Virtual Flexibility: A Reexamination of the Concept of Organizational Slack

This article reviews changes taking place in the business environment and in the field of strategic management, contrasting the traditional industrial organizational economics paradigm with the new hypercompetitive or Austrian paradigm. It then demonstrates the implications of this paradigm shift in a detailed examination of the concept of organizational slack, highlighting new forms, applications and value for slack in the new hypercompetitive environment

Confinement Effects on the Kinetics and Thermodynamics of Protein Dimerization

In the cell, protein complexes form relying on specific interactions between their monomers. Excluded volume effects due to molecular crowding would lead to correlations between molecules even without specific interactions. What is the interplay of these effects in the crowded cellular environment? We study dimerization of a model homodimer both when the mondimers are free or tethered to each other. We consider a structured environment: Two monomers first diffuse into a cavity of size $L$ and then fold and bind within the cavity. The folding and binding are simulated using molecular dynamics based on a simplified topology based model. The {\it confinement} in the cell is described by an effective molecular concentration $C \sim L^{-3}$. A two-state coupled folding and binding behavior is found. We show the maximal rate of dimerization occurred at an effective molecular concentration $C^{op}\simeq 1m$M which is a relevant cellular concentration. In contrast, for tethered chains the rate keeps at a plateau when $CC^{op}$. For both the free and tethered cases, the simulated variation of the rate of dimerization and thermodynamic stability with effective molecular concentration agrees well with experimental observations. In addition, a theoretical argument for the effects of confinement on dimerization is also made

Heterologous gene expression in the human gut bacteria Eubacterium rectale and Roseburia inulinivorans by means of conjugative plasmids

Acknowledgements The Rowett Institute (University of Aberdeen) receives financial support from the Scottish Government Rural and Environmental Sciences and Analytical Services (RESAS). POS was a PhD student supported by the Scottish Government (RESAS) and the Science Foundation Ireland, through a centre award (12/RC/2273) to APC Microbiome Ireland, Cork, Ireland.Peer reviewedPostprin

Reduced tillage, but not organic matter input, increased nematode diversity and food web stability in European long‐term field experiments

Soil nematode communities and food web indices can inform about the complexity, nutrient flows and decomposition pathways of soil food webs, reflecting soil quality. Relative abundance of nematode feeding and life‐history groups are used for calculating food web indices, i.e., maturity index (MI), enrichment index (EI), structure index (SI) and channel index (CI). Molecular methods to study nematode communities potentially offer advantages compared to traditional methods in terms of resolution, throughput, cost and time. In spite of such advantages, molecular data have not often been adopted so far to assess the effects of soil management on nematode communities and to calculate these food web indices. Here, we used high‐throughput amplicon sequencing to investigate the effects of tillage (conventional vs. reduced) and organic matter addition (low vs. high) on nematode communities and food web indices in 10 European long‐term field experiments and we assessed the relationship between nematode communities and soil parameters. We found that nematode communities were more strongly affected by tillage than by organic matter addition. Compared to conventional tillage, reduced tillage increased nematode diversity (23% higher Shannon diversity index), nematode community stability (12% higher MI), structure (24% higher SI), and the fungal decomposition channel (59% higher CI), and also the number of herbivorous nematodes (70% higher). Total and labile organic carbon, available K and microbial parameters explained nematode community structure. Our findings show that nematode communities are sensitive indicators of soil quality and that molecular profiling of nematode communities has the potential to reveal the effects of soil management on soil quality

Hard Spheres in Vesicles: Curvature-Induced Forces and Particle-Induced Curvature

We explore the interplay of membrane curvature and nonspecific binding due to excluded-volume effects among colloidal particles inside lipid bilayer vesicles. We trapped submicron spheres of two different sizes inside a pear-shaped, multilamellar vesicle and found the larger spheres to be pinned to the vesicle's surface and pushed in the direction of increasing curvature. A simple model predicts that hard spheres can induce shape changes in flexible vesicles. The results demonstrate an important relationship between the shape of a vesicle or pore and the arrangement of particles within it.Comment: LaTeX with epsfig; ps available at http://dept.physics.upenn.edu/~nelson/index.shtml Phys Rev Lett in press (1997

Astrophysical and Astrobiological Implications of Gamma-Ray Burst Properties

Combining results for the local cosmic rate and mean peak luminosity of GRBs with the cosmic history of the star formation rate, we provide estimates for the local GRB rate per unit blue luminosity in galaxies. We find a typical GRB rate per unit B luminosity of 2.4x10^-17 h_{70}^2/Lsun/yr. The corresponding mean rate in the Milky Way is 5.5x10^-7 h_{70}^2/yr. We conclude: 1) the ratio of supernova rate to isotropic equivalent GRB rate is large: more than 6000 SNIbc per GRB or 30,000 SNII per GRB. GRBs could arise in a large fraction of black hole-forming events only with collimation in the range 0.01 - 0.001 and a steep enough slope of the IMF; 2) GRBs cannot account for the majority of large HI holes observed in galaxies; 3) the probability that the solar system was exposed to a fluence large enough to melt the chondrules during the first 10^7 yr of solar system history is negligibly small; 4) Even for very opaque atmospheres, a significant fraction of the GRB energy is transmitted as UV lines due to excitation by secondary electrons. For eukaryotic-like organisms in thin atmospheres (e.g. contemporary Mars), or for UV line exposure in thick atmospheres (e.g. Earth), biologically significant events occur at a rate of about 100--500 /Gyr. The direct contribution of these "jolts" to mutational evolution may, however, be negligible because of the short duration of the GRBs. Evolutionary effects due to partial sterilizations and to longer-lived disruptions of atmospheric chemistry should be more important. (Abridged)Comment: 36 pages, no figures Accepted by Astrophysical Journal Oct. 2001. First submitted December,1999. Substantially rewritten discussion of burst source count distributions and of biological implication

Formation and Dynamical Evolution of the Neptune Trojans - the Influence of the Initial Solar System Architecture

In this work, we investigate the dynamical stability of pre-formed Neptune Trojans under the gravitational influence of the four giant planets in compact planetary architectures, over 10 Myr. In our modelling, the initial orbital locations of Uranus and Neptune (aN) were varied to produce systems in which those planets moved on non-resonant orbits, or in which they lay in their mutual 1:2, 2:3 and 3:4 mean-motion resonances (MMRs). In total, 420 simulations were carried out, examining 42 different architectures, with a total of 840000 particles across all runs. In the non-resonant cases, the Trojans suffered only moderate levels of dynamical erosion, with the most compact systems (those with aN less than or equal 18 AU) losing around 50% of their Trojans by the end of the integrations. In the 2:3 and 3:4 MMR scenarios, however, dynamical erosion was much higher with depletion rates typically greater than 66% and total depletion in the most compact systems. The 1:2 resonant scenarios featured disruption on levels intermediate between the non-resonant cases and other resonant scenarios, with depletion rates of the order of tens of percent. Overall, the great majority of plausible pre-migration planetary architectures resulted in severe levels of depletion of the Neptunian Trojan clouds. In particular, if Uranus and Neptune formed near their mutual 2:3 or 3:4 MMR and at heliocentric distances within 18 AU (as favoured by recent studies), we found that the great majority of pre-formed Trojans would have been lost prior to Neptune's migration. This strengthens the case for the great bulk of the current Neptunian Trojan population having been captured during that migration.Comment: 17 pages, 2 figures, MNRAS (in press). Abstract slightly reduced in size, but in original form in the PDF fil

Origin and Dynamical Evolution of Neptune Trojans - II: Long Term Evolution

We present results examining the fate of the Trojan clouds produced in our previous work. We find that the stability of Neptunian Trojans seems to be strongly correlated to their initial post-migration orbital elements, with those objects that survive as Trojans for billions of years displaying negligible orbital evolution. The great majority of these survivors began the integrations with small eccentricities (e < 0.2) and small libration amplitudes (A < 30 - 40{\deg}). The survival rate of "pre-formed" Neptunian Trojans (which in general survived on dynamically cold orbits (e < 0.1, i < 5 - 10{\deg})) varied between ~5 and 70%. By contrast, the survival rate of "captured" Trojans (on final orbits spread across a larger region of e-i element space) were markedly lower, ranging between 1 and 10% after 4 Gyr. Taken in concert with our earlier work, we note that planetary formation scenarios which involve the slow migration (a few tens of millions of years) of Neptune from an initial planetary architecture that is both resonant and compact (aN < 18 AU) provide the most promising fit of those we considered to the observed Trojan population. In such scenarios, we find that the current day Trojan population would number ~1% of that which was present at the end of the planet's migration, with the bulk being sourced from captured, rather than pre-formed objects. We note, however, that even those scenarios still fail to reproduce the currently observed portion of the Neptune Trojan population moving on orbits with e 20{\deg}. Dynamical integrations of the currently observed Trojans show that five out of the seven are dynamically stable on 4 Gyr timescales, while 2001 QR322, exhibits significant dynamical instability. The seventh Trojan object, 2008 LC18, has such large orbital uncertainties that only future studies will be able to determine its stability.Comment: 24 pages, 6 figures, accepted for publication in MNRAS (The abstract was shortened. Original version can be found in the pdf file

Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s)

Clostridium difficile infection (CDI) is the leading cause of hospital and community-acquired antibiotic-associated diarrhoea and currently represents a significant health burden. Although the role and contribution of C. difficile toxins to disease pathogenesis is being increasingly understood, at present other facets of C. difficile-host interactions, in particular, bacterial-driven effects on host immunity remain less studied. Using an ex-vivo model of infection, we report that the human gastrointestinal mucosa elicits a rapid and significant cytokine response to C. difficile. Marked increase in IFN-γ with modest increase in IL-22 and IL-17A was noted. Significant increase in IL-8 suggested potential for neutrophil influx while presence of IL-12, IL-23, IL-1β and IL-6 was indicative of a cytokine milieu that may modulate subsequent T cell immunity. Majority of C. difficile-driven effects on murine bone-marrow-derived dendritic cell (BMDC) activation were toxin-independent; the toxins were however responsible for BMDC inflammasome activation. In contrast, human monocyte-derived DCs (mDCs) released IL-1β even in the absence of toxins suggesting host-specific mediation. Infected DC-T cell crosstalk revealed the ability of R20291 and 630 WT strains to elicit a differential DC IL-12 family cytokine milieu which culminated in significantly greater Th1 immunity in response to R20291. Interestingly, both strains induced a similar Th17 response. Elicitation of mucosal IFN-γ/IL-17A and Th1/Th17 immunity to C. difficile indicates a central role for this dual cytokine axis in establishing antimicrobial immunity to CDI

The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains

<p>Abstract</p> <p>Background</p> <p><it>Clostridium difficile </it>is the major cause of antibiotic associated diarrhoea and in recent years its increased prevalence has been linked to the emergence of hypervirulent clones such as the PCR-ribotype 027. Characteristically, <it>C. difficile </it>infection (CDI) occurs after treatment with broad-spectrum antibiotics, which disrupt the normal gut microflora and allow <it>C. difficile </it>to flourish. One of the relatively unique features of <it>C. difficile </it>is its ability to ferment tyrosine to <it>para</it>-cresol via the intermediate <it>para</it>-hydroxyphenylacetate (<it>p-</it>HPA). <it>P</it>-cresol is a phenolic compound with bacteriostatic properties which <it>C. difficile </it>can tolerate and may provide the organism with a competitive advantage over other gut microflora, enabling it to proliferate and cause CDI. It has been proposed that the <it>hpdBCA </it>operon, rarely found in other gut microflora, encodes the enzymes responsible for the conversion of <it>p-</it>HPA to <it>p</it>-cresol.</p> <p>Results</p> <p>We show that the PCR-ribotype 027 strain R20291 quantitatively produced more <it>p</it>-cresol <it>in-vitro </it>and was significantly more tolerant to <it>p</it>-cresol than the sequenced strain 630 (PCR-ribotype 012). Tyrosine conversion to <it>p</it>-HPA was only observed under certain conditions. We constructed gene inactivation mutants in the <it>hpdBCA </it>operon in strains R20291 and 630Δ<it>erm </it>which curtails their ability to produce <it>p</it>-cresol, confirming the role of these genes in <it>p-</it>cresol production. The mutants were equally able to tolerate <it>p</it>-cresol compared to the respective parent strains, suggesting that tolerance to <it>p</it>-cresol is not linked to its production.</p> <p>Conclusions</p> <p><it>C. difficile </it>converts tyrosine to <it>p</it>-cresol, utilising the <it>hpdBCA </it>operon in <it>C. difficile </it>strains 630 and R20291. The hypervirulent strain R20291 exhibits increased production of and tolerance to <it>p-</it>cresol, which may be a contributory factor to the virulence of this strain and other hypervirulent PCR-ribotype 027 strains.</p