Ordering the cytochrome c-initiated caspase cascade:hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner

Exit of cytochrome c from mitochondria into the cytosol has been implicated as an important step in apoptosis. In the cytosol, cytochrome c binds to the CED-4 homologue, Apaf-1, thereby triggering Apaf-1-mediated activation of caspase-9. Caspase-9 is thought to propagate the death signal by triggering other caspase activation events, the details of which remain obscure. Here, we report that six additional caspases (caspases-2, -3, -6, -7, -8, and -10) are processed in cell-free extracts in response to cytochrome c, and that three others (caspases-1, -4, and -5) failed to be activated under the same conditions. In vitro association assays confirmed that caspase-9 selectively bound to Apaf-1, whereas caspases-1, -2, -3, -6, -7, -8, and -10 did not. Depletion of caspase-9 from cell extracts abrogated cytochrome c-inducible activation of caspases-2, -3, -6, -7, -8, and -10, suggesting that caspase-9 is required for all of these downstream caspase activation events. Immunodepletion of caspases-3, -6, and -7 from cell extracts enabled us to order the sequence of caspase activation events downstream of caspase-9 and reveal the presence of a branched caspase cascade. Caspase-3 is required for the activation of four other caspases (-2, -6, -8, and -10) in this pathway and also participates in a feedback amplification loop involving caspase-9.

Dense Multiperson Tracking with Robust Hierarchical Linear Assignment

We introduce a novel dual-stage algorithm for online multi-target tracking in realistic conditions. In the first stage, the problem of data association between tracklets and detections, given partial occlusion, is addressed using a novel occlusion robust appearance similarity method. This is used to robustly link tracklets with detections without requiring explicit knowledge of the occluded regions. In the second stage, tracklets are linked using a novel method of constraining the linking process that removes the need for ad-hoc tracklet linking rules. In this method, links between tracklets are permitted based on their agreement with optical flow evidence. Tests of this new tracking system have been performed using several public datasets.

Hierarchical demand response using dantzig-wolfe decomposition

Demand Side Management (DSM) programmes are designed to shift electrical loads from peak times. Demand Response (DR) algorithms automate this process for controllable loads. DR can be implemented explicitly in terms of Peak to Average Ratio Reduction (PARR), in which case the maximum peak load is minimised over a prediction horizon by manipulating the amount of energy given to controllable loads at different times. A hierarchical predictive PARR algorithm is presented here based on Dantzig-Wolfe decomposition. © 2013 IEEE.

RAS testing of colorectal carcinoma—a guidance document from the Association of Clinical Pathologists Molecular Pathology and Diagnostics Group

Analysis of colorectal carcinoma (CRC) tissue for KRAS codon 12 or 13 mutations to guide use of anti-epidermal growth factor receptor (EGFR) therapy is now considered mandatory in the UK. The scope of this practice has been recently extended because of data indicating that NRAS mutations and additional KRAS mutations also predict for poor response to anti-EGFR therapy. The following document provides guidance on RAS (i.e., KRAS and NRAS) testing of CRC tissue in the setting of personalised medicine within the UK and particularly within the NHS. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such RAS testing.

Markievicz Commission Report: Gender equality document

Report on implementation of the candidate gender quota in the Fianna Fail Party.

Hierarchical Demand Response for Peak Reduction using Dantzig‐Wolfe Decomposition

Demand Response (DR) algorithms manipulate the energy consumption schedules of controllable loads so as to satisfy grid objectives. Implementation of DR algorithms using a centralised agent can be problematic for scalability reasons, and there are issues related to the privacy of data and robustness to communication failures. Thus it is desirable to use a scalable decentralised algorithm for the implementation of DR. In this paper, a hierarchical DR scheme is proposed for Peak Minimisation (PM) based on Dantzig-Wolfe Decomposition (DWD). In addition, a Time Weighted Maximisation option is included in the cost function which improves the Quality of Service for devices seeking to receive their desired energy sooner rather than later. The paper also demonstrates how the DWD algorithm can be implemented more efficiently through the calculation of the upper and lower cost bounds after each DWD iteration.

Latent and Explicit Authority in Hierarchical Organizations

We consider the problem of the exercise of authority within social production organizations, embedding the decision makers into a structure of formal authority relationships. We distinguish two types of behavior. First, we introduce an equilibrium notion implementing latent authority under which subordinates submit themselves to authority even though such authority is not en- forced explicitly. Second, we compare this with a non-cooperative equilibrium concept describing explicit exercise of authority. We show that for low enough enforcement costs both forms of authority will be exercised in equilibrium, but for higher enforcement costs latent authority will be exercised while explicit authority will not.

Hierarchical energy management system for multi-source multi-product microgrids

This paper proposes a hierarchical energy management system for multi-source multi-product (MSMP) microgrids. Traditional energy hub based scheduling method is combined with a hierarchical control structure to incorporate transient characteristics of natural gas flow and dynamics of energy converters in microgrids. The hierarchical EMS includes a supervisory control layer, an optimizing control layer, and an execution control layer. In order to efficiently accommodate the systems multi time-scale characteristics, the optimizing control layer is decomposed into three sub-layers: slow, medium and fast. Thermal, gas and electrical management systems are integrated into the slow, medium, and fast control layer, respectively. Compared with wind energy, solar energy is easier to integrate and more suitable for the microgrid environment, therefore, potential impacts of the hierarchical EMS on MSMP microgrids is investigated based on a building energy system integrating photovoltaic and microturbines. Numerical studies indicate that by using a hierarchical EMS, MSMP microgrids can be economically operated. Also, interactions among thermal, gas, and electrical system can be effectively managed.

In situ preparation of 3D graphene aerogels@hierarchical Fe3O4 nanoclusters as high rate and long cycle anode materials for lithium ion batteries

We describe a novel strategy for in situ fabrication of hierarchical Fe₃O₄ nanoclusters-GAs. Fe₃O₄ NCs-GAs deliver excellent rate capability (the reversible capacities obtained were 1442, 392 and 118 mA h g^-1 at 0.1C, 12C and 35C rates), and a high reversible capacity of 577 mA h g^-1 over 300 cycles at the current density of 5.2 A g^-1 (6C).

Interpretable and Reconfigurable Clustering of Document Datasets by Deriving Word-based Rules

Clusters of text documents output by clustering algorithms are often hard to interpret. We describe motivating real-world scenarios that necessitate reconfigurability and high interpretability of clusters and outline the problem of generating clusterings with interpretable and reconfigurable cluster models. We develop two clustering algorithms toward the outlined goal of building interpretable and reconfigurable cluster models. They generate clusters with associated rules that are composed of conditions on word occurrences or nonoccurrences. The proposed approaches vary in the complexity of the format of the rules; RGC employs disjunctions and conjunctions in rule generation whereas RGC-D rules are simple disjunctions of conditions signifying presence of various words. In both the cases, each cluster is comprised of precisely the set of documents that satisfy the corresponding rule. Rules of the latter kind are easy to interpret, whereas the former leads to more accurate clustering. We show that our approaches outperform the unsupervised decision tree approach for rule-generating clustering and also an approach we provide for generating interpretable models for general clusterings, both by significant margins. We empirically show that the purity and f-measure losses to achieve interpretability can be as little as 3 and 5%, respectively using the algorithms presented herein.