Draft Genome Sequences of Four NDM-1-Producing Klebsiella pneumoniae Strains from a Health Care Facility in Northern California.

We report the draft genome sequences of Klebsiella pneumoniae strains from four patients at a northern California health care facility. All strains contained the New Delhi metallo-β-lactamase (NDM1) carbapenemase with extended antibiotic resistance, including resistance to expanded-spectrum cephalosporins, imipenem, ertapenem, and meropenem. NDM gene alignments revealed that the resistance was plasmid encoded

Hansen Technologies: MVP Kaizen Event

Hansen Technologies, based in Commerce GA, is a global leader in the production of industrial refrigeration. One of their most profitable product assembly cells, the Multivalve Platform cell, is not currently producing enough to meet increasing demand. The MVP team focused on analyzing and designing a system using Kaizen to improve the throughput of the MVP cell. After conducting a root cause analysis through Gemba and video analysis, key areas were noted for improvement. Small inconsistencies, such as losing grip on the heavy MVP and searching for materials can take a lot of time away from achieving higher throughput levels. By using different concepts such as operator balance charts, time studies, process flow maps, and decision matrices, the MVP team came up with four main solutions to increase the throughput of the cell. A prebuild table would take away the danger and time wasted building on an unstable cart. Adding a simple vise fixture to this table gives the builder a steady option for pre-building MVPs. A new universal fixture was designed to hold each MVP, with different features to aid the builder to improve cycle time. Finally, a full-cell layout redesign was used to improve the flow of material through the entire cell. After implementing these solutions through simulation, the throughput of the cell was expected to increase by at least 10-12 MVPs per day on average, equating to roughly a 30% increase in production

Quantifying Compliance Costs for Small Businesses in New Zealand

This paper reports on a small-scale study of the compliance costs of small New Zealand businesses. Participating firms were asked to keep a record of both time spent and expenditure directly incurred over a thirteen-week period. This differs from previous studies that rely on a firm's recall of how much time has been spent on compliance over the previous year. The results suggest that New Zealand small businesses on average spend less time and money on compliance than has been indicated in previous studies. However a number offirms do perceive compliance to be a major issue and in some cases this perception prevents firms from expanding

Universality of filamentous aggregation phenomena.

We use perturbative renormalization group theory to study the kinetics of protein aggregation phenomena in a unified manner across multiple timescales. Using this approach, we find that, irrespective of the specific molecular details or experimental conditions, filamentous assembly systems display universal behavior in time. Moreover, we show that the universality classes for protein aggregation correspond to simple autocatalytic processes and that the diversity of behavior in these systems is determined solely by the reaction order for secondary nucleation with respect to the protein concentration, which labels all possible universality classes. We validate these predictions on experimental data for the aggregation of several different proteins at several different initial concentrations, which by appropriate coordinate transformations we are able to collapse onto universal kinetic growth curves. These results establish the power of the perturbative renormalization group in distilling the ultimately simple temporal behavior of complex protein aggregation systems, creating the possibility to study the kinetics of general self-assembly phenomena in a unified fashion

One-particle many-body Green's function theory: Algebraic recursive definitions, linked-diagram theorem, irreducible-diagram theorem, and general-order algorithms

A thorough analytical and numerical characterization of the whole perturbation series of one-particle many-body Green’s function (MBGF) theory is presented in a pedagogical manner. Three distinct but equivalent algebraic (first-quantized) recursive definitions of the perturbation series of the Green’s function are derived, which can be combined with the well-known recursion for the self-energy. Six general-order algorithms of MBGF are developed, each implementing one of the three recursions, the ΔMPn method (where n is the perturbation order) [S. Hirata et al., J. Chem. Theory Comput. 11, 1595 (2015)], the automatic generation and interpretation of diagrams, or the numerical differentiation of the exact Green’s function with a perturbation-scaled Hamiltonian. They all display the identical, nondivergent perturbation series except ΔMPn, which agrees with MBGF in the diagonal and frequency-independent approximations at 1≤n≤3 but converges at the full-configuration-interaction (FCI) limit at n=∞ (unless it diverges). Numerical data of the perturbation series are presented for Koopmans and non-Koopmans states to quantify the rate of convergence towards the FCI limit and the impact of the diagonal, frequency-independent, or ΔMPn approximation. The diagrammatic linkedness and thus size-consistency of the one-particle Green’s function and self-energy are demonstrated at any perturbation order on the basis of the algebraic recursions in an entirely time-independent (frequency-domain) framework. The trimming of external lines in a one-particle Green’s function to expose a self-energy diagram and the removal of reducible diagrams are also justified mathematically using the factorization theorem of Frantz and Mills. Equivalence of ΔMPn and MBGF in the diagonal and frequency-independent approximations at 1≤n≤3 is algebraically proven, also ascribing the differences at n = 4 to the so-called semi-reducible and linked-disconnected diagrams

Crosstalk between host stress-induced translational control and infection by Porphyromonas gingivalis

Periodontitis, a chronic inflammatory gum disease, is caused in part by the periodontopathogen Porphyromonas gingivalis. Infection triggers activation of host inflammatory responses which induce stresses such as oxidative stress. Under such conditions, cells can activate the Integrated Stress Response (ISR), a signalling cascade which functions to determine cellular fate, by downregulating protein synthesis and either initiating a stressresponse gene expression program, or if stress cannot be overcome, initiating programmed cell death. Recent studies have implicated the ISR signalling in both host antimicrobial defences and within the pathomechanism of certain microbes. In this study, we investigated how P. gingivalis infection alters translation attenuation during oxidative stress-induced activation of the ISR pathway in oral epithelial cells. P. gingivalis infection alone did not result in ISR activation. In contrast, infection coupled with stress led to differential stress granule formation and composition, along with dysregulation of the microtubule network. Infection also heightened stress-induced translational repression, a response which could not be rescued by ISRIB, a potent ISR inhibitor. Heightened translational repression during stress was observed with both P. gingivalis conditioned media and outer membrane vesicles, implicating the role of a secretory factor, probably proteases known as gingipains, in this exacerbated translational repression. The effects of gingipain inhibitors and gingipains-deficient P. gingivalis mutants further confirmed these pathogen-specific proteases as the effector. Gingipains are known to degrade the mammalian target of rapamycin (mTOR) and these studies implicate the gingipain-mTOR axis as the effector of host translational dysregulation during stress

Nanoscale click-reactive scaffolds from peptide self-assembly.

Background Due to their natural tendency to self-assemble, proteins and peptides are important components for organic nanotechnology. One particular class of peptides of recent interest is those that form amyloid fibrils, as this self-assembly results in extremely strong, stable quasi-one-dimensional structures which can be used to organise a wide range of cargo species including proteins and oligonucleotides. However, as the amyloid state is accessible to a large number of proteins via misfolding, assembly of peptides already conjugated to proteins is limited to certain cargo species. Therefore, a general method is needed to conjugate proteins and other molecules to amyloid fibrils after the fibrils have self-assembled. Results Here we have designed an amyloidogenic peptide based on the TTR105-115 fragment of transthyretin to form fibrils that display an alkyne functionality, important for bioorthogonal chemical reactions, on their surface. The fibrils were formed and reacted both with an azide-containing amino acid and with an azide-functionalised dye by the Huisgen azidoalkyne cycloaddition, one of the class of “click” reactions. Mass spectrometry and total internal reflection fluorescence optical microscopy were used to show that peptides incorporated into the fibrils reacted with the azide while maintaining the structure of the fibril. These click-functionalised amyloid fibrils have a variety of potential uses in materials and as scaffolds for bionanotechnology. Discussion Although previous studies have produced peptides that can both form amyloid fibrils and undergo “click”-type reactions, this is the first example of amyloid fibrils that can undergo such a reaction after they have been formed. Our approach has the advantage that self-assembly takes place before click functionalization rather than pre-functionalised building blocks self-assembling. Therefore, the molecules used to functionalise the fibril do not themselves have to be exposed to harsh, amyloid-forming conditions. This means that a wider range of proteins can be used as ligands in this process. For instance, the fibrils can be functionalised with a green fluorescent protein that retains its fluorescence after it is attached to the fibrils, whereas this protein loses its fluorescence if it is exposed to the conditions used for aggregation