239 research outputs found
Steel industry restructuring and location
In this paper, we link technology-based competition, demand patterns, and managerial agency to describe and explain the process of restructuring in the American steel industry in terms of its economic geography and in the context of sweeping changes in the industry’s global structure. Between World War II and the end of the1960’s, the American steel industry was dominated by large integrated steel producers. During this period, competition was primarily among integrated firms and the location decisions taken during the period concerned individual production units within those firms. Between the 1970’s and the 1990’s, a new kind of competition re-shaped the economic geography of the American steel industry: employing scrap-based production methods, minimills emerged to challenge the integrated producers. Shifts in demand away from the previous geographical core combined with aggressive investments by minimill managers in production capacity and in capability upgrading to drive home the minimill advantage. Finally, with the turn of the century, world steel markets began to reshape based on globalization. Energized by liberalization and privatization in many parts of the world, and supported by information technology and managerial innovations that increased spans of control, steel firm managers employed aggressive mergers & acquisitions to create the first large-scale steel multinational corporations. During this period, consolidation redrew the boundaries of firm competition, and foreign steel firms emerged as owners of a major share of American steelmaking capacity. Moreover, increases in the world demand for steel and world steelmaking capacity had profound effect in reshaping the economic geography of the competitive landscape. By examining these critical periods of restructuring in the steel industry, the role of economic geography as a competitive factor is exposed, and context is provided for understanding the regional and spatial implications of competitive adjustment
Minimal irreversible quantum mechanics. The decay of unstable states
Brownian motion is modelled by a harmonic oscillator (Brownian particle)
interacting with a continuous set of uncoupled harmonic oscillators. The
interaction is linear in the coordinates and the momenta. The model has an
analytical solution that is used to study the time evolution of the reduced
density operator. It is derived in a closed form, in the one-particle sector of
the model. The irreversible behavior of the Brownian particle is described by a
reduced density matrix.Comment: 39 pages, 2 figure
Protein Design with Guided Discrete Diffusion
A popular approach to protein design is to combine a generative model with a
discriminative model for conditional sampling. The generative model samples
plausible sequences while the discriminative model guides a search for
sequences with high fitness. Given its broad success in conditional sampling,
classifier-guided diffusion modeling is a promising foundation for protein
design, leading many to develop guided diffusion models for structure with
inverse folding to recover sequences. In this work, we propose diffusioN
Optimized Sampling (NOS), a guidance method for discrete diffusion models that
follows gradients in the hidden states of the denoising network. NOS makes it
possible to perform design directly in sequence space, circumventing
significant limitations of structure-based methods, including scarce data and
challenging inverse design. Moreover, we use NOS to generalize LaMBO, a
Bayesian optimization procedure for sequence design that facilitates multiple
objectives and edit-based constraints. The resulting method, LaMBO-2, enables
discrete diffusions and stronger performance with limited edits through a novel
application of saliency maps. We apply LaMBO-2 to a real-world protein design
task, optimizing antibodies for higher expression yield and binding affinity to
several therapeutic targets under locality and developability constraints,
attaining a 99% expression rate and 40% binding rate in exploratory in vitro
experiments
Functional Approach to Quantum Decoherence and the Classical Final Limit
For a wide set of quantum systems it is demonstrated that the quantum regime
can be considered as the transient phase while the final classical statistical
regime is a permanent state. A basis where exact matrix decoherence appears for
these final states is found. The relation with the decoherence of histories
formalism is studied. A set of final intrinsically consistent histories is
found.Comment: 20 pages. Phys. Rev A in press 200
Measuring the Lyapunov exponent using quantum mechanics
We study the time evolution of two wave packets prepared at the same initial
state, but evolving under slightly different Hamiltonians. For chaotic systems,
we determine the circumstances that lead to an exponential decay with time of
the wave packet overlap function. We show that for sufficiently weak
perturbations, the exponential decay follows a Fermi golden rule, while by
making the difference between the two Hamiltonians larger, the characteristic
exponential decay time becomes the Lyapunov exponent of the classical system.
We illustrate our theoretical findings by investigating numerically the overlap
decay function of a two-dimensional dynamical system.Comment: 9 pages, 6 figure
Equitable and Effective Climate Policy: Integrating Less Developed Countries into a Global Climate Agreement
ISSN:1612-4804ISSN:1612-481
Differences in genome-wide gene expression response in peripheral blood mononuclear cells between young and old men upon caloric restriction
Background: Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different nonhuman organisms. Only a limited number of CR studies have been performed on humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a completely controlled 30 % CR diet on immune cells, as immune response is affected during aging. Ten healthy young men, aged 20–28, and nine healthy old men, aged 64–85, were subjected to a 2-week weight maintenance diet, followed by 3 weeks of 30 % CR. Before and after 30 % CR, the whole genome gene expression in peripheral blood mononuclear cells (PBMCs) was assessed. Results: Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in the immune response in young but not in old men. At baseline, immune response-related genes were higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling the immune response. Conclusions: Based on the gene expression data, we theorise that a short period of CR is not effective in old men regarding immune-related pathways while it is effective in young men
A Quorum-Sensing Factor in Vegetative Dictyostelium Discoideum Cells Revealed by Quantitative Migration Analysis
Background: Many cells communicate through the production of diffusible signaling molecules that accumulate and once a critical concentration has been reached, can activate or repress a number of target genes in a process termed quorum sensing (QS). In the social amoeba Dictyostelium discoideum, QS plays an important role during development. However little is known about its effect on cell migration especially in the growth phase. Methods and Findings: To investigate the role of cell density on cell migration in the growth phase, we use multisite timelapse microscopy and automated cell tracking. This analysis reveals a high heterogeneity within a given cell population, and the necessity to use large data sets to draw reliable conclusions on cell motion. In average, motion is persistent for short periods of time (tÆ’5min), but normal diffusive behavior is recovered over longer time periods. The persistence times are positively correlated with the migrated distances. Interestingly, the migrated distance decreases as well with cell density. The adaptation of cell migration to cell density highlights the role of a secreted quorum sensing factor (QSF) on cell migration. Using a simple model describing the balance between the rate of QSF generation and the rate of QSF dilution, we were able to gather all experimental results into a single master curve, showing a sharp cell transition between high and low motile behaviors with increasing QSF. Conclusion: This study unambiguously demonstrates the central role played by QSF on amoeboid motion in the growt
HER2 testing on core needle biopsy specimens from primary breast cancers: interobserver reproducibility and concordance with surgically resected specimens
<p>Abstract</p> <p>Background</p> <p>Accurate evaluation of human epidermal growth factor receptor type-2 (HER2) status based on core needle biopsy (CNB) specimens is mandatory for identification of patients with primary breast cancer who will benefit from primary systemic therapy with trastuzumab. The aim of the present study was to validate the application of HER2 testing with CNB specimens from primary breast cancers in terms of interobserver reproducibility and comparison with surgically resected specimens.</p> <p>Methods</p> <p>A total of 100 pairs of archival formalin-fixed paraffin-embedded CNB and surgically resected specimens of invasive breast carcinomas were cut into sections. All 100 paired sections were subjected to HER2 testing by immunohistochemistry (IHC) and 27 paired sections were subjected to that by fluorescence in situ hybridization (FISH), the results being evaluated by three and two observers, respectively. Interobserver agreement levels in terms of judgment and the concordance of consensus scores between CNB samples and the corresponding surgically resected specimens were estimated as the percentage agreement and κ statistic.</p> <p>Results</p> <p>In CNB specimens, the percentage interobserver agreement of HER2 scoring by IHC was 76% (κ = 0.71) for 3 × 3 categories (0-1+ <it>versus </it>2+ <it>versus </it>3+) and 90% (κ = 0.80) for 2 × 2 categories (0-2+ <it>versus </it>3+). These levels were close to the corresponding ones for the surgically resected specimens: 80% (κ = 0.77) for 3 × 3 categories and 92% (κ = 0.88) for 2 × 2 categories. Concordance of consensus for HER2 scores determined by IHC between CNB and the corresponding surgical specimens was 87% (κ = 0.77) for 3 × 3 categories, and 94% (κ = 0.83) for 2 × 2 categories. Among the 13 tumors showing discordance in the mean IHC scores between the CNB and surgical specimens, the results of consensus for FISH results were concordant in 11. The rate of successful FISH analysis and the FISH positivity rate in cases with a HER2 IHC score of 2+ differed among specimens processed at different institutions.</p> <p>Conclusion</p> <p>It is mandatory to study HER2 on breast cancers, and either CNB or surgical specimen can be used.</p
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