bluuebunny/crossref_metadata_2025 huggingface dataset:
Competition of hydrophobic and Coulombic interactions between nanosized solutes
Authors: Dzubiella J. , Hansen J.-P.
Published: September 2004

The solvation of charged, nanometer-sized spherical solutes in water, and the effective, solvent-induced force between two such solutes are investigated by constant temperature and pressure molecular dynamics simulations of model solutes carrying various charge patterns. The results for neutral solutes agree well with earlier findings, and with predictions of simple macroscopic considerations: substantial hydrophobic attraction may be traced back to strong depletion (“drying”) of the solvent between the solutes. This hydrophobic attraction is strongly reduced when the solutes are uniformly charged, and the total force becomes repulsive at sufficiently high charge; there is a significant asymmetry between anionic and cationic solute pairs, the latter experiencing a lesser hydrophobic attraction. The situation becomes more complex when the solutes carry discrete (rather than uniform) charge patterns. Due to antagonistic effects of the resulting hydrophilic and hydrophobic “patches” on the solvent molecules, water is once more significantly depleted around the solutes, and the effective interaction reverts to being mainly attractive, despite the direct electrostatic repulsion between solutes. Examination of a highly coarse-grained configurational probability density shows that the relative orientation of the two solutes is very different in explicit solvent, compared to the prediction of the crude implicit solvent representation. The present study strongly suggests that a realistic modeling of the charge distribution on the surface of globular proteins, as well as the molecular treatment of water, are essential prerequisites for any reliable study of protein aggregation.
Mechanism of anion formation in C 1s→π*-excited carbon dioxide
Authors: Rühl E. , Flesch R.
Published: September 2004

The mechanism of anion formation from core-excited carbon dioxide is investigated in the C 1s-excitation regime (280–340 eV), where negative-ion–positive-ion coincidences and negative-ion–positive-ion–positive-ion coincidences experiments are performed. O− formation occurs efficiently upon C 1s→π*-excitation (290.7 eV) from the singly charged cation CO2+. This anion is measured in coincidence with the singly charged atoms C+ and O+. The formation of atomic cations is accompanied by a substantial kinetic energy release. This suggests that an intermediate CO++ is formed together with O−, where the dication decays via fission. The results are discussed in terms of an anion formation mechanism from core-excited molecules considering previous experimental results.
Solvent effects on electronic properties from Wannier functions in a dimethyl sulfoxide/water mixture
Authors: Kirchner Barbara , Hutter Jürg
Published: September 2004

We present an efficient implementation for the calculation of maximally localized Wannier functions (MLWFs) during parallel Car-Parrinello molecular dynamics simulations. The implementation is based on a block Jacobi method. The calculation of MLWFs results in only a moderate (10%–20%) increase in computer time. Consequently it is possible to calculate MLWFs routinely during Car-Parrinello simulations. The Wannier functions are then applied to derive molecular dipole moments of dimethyl sulfoxide (DMSO) in gas phase and aqueous solution. We observe a large increase of the local dipole moment from 3.97 to 7.39 D. This large solvent effect is caused by strong hydrogen bonding at the DMSO oxygen atom and methyl groups. Decomposing the dipole moment into local contributions from the S-O bond and the methyl groups is used to understand the electrostatic response of DMSO in aqueous solution. A scheme is given to derive charges on individual atoms from the MLWFs using the D-RESP methodology. The charges also display large solvent effects and give insight into the transferability of recent force field models for DMSO.
Freezing on heating of liquid solutions
Authors: Plazanet M. , Floare C. , Johnson M. R. , Schweins R. , Trommsdorff H. P.
Published: September 2004

We report a reversible liquid–solid transition upon heating of a simple solution composed of a-cyclodextrine (αCD), water, and 4-methylpyridine. These solutions are homogeneous and transparent at ambient temperature and solidify when heated to temperatures between 45° and 75°. Quasielastic and elastic neutron scattering show that molecular motions are slowed down in the solid and that crystalline order is established. The solution “freezes on heating.” This process is fully reversible, on cooling the solid melts. A rearrangement of hydrogen bonds is postulated to be responsible for the observed phenomenon.
Stimulated emission three-pulse photo-echo peakshift: A mixed pump–probe and photon-echo technique for studying excited-state dynamics
Authors: Larsen Delmar S.
Published: September 2004

A novel four-pulse photon-echo technique for exploring condensed phase dynamics at different parts of the excited-state potential energy surface is presented. In contrast to traditional three-pulse photon-echo signals, the introduction of a fourth pump pulse allows the use of photon-echo techniques to probe excited-state phenomena. Here, a “proof of principle” experiment is presented where the excited-state solvent dynamics of the coumarin 153 chromophore dissolved in methanol is explored. The fluctuations of the stimulated emission transition is probed, in contrast to the ground-state absorption transition explored in traditional echo measurements. Distinctly different excited-state dynamics, in contrast to ground-state signals, is observed and discussed.
Fluorescent Sugar and Uridine Conjugates of 1,8-Naphthalimides with Methyl and Ferrocenyl Headgroups
Authors: Cavigiolio Giorgio , Morgan Joy L. , Robinson Brian H. , Simpson Jim
Published: September 2004

The first amphiphilic sugar and deoxyuridine conjugates with a 4-ethynyl-1,8-N-methylnaphthalimide linker, a 4-ethynyldeoxyuridine conjugate with a N-undecylferrocenyl headgroup, and a 1,8-naphthalimide with a 2,3,4,6-tetra-O-acetate-β-d-glucopyranoside headgroup have been synthesized. A novel acrylate monomeric precursor for sugar–ethynylnaphthalimide polymers is also reported. The ethynyl tether forms complexes with Co2(CO)8 and Co2(CO)6dppm. The single-crystal X-ray structures of 2′-propynyl-2,3,4,6-tetra-O-acetate-β-d-glucopyranoside 4 and 4-(2′-propynyl-2,3,4,6-tetra-O-acetate-β-d-glucopyranoside)-N-methyl-1,8-naphthalimide 6 are also reported. With the exception of the Co2 complexes, the sugar and deoxyuridine conjugates are strongly fluorescent. ‘On–off’ fluorescent switching is achieved in the deoxyuridine conjugate with an undecylferrocenyl headgroup.
The Design of Drugs that Target Tumour Hypoxia
Authors: Denny William A.
Published: September 2004

The occurrence of hypoxia in solid tumours is increasingly recognized as a limiting factor in the success of both radiotherapy and chemotherapy treatment, but at the same time offers a tumour-specific phenomenon for the activation of prodrugs. However, the design of clinically useful prodrugs that can be selectively activated in hypoxic cells has proved elusive. Specific reasons (activation by oxygen-insensitive two-electron reductases) have been proposed for the failure of quinone-based prodrugs, but a more general contributing factor may be inappropriate clinical trial design, and the failure to understand the critical importance of drug properties, such as efficient extra-vascular diffusion of the prodrug and back-diffusion of the activated drug in the tumour. Activation of prodrugs by therapeutic radiation and the use of hypoxia-selective gene therapy vectors, such as Clostridia, are exciting new mechanisms for prodrug research to explore, but are in much earlier stages of evaluation.
Peptidic Aldehydes Based on α- and β-Amino Acids: Synthesis, Inhibition of m-Calpain, and Anti-Cataract Properties
Authors: Payne Richard J. , Brown Karina M. , Coxon James M. , Morton James D. , Lee Hannah Yun-Young , Abell Andrew D.
Published: September 2004

We present a new synthesis of SJA6017 (a potent m-calpain inhibitor) and its adaptation in order to prepare analogues in which the constituent Leu and Val residues are systematically replaced with their corresponding β-amino acids and/or the N-terminal fluorophenylsulfonyl group is replaced by a water solubilizing N-pyridin-3-ylmethoxycarbonyl group. All compounds have been assayed against m-calpain, and the best inhibitor, SJA6017, has been shown to inhibit the development of opacity in a lens culture system design to mimic cataract.
The Synthesis of N-Ribosyl Transferase Inhibitors Based on a Transition State Blueprint
Authors: Evans Gary B.
Published: September 2004

A quarter of a century ago transition state analysis and transition state analogue design promised the prospect of extraordinarily potent enzyme inhibitors. The present overview describes the transition state analysis of a variety of N-ribosyl transferases, the design and synthesis of extremely powerful transition state analogue inhibitors of these nucleoside processing enzymes, and their current therapeutic uses and potentials.
A
Populus
EST resource for plant functional genomics
Authors: Sterky Fredrik , Bhalerao Rupali R. , Unneberg Per , Segerman Bo , Nilsson Peter , Brunner Amy M. , Charbonnel-Campaa Laurence , Lindvall Jenny Jonsson , Tandre Karolina , Strauss Steven H. , Sundberg Björn , Gustafsson Petter , Uhlén Mathias , Bhalerao Rishikesh P. , Nilsson Ove , Sandberg Göran , Karlsson Jan , Lundeberg Joakim , Jansson Stefan
Published: September 2004

Trees present a life form of paramount importance for terrestrial ecosystems and human societies because of their ecological structure and physiological function and provision of energy and industrial materials. The genus
Populus
is the internationally accepted model for molecular tree biology. We have analyzed 102,019
Populus
ESTs that clustered into 11,885 clusters and 12,759 singletons. We also provide >4,000 assembled full clone sequences to serve as a basis for the upcoming annotation of the
Populus
genome sequence. A public web-based EST database (
populusdb
) provides digital expression profiles for 18 tissues that comprise the majority of differentiated organs. The coding content of
Populus
and
Arabidopsis
genomes shows very high similarity, indicating that differences between these annual and perennial angiosperm life forms result primarily from differences in gene regulation. The high similarity between
Populus
and
Arabidopsis
will allow studies of
Populus
to directly benefit from the detailed functional genomic information generated for
Arabidopsis
, enabling detailed insights into tree development and adaptation. These data will also valuable for functional genomic efforts in
Arabidopsis
.
Inactivation of a bacterial virulence pheromone by phagocyte-derived oxidants: New role for the NADPH oxidase in host defense
Authors: Rothfork Jacob M. , Timmins Graham S. , Harris Michael N. , Chen Xian , Lusis Aldons J. , Otto Michael , Cheung Ambrose L. , Gresham Hattie D.
Published: September 2004

Quorum sensing triggers virulence factor expression in medically important bacterial pathogens in response to a density-dependent increase in one or more autoinducing pheromones. Here, we show that phagocyte-derived oxidants target these autoinducers for inactivation as an innate defense mechanism of the host. In a skin infection model, expression of phagocyte NADPH oxidase, myeloperoxidase, or inducible nitric oxide synthase was critical for defense against a quorum-sensing pathogen,
Staphylococcus aureus
, but not for defense against a quorum sensing-deficient mutant. A virulence-inducing peptide of
S. aureus
was inactivated
in vitro
and
in vivo
by reactive oxygen and nitrogen intermediates, including HOCl and ONOO
–
. Inactivation of the autoinducer prevented both the up-regulation of virulence gene expression and the downstream sequelae. MS analysis of the inactivated peptide demonstrated that oxidation of the C-terminal methionine was primarily responsible for loss of activity. Treatment of WT but not NADPH oxidase-deficient mice with
N-
acetyl methionine to scavenge the inhibitory oxidants increased
in vivo
quorum sensing independently of the bacterial burden at the site of infection. Thus, oxidant-mediated inactivation of an autoinducing peptide from
S. aureus
is a critical innate defense mechanism against infection with this pathogen.
A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice
Authors: Dufresne Andrew T. , Gromeier Matthias
Published: September 2004

Coxsackievirus A21 (CAV21) is classified within the species
Human enterovirus C
(HEV-C) of the
Enterovirus
genus of picornaviruses. HEV-C share striking homology with the polioviruses (PV), their closest kin among the enteroviruses. Despite a high level of sequence identity, CAV21 and PV cause distinct clinical disease typically attributed to their differential use of host receptors. PV cause poliomyelitis, whereas CAV21 shares a receptor and a propensity to cause upper respiratory tract infections with the major group rhinoviruses. As a model for CAV21 infection, we have developed transgenic mice that express human intercellular adhesion molecule 1, the cell-surface receptor for CAV21. Surprisingly, CAV21 administered to these mice via the intramuscular route causes a paralytic condition consistent with poliomyelitis. The virus appears to invade the CNS by retrograde axonal transport, as has been demonstrated to occur in analogous PV infections. We detected human intercellular adhesion molecule 1 expression on both transgenic mouse and human spinal cord anterior horn motor neurons, indicating that members of HEV-C may share PV's potential to elicit poliomyelitis in humans.
Counting primes, groups, and manifolds
Authors: Goldfeld Dorian , Lubotzky Alexander , Nikolov Nikolay , Pyber László
Published: September 2004

Let

\documentclass[12pt]{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\setlength{\oddsidemargin}{-69pt}
\begin{document}
\begin{equation*}{\Lambda}={\mathrm{SL}}_{2}({\mathbb{Z}})\end{equation*}\end{document}

be the modular group and let

c
n

(Λ) be the number of congruence subgroups of Λ of index at most
n
. We prove that

\documentclass[12pt]{minimal}
\usepackage{amsmath}
\usepackage{wasysym}
\usepackage{amsfonts}
\usepackage{amssymb}
\usepackage{amsbsy}
\usepackage{mathrsfs}
\setlength{\oddsidemargin}{-69pt}
\begin{document}
\begin{equation*}{\mathrm{lim}}_{n{\rightarrow}{\infty}}({\mathrm{log}}\hspace{.167em}c_{n}({\Lambda})/(({\mathrm{log}}\hspace{.167em}n)^{2}/{\mathrm{log}}\hspace{.167em}{\mathrm{log}}\hspace{.167em}n))=(3-2\sqrt{2})/4\end{equation*}\end{document}

. The proof is based on the Bombieri–Vinogradov “Riemann hypothesis on the average” and on the solution of a new type of extremal problem in combinatorial number theory. Similar surprisingly sharp estimates are obtained for the subgroup growth of lattices in higher rank semisimple Lie groups. If
G
is such a Lie group and Γ is an irreducible lattice of
G
it turns out that the subgroup growth of Γ is independent of the lattice and depends only on the Lie type of the direct factors of
G
. It can be calculated easily from the root system. The most general case of this result relies on the Generalized Riemann Hypothesis, but many special cases are unconditional. The proofs use techniques from number theory, algebraic groups, finite group theory, and combinatorics.
Synergistic interactions of lipids and myelin basic protein
Authors: Hu Yufang , Doudevski Ivo , Wood Denise , Moscarello Mario , Husted Cynthia , Genain Claude , Zasadzinski Joseph A. , Israelachvili Jacob
Published: September 2004

This report describes force measurements and atomic force microscope imaging of lipid–protein interactions that determine the structure of a model membrane system that closely mimics the myelin sheath. Our results suggest that noncovalent, mainly electrostatic and hydrophobic, interactions are responsible for the multilamellar structure and stability of myelin. We find that myelin basic protein acts as a lipid coupler between two apposed bilayers and as a lipid “hole-filler,” effectively preventing defect holes from developing. From our protein-mediated-adhesion and force–distance measurements, we develop a simple quantitative model that gives a reasonably accurate picture of the molecular mechanism and adhesion of bilayer-bridging proteins by means of noncovalent interactions. The results and model indicate that optimum myelin adhesion and stability depend on the difference between, rather than the product of, the opposite charges on the lipid bilayers and myelin basic protein, as well as on the repulsive forces associated with membrane fluidity, and that small changes in any of these parameters away from the synergistically optimum values can lead to large changes in the adhesion or even its total elimination. Our results also show that the often-asked question of which membrane species, the lipids or the proteins, are the “important ones” may be misplaced. Both components work synergistically to provide the adhesion and overall structure. A better appreciation of the mechanism of this synergy may allow for a better understanding of stacked and especially myelin membrane structures and may lead to better treatments for demyelinating diseases such as multiple sclerosis.
Regulation of chromosome stability by the histone H2A variant Htz1, the Swr1 chromatin remodeling complex, and the histone acetyltransferase NuA4
Authors: Krogan Nevan J. , Baetz Kristin , Keogh Michael-Christopher , Datta Nira , Sawa Chika , Kwok Trevor C. Y. , Thompson Natalie J. , Davey Michael G. , Pootoolal Jeff , Hughes Timothy R. , Emili Andrew , Buratowski Stephen , Hieter Philip , Greenblatt Jack F.
Published: September 2004

NuA4, the only essential histone acetyltransferase complex in
Saccharomyces cerevisiae
, acetylates the N-terminal tails of histones H4 and H2A. Affinity purification of NuA4 revealed the presence of three previously undescribed subunits, Vid21/Eaf1/Ydr359c, Swc4/Eaf2/Ygr002c, and Eaf7/Ynl136w. Experimental analyses revealed at least two functionally distinct sets of polypeptides in NuA4: (
i
) Vid21 and Yng2, and (
ii
) Eaf5 and Eaf7. Vid21 and Yng2 are required for bulk histone H4 acetylation and are functionally linked to the histone H2A variant Htz1 and the Swr1 ATPase complex (SWR-C) that assembles Htz1 into chromatin, whereas Eaf5 and Eaf7 have a different, as yet undefined, role. Mutations in Htz1, the SWR-C, and NuA4 cause defects in chromosome segregation that are consistent with genetic interactions we have observed between the genes encoding these proteins and genes encoding kinetochore components. Because SWR-C-dependent recruitment of Htz1 occurs in both transcribed and centromeric regions, a NuA4/SWR-C/Htz1 pathway may regulate both transcription and centromere function in
S. cerevisiae
.
Building for the Future: Housing-Related Sectors and the Welsh Economy
Authors: Munday Max , Pickernell David , Roberts Annette
Published: September 2004

Since the establishment of the Welsh Assembly Government there has been more emphasis on indigenous enterprises in relation to economic development policy. However, the housing-related sector has received little attention. This paper1 presents the results of research that has investigated this sector and its significance to the local economy. Whilst acknowledging the considerable data-related difficulties in this exercise, analysis of housing and housing-related functions (including construction, finance, legal services, management of housing stock) showed that the sector accounted for around 4.5% of Welsh employment, and had considerable potential for assisting in the future development of the regional economy.
Men's Health and Economic Well-being
Authors: Baker Peter
Published: September 2004

There is a clear relationship between people's health and well-being and the local economy. A healthy workforce is more likely to be productive, while hazardous working practices can have a major impact on health. This article focuses on the issue of men's health, arguing that measures to improve the health of men could be highly beneficial to the local economy and that workplaces provide a good setting for measures to improve male health.
Robust cell polarity is a dynamic state established by coupling transport and GTPase signaling
Authors: Wedlich-Soldner Roland , Wai Stephanie C. , Schmidt Thomas , Li Rong
Published: September 2004

Yeast cells can initiate bud formation at the G1/S transition in a cue-independent manner. Here, we investigate the dynamic nature of the polar cap and the regulation of the GTPase Cdc42 in the establishment of cell polarity. Using analysis of fluorescence recovery after photobleaching, we found that Cdc42 exchanged rapidly between the polar caps and cytosol and that this rapid exchange required its GTPase cycle. A previously proposed positive feedback loop involving actomyosin-based transport of the Cdc42 GTPase is required for the generation of robust cell polarity during bud formation in yeast. Inhibition of actin-based transport resulted in unstable Cdc42 polar caps. Unstable polarity was also observed in mutants lacking Bem1, a protein previously implicated in a feedback loop for Cdc42 activation through a signaling pathway. When Bem1 and actin were both inhibited, polarization completely failed. These results suggest that cell polarity is established through coupling of transport and signaling pathways and maintained actively by balance of flux.
The PYRIN Connection
Authors: Stehlik Christian , Reed John C.
Published: September 2004

Periodic fever syndromes (PFSs) comprise a subset of the hereditary autoinflammatory disorders that are defined by recurrent self-resolving attacks of systemic inflammatory reactions in the absence of infection or autoimmunity. Recent advances have led to the discovery that members of a new family of genes, the PYRIN family, account for several hereditary PFSs. Here we discuss new insights into the function of PYRIN proteins and the molecular basis of PFSs.
Molecular Characterization of Virus-induced Autoantibody Responses
Authors: Ludewig Burkhard , Krebs Philippe , Metters Helen , Tatzel Jutta , Türeci Özlem , Sahin Ugur
Published: September 2004

Here we present a comprehensive molecular mapping of virus-induced autoimmune B cell responses obtained by serological identification of antigens by recombinant expression cloning analysis. Immunoscreening of cDNA expression libraries of various organs (lung, liver, and spleen) using sera from mice infected with cytopathic (vaccinia virus [VV]) or noncytopathic (lymphocytic choriomeningitis virus [LCMV]) viruses revealed a broad specificity of the elicited autoantibody response. Interestingly, the majority of the identified autoantigens have been previously described as autoantigens in humans. We found that induction of virus-induced autoantibodies of the immunoglobulin G class largely depends on the CD40–CD40L-mediated interaction between T and B cells. Furthermore, antibody titers against a number of autoantigens were comparable to the concomitantly induced antiviral antibody response. Comparison of serum reactivity against a selected panel of autoantigens after infection with VV, LCMV, or vesicular stomatitis virus showed that the different virus infections triggered distinct autoantibody responses, suggesting that virus infections may leave specific “autoantibody fingerprints” in the infected host.
Dormancy Phenotype Displayed by Extracellular Mycobacterium tuberculosis within Artificial Granulomas in Mice
Authors: Karakousis Petros C. , Yoshimatsu Tetsuyuki , Lamichhane Gyanu , Woolwine Samuel C. , Nuermberger Eric L. , Grosset Jacques , Bishai William R.
Published: September 2004

Mycobacterium tuberculosis residing within pulmonary granulomas and cavities represents an important reservoir of persistent organisms during human latent tuberculosis infection. We present a novel in vivo model of tuberculosis involving the encapsulation of bacilli in semidiffusible hollow fibers that are implanted subcutaneously into mice. Granulomatous lesions develop around these hollow fibers, and in this microenvironment, the organisms demonstrate an altered physiologic state characterized by stationary-state colony-forming unit counts and decreased metabolic activity. Moreover, these organisms show an antimicrobial susceptibility pattern similar to persistent bacilli in current models of tuberculosis chemotherapy in that they are more susceptible to the sterilizing drug, rifampin, than to the bactericidal drug isoniazid. We used this model of extracellular persistence within host granulomas to study both gene expression patterns and mutant survival patterns. Our results demonstrate induction of dosR (Rv3133c) and 20 other members of the DosR regulon believed to mediate the transition into dormancy, and that relMtb is required for Mycobacterium tuberculosis survival during extracellular persistence within host granulomas. Interestingly, the dormancy phenotype of extracellular M. tuberculosis within host granulomas appears to be immune mediated and interferon-γ dependent.
MyD88 But Not TRIF Is Essential for Osteoclastogenesis Induced by Lipopolysaccharide, Diacyl Lipopeptide, and IL-1α
Authors: Sato Nobuaki , Takahashi Naoyuki , Suda Koji , Nakamura Midori , Yamaki Mariko , Ninomiya Tadashi , Kobayashi Yasuhiro , Takada Haruhiko , Shibata Kenichiro , Yamamoto Masahiro , Takeda Kiyoshi , Akira Shizuo , Noguchi Toshihide , Udagawa Nobuyuki
Published: September 2004

Myeloid differentiation factor 88 (MyD88) plays essential roles in the signaling of the Toll/interleukin (IL)-1 receptor family. Toll–IL-1 receptor domain-containing adaptor inducing interferon-β (TRIF)-mediated signals are involved in lipopolysaccharide (LPS)-induced MyD88-independent pathways. Using MyD88-deficient (MyD88−/−) mice and TRIF-deficient (TRIF−/−) mice, we examined roles of MyD88 and TRIF in osteoclast differentiation and function. LPS, diacyl lipopeptide, and IL-1α stimulated osteoclastogenesis in cocultures of osteoblasts and hemopoietic cells obtained from TRIF−/− mice, but not MyD88−/− mice. These factors stimulated receptor activator of nuclear factor-κB ligand mRNA expression in TRIF−/− osteoblasts, but not MyD88−/− osteoblasts. LPS stimulated IL-6 production in TRIF−/− osteoblasts, but not TRIF−/− macrophages. LPS and IL-1α enhanced the survival of TRIF−/− osteoclasts, but not MyD88−/− osteoclasts. Diacyl lipopeptide did not support the survival of osteoclasts because of the lack of Toll-like receptor (TLR)6 in osteoclasts. Macrophages expressed both TRIF and TRIF-related adaptor molecule (TRAM) mRNA, whereas osteoblasts and osteoclasts expressed only TRIF mRNA. Bone histomorphometry showed that MyD88−/− mice exhibited osteopenia with reduced bone resorption and formation. These results suggest that the MyD88-mediated signal is essential for the osteoclastogenesis and function induced by IL-1 and TLR ligands, and that MyD88 is physiologically involved in bone turnover.
Differential Regulation of the TRAIL Death Receptors DR4 and DR5 by the Signal Recognition Particle
Authors: Ren Yan-Guo , Wagner Klaus W. , Knee Deborah A. , Aza-Blanc Pedro , Nasoff Marc , Deveraux Quinn L.
Published: September 2004

TRAIL (TNF-related apoptosis-inducing ligand) death receptors DR4 and DR5 facilitate the selective elimination of malignant cells through the induction of apoptosis. From previous studies the regulation of the DR4 and DR5 cell-death pathways appeared similar; nevertheless in this study we screened a library of small interfering RNA (siRNA) for genes, which when silenced, differentially affect DR4- vs. DR5-mediated apoptosis. These experiments revealed that expression of the signal recognition particle (SRP) complex is essential for apoptosis mediated by DR4, but not DR5. Selective diminution of SRP subunits by RNA interference resulted in a dramatic decrease in cell surface DR4 receptors that correlated with inhibition of DR4-dependent cell death. Conversely, SRP silencing had little influence on cell surface DR5 levels or DR5-mediated apoptosis. Although loss of SRP function in bacteria, yeast and protozoan parasites causes lethality or severe growth defects, we observed no overt phenotypes in the human cancer cells studied—even in stable cell lines with diminished expression of SRP components. The lack of severe phenotype after SRP depletion allowed us to delineate, for the first time, a mechanism for the differential regulation of the TRAIL death receptors DR4 and DR5—implicating the SRP complex as an essential component of the DR4 cell-death pathway.
Training in the Smaller Business – Investment or Expense?
Authors: Blackburn Robert , Hankinson Alan
Published: September 2004

Two British surveys are examined which show skills shortages in
smaller companies. The reasons why little training is undertaken in
these firms are set out, the main one of which seems to be that they are
focused entirely on short‐term survival.
Training People in First Aid
Authors: Julian C.R.
Published: September 2004

A major training activity rarely mentioned in journals is reviewed.
First Aid is literally a lifesaver, rather than metaphorically so as in
much training. The change from a relatively amateur to a more
professional approach is spelled out.
Seeing is Believing – The Role of Personnel in Reading and Shaping the Metaphors that Govern Business Life
Authors: Thake Don
Published: September 2004

The metaphors used in various organisational cultures are reviewed
– such as club, family, team, pragmatist, intellectual. These
describe and explain behaviour prevalent in particular organisational
cultures, and are extremely powerful. It is concluded that existing
metaphors will be found inappropriate, as they treat people as an
expendable resource rather than a long‐term asset meriting continuous
renewal.
Taking Stock in Stockholm
Authors: Bown Geraldine
Published: September 2004

The 4th European Women′s Management Development Conference –
“The New Manager: Changes and Challenges” took place in
September 1988. The author provides an account of the highlights and her
comments on the papers presented and the activities that took place.
Practical Ideas for Managing Change and Making it Stick
Authors: Plant Roger
Published: September 2004

Three central questions come to mind when considering change: Why
does it happen? How does it happen? How can it be better managed? The
changes we are exploring are not smooth, natural transitions, but
periods of considerable turbulence and unnatural activity which require
careful and skilful management. The stages in change are described and a
helpful action checklist is suggested.
A Bridge to Reality: Simulations in Communication Skills Training
Authors: Cousins John Y. , McDougall Marilyn F.
Published: September 2004

The development of communication skills is increasingly a key
element in the training of staff who have a regular contact with the
public. The Glasgow Garden Festival took place over the summer of 1988.
For the purposes of staffing the information centre, the Inverclyde
Initiative chose to recruit 12 people who were registered unemployed.
Training was provided for these individuals in order to prepare them for
the job by improving their skills and thus their ability to perform a
successful role in the Festival. Details of the design of the
communication skills programme using simulations and role plays as
general features are considered in the article.
Creating a New Men’s Leadership
Authors: Simmons Michael
Published: September 2004

Programmes to create equal opportunities for women have taken place
in many organisations. The ensuing need, however, to find ways to enlist
male managers as allies for such programmes, has prompted many people to
begin to think about the specific training needs of men from a fresh
viewpoint. The need for men to understand ways in which they are
conditioned to behave is described. Such ways are both less effective
and inhibiting for women colleagues. Processes used by the author in
training men to recognise and overcome problems are set out.
“Return to Go”: Renewal Process in an Internal Organisation Development Unit
Authors: Edmonstone J.D.
Published: September 2004

The National Health Service is increasingly aware that the
development of organisations and management is crucial to the pursuit of
“excellence”. In light of this, the experience of one
internal grouping, the Trent Regional Health Authority Organisation
Development Unit, is reviewed as a guide to senior managers considering
the creation of similar cadres for management development purposes. The
article examines the history of the unit from the point of view of the
author and traces the roots of the Organisation Development approach
from its origins in the 1960s.
THE PRACTICAL APPLICATION OF INTERPLACE II
Authors: Woods Mike , Thomas Elwyn
Published: September 2004

Belbin′s Self‐Perception Inventory (SPI) has become a standard
trainers′ tool. Interplace II has developed the original concepts,
ironed out the weaknesses of the SPI and made progress in the field of
team building. Examples are given of the specific assistance that can be
obtained from the program, together with useful pointers for new users.
FROM COLLEAGUES IN ADVERSITY TO THE SYNERGY OF THE SET
Authors: Mead Mike
Published: September 2004

The author describes the process by which a group of six managers,
from a variety of disciplines, on an Action Learning programme
influenced each other. The support and encouragement offered is
illustrated and related to research carried out by Margerison and
Belbin. The article is based on the author′s own recollections leading
up to the MBA award, and also as a result of replies to a questionnaire
received from colleagues.
ACTION LEARNING: A STUDENT′S PERSPECTIVE
Authors: Mercer J.R.
Published: September 2004

The author, a 57‐year‐old managing director of a small engineering
company, describes why he decided to take an MSc Management by Action
Learning, and the benefits he gained. He sets out the processes of the
Action Learning Set, and how he and others learned from each other and
the tutors.
THE QUEST FOR COMPETENCE
Authors: Canning Roy
Published: September 2004

The concept of “competence” and how it is used in
management education and development is now at the forefront of debate
in the UK. A review of the current literature in the field is given and
the issue of whether you can usefully identify and use “generic
competencies” is raised. The author argues for a more pragmatic
and context‐specific approach to competence based on current good
practice. In doing so he also raises questions about the assumptions
underlying any management development strategy and makes linkages with
other well established learning methods used within the UK.
IT IS LEGITIMATE TO BE UNAVAILABLE
Authors: Coates Jonathan
Published: September 2004

Differences between controlled time (your choice of how to use your
time) and response time (meeting the demands on your time by other
people) are described. It is suggested that managers can increase their
controlled time, first by assessing priorities and second by screening
out demands, by establishing work processes that are right for you.
Examples of how to “close the door” in an open‐plan office
are given.
COMPETENCY‐BASED HUMAN RESOURCE DEVELOPMENT – MAKING
SENSE OF THE IDEAS
Authors: Elkin Graham
Published: September 2004

Recent attention to competencies, especially the McBer approach, is
reviewed. Different definitions focusing on personal qualities or task
performance are outlined and it is proposed that neither
macro‐competencies nor micro‐competencies are necessarily the practical
route, and job‐specific key competencies are recommended.
MANAGERIAL VISIONS AND EFFECTIVE TRAINING
Authors: Jones R.A. , Goss D.M.
Published: September 2004

In a study of companies operating in the mechanical, technical and
electronic engineering sector within the Portsmouth, Fareham and Gosport
travel‐to‐work areas in South Hampshire the authors found that high
training companies with an emphasis on the development of human
resources were far less affected by skill shortages than low training
companies which traditionally have emphasised the exploitation of human
resources. Organisations which fail to offer any development
possibilities may gradually lose their ability to retain and attract
labour into the enterprise so that they effectively become side‐lined
within the labour market. Organisations are urged to adopt a managerial
vision which stresses company responsibility for training and
development policies within a regenerative and community‐based framework
for the enterprise.
A SUCCESSFUL DEVELOPMENT PARTNERSHIP: KINGSWAY GROUP AND
SUNDRIDGE PARK MANAGEMENT CENTRE
Authors: Smith Arthur , Smith Bryan
Published: September 2004

The effective integration of on‐the‐job development with
off‐the‐job training does not happen often, but when it does the effects
can be dramatic. To realise this strategy one company, Kingsway,
recognised a need to make a major investment in the development of
managerial talent. A bold but essential strategic investment in
management trainees to counter an earlier lower priority to management
development is described. The effective link with a management centre
(Sundridge Park) is explored, particularly in relation to securing
learning while managing. The power of projects, as a development method
and part of this partnership, is described with bottom‐line benefits in
relation to achieving task goals and learning goals. It is shown that a
partnership between an enlightened company and a progressive management
centre can make such goals realistic.
CREATING A NEW LEADERSHIP INITIATIVE
Authors: Simmons Michael
Published: September 2004

A number of new concepts about leadership are described, together
with a new approach to improving organisational performance through the
creation of a New Leadership Initiative. It is argued that effective
leadership is the key to improving organisational performance, and the
limitations that traditional leadership imposes on the achievement of
this improvement is examined. A new definition of leadership is provided
which details the key attributes that leaders must develop.
Organisation‐wide strategies used in a number of different organisations
in the private and public sector during the last five years are looked
at.
A FRESH APPROACH TO THE MBA
Authors: Anderson Gordon
Published: September 2004

The Master of Business Administration (MBA) degree is generally
regarded as the principal postgraduate qualification in business. This
article describes the process by which a business school reviewed and
redesigned its MBA programme. The main changes were increased attention
to information technology, greater emphasis on skills and on integrative
framework not wholly reliant on the Business Policy course. The
programme can also be taken via a new diploma‐level course.
SKILL TRAINING NEEDED BY TOMORROW′S EXECUTIVES
Authors: Broscow David A. , Kleiner Brian H.
Published: September 2004

An examination of what management education should be accomplishing
in today′s companies to provide executives with the skills necessary to
lead their businesses into the future. Categories of executive skills
that should be considered in developing management development and
education programmes are discussed: anticipatory, visioning, value
congruence, empowerment and self‐understanding skills. Other
considerations are also examined. An experiential learning environment
is suggested for imparting the desired skills. The more frequently used
forms are discussed. The importance of assessment and changes to the
effectiveness of any programme, is stressed.
GIVE ME THE TOOLS AND I′LL FINISH THE JOB
Authors: Rhodes Jerry
Published: September 2004

The article explores the use of maps and models as conceptual tools
used by trainers. Experience is ordered by modelling in a way that
allows it to be readily passed on to someone else. With increasing
maturity in the profession a trainer needs to develop his or her own
models. The author presents an example of how this can be done: a tool
of a kind for instrumenting tasks. The example is intended to structure
brainstorming and the challenging of existing sets of concepts. It is
shown in verbal form for dealing with specifics and visual form to make
it easy to grasp. The example is derived from a set of 25 generic tools.
A PROGRAMME FOR TRAINING TRAINERS IN NIGERIA
Authors: Akande Adebowale
Published: September 2004

A review of a two‐week management exercise for training organisers
in Nigeria. Comments are made on the art and ingredients needed to
integrate training and participants′ goals/ resourcefulness.
MAKING HRD A FORCE IN STRATEGIC ORGANISATIONAL CHANGE
Authors: Noel James L. , Dennehy Robert F.
Published: September 2004

What is the role of the effective human resource development (HRD)
organisation in strategic business change. Best practices have emerged
which suggest a six‐step approach: (1) a focused strategic approach:
identify the key initiatives to which the organisation is committed and
build the HRD programmes around them; (2) involvement of top management:
grow from the vision and commitment of the chief executive officer; (3)
refocus course content: “softer” business skills are
essential for significant strategic change; (4) develop impactful
learning methods: action learning is a valuable tool for organisations
in transition; (5) focused participation: employees participate who can
provide the greatest leverage; and (6) empowered participants: provide a
learning atmosphere to lead the change. The six‐steps will help the HRD
professional become a force in strategic transformation.
SMALL FIRMS: THE TRAINING PROBLEM
Authors: Hankinson Alan
Published: September 2004

In an update to an article in Industrial and Commercial
Training, Vol. 21 No. 2, 1989, the problem of training within small
firms is reconsidered. The results of data collected during 1988‐1990
from a survey of small mechanical and electrical engineering firms in
the Solent region reflect the firms′ attitudes towards training. The
lack or low level of any kind of training is emphasised and it is
concluded that persistent neglect of this area reduces firms′ abilities
to compete with other larger organisations and could be severely
detrimental as 1992 approaches.
MANAGEMENT DEVELOPMENT‐CONSIDERATIONS AND IMPLEMENTATION
Authors: Huntley Stephen
Published: September 2004

This article aims to stimulate debate from management development
practitioners on process and outcomes of techniques by outlining a
number of aspects of the topic. The various aspects of expectations of
job seekers, selection criteria via competence, focused development and
the link with total quality management through continuous dialogue are
all included. The material is concerned with the process as it affects
managerial staff who, throughout Western Europe are becoming more
familiar with the competence approach. The debate on managerial
competence is, in many aspects, still in its infancy and this article
raises some issues, provision for which has not yet been made
adequately. Reference is made to an approach, currently being considered
for use in a major financial organisation based in the UK.
THE MANAGER AS COACH
Authors: Barry Tom
Published: September 2004

In the current economic climate, companies are increasingly
realizing that their management style has to change.
“Downsizing” has resulted in less opportunities for
promotion and managers must be able to motivate their staff and enable
them to develop in their jobs. The existing management paradigm focuses
heavily on control, order and compliance, with the consequence that
people become objectified, measured and expended. Looks at the manager
as coach and explores the importance and benefits of creating a strong
relationship between manager and employee, what makes a good manager and
the cultural changes necessary within an organization to bring this
about successfully. The importance of staff empowerment is discussed and
the argument put forward by experts Evered and Selman that coaching
skills are not just part of the range of tools that a manager must have
at his or her disposal, but are more important than any other management
skills.
REDEFINING HUMAN RESOURCE MANAGEMENT
Authors: Quillien Jenny , Olila Jim
Published: September 2004

Today, global competition and rapid market developments preoccupy
top management. They have less time for internal issues. If not checked,
this preoccupation with the external world will leave top management in
the same position as the military commander who may have a brilliant
battle plan but does not know or understand the nature of his own
troops. To be successful, top management requires in‐depth and quality
knowledge of the company′s people and the corporate culture which binds
them together. Typically, top management does not get quality
information. They work on unchecked hunches and shallow, filtered
information. By retooling the frequently underutilized human resource
manager with the analytical skills for cultural analysis, general
management can be strengthened with skilled and knowledgeable co‐pilots
and internal change agents. Discusses these issues and some of the basic
concepts of cultural anthropology useful for analysis in both domestic
and multinational corporations.
THE GENDER GAP IN MANAGEMENT: A CHALLENGING AFFAIR
Authors: Fischer Mary L. , Gleijm Hans
Published: September 2004

Studies the behaviour of men and women in working groups –
men through the analogy of the pecking order, i.e. hierarchical, and
women through that of the crab basket, i.e. equality. Discusses the
respective advantages and disadvantages of the two groups, which appear
to be complementary. Concludes, however, that, despite the apparent
complementariness, both sides need to show mutual understanding of their
respective codes before they can achieve constructive co‐operation in
management.
WOMEN AND MEN WORKING TOGETHER EFFECTIVELY
Authors: Whitaker Vivien , Megginson David
Published: September 2004

Identifies six issues which have to be addressed in the effective
co‐operation of men and women in an organization – identity,
values, valuing differences, barriers, vision and action, and from this
viewpoint reviews a particular course of management development
workshops. Concludes that as a result managers of both sexes have become
more focused, friendly, fast and flexible in their organizations.
WHOSE GRANT IS IT?
Authors: Burnaby Priscilla
Published: September 2004

Discusses a real‐life case study to illustrate discrimination
against women in educational institutions. Analyses male and female
student responses and concludes that not only are men harder on women
but also women are harder on other women. Therefore both men′s and
women′s attitudes need to change so that all members of an organization
can contribute to the best of their ability in a non‐combative and
trusting environment.
LEADING INTO A SUCCESSFUL FUTURE
Authors: Rupert
Published: September 2004

Examines the role of leadership at managerial and senior executive
level. Analyses research findings to show that managers want more
visionary team‐based leadership from their chief executive officers, but
there is a significant gap at present. Considers the historic leadership
style and role model “command and control”, how senior
executives still operate in variations of this role‐model, while middle
to senior managers have become much more supportive as their own
experience, role‐model and training has altered. Looks at how changes in
the external business environment suggest that a more empathetic,
visionary style of leadership is required. Concludes by highlighting how
the senior executives of today need to recognize the need for and
undertake training in visionary, team leadership to enable their
managers to be more effective leaders in the future.