were also investigated by theoretical calculations. It is found that in BaCl(HO) , the Ba-Cl distances increase very slowly with the cluster size.

Superresolution imaging reveals spatiotemporal propagation of human replication foci mediated by CTCF-organized chromatin structures.

Mammalian DNA replication is initiated at numerous replication origins, which are clustered into thousands of replication domains (RDs) across the genome. However, it remains unclear whether the replication origins within each RD are activated stochastically or preferentially near certain chromatin features. To understand how DNA replication in single human cells is regulated at the sub-RD level, we directly visualized and quantitatively characterized the spatiotemporal organization, morphology, and in situ epigenetic signatures of individual replication foci (RFi) across S-phase at superresolution using stochastic optical reconstruction microscopy.

Synthesis of Trifluoromethyl- and Ester Group-Substituted α-Carbolines via Iron-Catalyzed Tandem Cyclization Reaction.

An efficient approach to prepare trifluoromethyl-α-carbolines and ester group-substituted α-carbolines via the tandem cyclization reaction of 2-(2-aminophenyl)acetonitriles and trifluoromethyl 1,3-diones or β,γ-unsaturated α-ketoesters was reported. The transformation proceeded smoothly in the presence of catalytic environmental-benign iron salts, which are used to prepare the desired products in moderate to good yields.

Organic Semiconducting Alloys with Tunable Energy Levels.

Continuous band structure tuning, e.g., doping with different atoms, is one of the most important features of inorganic semiconductors.

Microscopic Insight into the Protein Denaturation Action of Urea and Its Methyl Derivatives.

We employ site-specific, linear and nonlinear infrared spectroscopic techniques as well as fluorescence spectroscopy and molecular dynamics simulations to investigate the binding interactions of urea and three of its derivatives, methylurea, 1,3-dimethylurea, and tetramethylurea, with protein aromatic and polar side chains. We find that (1) urea methylation leads to preferential interactions between the cosolvent molecules and aromatic side chains with an affinity that increases with the number of methyl groups; (2) interactions with tetramethylurea cause significant dehydration of aromatic side chains and the effect is most pronounced for tryptophan; and (3) while neither urea nor tetramethylurea shows preferential accumulation around a polar side chain, the number of hydrogen-bond donors around this side chain is significantly decreased in the presence of tetramethylurea. Taken together, our findings suggest that these urea derivatives, especially tetramethylurea, can effectively disrupt hydrophobic interactions in proteins.

The opposite effects of sodium and potassium cations on water dynamics.

Water rotational dynamics in NaSCN and KSCN solutions at a series of concentrations are investigated using femtosecond infrared spectroscopy and theory. Femtosecond infrared measurements, consistent with previous NMR observations, detect that sodium slows down while potassium accelerates the water O-H bond rotation. Results of reported neutron scattering measurements, on the other hand, suggested that these two cations have similar structure-breaking effects on water, and therefore should both accelerate water rotation through the presumably dominating large-amplitude angular jump component.

Combine umbrella sampling with integrated tempering method for efficient and accurate calculation of free energy changes of complex energy surface.

Umbrella sampling is an efficient method for the calculation of free energy changes of a system along well-defined reaction coordinates. However, when there exist multiple parallel channels along the reaction coordinate or hidden barriers in directions perpendicular to the reaction coordinate, it is difficult for conventional umbrella sampling to reach convergent sampling within limited simulation time. Here, we propose an approach to combine umbrella sampling with the integrated tempering sampling method.

Inhibitory mechanism of caspase-6 phosphorylation revealed by crystal structures, molecular dynamics simulations, and biochemical assays.

The apoptotic effector caspase-6 (CASP6) has been clearly identified as a drug target due to its strong association with neurodegeneration and axonal pruning events as well as its crucial roles in Huntington disease and Alzheimer disease. CASP6 activity is suppressed by ARK5-mediated phosphorylation at Ser(257) with an unclear mechanism. In this work, we solved crystal structures of ΔproCASP6S257E and p20/p10S257E, which mimicked the phosphorylated CASP6 zymogen and activated CASP6, respectively.

Molecular dynamics and ion mobility spectrometry study of model β-hairpin peptide, trpzip1.

Here, we explore the conformations of gas phase, protonated tryptophan zipper 1 (trpzip1) ions and its six derivatives by an enhanced sampling molecular dynamics, specially the integrated tempering sampling molecular dynamics simulation (ITS-MDS). The structural distributions obtained from ITS-MDS are compared with results obtained from matrix-assisted laser desorption ionization (MALDI)-ion mobility-mass spectrometry (IM-MS). The IM-MS measured collision cross-section (CCS) profiles compare well with the calculated CCS profiles obtained from ITS-MDS.

A combined theoretical and experimental study of the ammonia tunnel in carbamoyl phosphate synthetase.

The transfer of ammonia in carbamoyl phosphate synthetase (CPS) was investigated by molecular dynamics simulations and experimental characterization of mutations within the ammonia tunnel. In CPS, ammonia is derived from the hydrolysis of glutamine and this intermediate must travel approximately 45 A from the site of formation in the small subunit to the site of utilization in the large subunit. In this investigation, the migration of ammonia was analyzed from the exit of the small subunit through the large subunit where it ultimately reacts with the carboxy phosphate intermediate.

Mechanism for the transport of ammonia within carbamoyl phosphate synthetase determined by molecular dynamics simulations.

Carbamoyl phosphate synthetase (CPS) is a member of the amidotransferase family of enzymes that uses the hydrolysis of glutamine as a localized source of ammonia for biosynthetic transformations. Molecular dynamics simulations for the transfer of ammonia and ammonium through a tunnel in the small subunit of CPS resulted in five successful trajectories for ammonia transfer, while ammonium was immobilized in a water pocket inside the small subunit of the heterodimeric protein. The observed molecular tunnel for ammonia transport is consistent with that suggested by earlier X-ray crystallography and site-directed mutation studies.