Modeling of Common Terns, Sterna hirundo, on Lake Champlain and Predictions for the Future

The Common Tern, Sterna hirundo, is a small, migratory water bird whose extensive range includes nesting islands on Lake Champlain. The history of Common Terns in Vermont includes population declines from hunting and predation, leading to their addition to the state’s Endangered Species List in 1989. Since then, they have been managed intensively such that their population in Vermont has made a comeback, rising close to the threshold for downlisting to threatened: 200 breeding pairs with a reproductive rate of 0.6 fledglings per pair. This thesis analyzed past data to project the tern population size into the future to assess whether the Common Tern should be down listed. My model showed that while the population can maintain an average of 200 breeding pairs over 50 years, it was unable to reach 0.6 fledglings per pair rate, a second requirement for down listing. The model also evaluated the effect of high water events -which decrease chick survival- on the tern population’s probability to reach the recovery goals. An increase in the probability of a high water event above the current rate of 0.38 yielded a tern population that could not reach either of the recovery criteria. Without reaching a rate of 0.6 fledglings per pair, the Common Tern population cannot be down listed; however given the results it is unknown if the population can reach or maintain this rate. Now the question of down listing lies with the Scientific Advisory Group on Birds and the Endangered Species Committee as to whether the recovery goals should be relaxed or to maintain the goals with limited probability for recovery

Reproductive Ecology of Brown Pelicans (\u3ci\u3ePelecanus occidentalis carolinensis\u3c/i\u3e) in the Northern Gulf of Mexico

Brown Pelicans (Pelecanus occidentalis carolinensis) are numerous throughout the northern Gulf of Mexico, where they and many other coastal bird species utilize the diverse habitats available. Understanding the habitat needs of Brown Pelicans can help inform broader restoration and conservation efforts in the region, much of which is focused on seabird- orientated restoration and management projects; however, data gaps for a variety of different sea- and waterbirds have limited the success of many projects. I studied two aspects of the reproductive ecology of Brown Pelicans: survival of nests and broods, and prey utilization. In Chapter 2, I used generalized linear models to model the relationship between habitat and weather variables and the daily survival of nests and broods. My results suggest that weather conditions overwhelm the importance of habitat parameters on the survival of both nests and broods, and restoration should focus on habitat features that decrease the negative effects of weather on the reproductive success of Brown Pelicans. In Chapter 3, I described the taxonomic and proximate composition of meals from Brown Pelican chicks during 3 months of their maturation, compared the taxonomic composition of prey in chick meals to the prey species composition of available prey within Mobile Bay, and investigated the life history patterns of a focal prey species, Gulf Menhaden (Brevoortia patronus). My results provide support for the trophic importance of abundant forage fish, such as Gulf Menhaden and other small schooling fish species and suggest that freshwater and estuarine systems like Mobile Bay are important foraging areas during the breeding season. Together, these results can inform restoration and management of Brown Pelican breeding colonies throughout the Gulf of Mexico. Since both nest and prey quality affect nestling survival, and ultimately recruitment, my work helps to explain and clarify factors affecting Brown Pelican population parameters, and thus to inform conservation and management decisions

Detection of isorhamnetin glycosides in extracts of apples (Malus domestica cv. ‘Brettacher’) by HPLC-DAD and HPLC-APCI-MSy MS.

Extracts of apple fruits (Malus domestica cv. "Brettacher") were analysed by HPLC with photodiode array detection. An unknown peak was monitored displaying the same retention time as isorhamnetin 3-Oglucoside. Preliminary identification of the isorhamnetin aglycone was performed by comparison of UV spectral data of the unknown compound with a reference substance. Using atmospheric pressure chemical ionisation mass spectrometry in the negative ion mode, the presence of an isorhamnetin glycoside was supported by loss of 162 amu from the pseudomolecular ion (m/z 477). MS 2 product ion analysis of the parent ion m/z 477 provided a fragmentation pattern identical to the reference. Collision-induced dissociation of the aglycone (m/z 315) in the MS 3 product ion analysis allowed the differentiation of rhamnetin and isorhamnetin, and unambiguous assignment by comparison with standard compounds. A second isorhamnetin glycoside eluting prior to the glucoside was tentatively identified as isorhamnetin 3-Ogalactoside. To the best of our knowledge, this is the first report of isorhamnetin glycosides in apple fruit extracts. Results are discussed with respect to chemotaxonomic relevance within the genera Malus and Pyrus, and especially in consideration of the control of the authenticity of apple products

Interventions for hyperhidrosis in secondary care : a systematic review and value-of-information analysis

Background: Hyperhidrosis is uncontrollable excessive sweating that occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. The management of hyperhidrosis is uncertain and variable. Objective: To establish the expected value of undertaking additional research to determine the most effective interventions for the management of refractory primary hyperhidrosis in secondary care. Methods: A systematic review and economic model, including a value-of-information (VOI) analysis. Treatments to be prescribed by dermatologists and minor surgical treatments for hyperhidrosis of the hands, feet and axillae were reviewed; as endoscopic thoracic sympathectomy (ETS) is incontestably an end-of-line treatment, it was not reviewed further. Fifteen databases (e.g. CENTRAL, PubMed and PsycINFO), conference proceedings and trial registers were searched from inception to July 2016. Systematic review methods were followed. Pairwise meta-analyses were conducted for comparisons between botulinum toxin (BTX) injections and placebo for axillary hyperhidrosis, but otherwise, owing to evidence limitations, data were synthesised narratively. A decision-analytic model assessed the cost-effectiveness and VOI of five treatments (iontophoresis, medication, BTX, curettage, ETS) in 64 different sequences for axillary hyperhidrosis only. Results and conclusions: Fifty studies were included in the effectiveness review: 32 randomised controlled trials (RCTs), 17 non-RCTs and one large prospective case series. Most studies were small, rated as having a high risk of bias and poorly reported. The interventions assessed in the review were iontophoresis, BTX, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland (e.g. laser, microwave). There is moderate-quality evidence of a large statistically significant effect of BTX on axillary hyperhidrosis symptoms, compared with placebo. There was weak but consistent evidence for iontophoresis for palmar hyperhidrosis. Evidence for other interventions was of low or very low quality. For axillary hyperhidrosis cost-effectiveness results indicated that iontophoresis, BTX, medication, curettage and ETS was the most cost-effective sequence (probability 0.8), with an incremental cost-effectiveness ratio of £9304 per quality-adjusted life-year. Uncertainty associated with study bias was not reflected in the economic results. Patients and clinicians attending an end-of-project workshop were satisfied with the sequence of treatments for axillary hyperhidrosis identified as being cost-effective. All patient advisors considered that the Hyperhidrosis Quality of Life Index was superior to other tools commonly used in hyperhidrosis research for assessing quality of life. Limitations: The evidence for the clinical effectiveness and safety of second-line treatments for primary hyperhidrosis is limited. This meant that there was insufficient evidence to draw conclusions for most interventions assessed and the cost-effectiveness analysis was restricted to hyperhidrosis of the axilla. Future work: Based on anecdotal evidence and inference from evidence for the axillae, participants agreed that a trial of BTX (with anaesthesia) compared with iontophoresis for palmar hyperhidrosis would be most useful. The VOI analysis indicates that further research into the effectiveness of existing medications might be worthwhile, but it is unclear that such trials are of clinical importance. Research that established a robust estimate of the annual incidence of axillary hyperhidrosis in the UK population would reduce the uncertainty in future VOI analyses

SPaCIFY: a Formal Model-Driven Engineering for Spacecraft On-Board Software

International audienceThe aim of this article is to present a model- driven approach proposed by the SPaCIFY project for spacecraft on-board software development. This ap- proach is based on a formal globally asynchronous lo- cally synchronous language called Synoptic, and on a set of transformations allowing code generation and model verification

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Characterization of new target for antibiotic therapy in Staphylococcus aureus and development of an conditional in-vivo expression system

Bislang inhibieren antibakterielle Substanzen in erster Linie die Zellwandsynthese, den DNA- und RNA-Stoffwechsel sowie die Proteinsynthese. In dieser Arbeit wurde ein erster Versuch unternommen, neue Zielstrukturen für die Antibiotika-Therapie in S. aureus zu finden. Insgesamt wurden 10 Gene untersucht, die Funktion von 7 dieser Gene war in S. aureus unbekannt. Zunächst sollte herausgefunden werden, ob diese 10 Zielgene: topB, polA, nusG, SA1857, SA1444, SA1063, SA0453, SA0241, SA0245, SA0367, für S. aureus essentiell sind. Es wurde versucht, jedes dieser Gene in S. aureus zu deletieren. Außer den Genen SA1444, SA0245 und nusG konnten alle Zielgene deletiert werden und waren daher für S. aureus nicht essentiell. Die Deletionsmutanten ΔtopB, ΔpolA, ΔSA1857, ΔSA1063, ΔSA0453, ΔSA0241, ΔSA0367 wurden außerdem in einem Sepsismodell in Mäusen untersucht und waren nicht attenuiert. Gene, die weder in vitro noch in vivo essentiell sind, sind nur von geringem Interesse für die Entwicklung neuer Antibiotika. Zur Untersuchung essentieller Gene in S. aureus wurden vier verschiedene konditionale Expressionssystem untersucht. Bei drei dieser Systeme wurde der wildtypische Promotor gegen einen regulierbaren Promotor ausgetauscht. Bei einem weiteren System handelte es sich um einen Antisense-RNA-Ansatz. Zur Überprüfung der konditionalen Expressionssysteme („proof-of-principle“) wurden die bekannten essentiellen Gene ligA und dnaE in S. aureus mutiert. Eines dieser konditionalen Expressionssysteme, das pLL30/Pspac/pMJ8426-System, konnte erfolgreich in S. aureus angewandt werden. Die konditionale Expression von ligA und von SA0245 wurde mit diesem System erzielt. Der Temperatur-sensitive Shuttle-Vektor pLL30 dieses konditionalen Expressionssystems enthält eine Insertionskassette, die das Antibiotikaresistenzgen cat (Chloramphenicol-Acetyltransferase) sowie den regulierbaren Promotor Pspac enthält. Ein wesentliches Merkmal des pLL30/Pspac/pMJ8426-Systems ist die stabile Integration des Resistenzmarkers cat und des Pspac-Promotors durch ein doppeltes Crossover Ereignis vor dem Zielgen. Der Temperatur-sensitive Shuttle-Vektor pLL30 kann anschließend durch mehrfaches Subkultivieren der Bakterien bei nicht permissiver Temperatur eliminiert werden. Der Repressor LacI wird auf einem Extra-Plasmid pMJ8426 kodiert und wird nach erfolgter Integration des Pspac-Promotors vor dem Zielgen in die Bakterien transformiert. Mehrere Kopien des Repressorplasmids ermöglichen eine gute Repression an Pspac. Durch die Zugabe des Induktors IPTG kann der Repressor LacI inaktiviert und die Gen-Expression induziert werden. Insbesondere konnte dieses konditionale Expressionssystem erfolgreich im Tiermodell angewandt werden. Ein weiterer Schwerpunkt dieser Arbeit bildete die genetische und funktionelle Charakterisierung von SA0367. Durch biochemische Untersuchungen wurde gezeigt, dass dieses Gen für eine FMN-enthaltende Oxidoreduktase codiert. Auf Grundlage der in dieser Arbeit gewonnenen Erkenntnisse zur Funktion des Proteins wurde das Gen SA0367, in Analogie zum orthologen Gen nfrA aus B. subtilis, in nfrA umbenannt. Die Oxidoreduktase NfrA oxidiert NADPH in Gegenwart von FMN. In Gegenwart von NADPH und FMN zeigt das Enzym NfrA außerdem Nitroreduktase- und eine leichte Disulfidreduktase-Aktivität. Induktionsexperimente im Wildtyp zeigten, dass nfrA durch oxidativen Stress, verursacht von Diamide oder Nitrofurantoin, und durch Ethanol induziert wird. Ethanol und oxidativer Stress führt zu Denaturierung von Proteinen. NfrA könnte an der Reparatur geschädigter Proteine beteiligt sein. Die Induktion von nfrA in S. aureus erfolgt unabhängig vom alternativen Sigmafaktor SigB. Durch Primer Extension-Experimente wurde eine putative PerR-Box vor dem nfrA-Gen identifiziert. Diese könnte für die Regulation von nfrA wichtig sein. Außerdem wird nfrA während des gesamten Wachstumszyklus von einem SigAabhängigen Promotor exprimiert. Die Deletionsmutante ΔnfrA zeigt nur in Gegenwart hoher Ethanolkonzentrationen von 6,5 % einen leichten Wachstumsnachteil im Vergleich zum Wildtyp. Außerdem weist die ΔnfrA-Mutante eine höhere Resistenz gegenüber Nitrofurantoin auf. In weiteren Untersuchungen wurde begonnen die Funktion der Ser/Thr-Kinase SA1063 durch Microarray-Experimente aufzuklären. Hierbei wurde deutlich, dass dieses Gen eine regulatorische Rolle bei der Zellwandsynthese in S. aureus spielen könnte.So far, antimicrobial substances inhibit primarily the synthesis of the cell wall, DNA- and RNA as well as the synthesis of proteins. In this work, alternative targets for antibiotictherapy in S. aureus were investigated. Consequently, altogether ten different genes were analysed, seven of these genes were of unknown function in S. aureus. The ten target genes chosen were: topB, polA, nusG, SA1857, SA1444, SA1063, SA0453, SA0241, SA0245 and SA0367. First, it should be discovered whether or not these target genes are essential for bacterial survival. Therefore, deletion strains of each of these genes were constructed in S. aureus. All of these genes, except of SA1444, SA0245 and nusG, could be deleted, and were thus non-essential in S. aureus. The deletion strains ΔtopB, ΔpolA, ΔSA1857, ΔSA1063, ΔSA0453, SA0241, ΔSA0367 were analysed in a sepsis model of infection in mice. These experiments turned out that none of those strains were attenuated in this model which suggests that the factors investigated are neither in vitro nor in vivo essential for bacterial survival and virulence. Therefore, the potential of these determinants to serve as a target for the development of new antibiotics is rather low. To examine essential genes in S. aureus, four different conditional expression systems were analysed. In three of these systems the promoter of the wildtype gene was exchanged by an experimentally controllable promoter. Another approach involved antisense-RNA to counteract the transcription of the target genes. To verify that the conditional expression systems are functional in S. aureus (“proof-of-principle”), we first mutated two known essential genes, namely ligA and dnaE. One of these conditional expression systems, the pLL30/Pspac/pMJ8426-System could be applied successfully in S. aureus. Conditional mutants of ligA and SA0245 were obtained with this system. The temperature-sensitive shuttle-vector pLL30 of this expression system contains a DNA cassette for insertion in front of the target gene. This insertion-cassette encodes the resistance marker cat (chloramphenicol-acetyltransferase) as well as the Pspac promoter. One important feature of the pLL30/Pspac/pMJ8426-system is the stable integration of the resistance gene cat and the Pspac promoter in front of the target gene by a double crossover event. Following the integration of the cat-Pspac-cassette the temperature-sensitive vector can be eliminated by successive sub-culturing of the bacteria at non-permissive temperature. The repressor LacI is encoded on the Plasmid pMJ8426 which is transformed into the bacteria after integration of the cat-Pspac-cassette in front of the target gene. Several copies of the repressor-plasmid pMJ8426 give rise to high amounts of the repressor LacI and should allow tight repression of the target gene. By addition of the inductor IPTG the repressor LacI is inactivated and gene expression is induced. This conditional expression system was also successfully applied in an animal model of infection. Thus, a validated in vivo expression system is now applicable for the investigation of putative target genes in vivo. Furthermore, in the present work SA0367 was genetically and functionally characterized. Biochemical assays of the gene product revealed that it encodes a FMN-containing oxidoreductase. Based on the findings of this work about the function of the protein, the gene SA0367 was named nfrA, in analogy to the orthologous gene nfrA from B. subtilis. The oxidoreductase NfrA oxidizes NADPH in the presence of FMN. In addition, the enzyme NfrA showed nitroreductase-activity and a minor disulfidreductase-activity in the presence of FMN and NADPH. Induction experiments in the wildtype showed that nfrA is induced by oxidative stress caused by diamide or nitrofurantoin and by ethanol. Ethanol and oxidative stress cause denaturation of proteins. Therefore, NfrA could be involved in the repair of damaged proteins. The induction of nfrA is independent of the alternative sigma-factor SigB. Primer-extension experiments revealed a putative PerR-Box in front of the nfrA-gene. This PerR-Box could be important for the regulation of the expression of nfrA. Moreover, nfrA is transcribed throughout the whole life cycle of S. aureus from a SigA-dependent promoter. Growth of the deletion strain ΔnfrA was slightly reduced in the presence of 6,5 % ethanol as compared to the wildtype. The ΔnfrA-mutant also shows a higher resistance towards nitrofurantoin. In addition, the function of the Ser/Thr-kinase SA1063 was investigated by DNAmicroarray- experiments. Several genes were differentially regulated when comparing transcription of the wildtype and its isogenic ΔSA1063-mutant. The results of these experiments implicate a regulatory role of that SA1063 in the cell wall synthesis in S. aureus