Modelling within-host spatiotemporal dynamics of invasive bacterial disease

Mechanistic determinants of bacterial growth, death, and spread within mammalian hosts cannot be fully resolved studying a single bacterial population. They are also currently poorly understood. Here, we report on the application of sophisticated experimental approaches to map spatiotemporal population dynamics of bacteria during an infection. We analyzed heterogeneous traits of simultaneous infections with tagged Salmonella enterica populations (wild-type isogenic tagged strains [WITS]) in wild-type and gene-targeted mice. WITS are phenotypically identical but can be distinguished and enumerated by quantitative PCR, making it possible, using probabilistic models, to estimate bacterial death rate based on the disappearance of strains through time. This multidisciplinary approach allowed us to establish the timing, relative occurrence, and immune control of key infection parameters in a true host-pathogen combination. Our analyses support a model in which shortly after infection, concomitant death and rapid bacterial replication lead to the establishment of independent bacterial subpopulations in different organs, a process controlled by host antimicrobial mechanisms. Later, decreased microbial mortality leads to an exponential increase in the number of bacteria that spread locally, with subsequent mixing of bacteria between organs via bacteraemia and further stochastic selection. This approach provides us with an unprecedented outlook on the pathogenesis of S. enterica infections, illustrating the complex spatial and stochastic effects that drive an infectious disease. The application of the novel method that we present in appropriate and diverse host-pathogen combinations, together with modelling of the data that result, will facilitate a comprehensive view of the spatial and stochastic nature of within-host dynamics. © 2008 Grant et al.

Jet diameters and velocity profiles in continuous ink-jets

Theoretical predictions of the diameters of continuous ink-jets downstream of long nozzles are generalized to include the important cases of ink-jet fluids and shorter nozzles where the velocity profile at the nozzle exit is undeveloped (non-parabolic). Comparisons of the new predictions with experiments and simulations are made for fairly long nozzles with tapered profiles and short nozzles with conical profiles; experimental and simulated profiles are also compared downstream of the nozzle exit for both industrial and large scale ink-jet print heads. Precise measurements of the un-modulated jet diameters downstream of the nozzle exit can set really useful limits to the possible shapes of the flow profile right at the nozzle exit, and in particular allow some assessment of the axial velocity gradients and fluid shear rates at the nozzle exit where direct speed measurement is usually impractical. Simulations allow further study of the relaxation of the velocity profile downstream of the nozzle exit, and are reported for both un-modulated and modulated CIJ jetting. Implications of this work include speeding up CIJ simulations, absolute calibration of the applied CIJ system modulation, and the likely magnitude of dynamic surface tension effects on observed CIJ satellite speeds.

Methods of Obtaining Instantaneous Modulus of Viscoelastic Solids Using Displacement-Controlled Instrumented Indentation with Axisymmetric Indenters of Arbitrary Smooth Profiles

We derive a relationship between the initial unloading slope, contact depth, and the instantaneous relaxation modulus for displacement-controlled indentation in linear viscoelastic solids by a rigid indenter with an arbitrary axisymmetric smooth profile. While the same expression is well known for indentation in elastic and in elastic–plastic solids, we show that it is also true for indentation in linear viscoelastic solids, provided that the unloading rate is sufficiently fast. When the unloading rate is slow, a “hold” period between loading and unloading can be used to provide a correction term for the initial unloading slope equation. Finite element calculations are used to illustrate the methods of fast unloading and “hold-at-the-maximum-indenter-displacement” for determining the instantaneous modulus using spherical indenters.

Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?

Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific beta-amyloid (A beta) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in Nv (number of cell/mm(3)) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes Nv (33.26%) occurs at 18 months. This Nv reduction of GSIR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR Nv changes are directly associated with the presence of A beta deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of A beta. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.

Beach monitoring project Sand Key Phase II Beach nourishment program (North Redington Beach and Redington Shores) Post-Nourishment Report Part II Offshore Profiles and Wave Data

This study presents the third post-nourishment survey (January 1989) results for the Sand Key Phase II beach nourishment project carried out in June, 1988. The monitoring program to this beach nourishment project is a joint effort between the University of South Florida and University of Florida. The field surveys include a total of 26 profiles, encompassing approximately 3 miles of shoreline extending from DNR R-96 to R-1ll. The total calculated volume loss of sand in the nourished segment (from R-99G to R-107) between the July 88 and January 89 surveys is 51,113 cubic yards, which is a loss about 9.7 percent of 529,150 cubic yards actually placed in the nourishment project. The total loss of sand computed in the entire survey area is 26,796 cubic yards, which is only 5.1 percent of the sand placed in the nourishment project. It is stressed that a part of these net volume reductions is due to the background erosion and not due to spreading losses induced by the nourishment project. (PDF contains 168 pages.)

Length of concentrate finishing affects the fatty acid composition of grass-fed andgenetically lean beef: an emphasis on trans-18:1 and conjugated linoleic acid profiles

2.4. The author may post the VoR version of the article (in PDF or HTML form) in the Institutional Repository of the institution in which the author worked at the time the article was first submitted, or (for appropriate journals) in PubMed Central or UK PubMed Central or arXiv, no sooner than one year after first publication of the article in the Journal, subject to file availability and provided the posting includes a prominent statement of the full bibliographical details, a copyright notice in the name of the copyright holder (Cambridge University Press or the sponsoring Society, as appropriate), and a link to the online edition of the Journal at Cambridge Journals Online.

GFAP Isoforms in Adult Mouse Brain with a Focus on Neurogenic Astrocytes and Reactive Astrogliosis in Mouse Models of Alzheimer Disease

24 p.

Methods of Obtaining Instantaneous Modulus of Viscoelastic Solids Using Displacement-Controlled Instrumented Indentation with Axisymmetric Indenters of Arbitrary Smooth Profiles

We derive a relationship between the initial unloading slope, contact depth, and the instantaneous relaxation modulus for displacement-controlled indentation in linear viscoelastic solids by a rigid indenter with an arbitrary axisymmetric smooth profile. While the same expression is well known for indentation in elastic and in elastic-plastic solids, we show that it is also true for indentation in linear viscoelastic solids, provided that the unloading rate is sufficiently fast. When the unloading rate is slow, a "hold" period between loading and unloading can be used to provide a correction term for the initial unloading slope equation. Finite element calculations are used to illustrate the methods of fast unloading and "hold-at-the-maximum-indenter-displacement" for determining the instantaneous modulus using spherical indenters.

Species Profiles: Life Histories and Environmental Requirements of Coastal Fishes and Invertebrates (Pacific Southwest): Black, green, and red abalones

All abalones belong to the genus Haliotis sensu latu, family Haliotidae. The 75 species known worldwide (Booloot ian et, al. 1962) are anatomically similar and all are adapted for attachment to hard substrates. Seven species are widely distributed along the coast of California (Cox 1962; Mottet 19781, of which several are important in the comercial and sport fisheries of the Pacific Southwest. (PDF has 19 pages.)

Coral Disease and Health Workshop: Coral Histopathology II

The health and continued existence of coral reef ecosystems are threatened by an increasing array of environmental and anthropogenic impacts. Coral disease is one of the prominent causes of increased mortality among reefs globally, particularly in the Caribbean. Although over 40 different coral diseases and syndromes have been reported worldwide, only a few etiological agents have been confirmed; most pathogens remain unknown and the dynamics of disease transmission, pathogenicity and mortality are not understood. Causal relationships have been documented for only a few of the coral diseases, while new syndromes continue to emerge. Extensive field observations by coral biologists have provided substantial documentation of a plethora of new pathologies, but our understanding, however, has been limited to descriptions of gross lesions with names reflecting these observations (e.g., black band, white band, dark spot). To determine etiology, we must equip coral diseases scientists with basic biomedical knowledge and specialized training in areas such as histology, cell biology and pathology. Only through combining descriptive science with mechanistic science and employing the synthesis epizootiology provides will we be able to gain insight into causation and become equipped to handle the pending crisis. One of the critical challenges faced by coral disease researchers is to establish a framework to systematically study coral pathologies drawing from the field of diagnostic medicine and pathology and using generally accepted nomenclature. This process began in April 2004, with a workshop titled Coral Disease and Health Workshop: Developing Diagnostic Criteria co-convened by the Coral Disease and Health Consortium (CDHC), a working group organized under the auspices of the U.S. Coral Reef Task Force, and the International Registry for Coral Pathology (IRCP). The workshop was hosted by the U.S. Geological Survey, National Wildlife Health Center (NWHC) in Madison, Wisconsin and was focused on gross morphology and disease signs observed in the field. A resounding recommendation from the histopathologists participating in the workshop was the urgent need to develop diagnostic criteria that are suitable to move from gross observations to morphological diagnoses based on evaluation of microscopic anatomy. (PDF contains 92 pages)

Preprocess and data analysis techniques for affymetrix DNA microarrays using bioconductor: a case study in Alzheimer disease

DNA microarray, or DNA chip, is a technology that allows us to obtain the expression level of many genes in a single experiment. The fact that numerical expression values can be easily obtained gives us the possibility to use multiple statistical techniques of data analysis. In this project microarray data is obtained from Gene Expression Omnibus, the repository of National Center for Biotechnology Information (NCBI). Then, the noise is removed and data is normalized, also we use hypothesis tests to find the most relevant genes that may be involved in a disease and use machine learning methods like KNN, Random Forest or Kmeans. For performing the analysis we use Bioconductor, packages in R for the analysis of biological data, and we conduct a case study in Alzheimer disease. The complete code can be found in https://github.com/alberto-poncelas/ bioc-alzheimer