Towards Explaining the Tasks and Roles of the Boards of Directors

While previous research has helped to improve our understanding of corporate governance and boards of directors, less is known about the factors that affect boards’ tasks and roles and directors’ motivation and engagement. This requires knowledge of how board decisions are being made and the internal and external factors that affect the decision-making process. Large inferential leaps have been made from board demographics to firm performance with equivocal results. This thesis concentrates on how the institutional, behavioral and social identification factors impact the enactment of board roles and tasks. Data used in this thesis were collected in 2009 through a mailed survey to Finnish large and middle-sized corporations. The findings suggest that firstly, the national context of an organization is reflected in board roles and shapes how and for what reasons the board roles are carried out; secondly, the directors’ human and external social capital invariably impacts their engagement in board tasks and that conflicts among directors moderate those relationships; finally, directors’ identification with the organization, its shareholders and its customers affect the directors’ involvement in board tasks. By addressing the impact of organisational context, board-internal behaviour and social identification of board members on board roles and tasks, this thesis firstly complements the shareholder supremacy view as the only reason for the board’s involvement with specific tasks; secondly questions the existence of the board as separate from its institutional context; and thirdly questions the view that a board is a ‘black box’, subject to a selection of input demographic variables and producing quantifiable results. The thesis demonstrates that boards are complex organisational bodies, which involve much interaction among board members. Director behaviour and its influence on board decision making is an important determinant of board tasks and boards are likely subjected to inter-group tensions and are susceptible to the influence of internal and external social forces.

The roles of nitrification and nitrate reduction pathways in nitrogen cycling of Baltic Sea

The Baltic Sea is one of the largest brackish water bodies in the world. Primary production in the Baltic Sea is limited by nitrogen (N) availability with the exception of river outlets and the northernmost phosphorus limited basin. The excess human induced N load from the drainage basin has caused severe eutrophication of the sea. The excess N loads can be mitigated by microbe mediated natural N removal processes that are found in the oxic-anoxic interfaces in sediments and water column redoxclines. Such interfaces allow the close coupling between the oxic nitrification process, and anoxic denitrification and anaerobic ammonium oxidation (anammox) processes that lead to the formation of molecular nitrogen gas. These processes are governed by various environmental parameters. The effects of these parameters on N processes were investigated in the northern Baltic Sea sediments. During summer months when the sediment organic content is at its highest, nitrification and denitrification reach their maximum rates. However, nitrification had no excess potential, which was probably because of high competition for molecular oxygen (O2) between heterotrophic and nitrification microbes. Subsequently, the limited nitrate (NO3-) availability inhibited denitrification. In fall, winter and spring, nitrification was limited by ammonium availability and denitrification limited by the availability of organic carbon and occasionally by NO3-. Anaerobic ammonium oxidation (anammox) was not an important N removal process in the northern Baltic Sea. Modeling studies suggest that when hypoxia expands in the Baltic Sea, N removal intensifies. However, the results of this study suggest the opposite because bottom water hypoxia (O2< 2 ml l-1) decreased the denitrification rates in sediments. Moreover, N was recycled by the dissimilatory nitrate reduction to ammonium (DNRA) process instead of being removed from the water ecosystem. High N removal potentials were found in the anoxic water column in the deep basins of the Baltic Proper. However, the N removal in the water column appeared to be limited by low substrate availability, because the water at the depths at which the substrate producing nitrification process occurred, rarely mix with the water at the depths at which N removal processes were found. Overall, the natural N removal capacity of the northern Baltic Sea decreased compared to values measured in mid 1990s and early 2000. The reason for this appears to be increasing hypoxia.

Synergetic roles of concrete ingredients in strength development

Concrete is basically a heterogeneous material made up of ingredients with distinct physical and mechanical properties. As a result, the presence of interphases is inevitable. In the processing of concrete, fresh and hardened states are the two distinct stages. In the fresh state, the presence of inert constituents in the cement mortar matrix only dilutes the overall potential of concrete to flow. In the hardened state the synergetics play a dominant role in strength development. When the strength of coarse aggregate is far higher than the strength levels for which the matrix or concrete is processed, interphase bonding plays a dominant role on the strength. When the matrix strength is comparable to that of the aggregate strength, in contrast, the concrete strength is affected by the aggregate strength. Besides these aspects, the effects of the size and the surface texture of coarse aggregates have also been analysed. Copyright (C) 1996 Elsevier Science Ltd.

Multifaceted roles of curcumin: two sides of a coin!

Introduction: Curcumin has been a front-line topic of mainstream scientific research for a variety of diseases from cancer to Alzheimer's to infectious diseases. Curcumin suppresses the type 1 immune response, which might lead to alleviation of type 1 immune response disorders. However, the inhibition of type 1 immune response might invite infections with opportunistic pathogens. Considering its low bioavailability, several curcumin derivatives have been designed to improve its functionality. Areas covered: This is a consolidated review which aims to compare and contrast diverse aspects of curcumin in variety of diseases. The intricate underlying mechanisms and the functional determinants of curcumin are discussed. Expert opinion: Curcumin being considered as a spicy panacea, is not a remedy for all diseases. However, its ability to act differentially as an antioxidant or pro-oxidant akin to that of a double-edged sword/friend turning foe can be either beneficial or harmful for the host. It exhibits antioxidant properties at concentrations achievable in the body, making the host vulnerable to infections due to the suppression of innate immune responses. With the increase in knowledge of its functional groups, production of analogues of curcumin is underway to enhance its bioavailability and hence its therapeutic potency.

Immunotherapeutic efficacy of Mycobacterium indicus pranii in eliciting anti-tumor T cell responses: Critical roles of IFN gamma

Mycobacterium indicus pranii (MIP) is approved for use as an adjuvant (Immuvac/Cadi-05) in the treatment of leprosy. In addition, its efficacy is being investigated in clinical trials on patients with tuberculosis and different tumors. To evaluate and delineate the mechanisms by which autoclaved MIP enhances anti-tumor responses, the growth of solid tumors consisting of Sp2/0 (myeloma) and EL4 (thymoma) cells was studied in BALB/c and C57BL/6 mice, respectively. Treatment of mice with a single intra-dermal (i.d.) injection of MIP 3 days after Sp2/0 implantation greatly suppresses tumor growth. MIP treatment of tumor bearing mice lowers Interleukin (IL)6 but increases IL12p70 and IFN? amounts in sera. Also, increase in CD8+ T cell mediated lysis of specific tumor targets and production of high amounts of IL2 and IFN? by CD4+ T cells upon stimulation with specific tumor antigens in MIP treated mice is observed. Furthermore, MIP is also effective in reducing the growth of EL4 tumors; however, this efficacy is reduced in Ifn?-/- mice. In fact, several MIP mediated anti-tumor responses are greatly abrogated in Ifn?-/- mice: increase in serum Interleukin (IL)12p70 amounts, induction of IL2 and lysis of EL4 targets by splenocytes upon stimulation with specific tumor antigens. Interestingly, tumor-induced increase in serum IL12p70 and IFN? and reduction in growth of Sp2/0 and EL4 tumors by MIP are not observed in nonobese diabetic severe combined immunodeficiency mice. Overall, our study clearly demonstrates the importance of a functional immune network, in particular endogenous CD4+ and CD8+ T cells and IFN?, in mediating the anti-tumor responses by MIP.

Roles of Salmonella enterica serovar Typhimurium encoded Peptidase N during systemic infection of Ifnγ(-/-) mice.

Pathogen encoded peptidases are known to be important during infection; however, their roles in modulating host responses in immunocompromised individuals are not well studied. The roles of S. typhimurium (WT) encoded Peptidase N (PepN), a major aminopeptidase and sole M1 family member, was studied in mice lacking Interferon-γ (IFNγ), a cytokine important for immunity. S. typhimurium lacking pepN (ΔpepN) displays enhanced colony forming units (CFU) compared to WT in peripheral organs during systemic infection in C57BL/6 mice. However, Ifnγ(-/-) mice show higher CFU compared to C57BL/6 mice, resulting in lower fold differences between WT and ΔpepN. Concomitantly, reintroduction of pepN in ΔpepN (ΔpepN/pepN) reduces CFU, demonstrating pepN-dependence. Interestingly, expression of a catalytically inactive PepN (ΔpepN/E298A) also lowers CFU, demonstrating that the decrease in CFU is independent of the catalytic activity of PepN. In addition, three distinct differences are observed between infection of C57BL/6 and Ifnγ(-/-) mice: First, serum amounts of TNFα and IL1β post infection are significantly lower in Ifnγ(-/-) mice. Second, histological analysis of C57BL/6 mice reveals that damage in spleen and liver upon infection with WT or ΔpepN is greater compared to ΔpepN/pepN or ΔpepN/E298A. On the other hand, Ifnγ(-/-) mice are highly susceptible to organ damage by all strains of S. typhimurium used in this study. Finally, greater survival of C57BL/6, but not Ifnγ(-/-) mice, is observed upon infection with ΔpepN/pepN or ΔpepN/E298A. Overall, the roles of the host encoded IFNγ during infection with S. typhimurium strains with varying degrees of virulence are highlighted.

Distinct Roles of FANCO/RAD51C Protein in DNA Damage Signaling and Repair Implications for Fanconi Anemia and Breast Cancer Susceptibility

RAD51C, a RAD51 paralog, has been implicated in homologous recombination (HR), and germ line mutations in RAD51C are known to cause Fanconi anemia (FA)-like disorder and breast and ovarian cancers. The role of RAD51C in the FA pathway of DNA interstrand cross-link (ICL) repair and as a tumor suppressor is obscure. Here, we report that RAD51C deficiency leads to ICL sensitivity, chromatid-type errors, and G(2)/M accumulation, which are hallmarks of the FA phenotype. We find that RAD51C is dispensable for ICL unhooking and FANCD2 monoubiquitination but is essential for HR, confirming the downstream role of RAD51C in ICL repair. Furthermore, we demonstrate that RAD51C plays a vital role in the HR-mediated repair of DNA lesions associated with replication. Finally, we show that RAD51C participates in ICL and double strand break-induced DNA damage signaling and controls intra-S-phase checkpoint through CHK2 activation. Our analyses with pathological mutants of RAD51C that were identified in FA and breast and ovarian cancers reveal that RAD51C regulates HR and DNA damage signaling distinctly. Together, these results unravel the critical role of RAD51C in the FA pathway of ICL repair and as a tumor suppressor.

Roles of residues in the interface of transient protein-protein complexes before complexation

Transient protein-protein interactions play crucial roles in all facets of cellular physiology. Here, using an analysis on known 3-D structures of transient protein-protein complexes, their corresponding uncomplexed forms and energy calculations we seek to understand the roles of protein-protein interfacial residues in the unbound forms. We show that there are conformationally near invariant and evolutionarily conserved interfacial residues which are rigid and they account for similar to 65% of the core interface. Interestingly, some of these residues contribute significantly to the stabilization of the interface structure in the uncomplexed form. Such residues have strong energetic basis to perform dual roles of stabilizing the structure of the uncomplexed form as well as the complex once formed while they maintain their rigid nature throughout. This feature is evolutionarily well conserved at both the structural and sequence levels. We believe this analysis has general bearing in the prediction of interfaces and understanding molecular recognition.

Pleiotropic Roles of a Ribosomal Protein in Dictyostelium discoideum

The cell cycle phase at starvation influences post-starvation differentiation and morphogenesis in Dictyostelium discoideum. We found that when expressed in Saccharomyces cerevisiae, a D. discoideum cDNA that encodes the ribosomal protein S4 (DdS4) rescues mutations in the cell cycle genes cdc24, cdc42 and bem1. The products of these genes affect morphogenesis in yeast via a coordinated moulding of the cytoskeleton during bud site selection. D. discoideum cells that over-or under-expressed DdS4 did not show detectable changes in protein synthesis but displayed similar developmental aberrations whose intensity was graded with the extent of over-or under-expression. This suggested that DdS4 might influence morphogenesis via a stoichiometric effect - specifically, by taking part in a multimeric complex similar to the one involving Cdc24p, Cdc42p and Bem1p in yeast. In support of the hypothesis, the S. cerevisiae proteins Cdc24p, Cdc42p and Bem1p as well as their D. discoideum cognates could be co-precipitated with antibodies to DdS4. Computational analysis and mutational studies explained these findings: a C-terminal domain of DdS4 is the functional equivalent of an SH3 domain in the yeast scaffold protein Bem1p that is central to constructing the bud site selection complex. Thus in addition to being part of the ribosome, DdS4 has a second function, also as part of a multi-protein complex. We speculate that the existence of the second role can act as a safeguard against perturbations to ribosome function caused by spontaneous variations in DdS4 levels.

Comparative Transcriptomics of H. pylori Strains AM5, SS1 and Their hpyAVIBM Deletion Mutants: Possible Roles of Cytosine Methylation

Helicobacter pylori is an important human pathogen and one of the most successful chronic colonizers of the human body. H. pylori uses diverse mechanisms to modulate its interaction with the host in order to promote chronic infection and overcome host immune response. Restriction-modification genes are a major part of strain-specific genes present in H. pylori. The role of N-6 -adenine methylation in bacterial gene regulation and virulence is well established but not much is known about the effect of C-5 -cytosine methylation on gene expression in prokaryotes. In this study, it was observed by microarray analysis and RT-PCR, that deletion of an orphan C-5 -cytosine methyltransferase, hpyAVIBM in H. pylori strains AM5and SS1 has a significant effect on the expression of number of genes belonging to motility, adhesion and virulence. AM Delta DhpyAVIBM mutant strain has a different LPS profile and is able to induce high IL-8 production compared to wild-type. hpyAVIBM from strain 26695 is able to complement mutant SS1 and AM5 strains. This study highlights a possible significance of cytosine methylation in the physiology of H. pylori.

The multiple and enigmatic roles of guanylyl cyclase C in intestinal homeostasis

Guanylyl cyclase C (GC-C) is predominantly expressed in intestinal epithelial cells and serves as the receptor for the gastrointestinal hormones guanylin and uroguanylin, and the heat-stable enterotoxin, the causative agent for Travellers' Diarrhea. Activation of GC-C results in an increase in intracellular levels of cGMP, which can regulate fluid and ion secretion, colon cell proliferation, and the gut immune system. This review highlights recent findings arising from studies in the GC-C knockout mouse, along with enigmatic results obtained from the first descriptions of human disease caused by mutations in the GC-C gene. We provide some insight into these new findings and comment on areas of future study, which may enhance our knowledge of this evolutionarily conserved receptor and signaling system. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

Relative roles of instruction count and cycles per instruction in WCET estimation

Most of the existing WCET estimation methods directly estimate execution time, ET, in cycles. We propose to study ET as a product of two factors, ET = IC * CPI, where IC is instruction count and CPI is cycles per instruction. Considering directly the estimation of ET may lead to a highly pessimistic estimate since implicitly these methods may be using worst case IC and worst case CPI. We hypothesize that there exists a functional relationship between CPI and IC such that CPI=f(IC). This is ascertained by computing the covariance matrix and studying the scatter plots of CPI versus IC. IC and CPI values are obtained by running benchmarks with a large number of inputs using the cycle accurate architectural simulator, Simplescalar on two different architectures. It is shown that the benchmarks can be grouped into different classes based on the CPI versus IC relationship. For some benchmarks like FFT, FIR etc., both IC and CPI are almost a constant irrespective of the input. There are other benchmarks that exhibit a direct or an inverse relationship between CPI and IC. In such a case, one can predict CPI for a given IC as CPI=f(IC). We derive the theoretical worst case IC for a program, denoted as SWIC, using integer linear programming(ILP) and estimate WCET as SWIC*f(SWIC). However, if CPI decreases sharply with IC then measured maximum cycles is observed to be a better estimate. For certain other benchmarks, it is observed that the CPI versus IC relationship is either random or CPI remains constant with varying IC. In such cases, WCET is estimated as the product of SWIC and measured maximum CPI. It is observed that use of the proposed method results in tighter WCET estimates than Chronos, a static WCET analyzer, for most benchmarks for the two architectures considered in this paper.

Efficient energy transport in photosynthesis: roles of coherence and entanglement

Recently it has been discovered---contrary to expectations of physicists as well as biologists---that the energy transport during photosynthesis, from the chlorophyll pigment that captures the photon to the reaction centre where glucose is synthesised from carbon dioxide and water, is highly coherent even at ambient temperature and in the cellular environment. This process and the key molecular ingredients that it depends on are described. By looking at the process from the computer science view-point, we can study what has been optimised and how. A spatial search algorithmic model based on robust features of wave dynamics is presented.

Biochemical Properties of MutT2 Proteins from Mycobacterium tuberculosis and M. smegmatis and Their Contrasting Antimutator Roles in Escherichia coli

Mycobacterium tuberculosis, the causative agent of tuberculosis, is at increased risk of accumulating damaged guanine nucleotides such as 8-oxo-dGTP and 8-oxo-GTP because of its residency in the oxidative environment of the host macrophages. By hydrolyzing the oxidized guanine nucleotides before their incorporation into nucleic acids, MutT proteins play a critical role in allowing organisms to avoid their deleterious effects. Mycobacteria possess several MutT proteins. Here, we purified recombinant M. tuberculosis MutT2 (MtuMutT2) and M. smegmatis MutT2 (MsmMutT2) proteins from M. tuberculosis (a slow grower) and M. smegmatis (fast growing model mycobacteria), respectively, for their biochemical characterization. Distinct from the Escherichia coli MutT, which hydrolyzes 8-oxo-dGTP and 8-oxo-GTP, the mycobacterial proteins hydrolyze not only 8-oxo-dGTP and 8-oxo-GTP but also dCTP and 5-methyl-dCTP. Determination of kinetic parameters (K-m and V-max) revealed that while MtuMutT2 hydrolyzes dCTP nearly four times better than it does 8-oxo-dGTP, MsmMutT2 hydrolyzes them nearly equally. Also, MsmMutT2 is about 14 times more efficient than MtuMutT2 in its catalytic activity of hydrolyzing 8-oxo-dGTP. Consistent with these observations, MsmMutT2 but not MtuMutT2 rescues E. coli for MutT deficiency by decreasing both the mutation frequency and A-to-C mutations (a hallmark of MutT deficiency). We discuss these findings in the context of the physiological significance of MutT proteins.