The Waddlia genome: a window into chlamydial biology.

Growing evidence suggests that a novel member of the Chlamydiales order, Waddlia chondrophila, is a potential agent of miscarriage in humans and abortion in ruminants. Due to the lack of genetic tools to manipulate chlamydia, genomic analysis is proving to be the most incisive tool in stimulating investigations into the biology of these obligate intracellular bacteria. 454/Roche and Solexa/Illumina technologies were thus used to sequence and assemble de novo the full genome of the first representative of the Waddliaceae family, W. chondrophila. The bacteria possesses a 2'116'312 bp chromosome and a 15'593 bp low-copy number plasmid that might integrate into the bacterial chromosome. The Waddlia genome displays numerous repeated sequences indicating different genome dynamics from classical chlamydia which almost completely lack repetitive elements. Moreover, W. chondrophila exhibits many virulence factors also present in classical chlamydia, including a functional type III secretion system, but also a large complement of specific factors for resistance to host or environmental stresses. Large families of outer membrane proteins were identified indicating that these highly immunogenic proteins are not Chlamydiaceae specific and might have been present in their last common ancestor. Enhanced metabolic capability for the synthesis of nucleotides, amino acids, lipids and other co-factors suggests that the common ancestor of the modern Chlamydiales may have been less dependent on their eukaryotic host. The fine-detailed analysis of biosynthetic pathways brings us closer to possibly developing a synthetic medium to grow W. chondrophila, a critical step in the development of genetic tools. As a whole, the availability of the W. chondrophila genome opens new possibilities in Chlamydiales research, providing new insights into the evolution of members of the order Chlamydiales and the biology of the Waddliaceae.

GLUT2 in pancreatic and extra-pancreatic gluco-detection (review).

Detection of variations in blood glucose concentrations by pancreatic beta-cells and a subsequent appropriate secretion of insulin are key events in the control of glucose homeostasis. Because a decreased capability to sense glycemic changes is a hallmark of type 2 diabetes, the glucose signalling pathway leading to insulin secretion in pancreatic beta-cells has been extensively studied. This signalling mechanism depends on glucose metabolism and requires the presence of specific molecules such as GLUT2, glucokinase and the K(ATP) channel subunits Kir6.2 and SUR1. Other cells are also able to sense variations in glycemia or in local glucose concentrations and to modulate different physiological functions participating in the general control of glucose and energy homeostasis. These include cells forming the hepatoportal vein glucose sensor, which controls glucose storage in the liver, counterregulation, food intake and glucose utilization by peripheral tissues and neurons in the hypothalamus and brainstem whose firing rates are modulated by local variations in glucose concentrations or, when not protected by a blood-brain barrier, directly by changes in blood glucose levels. These glucose-sensing neurons are involved in the control of insulin and glucagon secretion, food intake and energy expenditure. Here, recent physiological studies performed with GLUT2-/- mice will be described, which indicate that this transporter is essential for glucose sensing by pancreatic beta-cells, by the hepatoportal sensor and by sensors, probably located centrally, which control activity of the autonomic nervous system and stimulate glucagon secretion. These studies may pave the way to a fine dissection of the molecular and cellular components of extra-pancreatic glucose sensors involved in the control of glucose and energy homeostasis.

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Lung cancer treatment strategy relies on an accurate staging of the disease and a careful evaluation of patient characteristics, including capability of undergoing and tolerating a defined treatment plan. Therefore, a solid knowledge on all intervention-related adverse events and drug toxicities is essential for a reliable decision-making process. Most lung cancer patients are diagnosed at an advanced stage of the disease, correlated with a dismal prognosis. Systemic therapy is the mainstay, and drug selection still strongly relies on expected toxicity profile. This chapter first describes the drug standard options and their respective toxicities in this context. Side effects of more complex multimodality combined treatments of early non-small-cell lung cancer as well as small-cell lung cancer, usually involving use of the same cytotoxic agents jointly with surgery and radiotherapy, are discussed in the second part of this chapter.

Comprehensive analysis of proteins secreted by dermatophytes in a protein medium which to some extent mimic "in vivo" growth parameters

RESUME : Les dermatophytes sont les agents infectieux les plus fréquents responsables de la plupart des mycoses superficielles chez les humains et chez les animaux. Ces infections, dermatophytoses, également appelées tineas ou teignes, sont fréquentes et causent des problèmes de santé publique au niveau mondial. La capacité d'envahir et de progresser au sein des structures kératinisées est probablement liée à la sécrétion de différentes enzymes kératinolytiques, qui sont considérées comme la principale caractéristique liée à la pathogénicité de ces champignons. L'objectif de ma thèse a été premièrement de progresser dans l'identification et la caractérisation des nouvelles protéines sécrétées, afin de mieux comprendre a) la capacité globale des dermatophytes à envahir les structures kératinisées, et b) les différences dans la virulence et la spécificité d'hôte que présentent les espèces étudiées .Pour progresser dans l'identification et la caractérisation de ces nouvelles protéines, les secretomes de six espèces de dermatophytes (Trichophyton rubrum, Trichophyton violaceum, Trichophyton soudanense, Trichophyton equinum, Arthroderma vanbreuseghemii et Trichophyton tonsurans) ont été étudiés. Bien qu'il y ait un niveau globalement élevé de similitude entre les protéases sécrétées, les différentes espèces de dermatophytes sécrètent des profiles protéiques distincts lorsqu'elles sont cultivées dans les mêmes conditions de culture, et donc une signature spécifique a pu être associé à chaque espèce. Ces profiles ont été un outil avantageux pour identifier et cartographier les protéines orthologues aux six espèces et ont aussi permit la discrimination d'espèces très proches comme T. tonsurans et T. equinum qui ne peuvent pas être différenciées par l'ADN ribosomal. Ce travail également présente ce que l'on croit être la première identification global des protéines sécrétées par les dermatophytes dans des conditions de culture que incitent l'activité protéolytique extracellulaire. Ce catalogue de protéines, comprenant des endo- and exo- proteases, autres hydrolases, oxydoreductases et des protéines avec fonction inconnue, représente probablement le spectre d'enzymes qui permettent la dégradation des tissus kératinisés en composés qui peuvent être assimilés par le champignon. Les résultats suggèrent qu'un changement écologique pourrait être associé à une expression différentielle des gènes codant les protéines sécrétées, en particulier, les protéases, plutôt qu'à des divergences génétiques au niveau des gènes codant les protéines orthologues. Une sécrétion différentielle des protéines par les dermatophytes pourrait également être responsable de la variabilité inflammatoire qui causent ces agents infectieux chez les différents hôtes. Par conséquent, les protéines identifiées ici sont également importantes pour faire la lumière sur la réponse immunitaire de l'hôte au cours du processus infectieux. SUMMARY : Dermatophytes are the most common infectious agents responsible for superficial mycosis in humans and animals. Dermatophytoses, also called tineas or ringworm, are frequent and cause public health problems worldwide. The secretion of different keratinolytic enzymes is believed to be a key pathogenicity-related characteristic of these fungi. The aim of this work was first to progress in the identification and characterization of novel secreted proteins, in order to better understand a) the overall capability of dermatophytes to invade keratinised structures, and b) differences in virulence and host-specificity of the investigated species. To progress in the identification and characterization of novel proteins, the secretomes from Trichophyton rubrum, Trichophyton violaceum, Trichophyton soudanense, Trichophyton equinum, Arthroderma vanbreuseghemii and Trichophyton tonsurans were studied. Although there is a high global level of similarity among the secreted proteases, different dermatophyte species produce distinct patterns of proteins when grown in the same culture medium, and so a specific signature could be associated to each species. These patterns were useful to identify and map orthologous proteins among the six species, as well as to discriminate the closely related species T. tonsurans and T. equinum, which cannot be differentiated by ribosomal DNA. This work also presents the first in-depth identification of the major proteins secreted by dermatophytes growing under conditions promoting extracellular proteolytic activity. This catalogue of proteins, which include several endo- and exo- proteases, other hydrolases, oxydoreductases, and proteins of unknown function, probably represents the spectrum of enzymes that allow the degradation of keratinized tissues into compounds which can be assimilated by the fungus. The results suggest that ecological switching could be related to a differential expression of genes encoding secreted proteins, particularly, proteases, rather than genetic divergences of the genes encoding orthologous proteins. Differential secretion of proteins by Dermatophyte species could also be responsible for the variable inflammation caused by the infectious agent within the host. Therefore, the proteins here identified are also important to shed light into the immune response of the host during the infection process.

The use of micro-XRD for the study of glaze color decorations

The compounds responsible for the colours and decorations in glass and glazed ceramics include: colouring agents (transition metal ions), pigments (micro-and nano-precipitates of compounds that either do not dissolve or recrystallize in the glassy matrix) and opacifiers (microcrystalline compounds with high light scattering capability). Their composition, structure and range of stability are highly dependent not only on the composition but also on the procedures followed to obtain them. Chemical composition of the colorants and crystallites may be obtained by means of SEM-EDX and WDX. Synchrotron Radiation micro-X-ray Diffraction has a small beam size adequate (10 to 50 microns footprint size) to obtain the structural information of crystalline compounds and high brilliance, optimal for determining the crystallites even when present in low amounts. In addition, in glass decorations the crystallites often appear forming thin layers (from 10 to 100 micrometers thick) and they show a depth dependent composition and crystal structure. Their nature and distribution across the glass/glazes decorations gives direct information on the technology of production and stability and may be related to the color and appearance. A selection of glass and glaze coloring agents and decorations are studied by means of SR-micro- XRD and SEM-EDX including: manganese brown, antimony yellow, red copper lusters and cobalt blue. The selection includes Medieval (Islamic, and Hispano Moresque) and renaissance tin glazed ceramics from the 10th to the 17th century AD.

Evaluation of the PAVEDEX Road Survey System in Iowa, HR-547, 1990

The Iowa Department of Transportation (DOT) evaluated the PAS I Road Survey System from PAVEDEX, Inc. of Spokane, Washington. This system uses video photograph to identify and quantify pavement cracking and patching distresses. Comparisons were made to procedures currently used in the State. Interstate highway, county roads and city streets, and two shoulder sections were evaluated. Variables included travel speeds, surface type and texture, and traffic control conditions. Repeatability and distress identification were excellent on rigid pavements. Differences in distress identification and the effect of surface textures in the flexible test sections limited the repeatability and correlation of data to that of the Iowa DOT method. Cost data indicates that PAVEDEX is capable of providing comparable results with improved accuracy at a reasonable cost, but in excess of that experienced currently by the Iowa DOT. PAVEDEX is capable of providing network level pavement condition data at highway speeds and analysis of the data to identify 1/8-inch cracks at approximately 2-3 lane miles per hour with manual evaluation. Photo-logging capability is also included in the unit.

The First 5 Years, April 2000 - March 2005, 2005

This report discusses the accomplishments of the Center for Portland Cement Concrete Pavement Technology (PCC Center) at Iowa State University, which was founded in April 2000. The report discusses the advisory groups that guide the Center, and describes the facilities included in the Center. The two Center facilities are the PCC Pavement and Materials Research Laboratory and the Mobile Concrete Research Lab. The report details the combined test capability of the Center's two labs, and describes the research undertaken at the Center. Also included in the publication are long-term planning efforts and technology transfer studies.

The redox state of cytochrome C modulates resistance to methotrexate in human MCF7 breast cancer cells

Background: Methotrexate is a chemotherapeutic agent used to treat a variety of cancers. However, the occurrence of resistance limits its effectiveness. Cytochrome c in its reduced state is less capable of triggering the apoptotic cascade. Thus, we set up to study the relationship among redox state of cytochrome c, apoptosis and the development of resistance to methotrexate in MCF7 human breast cancer cells. Results: Cell incubation with cytochrome c-reducing agents, such as tetramethylphenylenediamine, ascorbate or reduced glutathione, decreased the mortality and apoptosis triggered by methotrexate. Conversely, depletion of glutathione increased the apoptotic action of methotrexate, showing an involvement of cytochrome c redox state in methotrexateinduced apoptosis. Methotrexate-resistant MCF7 cells showed increased levels of endogenous reduced glutathione and a higher capability to reduce exogenous cytochrome c. Using functional genomics we detected the overexpression of GSTM1 and GSTM4 in methotrexate-resistant MCF7 breast cancer cells, and determined that methotrexate was susceptible of glutathionylation by GSTs. The inhibition of these GSTM isoforms caused an increase in methotrexate cytotoxicity in sensitive and resistant cells. Conclusions: We conclude that overexpression of specific GSTMs, GSTM1 and GSTM4, together with increased endogenous reduced glutathione levels help to maintain a more reduced state of cytochrome c which, in turn, would decrease apoptosis, thus contributing to methotrexate resistance in human MCF7 breast cancer cells.

Evaluation of High-Slump Concrete for Bridge Deck Overlays, TR-427, 2005

The Iowa Method for bridge deck overlays has been very successful in Iowa since its adoption in the 1970s. This method involves removal of deteriorated portions of a bridge deck followed by placement of a layer of dense (Type O) Portland Cement Concrete (PCC). The challenge encountered with this type of bridge deck overlay is that the PCC must be mixed on-site, brought to the placement area and placed with specialized equipment. This adds considerably to the cost and limits contractor selection, because not all contractors have the capability or equipment required. If it is possible for a ready-mix supplier to manufacture and deliver a dense PCC to the grade, then any competent bridge deck contractor would be able to complete the job. However, Type O concrete mixes are very stiff and generally cannot be transported and placed with ready-mix type trucks. This is where a “super-plasticizer” comes in to use. Addition of this admixture provides a substantial increase in the workability of the concrete – to the extent that it can be delivered to the site and placed on the deck directly out of a ready-mix truck. The objective of this research was to determine the feasibility of placing a deck overly of this type on county bridges within the limits of county budgets and workforce/contractor availability.

Economics of Using Calcium Chloride vs. Sodium Chloride for Deicing/Anti-Icing, TR-488, 2008

The use of chemicals is a critical part of a pro-active winter maintenance program. However, ensuring that the correct chemicals are used is a challenge. On the one hand, budgets are limited, and thus price of chemicals is a major concern. On the other, performance of chemicals, especially at lower pavement temperatures, is not always assured. Two chemicals that are used extensively by the Iowa Department of Transportation (Iowa DOT) are sodium chloride (or salt) and calcium chloride. While calcium chloride can be effective at much lower temperatures than salt, it is also considerably more expensive. Costs for a gallon of salt brine are typically in the range of $0.05 to $0.10, whereas calcium chloride brine may cost in the range of $1.00 or more per gallon. These costs are of course subject to market forces and will thus change from year to year. The idea of mixing different winter maintenance chemicals is by no means new, and in general discussions it appears that many winter maintenance personnel have from time to time mixed up a jar of chemicals and done some work around the yard to see whether or not their new mix “works.” There are many stories about the mixture turning to “mayonnaise” (or, more colorfully, to “snot”) suggesting that mixing chemicals may give rise to some problems most likely due to precipitation. Further, the question of what constitutes a mixture “working” in this context is a topic of considerable discussion. In this study, mixtures of salt brine and calcium chloride brine were examined to determine their ice melting capability and their freezing point. Using the results from these tests, a linear interpolation model of the ice melting capability of mixtures of the two brines has been developed. Using a criterion based upon the ability of the mixture to melt a certain thickness of ice or snow (expressed as a thickness of melt-water equivalent), the model was extended to develop a material cost per lane mile for the full range of possible mixtures as a function of temperature. This allowed for a comparison of the performance of the various mixtures. From the point of view of melting capacity, mixing calcium chloride brine with salt brine appears to be effective only at very low temperatures (around 0° F and below). However, the approach described herein only considers the material costs, and does not consider application costs or other aspects of the mixture performance than melting capacity. While a unit quantity of calcium chloride is considerably more expensive than a unit quantity of sodium chloride, it also melts considerably more ice. In other words, to achieve the same result, much less calcium chloride brine is required than sodium chloride brine. This is important in considering application costs, because it means that a single application vehicle (for example, a brine dispensing trailer towed behind a snowplow) can cover many more lane miles with calcium chloride brine than with salt brine before needing to refill. Calculating exactly how much could be saved in application costs requires an optimization of routes used in the application of liquids in anti-icing, which is beyond the scope of the current study. However, this may be an area that agencies wish to pursue for future investigation. In discussion with winter maintenance personnel who use mixtures of sodium chloride and calcium chloride, it is evident that one reason for this is because the mixture is much more persistent (i.e. it stays longer on the road surface) than straight salt brine. Operationally this persistence is very valuable, but at present there are not any established methods to measure the persistence of a chemical on a pavement. In conclusion, the study presents a method that allows an agency to determine the material costs of using various mixtures of salt brine and calcium chloride brine. The method is based upon the requirement of melting a certain quantity of snow or ice at the ice-pavement interface, and on how much of a chemical or of a mixture of chemicals is required to do that.

Feasibility Investigation of Segmentally Precast Bridge Piers for Accelerated Construction, TR-556, 2009

An innovative structural system for pier columns was investigated through a series of laboratory experiments. The columns and connections examined were comprised of precast concrete segments to accelerate construction. In addition some of the columns employed unbonded post-tensioning to self-center the columns when subjected to lateral loads and structural fuses to control large lateral deflections, dissipate energy, and expedite repair in the event of a catastrophic loading event. Six cantilever columns with varying component materials and connection details were subjected to a regimen of vertical dead loads and cyclic, quasi-static lateral loads. One column was designed as a control column to represent the behavior of a conventional reinforced concrete column and provide a basis for comparison with the remaining five jointed columns designed with the proposed structural system. After sustaining significant damage, the self-centering, jointed columns were repaired by replacing the structural fuses and retested to failure to investigate the effectiveness of the repair. The experiments identified both effective and unsatisfactory details for the jointed system. Two of the jointed columns demonstrated equivalent lateral strength, greater lateral stiffness, and greater lateral deformation capacity than the control column. The self-centering capability of the jointed columns was clearly demonstrated as well, and the repair technique proved effective as demonstrated by nearly identical pre and post repair behavior. The authors believe the proposed system to be a feasible alternative to conventional pier systems and recommend further development of details.

Wireless Sensor Networks for Infrastructure Monitoring, TR-611, 2010

A good system of preventive bridge maintenance enhances the ability of engineers to manage and monitor bridge conditions, and take proper action at the right time. Traditionally infrastructure inspection is performed via infrequent periodical visual inspection in the field. Wireless sensor technology provides an alternative cost-effective approach for constant monitoring of infrastructures. Scientific data-acquisition systems make reliable structural measurements, even in inaccessible and harsh environments by using wireless sensors. With advances in sensor technology and availability of low cost integrated circuits, a wireless monitoring sensor network has been considered to be the new generation technology for structural health monitoring. The main goal of this project was to implement a wireless sensor network for monitoring the behavior and integrity of highway bridges. At the core of the system is a low-cost, low power wireless strain sensor node whose hardware design is optimized for structural monitoring applications. The key components of the systems are the control unit, sensors, software and communication capability. The extensive information developed for each of these areas has been used to design the system. The performance and reliability of the proposed wireless monitoring system is validated on a 34 feet span composite beam in slab bridge in Black Hawk County, Iowa. The micro strain data is successfully extracted from output-only response collected by the wireless monitoring system. The energy efficiency of the system was investigated to estimate the battery lifetime of the wireless sensor nodes. This report also documents system design, the method used for data acquisition, and system validation and field testing. Recommendations on further implementation of wireless sensor networks for long term monitoring are provided.

Seal properties of TachoSil: in vitro hemodynamic measurements.

Fibrin glue products and collagen patches are frequently used as a sealing product, preventing surgical side bleedings. This is especially true in the field of cardiovascular surgery, where increasing numbers of patients are being operated with antiplatelet and anticoagulation therapy. The aim of this report was, in an in vitro hemodynamic setting, to examine the sealant properties of the TachoSil (Nycomed Pharma, Linz, Austria) patch. Burst pressure and normal force of 15 TachoSil sealed defects were measured. This was determined in a closed hydraulic system. Mean burst pressure load for a 5-mm defect was 69+/-11.4 mmHg; for a 7-mm defect was 63+/-16 mmHg; and, 62+/-16 mmHg for the defect with a diameter of 10 mm (P>0.05). The mean calculated normal force was as follows: 0.91+/-0.15 N for the 5 mm defect, 6.5+/-1.6 N for the 7 mm, and 8.1+/-0.75 N for the 10 mm defect. The TachoSil patch has the capability to seal small defects. However, at the larger defects the seal character was significantly reduced. These results suggest that the device may be a good alternative for hemostasis for small defects. The capacity to curtail or stop hemorrhage at the larger defects is unlikely.

Uncovering the genetic basis of adaptive change: on the intersection of landscape genomics and theoretical population genetics

A workshop recently held at the Ecole Polytechnique Federale de Lausanne (EPFL, Switzerland) was dedicated to understanding the genetic basis of adaptive change, taking stock of the different approaches developed in theoretical population genetics and landscape genomics and bringing together knowledge accumulated in both research fields. Indeed, an important challenge in theoretical population genetics is to incorporate effects of demographic history and population structure. But important design problems (e.g. focus on populations as units, focus on hard selective sweeps, no hypothesis-based framework in the design of the statistical tests) reduce their capability of detecting adaptive genetic variation. In parallel, landscape genomics offers a solution to several of these problems and provides a number of advantages (e.g. fast computation, landscape heterogeneity integration). But the approach makes several implicit assumptions that should be carefully considered (e.g. selection has had enough time to create a functional relationship between the allele distribution and the environmental variable, or this functional relationship is assumed to be constant). To address the respective strengths and weaknesses mentioned above, the workshop brought together a panel of experts from both disciplines to present their work and discuss the relevance of combining these approaches, possibly resulting in a joint software solution in the future.

Iowa Strategy for Homeland Security and Emergency Management 2015-2017, October 1, 2014

Address sustainability in all efforts. Sustainability should be at the core of all levels of homeland security and emergency management effort in Iowa. Capabilities need to be built for the long term, and without a sustainability plan in place, projects can quickly deplete uncertain levels of funding. Utilize an all-hazards methodology. Developing capabilities that are effective during a variety of disaster and emergency scenarios represents sound planning and resource management. Enhance capabilities through joint planning, training and exercise. Effective capabilities developed through coordinated planning efforts and an ongoing joint training and exercising program to ensure substantiate of prepared response. Utilize a collaborative approach to build capability. We will utilize whatever partnerships are necessary to build capability in the most effective manner possible. Regional partnerships have been, and will continue to be, in the forefront of the State of Iowa’s efforts to build and enhance capability. Enhance statewide capabilities. Whenever possible, we will identify and augment existing resources to provide statewide capability during a disaster or terrorist attack. Awareness, outreach and education. Open communication is critical to the success of any initiative. All projects implemented will have awareness, education and outreach components to ensure that all stakeholders are informed as to their responsibilities, capabilities and access. Information sharing and a common operating picture. The timely exchange of critical/actionable information is imperative to the success of every operation. The identification of a common operating picture allows decision makers to make informed decisions based on a unified understanding of the events around them.