The simultaneous role of an alveolus as flow mixer and flow feeder for the deposition of inhaled submicron particles

In an effort to understand the fate of inhaled submicron particles in the small sacs, or alveoli, comprising the gas-exchange region of the lung, we calculated the flow in three-dimensional (3D) rhythmically expanding models of alveolated ducts. Since convection toward the alveolar walls is a precursor to particle deposition, it was the goal of this paper to investigate the streamline maps' dependence upon alveoli location along the acinar tree. On the alveolar midplane, the recirculating flow pattern exhibited closed streamlines with a stagnation saddle point. Off the midplane we found no closed streamlines but nested, funnel-like, spiral, structures (reminiscent of Russian nesting dolls) that were directed towards the expanding walls in inspiration, and away from the contracting walls in expiration. These nested, funnel-like, structures were surrounded by air that flowed into the cavity from the central channel over inspiration and flowed from the cavity to the central channel over expiration. We also found that fluid particle tracks exhibited similar nested funnel-like spiral structures. We conclude that these unique alveolar flow structures may be of importance in enhancing deposition. In addition, due to inertia, the nested, funnel-like, structures change shape and position slightly during a breathing cycle, resulting in flow mixing. Also, each inspiration feeds a fresh supply of particle-laden air from the central channel to the region surrounding the mixing region. Thus, this combination of flow mixer and flow feeder makes each individual alveolus an effective mixing unit, which is likely to play an important role in determining the overall efficiency of convective mixing in the acinus.

The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development

OBJECTIVE: During postnatal development, mammalian articular cartilage acts as a surface growth plate for the underlying epiphyseal bone. Concomitantly, it undergoes a fundamental process of structural reorganization from an immature isotropic to a mature (adult) anisotropic architecture. However, the mechanism underlying this structural transformation is unknown. It could involve either an internal remodelling process, or complete resorption followed by tissue neoformation. The aim of this study was to establish which of these two alternative tissue reorganization mechanisms is physiologically operative. We also wished to pinpoint the articular cartilage source of the stem cells for clonal expansion and the zonal location of the chondrocyte pool with high proliferative activity. METHODS: The New Zealand white rabbit served as our animal model. The analysis was confined to the high-weight-bearing (central) areas of the medial and lateral femoral condyles. After birth, the articular cartilage layer was evaluated morphologically at monthly intervals from the first to the eighth postnatal month, when this species attains skeletal maturity. The overall height of the articular cartilage layer at each juncture was measured. The growth performance of the articular cartilage layer was assessed by calcein labelling, which permitted an estimation of the daily growth rate of the epiphyseal bone and its monthly length-gain. The slowly proliferating stem-cell pool was identified immunohistochemically (after labelling with bromodeoxyuridine), and the rapidly proliferating chondrocyte population by autoradiography (after labelling with (3)H-thymidine). RESULTS: The growth activity of the articular cartilage layer was highest 1 month after birth. It declined precipitously between the first and third months, and ceased between the third and fourth months, when the animal enters puberty. The structural maturation of the articular cartilage layer followed a corresponding temporal trend. During the first 3 months, when the articular cartilage layer is undergoing structural reorganization, the net length-gain in the epiphyseal bone exceeded the height of the articular cartilage layer. This finding indicates that the postnatal reorganization of articular cartilage from an immature isotropic to a mature anisotropic structure is not achieved by a process of internal remodelling, but by the resorption and neoformation of all zones except the most superficial (stem-cell) one. The superficial zone was found to consist of slowly dividing stem cells with bidirectional mitotic activity. In the horizontal direction, this zone furnishes new stem cells that replenish the pool and effect a lateral expansion of the articular cartilage layer. In the vertical direction, the superficial zone supplies the rapidly dividing, transit-amplifying daughter-cell pool that feeds the transitional and upper radial zones during the postnatal growth phase of the articular cartilage layer. CONCLUSIONS: During postnatal development, mammalian articular cartilage fulfils a dual function, viz., it acts not only as an articulating layer but also as a surface growth plate. In the lapine model, this growth activity ceases at puberty (3-4 months of age), whereas that of the true (metaphyseal) growth plate continues until the time of skeletal maturity (8 months). Hence, the two structures are regulated independently. The structural maturation of the articular cartilage layer coincides temporally with the cessation of its growth activity - for the radial expansion and remodelling of the epiphyseal bone - and with sexual maturation. That articular cartilage is physiologically reorganized by a process of tissue resorption and neoformation, rather than by one of internal remodelling, has important implications for the functional engineering and repair of articular cartilage tissue.

Management, feeding, production, reproduction and udder health on organic and conventional Swiss dairy farms

Organic dairy farms (OP; n=60) and conventional dairy farms (integrated production, IP; n=60), matched in size, location, and agricultural zone (altitude), were studied for possible differences in management, feeding, production, reproduction and udder health. OP and IP farms were similar in size (17.7 and 16.9 ha), milk quota (65900 and 70,000 kg/year), cow number (14 and 15), cow age (5.3 and 5.2 years), housing of cows of the Simmental x Red Holstein or Holstein breeds (87 and 75%; 45 and 60%), but differed significantly with respect to loose housing systems (18 and 7%), outside paddocks (98 and 75%), energy-corrected 305-d milk yield (5,695 and 6,059 kg), milk protein content (31.8 and 32.7 g/kg), use of bucket milking systems (73 and 33%), observance of regular (12-h) milking intervals (47 and 68%), routine application of the California-Mastitis-Test (10 and 28%), teat dipping after milking (25 and 43%) and blanket dry cow treatments (0 and 45%). Milk somatic cell counts on OP and IP farms (119 000 and 117,000/mL) and reproduction data were similar and there were no significant differences between OP and IP farms as concerns available feeds, planning and management of feeding. Alternative veterinary treatments were used more often on OP than IP farms (55 and 17%). Main causes for cow replacements on OP and IP farms were fertility disorders (both 45%), age (40 and 42%), sale (30 and 37%) and udder health (35 and 13%).Between OP and IP Swiss dairy farms thus relatively few larger differences were found.

THE POTENTIAL OF INDUSTRIAL WASTE AND AGRICULTURAL FEEDSTOCK TOWARDS SUSTAINABLE BIOFUELS PRODUCTION: TECHNO-ECONOMIC AND ENVIRONMENTAL IMPACT PERSPECTIVES

This Ph.D. research is comprised of three major components; (i) Characterization study to analyze the composition of defatted corn syrup (DCS) from a dry corn mill facility (ii) Hydrolysis experiments to optimize the production of fermentable sugars and amino acid platform using DCS and (iii) Sustainability analyses. Analyses of DCS included total solids, ash content, total protein, amino acids, inorganic elements, starch, total carbohydrates, lignin, organic acids, glycerol, and presence of functional groups. Total solids content was 37.4% (± 0.4%) by weight, and the mass balance closure was 101%. Total carbohydrates [27% (± 5%) wt.] comprised of starch (5.6%), soluble monomer carbohydrates (12%) and non-starch carbohydrates (10%). Hemicellulose components (structural and non-structural) were; xylan (6%), xylose (1%), mannan (1%), mannose (0.4%), arabinan (1%), arabinose (0.4%), galatactan (3%) and galactose (0.4%). Based on the measured physical and chemical components, bio-chemical conversion route and subsequent fermentation to value added products was identified as promising. DCS has potential to serve as an important fermentation feedstock for bio-based chemicals production. In the sugar hydrolysis experiments, reaction parameters such as acid concentration and retention time were analyzed to determine the optimal conditions to maximize monomer sugar yields while keeping the inhibitors at minimum. Total fermentable sugars produced can reach approximately 86% of theoretical yield when subjected to dilute acid pretreatment (DAP). DAP followed by subsequent enzymatic hydrolysis was most effective for 0 wt% acid hydrolysate samples and least efficient towards 1 and 2 wt% acid hydrolysate samples. The best hydrolysis scheme DCS from an industry's point of view is standalone 60 minutes dilute acid hydrolysis at 2 wt% acid concentration. The combined effect of hydrolysis reaction time, temperature and ratio of enzyme to substrate ratio to develop hydrolysis process that optimizes the production of amino acids in DCS were studied. Four key hydrolysis pathways were investigated for the production of amino acids using DCS. The first hydrolysis pathway is the amino acid analysis using DAP. The second pathway is DAP of DCS followed by protein hydrolysis using proteases [Trypsin, Pronase E (Streptomyces griseus) and Protex 6L]. The third hydrolysis pathway investigated a standalone experiment using proteases (Trypsin, Pronase E, Protex 6L, and Alcalase) on the DCS without any pretreatment. The final pathway investigated the use of Accellerase 1500® and Protex 6L to simultaneously produce fermentable sugars and amino acids over a 24 hour hydrolysis reaction time. The 3 key objectives of the techno-economic analysis component of this PhD research included; (i) Development of a process design for the production of both the sugar and amino acid platforms with DAP using DCS (ii) A preliminary cost analysis to estimate the initial capital cost and operating cost of this facility (iii) A greenhouse gas analysis to understand the environmental impact of this facility. Using Aspen Plus®, a conceptual process design has been constructed. Finally, both Aspen Plus Economic Analyzer® and Simapro® sofware were employed to conduct the cost analysis as well as the carbon footprint emissions of this process facility respectively. Another section of my PhD research work focused on the life cycle assessment (LCA) of commonly used dairy feeds in the U.S. Greenhouse gas (GHG) emissions analysis was conducted for cultivation, harvesting, and production of common dairy feeds used for the production of dairy milk in the U.S. The goal was to determine the carbon footprint [grams CO2 equivalents (gCO2e)/kg of dry feed] in the U.S. on a regional basis, identify key inputs, and make recommendations for emissions reduction. The final section of my Ph.D. research work was an LCA of a single dairy feed mill located in Michigan, USA. The primary goal was to conduct a preliminary assessment of dairy feed mill operations and ultimately determine the GHG emissions for 1 kilogram of milled dairy feed.

Prevalence and risk-factor analysis of Shiga toxigenic Escherichia coli in faecal samples of organically and conventionally farmed dairy cattle

Cattle are a natural reservoir for Shiga toxigenic Escherichia coli (STEC), however, no data are available on the prevalence and their possible association with organic or conventional farming practices. We have therefore studied the prevalence of STEC and specifically O157:H7 in Swiss dairy cattle by collecting faeces from approximately 500 cows from 60 farms with organic production (OP) and 60 farms with integrated (conventional) production (IP). IP farms were matched to OP farms and were comparable in terms of community, agricultural zone, and number of cows per farm. E. coli were grown overnight in an enrichment medium, followed by DNA isolation and PCR analysis using specific TaqMan assays. STEC were detected in all farms and O157:H7 were present in 25% of OP farms and 17% of IP farms. STEC were detected in 58% and O157:H7 were evidenced in 4.6% of individual faeces. Multivariate statistical analyses of over 250 parameters revealed several risk-factors for the presence of STEC and O157:H7. Risk-factors were mainly related to the potential of cross-contamination of feeds and cross-infection of cows, and age of the animals. In general, no significant differences between the two farm types concerning prevalence or risk for carrying STEC or O157:H7 were observed. Because the incidence of human disease caused by STEC in Switzerland is low, the risk that people to get infected appears to be small despite a relatively high prevalence in cattle. Nevertheless, control and prevention practices are indicated to avoid contamination of animal products.

Quality evaluation of the available Internet information regarding pain during orthodontic treatment

OBJECTIVE To investigate the quality of the data disseminated via the Internet regarding pain experienced by orthodontic patients. MATERIALS AND METHODS A systematic online search was performed for 'orthodontic pain' and 'braces pain' separately using five search engines. The first 25 results from each search term-engine combination were pooled for analysis. After excluding advertising sites, discussion groups, video feeds, and links to scientific articles, 25 Web pages were evaluated in terms of accuracy, readability, accessibility, usability, and reliability using recommended research methodology; reference textbook material, the Flesch Reading Ease Score; and the LIDA instrument. Author and information details were also recorded. RESULTS Overall, the results indicated a variable quality of the available informational material. Although the readability of the Web sites was generally acceptable, the individual LIDA categories were rated of medium or low quality, with average scores ranging from 16.9% to 86.2%. The orthodontic relevance of the Web sites was not accompanied by the highest assessment results, and vice versa. CONCLUSIONS The quality of the orthodontic pain information cited by Web sources appears to be highly variable. Further structural development of health information technology along with public referral to reliable sources by specialists are recommended.

Design and Impact of Awareness Functions – A Study about Social Media in Virtual Teams

The usage of social media in leisure time settings has become a prominent research topic. However, less research has been done on the design of social media in collaboration settings. In this study, we investigate how social media can support asynchronous collaboration in virtual teams and specifically how they can increase activity awareness. On the basis of an open source social networking platform, we present two prototype designs: a standard platform with basic support for information processing, communication and process – as suggested by Zigurs and Buckland (1998) – and an advanced platform with additional support for activity awareness via specialfeed functions. We argue that the standard platform already conveys activity awareness to a certain extent, however, that this awareness can be increased even more by the feeds in the advanced platform. Both prototypes are tested in a field experiment and evaluated with respect to their impact on perceived activity awareness, coordination and satisfaction. We show that the advanced design increases coordination and satisfaction through increased perceived activity awareness.

Relative Feeding Value of Wet Corn Steep Liquor When Fed to Finishing Cattle

Corn steep liquor is a liquid by-product containing condensed steep water and condensed distillers solubles from a wet corn milling plant. Finishing steers weighing nine hundred and seventy-five pounds were fed cornbased finishing diets containing 0%, 6%, or 12% corn steep liquor for 84 days. Feeding corn steep liquor did not affect performance of the steers or carcass characteristics. Based on value of feeds replaced in the diet, steep liquor had a value of $55 to $60/ton (50% dry matter) when used to replace corn and supplemental protein in a corn-based finishing diet.

Diet Roughage Ingredients for Newly Weaned Calves

Several commodity feeds that are high in fiber are available that may substitute for corn cobs in a complete starting ration. This study was designed to evaluate the use of soyhulls and sunflower meal as substitutes for corncobs as a roughage source for newly weaned calves. One-hundred-and-fifty calves from the ISU Rhodes Research Farm were weaned, weighed, sorted by sex, and stratified by weight to eight pens. Two pens of each sex were assigned to one of two diet treatments. Calves fed the corncob diet consumed two pounds more feed dry matter, gained 1.5 pounds more per day, and were more efficient the first 14 days on feed. The soyhull diet was quite fine in particle size, and some feed particle separation occurred in the bunk. Some compensatory performance may have occurred with the soyhull diet the second 14 days on feed, although no statistical differences existed. This suggests that palatability, feed presentation, and bunk characteristics are important considerations in selecting roughage sources for complete starting diets for newly weaned calves.

REGULATION OF HGF EXPRESSION BY ΔEGFR-MEDIATED C-MET ACTIVATION IN GLIOBLASTOMA CELLS

Overexpression of the hepatocyte growth factor receptor (c-Met) and its ligand, the hepatocyte growth factor (HGF), and a constitutively active mutant of the epidermal growth factor receptor (∆EGFR/EGFRvIII), occur frequently in glioblastoma. c-Met is activated in a ligand-dependent manner by HGF or in a ligand-independent manner by ∆EGFR. Dysregulated c-Met signaling contributes to the aggressive phenotype of glioblastoma, yet the mechanisms underlying the production of HGF in glioblastoma are poorly understood. We found a positive correlation between HGF and c-Met expression in glioblastoma, suggesting that they are coregulated. This is supported by the finding that in a c-Met/HGF axis-dependent glioblastoma cell line, shRNA-mediated silencing of c-Met, or treatment with the c-Met inhibitor SU11274, attenuated HGF expression. Biologically, c-Met knockdown decreased anchorage-independent colony formation and the tumorigenicity of intracranial xenografts. Building on prior findings that ∆EGFR enhanced c-Met activation, we found that ∆EGFR also led to increased HGF expression, which was reversed upon ∆EGFR inhibition with AG1478. ∆EGFR required c-Met to maintain elevated HGF expression, colony formation of glioblastoma cells, and the tumorigenicity of orthotopic xenografts. An unbiased mass spectrometry-based approach identified phosphotyrosine-related signaling changes that occurred with c-Met knockdown in a glioblastoma cell line expressing ΔEGFR and in parental cells. Notably, phosphorylation of STAT3, a master regulator of the mesenchymal GBM subtype and a known target of ∆EGFR, also decreased when c-Met was silenced in these cells, suggesting that the signals from these receptors converge on STAT3. Using a STAT3 inhibitor, WP1193, we showed that STAT3 inhibition decreased HGF mRNA expression in ΔEGFR-expressing glioblastoma cells. Consistent with these findings, constitutively active STAT3 partially restored HGF expression and anchorage-independent growth of c-Met knockdown glioblastoma cells that overexpressed ΔEGFR. We found that higher levels of HGF and c-Met expression associated with the mesenchymal GBM subtype. Taken together, these results suggest that the activity of c-Met regulates the expression of HGF in glioblastoma cells, that ∆EGFR feeds positively into this autocrine loop, that signaling of the two receptors together modulate HGF expression via STAT3, and that the HGF/c-Met axis may therefore be a good additional target for therapy of mesenchymal GBM tumors.

A Compensating Anastigmatic Submillimeter Array Imaging System for STEAMR

In this paper, we present a novel technique for the removal of astigmatism in submillimeter-wave optical systems through employment of a specific combination of so-called astigmatic off-axis reflectors. This technique treats an orthogonally astigmatic beam using skew Gaussian beam analysis, from which an anastigmatic imaging network is derived. The resultant beam is considered truly stigmatic, with all Gaussian beam parameters in the orthogonal directions being matched. This is thus considered an improvement over previous techniques wherein a beam corrected for astigmatism has only the orthogonal beam amplitude radii matched, with phase shift and phase radius of curvature not considered. This technique is computationally efficient, negating the requirement for computationally intensive numerical analysis of shaped reflector surfaces. The required optical surfaces are also relatively simple to implement compared to such numerically optimized shaped surfaces. This technique is implemented in this work as part of the complete optics train for the STEAMR antenna. The STEAMR instrument is envisaged as a mutli-beam limb sounding instrument operating at submillimeter wavelengths. The antenna optics arrangement for this instrument uses multiple off-axis reflectors to control the incident radiation and couple them to their corresponding receiver feeds. An anastigmatic imaging network is successfully implemented into an optical model of this antenna, and the resultant design ensures optimal imaging of the beams to the corresponding feed horns. This example also addresses the challenges of imaging in multi-beam antenna systems.

Steroidogenesis of the testis - new genes and pathways

Defects of androgen biosynthesis cause 46,XY disorder of sexual development (DSD). All steroids are produced from cholesterol and the early steps of steroidogenesis are common to mineralocorticoid, glucocorticoid and sex steroid production. Genetic mutations in enzymes and proteins supporting the early biosynthesis pathways cause adrenal insufficiency (AI), DSD and gonadal insufficiency. The classic androgen biosynthesis defects with AI are lipoid CAH, CYP11A1 and HSD3B2 deficiencies. Deficiency of CYP17A1 rarely causes AI, and HSD17B3 or SRD5A2 deficiencies only cause 46,XY DSD and gonadal insufficiency. All androgen biosynthesis depends on 17,20 lyase activity of CYP17A1 which is supported by P450 oxidoreductase (POR) and cytochrome b5 (CYB5). Therefore 46,XY DSD with apparent 17,20 lyase deficiency may be due to mutations in CYP17A1, POR or CYB5. Illustrated by patients harboring mutations in SRD5A2, normal development of the male external genitalia depends largely on dihydrotestosterone (DHT) which is converted from circulating testicular testosterone (T) through SRD5A2 in the genital skin. In the classic androgen biosynthetic pathway, T is produced from DHEA and androstenedione/-diol in the testis. However, recently found mutations in AKR1C2/4 genes in undervirilized 46,XY individuals have established a role for a novel, alternative, backdoor pathway for fetal testicular DHT synthesis. In this pathway, which has been first elucidated for the tammar wallaby pouch young, 17-hydroxyprogesterone is converted directly to DHT by 5α-3α reductive steps without going through the androgens of the classic pathway. Enzymes AKR1C2/4 catalyse the critical 3αHSD reductive reaction which feeds 17OH-DHP into the backdoor pathway. In conclusion, androgen production in the fetal testis seems to utilize two pathways but their exact interplay remains to be elucidated.

CHEOPS: a space telescope for ultra-high precision photometry of exoplanet transits

The CHaracterising ExOPlanet Satellite (CHEOPS) is a joint ESA-Switzerland space mission (expected to launch in 2017) dedicated to search for exoplanet transits by means of ultra-high precision photometry. CHEOPS will provide accurate radii for planets down to Earth size. Targets will mainly come from radial velocity surveys. The CHEOPS instrument is an optical space telescope of 30 cm clear aperture with a single focal plane CCD detector. The tube assembly is passively cooled and thermally controlled to support high precision, low noise photometry. The telescope feeds a re-imaging optic, which supports the straylight suppression concept to achieve the required Signal to Noise. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Drought coping and adaptation strategies: Understanding adaptations to climate change in agro-pastoral livestock production in Makueni district, Kenya

Using drought as a lens, this article analyses how agro-pastoralists in Makueni district, Kenya adapt their livestock production to climate variability and change. Data were collected from a longitudinal survey of 127 agro-pastoral households. Approximately one-third of the households have inadequate feeds, and livestock diseases are major challenges during non-drought and drought periods. Agro-pastoralists’ responses to drought are reactive and mainly involve intensifying exploitation of resources and the commons. Proactive responses such as improving production resources are few. Poverty, limited responses to market dynamics and inadequate skills constrain adaptations. Many agro-pastoralists’ attachment to livestock deters livestock divestment, favouring disadvantageous sales that result in declining incomes. To improve adaptive capacity, interventions should expose agro-pastoralists to other forms of savings, incorporate agro-pastoralists as agents of change by building their capacity to provide extension services, and maintain infrastructure. Securing livestock mobility, pasture production and access is crucial under the variable social-ecological conditions.

Respiratory rhythm generation: A modeling study of the respiratory central pattern generator and the phrenic motor neuron

The respiratory central pattern generator is a collection of medullary neurons that generates the rhythm of respiration. The respiratory central pattern generator feeds phrenic motor neurons, which, in turn, drive the main muscle of respiration, the diaphragm. The purpose of this thesis is to understand the neural control of respiration through mathematical models of the respiratory central pattern generator and phrenic motor neurons. ^ We first designed and validated a Hodgkin-Huxley type model that mimics the behavior of phrenic motor neurons under a wide range of electrical and pharmacological perturbations. This model was constrained physiological data from the literature. Next, we designed and validated a model of the respiratory central pattern generator by connecting four Hodgkin-Huxley type models of medullary respiratory neurons in a mutually inhibitory network. This network was in turn driven by a simple model of an endogenously bursting neuron, which acted as the pacemaker for the respiratory central pattern generator. Finally, the respiratory central pattern generator and phrenic motor neuron models were connected and their interactions studied. ^ Our study of the models has provided a number of insights into the behavior of the respiratory central pattern generator and phrenic motor neurons. These include the suggestion of a role for the T-type and N-type calcium channels during single spikes and repetitive firing in phrenic motor neurons, as well as a better understanding of network properties underlying respiratory rhythm generation. We also utilized an existing model of lung mechanics to study the interactions between the respiratory central pattern generator and ventilation. ^