Identification and characterisation of alveolar epithelial biomarkers

The alveolar epithelial surface has been shown to be important in many forms of lung injury (e.g. ARDS, pneumonia and fibrosis). Markers of cell specific injury to the lung that can be measured in bronchioalveolar lavage would be advantageous as they might allow study of damage to the alveoli in a non-invasive mariner. In this thesis a strategy is described, using a bacterial model of pneumonia, for identifying markers specific for individual cell types within the alveoli. Also, two putative cell specific antibodies (MMC4 and MMC6) are further characterised to establish their potential as markers of alveoli injury. A rat model of pneumonia, caused by instillation of Staphylococcus aureus, has shown a decrease in alveolar epithelial type I cells (AETI cells) and an increase in alveolar epithelial type II cells (AETII cells) seventy two hours post-infection. Injured regions from seventy two hour post Staphylococcus aureus infected lungs were analysed via global gene analysis using Affymetrix® U34 gene chips. Overall 67 genes were found to increase greater than 2 fold (F>0.05, P≤0.001); of which 49 encode from known proteins. 197 genes decreased 2 fold of greater (F>0.05, P≤0.001) of which 125 translate to known proteins. Searching the genes that decreased identified some proteins associated with AETI cells (e.g. caveolin: 7 fold decease, P=0.017 and aquaporin 5:2 fold decrease, P =0.01). This suggests that this group of down regulated genes could potentially contain novel markers that could identify reduced numbers of AETI cells. Within this group CD9 was found to decrease. This was unexpected due to the influx of macrophages (known to be CD9 positive) into the site of injury. However, a literature search showed that CD9 is known to be expressed in the alveoli, but is not thought to be cell specific. Immunohistochemistry of frozen lung sections showed that anti-CD9 antibodies co-localised with AETI markers (caveolin, MMC6) but not AETII markers (RTII₇₀, MMC4). MMC4 monoclonal antibody (IgG2a) has been proposed as an AETII and Clara cell marker that recognises a protein novel to these two cell types within the lung, but the antigen has not been characterised. MMC4 antigen was immunoprecipitated from detergent-solubilized fractions of organ homogenates using antibody-bound magnetic beads. The resulting purified protein was trypsin digested and analysed via MALDI-TOF and tandem mass spectrometry. The top 'hit' in SWISSPROT for the antigen was aminopeptidase N (APN). The MMC4 monoclonal antibody was found to recognise a commercially purified APN. Further analysis showed that the MMC4 monoclonal antibody was not a functional inhibitor of APN and that the antibody was not binding to a glycans attached to APN. MMC6 monoclonal antibody (IgG2b) was created at the same time as the MMC4 antibody. Initial studies showed that MMC6 recognises AETI cells within the lung. This study shows that the antibody is recognising an antigen that is specific for the lung and is only located on AETI cells within the lung. The antigen has been found to be an integral membrane protein. Attempts at solubilizing the MMC6 antigen from the cell membranes were not successful; however mechanical disruption did partially remove the antigen from the cell membranes. Magnetic bead immuno-precipitation eluted a protein of 60kDa. Unfortunately, due to low yields of the protein, identification was not possible by MALDI-TOF or Edman degradation. This thesis proposes a new way of interpreting global gene data to find proteins specific to different cell types. We cast doubts on the specificity of some previously proposed "specific" markers. It also highlights the pitfalls of claiming an antibody is a useful marker of injury until the candidate biomarker has been fully investigated. The continued emergence of CD proteins on alveolar epithelial cells within this study suggest that the alveolar epithelium may have more influence over the immune response within the lung than previously realised

Adolph Murie: Denali's Wilderness Conscience

Thesis (M.A.) University of Alaska Fairbanks, 2004Denali National Park, Alaska substantially owes its stature as Alaska's premier wilderness park to Adolph Murie. Forty years after he retired as park biologist, Murie still influences the perception and management of Denali National Park. Murie's development from childhood to esteemed scientist and wilderness advocate followed a linear progression. His rural upbringing under the tutelage of his older brother, Olaus Murie, cultivated his desire to be a biologist and his appreciation for wild places. His academic training in animal ecology solidified his belief that the management of natural areas must consider all species as essential and equally valuable. His pioneering wildlife studies as one of the National Park Service's first biologists changed national opinion. He led the opposition against plans for extensive construction and development in Denali National Park during the Mission 66 era. In doing so he left the imprint of his wilderness ethic on the park

Batch-to-Batch Iterative Learning Control of a Fed-Batch Fermentation Process

In this work, Iterative Learning Control on a fed-batch fermentation process using linearised models has been studied. The repetitive nature of batch processes enables ILC to obtain information from a previous batch in order to improve the performance of the current batch such that the product quality converges asymptotically to the desired trajectory The basic batch to batch ILC law presents the control action of a current batch as a summation of the control action from the previous batch and the deviation of the output trajectory from the desired reference trajectory incorporation with a learning rate. In a bid to address the issue of the process non-linearity, the control policy and the output trajectory were linearised around their respective nominal trajectories. The linearised models were then identified using Multi Linear Regression (MLR), Principal Component Analysis (PCR) and Partial Least Squares (PLS). In order to curb the effects of plant-model mismatches and process variations, the linearised models were reidentified after each batch operation. This was done by selecting the immediate previous batch as the nominal batch and then adding the recently obtained process data into the historical data batch on completion of the current batch run. The weighting matrices in the objective function were carefully selected taking into consideration that they have a major influence on the robust performance of the process. In using PLS and PCR models the issue of process collinearity was effectively addressed. The proposed batch to batch ILC strategy was applied to a simulated fed-batch fermentation process for the production of secreted protein. The results of the optimal control policy were comparable to that obtained in using full mechanistic model. ILC, a simple but yet an effective optimal control strategy has demonstrated to be a viable option in complex processes such as batch processes where mechanistic models are difficult to develop. Keywords: Iterative Learning Control, batch process, fed-batch fermentation, batch to batch ILC, control policy. DOI: 10.7176/CMR/14-3-02 Publication date:August 31st 202

The carbon bonus of organic nitrogen enhances nitrogen use efficiency of plants

The importance of organic nitrogen (N) for plant nutrition and productivity is increasingly being recognized. Here we show that it is not only the availability in the soil that matters, but also the effects on plant growth. The chemical form of N taken up, whether inorganic (such as nitrate) or organic (such as amino acids), may significantly influence plant shoot and root growth, and nitrogen use efficiency (NUE). We analysed these effects by synthesizing results from multiple laboratory experiments on small seedlings (Arabidopsis, poplar, pine and spruce) based on a tractable plant growth model. A key point is that the carbon cost of assimilating organic N into proteins is lower than that of inorganic N, mainly because of its carbon content. This carbon bonus makes it more beneficial for plants to take up organic than inorganic N, even when its availability to the roots is much lower - up to 70% lower for Arabidopsis seedlings. At equal growth rate, root:shoot ratio was up to three times higher and nitrogen productivity up to 20% higher for organic than inorganic N, which both are factors that may contribute to higher NUE in crop production

Early Initiation of and Exclusive Breastfeeding in Large-scale Community-based Programmes in Bolivia and Madagascar

About one-fourth to one-half of all infant deaths in developing countries occur in the first week of life. Immediate breastfeeding within the first hour, followed by early exclusive breastfeeding, improves the health and survival status of newborns. The aim of this study was to demonstrate that breastfeeding practices, crucial to infant health, can be improved at scale in developing countries. During 1999-2003, the LINKAGES Project, funded by the United States Agency for International Development, implemented its community-based model to bring about rapid change in individual behaviours and community norms regarding early and exclusive breastfeeding, at a scale [LINKAGES' definition of 'scale' was adapted from a CORE Group background paper on \u2018Scaling-up' maternal, newborn, and child health services, 11 July 2005] that could achieve significant public-health impact. 'Scale' was defined as bringing improved infant-feeding practices to more people over a wider geographic area, more quickly, more equitably, and with sustainability as a goal. During this time, country-specific programmes were designed and implemented in Bolivia and Madagascar, with catchment populations of one million and six million respectively. These country programmes were implemented with multiple local government, private voluntary organizations, and partners of non-governmental organizations (NGOs) through existing health and nutrition activities. Breastfeeding was an entry point to work at all levels of the healthcare system and, within communities, using policy/advocacy and training for healthcare workers, with a particular emphasis on front-line health workers and community members. Harmonized messages and materials, including mass media, were developed and used by partners. Timely initiation of breastfeeding was one indicator measured. Data collected through rapid assess\uadment surveys showed statistically significant increases (p<0.001) in timely initiation of breastfeeding in both the countries. In Bolivia, timely initiation of breastfeeding went from 56% in 2000 to 69% in 2001 and reached 74% by the end of 2003. In Madagascar, the initiation rate went from 34% at baseline in 2000 to 69% in 2001, 76% in 2002, and rose to 78% in 2004. Exclusive breastfeeding during the first month of life was also measured. At baseline in Bolivia, the rate of exclusive breastfeeding for the first month of life was 81% (2000), decreased slightly in 2001, and then increased to 88% by the end of the Project in 2003. In Madagascar, it started high at 86% in 2000, increased during the implementation of the programme, and by 2004, was 91%. These results were achieved quickly and sustained over the course of the intervention

Improving Rural Bone Health and Minimizing Fracture Risk in West Virginia: Validation of the World Health Organization FRAX® Assessment Tool as a Phone Survey for Osteoporosis Detection

West Virginia ranks second nationally in population ≥ 65 years old placing our state at greater risk for osteoporosis and fracture. The gold standard for detecting osteoporosis is dual X-ray absorptiometry (DXA), yet over half of West Virginia’s counties do not have this machine. Due to access barriers, a validated phone-administered fracture prediction tool would be beneficial for osteoporosis screening. The World Health Organization’s FRAX® fracture prediction tool was administered as a phone survey to 45 patients; these results were compared to DXA bone mineral density determination. Results confirmed that the FRAX® phone survey is as reliable as DXA in detecting osteoporosis or clinically significant osteopenia: 92% positive predictive value, 100% negative predictive value, 100% sensitivity and 91% specificity when compared to the gold standard. These promising results allow for the development of telephone-based protocols to improve osteoporosis detection, referral and treatment especially in areas with health care access barriers

Updating ACSM's Recommendations for Exercise Preparticipation Health Screening

The purpose of the American College of Sports Medicine's (ACSM) exercise preparticipation health screening process is to identify individuals who may be at elevated risk for exercise-related sudden cardiac death and/or acute myocardial infarction. Recent studies have suggested that using the current ACSM exercise preparticipation health screening guidelines can result in excessive physician referrals, possibly creating a barrier to exercise participation. In addition, there is considerable evidence that exercise is safe for most people and has many associated health and fitness benefits; exercise-related cardiovascular events are often preceded by warning signs/symptoms; and the cardiovascular risks associated with exercise lessen as individuals become more physically active/fit. Consequently, a scientific roundtable was convened by the ACSM in June 2014 to evaluate the current exercise preparticipation health screening recommendations. The roundtable proposed a new evidence-informed model for exercise preparticipation health screening on the basis of three factors: 1) the individual's current level of physical activity, 2) presence of signs or symptoms and/or known cardiovascular, metabolic, or renal disease, and 3) desired exercise intensity, as these variables have been identified as risk modulators of exercise-related cardiovascular events. Identifying cardiovascular disease risk factors remains an important objective of overall disease prevention and management, but risk factor profiling is no longer included in the exercise preparticipation health screening process. The new ACSM exercise preparticipation health screening recommendations reduce possible unnecessary barriers to adopting and maintaining a regular exercise program, a lifestyle of habitual physical activity, or both, and thereby emphasize the important public health message that regular physical activity is important for all individuals

The Ursinus Weekly, May 3, 1965

Y retreat emphasizes creation of ideal college • Stage set for Fenwickian mouse • Ferguson, Dawson report $1,700 for Campus Chest • Psych Club elects officers • Bishop\u27s Players present An enemy of the people • Waiters\u27 banquet • Starvation: Paradox of plenty • Bali Ha\u27i theme for annual Spring Festival • Active electioneering marks class elections • Editorial: MSGA election; UC traditions and manners • Letters to the editor • One language for the world • Nine overseas students enrolled at Ursinus • Admissions dilemma • Injured thinclads bow at PMC; Win triangular meet at Hopkins • UC nine wins two: Beat F&M, Lebanon Valley • UC girls drop match to W.C. • Lacrosse team whips W. Chester • Greek gleanings • Advertising and PR seminarhttps://digitalcommons.ursinus.edu/weekly/1248/thumbnail.jp