13 research outputs found
Dissertatio Politico Juridica, De Majestate Laesa
No full textGreifswald, Univ., Jur. Diss., 1703Qvam ... Præside Dn. Henn. Christoph. Gerdesio, J. U. L. & Profess. Ordinario, ... in Auditorio Majori ad Diem VII. Junii, Anno M D CCIII. horis consuetis Modesto Eruditorum Examini & publicæ ventilationi submittit Martinus Bernhardi, Colberg. Pom. Author & RespondensAutopsie nach Ex. der ULB Sachsen-AnhaltVorlageform des Erscheinungsvermerks: Gryphiswaldiæ, Typis Danielis Benjaminis Starckii, Reg. Academ. Typogr
M.D. Snodgrass: The Founder Of The Alaska State Fair
No full textDissertation (Ph.D.) University of Alaska Fairbanks, 2008This dissertation presents the life of M.D. Snodgrass as an example of how the Alaskan frontier transformed an unremarkable middle aged migrant into a socially prominent civic leader. The life of M.D. Snodgrass exemplifies how American frontier society provides ordinary people with exceptional opportunities to flourish and prosper. One of the end results of Snodgrass's taking advantage of Alaskan frontier opportunity was the Alaska State Fair. The dissertation divides the life of Snodgrass into four phases with the following findings: (1) The first thirty-one years of Snodgrass's life was spent outside of Alaska. His early life in Kansas demonstrates: the forces which formed Snodgrass, the absence of noteworthy activities and the habits he embraced that would remain constant in his long life. (2) The second thesis section documents: how upon arrival in Alaska he was immediately confronted with challenges and opportunities in the wilderness that built his self-confidence, and how he devoted most of the last six decades of his life to advancement of agriculture in Alaska. (3) The third part addresses his political career, with the following observations: the unsettled frontier society had no established upper class and he became socially mobile; being present at the creation of a political system allowed him to attain extraordinary prominence rapidly; and he learned to take risks, to lose and yet keep trying. (4) The final phase demonstrates that by definition a frontier society lacks institutions, and Snodgrass seized the opportunity to be a participant in the creation of two colleges and became the founding figure of the Alaska State Fair. The author concludes that had M.D. Snodgrass never left Kansas he probably would never have been a representative, senator, college trustee, founder of experiment stations, state presidential elector, or the founder of a state fair. A normal individual can accomplish exceptional feats in a frontier setting where the open environment encourages the development of human potential
Improved iGAL 2.0 Metric Empowers Pharmaceutical Scientists to Make Meaningful Contributions to United Nations Sustainable Development Goal 12
No full textThe large and steadily growing demand for medicines combined with their inherent resource-intensive manufacturing necessitates a relentless push for their sustainable production. Pharmaceutical companies are constantly seeking to perform reliable life cycle assessments of their medicinal products and assess the true value of their sustainable development achievements; however, they find themselves impeded by the lack of a universal metric system that allows for objective quantification of the underlying core denominators. Guided by the unambivalent purpose of the United Nations Sustainable Development Goal 12, which aims at substantially reducing production waste by 2030, and driven by a vision to catalyze greener active pharmaceutical ingredient (API) manufacturing around the globe, the authors set out to overcome current obstacles by defining an improved model for the metric named innovation green aspiration level, iGAL 2.0. We propose yield and convergence as new key sustainability indicators and include a new formula for convergence with potential applicability in computer assisted synthesis planning (CASP) algorithms. The improved statistical model of iGAL 2.0 represents a valuable extension to the common API process waste metrics, process mass intensity (PMI) and complete E factor (cEF), by putting those measures into perspective: iGAL 2.0 enables determination of relative process greenness (RPG) to identify potentially underperforming and environmentally concerning processes early and thereby deliver environmental value. At the same time, iGAL 2.0 generates economic value since reduced waste correlates to lower API production costs. The metric is complemented by its scorecard companion to highlight the impact of innovation on reductions of API manufacturing waste, enabling scientists to readily communicate the value of their work to their peers, managers, and the general public. We believe that iGAL 2.0 can readily be adopted by pharmaceutical firms around the globe and thereby empower and inspire their scientists to make meaningful and significant contributions to global sustainability. BT/Biocatalysi
Fast Identification of Bound Structures in Large N-body Simulations
No full textWe present an algorithm that is designed to allow the efficient identification and preliminary dynamical analysis of thousands of structures and substructures in large N-body simulations. First, we utilize a refined density gradient system (based on denmax) to identify the structures and then apply an iterative approximate method to identify unbound particles, allowing fast calculation of bound substructures. After producing a catalogue of separate energetically bound substructures, we check to see which of these are energetically bound to adjacent substructures. For such bound complex subhaloes, we combine components and check if additional free particles are also bound to the union, repeating the process iteratively until no further changes are found. Thus, our subhaloes can contain more than one density maximum, but the scheme is stable: starting with a small smoothing length initially produces small structures that must be combined later and starting with a large smoothing length produces large structures within which sub-substructure is found. We apply this algorithm to three simulations. Two that are using the TPM algorithm by Bode, Ostriker & Xu and one on a simulated halo by Diemand, Moore & Stadel. For all these haloes, we find about 5–8 per cent of the mass in substructures
The SCUBA half-degree extragalactic survey - I. Survey motivation, design and data processing
No full textThe Submillimetre Common-User Bolometer Array ( SCUBA) Half-Degree Extragalactic Survey ( SHADES) is a major new blank-field extragalactic submillimetre (submm) survey currently underway at the James Clerk Maxwell Telescope (JCMT). Ultimately, SHADES aims to cover half a square degree at 450 and 850 mu m to a 4 sigma depth of similar or equal to 8 mJy at 850 mu m. Two fields are being observed, the Subaru/XMM-Newton Deep Field (SXDF) (02(h)18(m) - 05 degrees.) and the Lockman Hole East (10(h)52(m) + 57 degrees). The survey has three main aims: (i) to investigate the population of high-redshift submm galaxies and the cosmic history of massive dust-enshrouded star formation activity; (ii) to investigate the clustering properties of submm-selected galaxies in order to determine whether these objects could be progenitors of present-day massive ellipticals; and (iii) to investigate the fraction of submm-selected sources that harbour active galactic nuclei. To achieve these aims requires that the submm data be combined with cospatial information spanning the radio-to-X-ray frequency range. Accordingly, SHADES has been designed to benefit from ultra-deep radio imaging obtained with the Very Large Array (VLA), deep mid-infrared observations from the Spitzer Space Telescope, submm mapping by the Balloon-borne Large Aperture Submillimetre Telescope ( BLAST), deep near-infrared imaging with the United Kingdom Infrared Telescope, deep optical imaging with the Subaru Telescope and deep X-ray observations with the XMM-Newton observatory. It is expected that the resulting extensive multiwavelength data set will provide complete photometric redshift information accurate to delta(z) 3 sigma at 850 mu m. Although uncorrected for Eddington bias, this source density is more than sufficient for providing enough sources to answer the science goals of SHADES, once half a square degree is observed. A refined reanalysis of the original 8-mJy survey Lockman hole data was carried out in order to evaluate the new data-reduction pipeline. Of the 17 most secure sources in the original sample, 12 have been reconfirmed, including 10 of the 11 for which radio identifications were previously secured
Performativities, Virtualities, Abstractions, and Cunningham's BIPED
No full textThis thesis explores the complex relations between subjective perception and dance movements, mainly exemplified by drawing on two short extracts from Merce Cunningham's choreography BIPED (1999). The central aim of the study is to formulate a performative phenomenological inquiry, which moves beyond an identification of essences, and towards an understanding of the lived experience of a dance performance as being grounded on iterations of the "abstract". The concept of the abstract primarily signifies an alternative mode of understanding Henry Bergson's notion of duration. Considering Gilles Deleuze's reading of Bergson's intuition as a method to divide the experience of a lived present into a temporal difference in kind between the virtual and the actual, this thesis suggests a complementary division of duration into virtual and actual kinds of abstraction.
In addition to Bergson's method of intuition, the discussion is phenomenologically rooted in Maurice Merleau-Ponty's concept of the body image and Gaston Bachelards idea of non-causal reverberation. As with the case of intuition, those phenomenological concepts are applied unconventionally. Rather than serving as a pre-objective ontological basis for an analytical and scientific understanding of subjective embodiment, the notion of a reverberating body image is here treated as a form of mimesis, performatively constituted through symbolic and representational practices. Hence, in phenomenological terms, the rationale of the thesis is predominantly sustained by the philosophy of Ernst Cassirer, arguing that reality cannot be approached directly, but only through the concept of the symbol.
The viewpoint from where I speak has performative cybernetic characteristics, continuously and dynamically transgressing boundaries and reconstituting itself through iterative and citational practices. Additionally, as I move between the analytical and the intuitive, as well as between the virtual and the actual, the formal structure of the thesis corresponds to a liminal transformation of the speaking subjectivity
Exposure to indoor microbial agents, allergens and pets, and their relation to asthma and allergy prevalence in farmers' children and their peers from rural areas : Diploma thesis
No full textBackground In ‘westernised’ countries, the prevalence of childhood asthma and allergy have risen throughout the last three decades. Changes in lifestyle and environmental factors like an increase in exposure to air pollutants, environmental tobacco smoke, or indoor allergen and pet exposure have been considered as plausible explanations. However, little evidence in support of these causal risk factors for these common chronic childhood diseases has been found. Lower risk of hay fever and atopic sensitisation were reported in children with more siblings, and later also in children who attended day care centres early in infancy. These findings were summarised in the so-called ‘hygiene hypothesis’: limited exposure to bacterial and viral pathogens during early childhood results in a higher risk of developing allergic diseases. Recent allergy research has focused on the interaction between the innate and adaptive immunity: innate immunity receptors of pathogens seem to modulate the activation of adaptive immunity mechanisms. Three independent studies showed reduced prevalence of asthma and allergy among farmers’ children compared to their peers from the same rural areas from Switzerland, Austria, and Germany. A series of epidemiological studies in Europe, Canada, and Australia consistently confirmed and extended these findings. These results have been seen as an extension of the ‘hygiene hypothesis’, since a farm environment provides an enormous habitat for micro-organisms. A potential candidate that may explain these differences in the prevalence of childhood asthma and allergy is environmental exposure to endotoxin, a component of the outer membrane of gram-negative bacteria. Aim To assess the exposure to indoor microbial agents, allergens and pets in farmers’ children and their peers of non-farming families, and to estimate whether these exposures are associated with the prevalence of childhood asthma and allergies. Methods The ALEX (Allergy and Endotoxin) study was a cross-sectional survey in rural areas of Germany, Austria, and Switzerland. 2618 parents of 6-13 year-old children completed a standardised questionnaire including questions about asthma and allergy from the ISAAC study
and questions about the child’s activities on farms, and characteristics of the home environment.
Blood samples were obtained from selected children and tested for atopic sensitisation,
specially for specific IgE and IgG4 antibodies to grass pollen and cat allergen. Endotoxin and
cat allergen levels were measured in indoor dust samples and in settled dust from stables.
Complete data were available for 812 children. In a subgroup of 553 children mattress dust
muramic acid levels, another marker for exposure to bacteria, were determined.
Results
Higher levels of indoor endotoxin exposure were associated with reduced allergen sensitisation,
decreased prevalence of hay fever, atopic asthma and wheeze in a dose-dependent
manner. The associations were equally strong among the sub sample children from nonfarming
families, indicating that even lower levels of endotoxin may favourably influence the
risk of atopic diseases.
Endotoxin levels in stables were not correlated with the amount of endotoxin measured
indoors, but a dose-dependent association between the child’s activity on the farm and indoor
home endotoxin levels was observed, both in farmers’ and in non-farmers’ children. Pet keeping,
full time farming (compared to part time farming), and younger age of the children contributed
additionally to increased indoor endotoxin levels. Endotoxin levels in stables increased
with the number of cattle (but only up to the highest quartile), with hay feeding (compared
to feeding of mainly silage), and additionally with provision of accommodation of
horses, pigs, sheep or goats in the cattle stable. All these predictors might be surrogate measures
for traditional dairy farming in hilly German speaking areas.
Children’s mattress’ muramic acid levels were significantly higher in farmers’ children
than in non-farmers’ children. Mattress muramic acid and endotoxin levels were partially correlated,
indicating that both substances are markers for the exposure to micro-organisms. Independent
of being a farmers’ child, mattress dust from homes heated with wood or coal and
less frequently cleaned mattresses showed increasing muramic acid levels.
Independent of the endotoxin exposure, increasing muramic acid levels in mattress dust
was associated with a lower frequency of current wheeze, but not with atopic sensitisation or
hay fever. The protective effect on wheeze and diagnosed asthma was more pronounced in
non-sensitised children. The different effect spectrum for muramic acid and endotoxin exposure
suggest that different micro-organisms might contribute to the lower prevalence of
asthma and allergy among farmers’ children, compared to non-farmers’ children.
Current contact to dogs was inversely associated with diagnosed hay fever, asthma, and
specific sensitisation to grass pollen and to cat allergen, but not with increased IgG4 levels.
Early and current exposure to cats – but not to dogs – was associated with lower frequency of
wheeze and grass pollen sensitisation. None of these inverse associations were greatly affected
by additionally taking into account the indoor endotoxin or cat allergen levels, but additionally
adjustment for early or current exposure to farm animals attenuated the protective
effects. Although pet exposure was frequent in this rural population, the protective effects of
pet keeping observed in other peer-reviewed studies may be masked by frequent contact to
farming environments.
Conclusions and outlook
Endotoxin and muramic acid may be surrogate markers of a much broader spectrum of
microbial compounds. Thus, further studies have not only to confirm the lower risk of children
with contact to livestock or with higher exposure to micro-organisms early in life, but
also to find the relevant mixture of protective components in the farm dust. In addition, as
ingestion is another plausible route of exposure to micro-organisms, epidemiology may focus
on differences in nutrition and their association with childhood asthma and allergy. The PARSIFAL
(Prevention of allergy – Risk factors for sensitisation in children related to farming
and anthroposophic lifestyle) study offers the opportunity to do so, as this study include children’s
populations growing up with different lifestyles. Experimental studies may focus on
the relevant exposure route (inhalation, ingestion) of different patterns of micro-organisms.
The genetic dimension has to be kept in mind in the discussion of environmental exposure to
micro-organisms by identifying particularly sensitive groups through genetic investigations,
as the available data in the ALEX study was limited.
Current scientific evidence has not developed strongly enough to provide a reliable
course of action for primary prevention or therapy. Infectious diseases resulting from exposure
to pathogens continue to be a serious public health problem. Thus, the protective effect
of a microbial environment on the development of asthma and atopy should be balanced
against the benefits of established hygiene standards
mTOR complex 2 - akt signaling is physically and functionally at mam
No full textThe target of rapamycin (TOR) is a conserved protein kinase and a
central controller of growth. TOR can be part of two structurally and
functionally distinct complexes, termed TOR complex 1 and TOR
complex 2. Mammalian TOR complex 2 (mTORC2) is composed of
mTOR, Rictor, Sin1 and mLST8. Both mTORC1 and mTORC2 are activated
by growth factors. The mechanism via which growth factors
regulate mTORC2 has been elusive until recently. mTORC2 binds ribosomes
in a growth factor stimulated manner and this association is
required for mTORC2 activity.
mTOR complex 2 functions include control of spatial cell growth
and metabolism and thus, mTORC2 deregulation has been linked
to various disorders including cancer and diabetes. mTORC2 phosphorylates
and thereby activates the AGC kinase family member Akt
(PKB). Akt has many different targets and functions, not all of which
depend on mTORC2 mediated Akt phosphorylation.
In order to gain a better understanding of mTORC2 function, we
asked where mTORC2 signaling is localized. A number of studies
localized mTORC2, functionally or physically, either to the endoplasmic
reticulum (ER) or to mitochondria.We investigated whether these
seemingly unrelated observations concerning mTORC2 localization,
might be the consequence of mTORC2 signaling at MAM. MAM
or mitochondria-associated ER membrane is a quasi-synaptic subdomain
between the ER and mitochondria. MAM plays a crucial role in
the regulation of mitochondrial metabolism and cell survival by gating
both the calcium flux and phospholipid trafficking between the
ER and mitochondria.
First, we analyzed mTORC2 subcellular localization. mTORC2 is
localized to the ER adjacent to mitochondria and mTORC2 can be
biochemically isolated from MAM structures. mTOR complex 2 interacts
with the IP3R-Grp75-VDAC1 complex, a tether that connects ER
and mitochondria at MAM. Insulin stimulates mTORC2 localization
to MAM and mTORC2 interaction with the IP3R-Grp75-VDAC1 complex.
MAM localization of mTORC2 depends on mTORC2-ribosome
interaction.
Next we investigated the function of mTORC2 at MAM. Rictor
(mTORC2) knockout causes a decrease in MAM formation. Growth
factors stimulate MAM formation via mTORC2 and the Akt substrate
PACS2, a MAM resident protein. As expected for MAM deficient
cells, mTORC2 disruption changes the calcium flux from the ER to
mitochondria at MAM. Furthermore, we observe a reduction of Akt
mediated phosphorylation of the MAM calcium channel IP3R upon
Rictor knockout. Thus, mTORC2 signaling at MAM controls MAM mediated
calcium release via the Akt targets PACS2 and IP3R.
Since MAM disruption and calcium signaling both affect mitochondrial
metabolism, we proceeded by analyzing the mitochondrial physiology
of mTORC2 deficient cells. Rictor knockout cells exhibit a disruption
of VDAC1-HK2 binding, caused by a lack of Akt mediated
phosphorylation of HK2 at MAM. This, together with the defect in
MAM, induces an increase in basal respiration, mitochondrial inner
membrane potential, and ATP production in the mTORC2 deficient
cells, culminating in apoptosis. Thus, mTORC2 at MAM appears to
control several aspects of mitochondrial physiology.
These findings emphasize the role of MAM as a signaling hub that
controls cell physiology. By identifying the integral role of mTORC2
at the core of this platform, our results provide new insights on
the mechanisms that regulate growth and metabolism. These observations
may offer new therapeutic strategies against mTORC2 and
MAM driven diseases such as diabetes, Alzheimer’s and cancer
Geostatistical modelling of health inequalities associated with exposure to road-transport emissions
No full textRoad-transport accounts for a substantial proportion of the air quality objective pollutants experienced within the post-industrial cityscape. Traditionally, investigations have quantified the temporal health effects of such pollutants, yet the confined nature of European intraurban
environments often determine spatial variations in traffic pollutant levels, which tend to be associated with a plethora of social disparities. Recently, elements of spatial heterogeneity have attracted the attention of governmental advisory committees, whom acknowledge a
limited understanding of spatially inclusive practices in-spite of their potentially valuable applications (COMEAP 2006). Through considering spatial variations in children’s respiratory health, across the model British multicultural City of Leicester (Vidal-Hall 2003), this project
aimed to address the inadequacies of temporal models in capturing Pearce et al’s (2010) wider ‘triple jeopardy’.
The projects findings indicated significant global relationships to exist between children’s hospitalisations, social-economic-status, ethnic minorities, and PM10 road-transport emissions within Leicester. ‘Local Indicators of Spatial Association’ and ‘Geographically Weighted Regression’ identified important localised variations within the dataset, specifically relating to a ‘double-burden’ of residentially experienced road-transport emissions and deprivation effecting inner-city children’s respiratory health. Further examination of the spatial
field’s, revealed critical distance-responses to exist between respiratory health fronts and select socio-environmental phenomenon, thus recognising the importance of exposure gradients found in the every-day environment.
It was suggested that exposure to detrimental socio-environmental factors initiated upper respiratory episodes, with prolonged contact impeding recovery leaving the child
vulnerable to infection, exacerbating previous complaints and potentially causing conditions of greater severity. These findings provide a preliminary link between extreme cases of ‘Catarrhal Child Syndrome’ and socio-environmental influences, a conclusion previously eluding medical
practitioners. Interestingly, affluent intra-urban communities tended to contribute the highest levels of emission from private transport, whilst residentially experiencing few environmental burdens. Thus, indicating that environmental injustices prevail across the model British multicultural city of Leicester. To readdress such environmental imbalances, the project suggested and explored a selection of general and community tailored transport schemes. In conclusion, geostatistical approaches are viewed to be an effective set of tools for health and
urban planners, in the management of localised issues, which have previously been ‘filtered’ out by temporal practices
Using Polarized Spectroscopy to Investigate Order in Thin-Films of Ionic Self-Assembled Materials Based on Azo-Dyes
No full textThree series of ionic self-assembled materials based on anionic azo-dyes and cationic benzalkonium surfactants were synthesized and thin films were prepared by spin-casting. These thin films appear isotropic when investigated with polarized optical microscopy, although they are highly anisotropic. Here, three series of homologous materials were studied to rationalize this observation. Investigating thin films of ordered molecular materials relies to a large extent on advanced experimental methods and large research infrastructure. A statement that in particular is true for thin films with nanoscopic order, where X-ray reflectometry, X-ray and neutron scattering, electron microscopy and atom force microscopy (AFM) has to be used to elucidate film morphology and the underlying molecular structure. Here, the thin films were investigated using AFM, optical microscopy and polarized absorption spectroscopy. It was shown that by using numerical method for treating the polarized absorption spectroscopy data, the molecular structure can be elucidated. Further, it was shown that polarized optical spectroscopy is a general tool that allows determination of the molecular order in thin films. Finally, it was found that full control of thermal history and rigorous control of the ionic self-assembly conditions are required to reproducibly make these materials of high nanoscopic order. Similarly, the conditions for spin-casting are shown to be determining for the overall thin film morphology, while molecular order is maintained
