Starting from the end: What to do when restricted data is released

© 2017 The Author(s).Repository managers can never be one hundred percent sure of the security of hosted research data. Even assuming that human errors and technical faults will never happen, repositories can be subject to hacking attacks. Therefore, repositories accepting personal/sensitive data (or other forms of restricted data) should have workflows in place with defined procedures to be followed should things go wrong and restricted data is inappropriately released. In this paper we will report on our considerations and procedures when restricted data from our institution was inappropriately released

4-(4-Chloro­phen­yl)-6-meth­oxy-2,2′-bipyridine-5-carbonitrile

There are two independent mol­ecules in the asymmetric unit of the title compound, C18H12ClN3O. The two pyridine rings are almost coplanar [dihedral angles between the rings: 2.87 (15) and 5.36 (16)°] while the chloro­phenyl rings are twisted out of the plane of the adjacent bipyridine ring by 44.1 (1) and 43.8 (1)° in the two mol­ecules. The crystal packing is stabilized by C—H⋯N and C—H⋯Cl inter­actions

Separating the influences of prereading skills on early word and nonword reading

The essential first step for a beginning reader is to learn to match printed forms to phonological representations. For a new word, this is an effortful process where each grapheme must be translated individually (serial decoding). The role of phonological awareness in developing a decoding strategy is well known. We examined whether beginning readers recruit different skills depending on the nature of the words being read (familiar words vs. nonwords). Print knowledge, phoneme and rhyme awareness, rapid automatized naming (RAN), phonological short-term memory (STM), nonverbal reasoning, vocabulary, auditory skills, and visual attention were measured in 392 prereaders 4 and 5 years of age. Word and nonword reading were measured 9 months later. We used structural equation modeling to examine the skills–reading relationship and modeled correlations between our two reading outcomes and among all prereading skills. We found that a broad range of skills were associated with reading outcomes: early print knowledge, phonological STM, phoneme awareness and RAN. Whereas all of these skills were directly predictive of nonword reading, early print knowledge was the only direct predictor of word reading. Our findings suggest that beginning readers draw most heavily on their existing print knowledge to read familiar words

Under What Conditions Can Recursion Be Learned? Effects of Starting Small in Artificial Grammar Learning of Center-Embedded Structure

It has been suggested that external and/or internal limitations paradoxically may lead to superior learning, that is, the concepts of starting small and less is more (Elman,; Newport,). In this paper, we explore the type of incremental ordering during training that might help learning, and what mechanism explains this facilitation. We report four artificial grammar learning experiments with human participants. In Experiments 1a and 1b we found a beneficial effect of starting small using two types of simple recursive grammars: right-branching and center-embedding, with recursive embedded clauses in fixed positions and fixed length. This effect was replicated in Experiment 2 (N = 100). In Experiment 3 and 4, we used a more complex center-embedded grammar with recursive loops in variable positions, producing strings of variable length. When participants were presented an incremental ordering of training stimuli, as in natural language, they were better able to generalize their knowledge of simple units to more complex units when the training input “grew” according to structural complexity, compared to when it “grew” according to string length. Overall, the results suggest that starting small confers an advantage for learning complex center-embedded structures when the input is organized according to structural complexity

Differential Affinity and Catalytic Activity of CheZ in E. coli Chemotaxis

Push–pull networks, in which two antagonistic enzymes control the activity of a messenger protein, are ubiquitous in signal transduction pathways. A classical example is the chemotaxis system of the bacterium Escherichia coli, in which the kinase CheA and the phosphatase CheZ regulate the phosphorylation level of the messenger protein CheY. Recent experiments suggest that both the kinase and the phosphatase are localized at the receptor cluster, and Vaknin and Berg recently demonstrated that the spatial distribution of the phosphatase can markedly affect the dose–response curves. We argue, using mathematical modeling, that the canonical model of the chemotaxis network cannot explain the experimental observations of Vaknin and Berg. We present a new model, in which a small fraction of the phosphatase is localized at the receptor cluster, while the remainder freely diffuses in the cytoplasm; moreover, the phosphatase at the cluster has a higher binding affinity for the messenger protein and a higher catalytic activity than the phosphatase in the cytoplasm. This model is consistent with a large body of experimental data and can explain many of the experimental observations of Vaknin and Berg. More generally, the combination of differential affinity and catalytic activity provides a generic mechanism for amplifying signals that could be exploited in other two-component signaling systems. If this model is correct, then a number of recent modeling studies, which aim to explain the chemotactic gain in terms of the activity of the receptor cluster, should be reconsidered

Angiotensin-(1–7) and the G Protein-Coupled Receptor Mas Are Key Players in Renal Inflammation

Angiotensin (Ang) II mediates pathophysiologial changes in the kidney. Ang-(1–7) by interacting with the G protein-coupled receptor Mas may also have important biological activities

Geometric and Electronic Structures of the NiI and Methyl−NiIII Intermediates of Methyl-Coenzyme M Reductase†

ABSTRACT: Methyl-coenzyme M reductase (MCR) catalyzes the terminal step in the formation of biological methane from methyl-coenzyme M (Me-SCoM) and coenzyme B (CoBSH). The active site in MCR contains a Ni-F430 cofactor, which can exist in different oxidation states. The catalytic mechanism of methane formation has remained elusive despite intense spectroscopic and theoretical investigations. On the basis of spectroscopic and crystallographic data, the first step of the mechanism is proposed to involve a nucleophilic attack of the NiI active state (MCRred1) on Me-SCoM to form a NiIII-methyl intermediate, while computational studies indicate that the first step involves the attack of NiI on the sulfur of Me-SCoM, forming a CH3 radical and a NiII-thiolate species. In this study, a combination of Ni K-edge X-ray absorption spectroscopic (XAS) studies and density functional theory (DFT) calculations have been performed on the NiI (MCRred1), NiII (MCRred1-silent), and NiIII-methyl (MCRMe) states of MCR to elucidate the geometric and electronic structures of the different redox states. Ni K-edge EXAFS data are used to reveal a five-coordinate active site with an open upper axial coordination site in MCRred1. Ni K-pre-edge and EXAFS data and time-dependent DFT calculations unambiguously demonstrate the presence of a long Ni-C bond (∼2.04 Å) in the NiIII-methyl state of MCR. The formation and stability of this species support mechanism I, and the Ni-C bond length suggests a homolytic cleavage of the NiIII-methyl bon

FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa

Pseudomonas aeruginosa, a ubiquitous bacteria found in diverse ecological niches, is an important cause of acute infections in immunocompromised individuals and chronic infections in patients with Cystic Fibrosis. One signaling molecule required for the coordinate regulation of virulence factors associated with acute infections is 3′, 5′-cyclic adenosine monophosphate, (cAMP), which binds to and activates a catabolite repressor homolog, Vfr. Vfr controls the transcription of many virulence factors, including those associated with Type IV pili (TFP), the Type III secretion system (T3SS), the Type II secretion system, flagellar-mediated motility, and quorum sensing systems. We previously identified FimL, a protein with histidine phosphotransfer-like domains, as a regulator of Vfr-dependent processes, including TFP-dependent motility and T3SS function. In this study, we carried out genetic and physiologic studies to further define the mechanism of action of FimL. Through a genetic screen designed to identify suppressors of FimL, we found a putative cAMP-specific phosphodiesterase (CpdA), suggesting that FimL regulates cAMP levels. Inactivation of CpdA increases cAMP levels and restores TFP-dependent motility and T3SS function to fimL mutants, consistent with in vivo phosphodiesterase activity. By constructing combinations of double and triple mutants in the two adenylate cyclase genes (cyaA and cyaB), fimL, and cpdA, we show that ΔfimL mutants resemble ΔcyaB mutants in TM defects, decreased T3SS transcription, and decreased cAMP levels. Similar to some of the virulence factors that they regulate, we demonstrate that CyaB and FimL are polarly localized. These results reveal new complexities in the regulation of diverse virulence pathways associated with acute P. aeruginosa infections