Background The discovery and development of inhibitors for the PI3K/AKT/mTOR signaling pathway is an attractive area of research due to its association with several oncogenic malignancies. This signaling pathway controls cellular growth as well as survival via regulation of widely divergent physiological processes, i.e. cell cycle progression, differentiation, transcription, translation and apoptosis. Constitutive activation of the PI3 kinase alpha and/or the downstream protein mTOR has been implicated in the progression of a large variety of solid tumors. Literature reports suggest the importance of developing combined and specific inhibitor of both PI3K and mTOR kinases. Described herein is the discovery of a novel small molecule, SPR965, a potent, and orally bioavailable inhibitor for class 1 PI3 Kinase and mTOR kinases with the potential for the clinical treatment of various solid tumors, specifically prostate, ovarian and colon cancers. The complete preclinical profile of SPR965 is presented in detail. Methods Drug candidates were evaluated in an in vitro enzyme assays to determine their inhibitory activity PI3 and mTOR C1/ C2 kinases. Promising candidates were then evaluated in proliferation assays using various human cancer cell lines (PC3 - prostate, SKOV3 - ovarian, HCT-116 - colon and A2780 - ovarian). The most promising leads were then evaluated against a panel of 456 kinases to determine the level of selectivity for our primary targets - PI3K and mTOR C1/C2. Compounds meeting the desired threshold of potency and selectivity were evaluated for their in vivo pharmacokinetic profile (iv/ po) in rodents followed by studies in mouse xenograft models (SKOV3 and HCT-116). Results SPR965 is a potent inhibitor of PI3K alpha and mTOR with an IC50 of 24 and 25 nM respectively. SPR965 is also a highly selective inhibitor of PI3 and mTOR C1/C2 kinases when evaluated in a screen against 456 kinases. Further studies demonstrated that SPR965 is a potent inhibitor of proliferation in a multiple cell lines and in several xenograft models. The proliferation inhibition activity (EC50) in A2780 is 17 nM, PC3 is 30 nM, SKOV3 is 74 nM, and HCT-116 is 163 nM. SPR965 is one of the most efficacious PI3/mTOR kinase inhibitor yet reported, with ED50 = 0.5 mg/Kg as determined in a SKOV3 xenograft mouse model and ED50 = 0.6 mg/ Kg in HCT-116 xenograft mouse model. This dose level is markedly lower than those reported for other reported inhibitors of this pathway. Pharmacokinetic studies in Sprague Dawley rats and in NUDE mice indicated that the oral bioavailability of SPR965was ∼100% and 75% respectively. Conclusion SPR965 is one of the most efficacious inhibitor of the PI3 and mTOR kinases when compared to the reported ED50s of other reported compounds. It also is one of the most selective and highly bioavailable inhibitor of the PI3 and mTOR kinases. Further studies are underway to support first-in-human trials with SPR965 where we hope to demonstrate its unique therapeutic benefits. Citation Format: Reena Arora, Bakul K. Dutta, Ravinder Goel, Frank P. Hollinger, Bilash Kulia, Dinesh Mahajan, Amal R. Mahapatra, Milind Sagar, Somdutta Sen, Amit Sharma, Sundeep Dugar. SPR965: an oral PI3K/ mTOR C1/C2 inhibitor for the treatment of solid tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4515. doi:10.1158/1538-7445.AM2014-4515


BACKGROUND
n-3 (omega-3) Polyunsaturated fatty acids (PUFAs), fish, and nuts can regulate inflammatory processes and responses.

OBJECTIVE
We investigated whether dietary intakes of PUFAs [n-3, n-6 (omega-6), and α-linolenic acid], fish, and nuts were associated with 15-y mortality attributed to noncardiovascular, noncancer inflammatory diseases.

DESIGN
The analyses involved 2514 participants aged ≥49 y at baseline. Dietary data were collected by using a semiquantitative food-frequency questionnaire, and PUFA, fish, and nut intakes were calculated. Inflammatory disease mortality was confirmed from the Australian National Death Index.

RESULTS
Over 15 y, 214 subjects died of inflammatory diseases. Women in the highest tertiles of total n-3 PUFA intake, compared with those in the lowest tertile of intake at baseline, had a 44% reduced risk of inflammatory disease mortality (P for trend = 0.03). This association was not observed in men. In both men and women, each 1-SD increase in energy-adjusted intake of α-linolenic acid was inversely associated with inflammatory mortality (hazard ratio: 0.83; 95% CI: 0.71, 0.98). Subjects in the second and third tertiles of nut consumption had a 51% and 32% reduced risk of inflammatory disease mortality, respectively, compared with those in the first tertile (reference). Dietary intakes of long-chain n-3 and n-6 PUFAs and fish were not associated with inflammatory disease mortality.

CONCLUSIONS
We report on a novel link between dietary intake of total n-3 PUFA and risk of inflammatory disease mortality in older women. Furthermore, our data indicate a protective role of nuts, but not fish, against inflammatory disease mortality.


This paper describes and give insight about the use of Facebook to assist learning in Jakarta and several countries outside Indonesia. There are so many problems that will arise based on the factual sight such users tend to find difficulties in searching, analyzing and accessing information that they need, particularly materials in their academic life. This paper explores how social network site (Facebook) has the potential to creating new resource in information and technology to assist learning in groups for finding information needs and also in distance learning system of Universitas Terbuka's students who live in Jakarta, Taiwan and Hong Kong. Generally, most of students are working from Monday to Friday and even on Saturday and Sunday, they really have problems in having face to face tutorial or even try to get information about their academic life. This paper was conducted with several communities of Facebook groups, the result showed that they specifically used Facebook group to assist them to finish their academic life such as tasks, examination, group discussion or even information. As the most popular social network in Indonesia, Facebook which accessible, effective and efficient is one of many communities to assist students in making new friends and tutors as well as keeping in touch with information on upcoming events, competitions, seminars, library announcements, new books materials, registration, online tutorial, webinar, examination and other general information.


One of the largest factors of uncertainty in the surface mass balance of the polar ice sheets is the amount of snow accumulation. Despite a large number of field campaigns, the entire spatial extent of the ice sheets cannot be covered by in-situ measurements at a sufficient spatial and temporal resolution.Because of independence of solar illumination and cloud cover, microwave remote sensing is a well-established method of gathering data from the Polar Regions and thus has the potential to fill the spatial gaps between snow accumulation field measurements. Due to the complexity of snow-microwave interaction, large uncertainties still exist in the methods developed to retrieve snow accumulation from microwave remote sensing.This study will present a coupled snow microstructure/radiative transfer model to examine the interaction between electromagnetic radiation in the microwave frequency region and the snow volume in the dry snow zones of the polar ice sheets. Data from active and passive microwave sensors at different frequencies and resolutions are combined with snow microstructure data to verify the model and evaluate its sensitivity to different snowpack parameters.Theoretical assumptions made in earlier snow accumulation retrieval algorithms are reviewed using snow microstructure data measured at different firn cores. The description of snow densification and grain growth processes is refined on the basis of available field data. The radiative transfer model is improved to consider dense-medium effects in order to describe the microwave interaction with the snow pack in a more realistic fashion.The aim of this work is to establish a more robust method to estimate snow accumulation in the dry snow regions of the polar ice sheets.


Chemists worldwide have accepted the challenge of developing methods to access a variety of compounds as single enantiomers, including the use of enzymes, chiral auxiliaries, and resolutions. In particular, dynamic resolutions offer a unique way to access chiral compounds using a few controllable steps, including the variation of both time and temperature. Many groups have implemented this methodology to generate various polysubstituted pyrrolidines and piperidines, which are substructures ranking high on the list of nitrogen–containing pharmaceuticals. The Gawley group revealed a catalytic dynamic resolution (CDR) of N–Boc–piperidine using a chiral ligand. Impressively, the chemistry was tolerant of a variety of electrophiles and generated the products with high enantioselectivity. However, due to unknown reasons, reproducibility emerged as an issue regarding this methodology. In this document, meticulous studies on factors that affect the CDR are discussed, including ligand purity, temperature studies, and impurity detection. Additionally, studies on the diastereoselective synthesis of α,α,α'– trisubstituted is presented, including 2D NMR data that aided in determining the relative configurations of select products. Another focus was also pursued due to the unexpected passing of Dr. Bob Gawley. Visible light has recently emerged as a valuable reagent in the synthesis of organic molecules in the presence of a photoredox catalyst. This discovery has opened the doors for synthetic chemists to provide important molecules using sustainable methods. Nan Zheng recently revealed an oxidative C–N bond–forming cascade of styrenyl anilines to yield a variety of substituted indoles using visible light photoredox catalysis. They proposed a benzylic cation intermediate that ultimately forms an indole by deprotonation in an E1 fashion. In this document, the synthesis of C2,C3 fused indolines is presented using a similar approach. Using styryl anilines tethered with a nucleophile, the benzylic cation intermediate was effectively trapped in a SN1 fashion to generate various fused indolines as single diastereomers. Additionally, detailed synthetic routes, including the challenges in substrate syntheses, as well as the limits of this photoredox cascade is presented.


We propose a two-fold approach to model reduction of fluid-structure interaction. The state equations for the fluid are solved with reduced basis methods. These are model reduction methods for parametric partial differential equations using well-chosen snapshot solutions in order to build a set of global basis functions. The other reduction is in terms of the geometric complexity of the moving fluidstructure interface. We use free-form deformations to parameterize the perturbation of the flow channel at rest configuration. As a computational example we consider a steady fluid-structure interaction problem: an incompressible Stokes flow in a channel that has a flexible wall.


A liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed for the determination of phenolic acids and flavonoids in a medicinal Chinese herb Taraxacum formosanum Kitam. Initially, both phenolic acids and flavonoids were extracted with 50% ethanol in a water-bath at 60 °C for 3 h and eventually separated into acidic fraction and neutral fraction by using a C18 cartridge. A total of 29 compounds were separated within 68 min by employing a Gemini C18 column and a gradient solvent system of 0.1% formic acid and acetonitrile at a flow rate of 1.0 mL/min. Based on the retention behavior as well as absorption and mass spectra, 19 phenolic acids and 10 flavonoids were identified and quantified in T. formosanum, with the former ranging from 14.1 μg/g to 10,870.4 μg/g, and the latter from 9.9 μg/g to 325.8 μg/g. For further identification of flavonoids, a post-column derivatization method involving shift reagents such as sodium acetate or aluminum chloride was used and the absorption spectral characteristics without or with shift reagents were compared. An internal standard syringic acid was used for quantitation of phenolic acids, whereas (±) naringenin was found suitable for quantitation of flavonoids. The developed LC-MS/MS method showed high reproducibility, as evident from the relative standard deviation (RSD) values for intra-day and inter-day variability being 1.0–6.8% and 2.0–7.7% for phenolic acids and 3.7–7.4% and 1.5–8.1% for flavonoids, respectively, and thus may be applied for simultaneous determination of phenolic acids and flavonoids in Chinese herb and nutraceuticals.


Abstract. Documenting natural behaviours may be an important component of conservation management of threatened species in that deviations from some behaviours may serve as early warning signs of subsequent deteriorating condition and the possible need for intervention. We described predation behaviour of the endangered Australian scincid lizard Tiliqua adelaidensis from 23 burrows by watching video images from cameras over 10 days each month for five months in spring and summer. We observed 341 predation attempts, of which 277 were successful. These lizards predominantly ambush passing prey from their burrow entrance without completely emerging from the burrow. Orthopterans were the major component of their captures; prey captures peaked in November and December. We measured the proportion of unsuccessful foraging attempts, the proportion of foraging attempts that involved full emergence, the mean distance a lizard moved away from the burrow entrance, and the proportion of plant parts in the diet. We suggest that if any of these parameters increase it could indicate the requirement for intervention management. Our study supports the view that behavioural monitoring could be considered as an integral component of any conservation management of endangered animal species.


This book is a rich collection of philosophical essays radically interrogating key notions and preoccupations of the phenomenological tradition. While using Heidegger's Being and Time as its permanent point of reference and dispute, this collection also confronts other important philosophers, such as Kant, Nietzsche, and Derrida. The projects of these pivotal thinkers of finitude are relentlessly pushed to their extreme, with respect both to their unexpected horizons and to their as yet unexplored analytical potential. A Finite Thinking shows that, paradoxically, where the thought of finitude comes into its own it frees itself, not only to reaffirm a certain transformed and transformative presence, but also for a non-religious reconsideration and reaffirmation of certain theologemes, as well as of the body, heart, and love. This book shows the literary dimension of philosophical discourse, providing important enabling ideas for scholars of literature, cultural theory, and philosophy.


OBJECTIVE
To examine how participation is conceptualized by different rehabilitation stakeholder groups.

DESIGN
Qualitative case study design.

SUBJECTS
A total of 148 participants from different stakeholder groups in 2 US states and the District of Columbia. Stakeholders included people with disabilities (n = 63), caregivers (n = 28), rehabilitation professionals (n = 32), funders (n = 10), and policy makers (n = 15).

METHODS
Eighteen focus groups were conducted to examine what participation means, how it is conceptualized, and the barriers to realizing full participation. Focus groups were transcribed verbatim; transcripts were analyzed using a constructivist grounded theory approach.

RESULTS
Stakeholders agreed on 3 primary domains of participation: (i) productivity and economic participation; (ii) social participation and relationships; and (iii) leisure/recreational participation. Participation within each domain was characterized by its diversity, individuality and environmental influences. Differences emerged in the emphasis stakeholders placed on the relevance of the participation domains in the lives of people with disabilities. Stakeholders' emphasis was influenced by their roles within the rehabilitation process and created distinct needs for participation outcome measures.

CONCLUSION
While there was agreement about what constitutes participation, stakeholders emphasized different aspects of participation based on their positions in the rehabilitation process. Recommendations are offered for integrating study findings into the development of new participation measures.


Emergency departments (EDs) in many developed countries are experiencing increasing pressure due to rising numbers of patient presentations and emergency admissions. Reported increases range up to 7% annually. Together with limited inpatient bed capacity, this contributes to prolonged lengths of stay in the ED; disrupting timely access to urgent care, posing a threat to patient safety. The aim of this review is to summarise the findings of studies that have investigated the extent of and the reasons for increasing emergency presentations. To do this, a systematic review and synthesis of published and unpublished reports describing trends and underlying drivers associated with the increase in ED presentations in developed countries was conducted. Most published studies provided evidence of increasing ED attendances within developed countries. A series of inter-related factors have been proposed to explain the increase in emergency demand. These include changes in demography and in the organisation and delivery of healthcare services, as well as improved health awareness and community expectations arising from health promotion campaigns. The factors associated with increasing ED presentations are complex and inter-related and include rising community expectations regarding access to emergency care in acute hospitals. A systematic investigation of the demographic, socioeconomic and health-related factors highlighted by this review is recommended. This would facilitate untangling the dynamics of the increase in emergency demand.


Home > Printer-friendly PDF > Residence Halls Residence Halls Visit interactive map and details at https://maps.unc.edu/buildings/residence-halls/ [1] There are 32 residence halls on the campus of UNC-Chapel Hill, divided into 13 different residential communities. A residential community may contain one or several buildings and has a dedicated staff including a Community Director, Community Manager, Resident Advisors and Office Assistants. Browse residence halls By Location [2]. Browse residence halls By Residential Learning Program [3]. Model Room For the safety and privacy of our residents and summer guests, we do not offer tours of occupied buildings. There is a model room [4] that will give you a good idea of what a room is like inside. Hours of operation and location depend upon the time of year. Please check details prior to planning a visit to see the model room.


AIMS
Atrial fibrillation (AF) cycle length (CL) has been demonstrated to be one of the predictors for termination during ablation for AF. We evaluated the AF CL gradient between right atrium (RA) and left atrium (LA) and their mean AF CL in predicting the extent of substrate ablation.

METHODS AND RESULTS
One-hundred and thirty-six patients undergoing first ablation for persistent AF were studied. Stepwise ablation, sequentially in the following order: pulmonary veins (PV), LA, and RA, was performed to achieve AF termination. Stepwise ablation terminated AF in 110 patients (81%). In the AF termination group, AF was terminated by PV isolation (PVI) (Group P), PVI plus LA ablation (Group L), and PVI plus LA plus RA ablation (Group R) in 14 patients (13%), 49 patients (44%), and 47 patients (43%), respectively. Group R had much shorter mean AF CL than Group L (156 ± 18 vs. 174 ± 24 ms, P < 0.001) and mean AF CL in Group L was much shorter than Group P (174 ± 24 vs. 209 ± 36 ms, P = 0.004). The RA to LA AF CL gradient was not significantly different between left-side ablation (Group P + Group L) and additional RA ablation (Group R) (P = 0.177). Mean AF CL >180.50 ms predicted AF termination by PVI (Group P) with 79% sensitivity and 84% specificity while mean AF CL >165.25 ms predicted AF termination by left-side ablation (Group P + Group L) with 67% sensitivity and 75% specificity. After a mean follow-up of 15 ± 7 months, freedom from arrhythmia recurrence was significantly higher in left-side ablation (Group P + Group L) than additional RA ablation (Group R) (P = 0.024).

CONCLUSION
Baseline mean AF CL may identify the subset of patients in whom persistent AF can be terminated by different extent of substrate ablation, which may in turn predict the chance of recurrence. However, baseline RA to LA AF CL gradient cannot predict the need for additional RA ablation.


Abstract Although planting of genetically modified (GM) crops has topped 148 million ha. worldwide, direct consumption of GM foods remains extremely rare. The obstacles to GM foods are highly varied and they can provide windows into important cultural dynamics. India's heated controversy over its would-be first GM food—Bt brinjal (eggplant)—is driven not only by common concerns over testing and corporate control of food, but by its clash with the Ayurvedic medical establishment. GM brinjal may outcross with wild relatives commonly used in Ayurvedic medicine, and claims that outcrossing would not affect medical efficacy miss the point. Ayurveda emphasizes polyherbal treatments and has developed an epistemology oriented towards complex combinations of compounds. As such it does not recognize the authority of specific studies of transgene effects. The conflict is not with genetic modification per se, but with the reductionism that is central to the biotechnology approvals process. This opposition has played a significant role in the government moratorium on the plant.


There have been numerous critical articles on what really happened on the otherwise beautiful morning of 11 September 2001. Beyond doubt, the bulk of the critical responses to the terrorist attacks focused on the ethical and humanitarian, or rather the unethical and inhumane implications of the atrocious act, leaving no room for any philosophical reflection on the potential assessment or reception of the event from the perspective of art and aesthetics. The few years that have gone by since 2001 have provided us with some a sense of emotional detachment from the horror of that day, a detachment that may have awakened our aesthetic and artistic instincts with regard to the attacks themselves as well as their visual representation. Chronological distance renders an unprejudiced and independent stance more possible now than ever. It also allows us to reconsider our initial politically correct and ethically justified repulsion of the efforts made by a few artists to aestheticize 9/11. Such repulsion, however, was associated with the delusion that by denouncing aesthetics we were really securing the prevalence of politics, morality and ethical responsibility in a terror-afflicted society. My point in this paper is that there is a need for aesthetic appreciation when contemplating a violent event such as the 9/11 terrorist attacks. What is more, appreciation of the beautiful, even in case of a 9/11, seems necessary because it is a key to establishing an ethical stance towards terror, life, and art. It should be stressed that independent aesthetic experience is not important in itself but is a means of cultivating an authentic moral and ethical judgment.


This research work presents an oesophageal speech improvement algorithm using Wavelet and Kalman Filtering approach. In both techniques, it has been used different mother wavelet for wavelet approach and different measurement noises for Kalman filtering. People who have suffered from larynx cancer have enormously low intelligibility due to the surgery. A new algorithm has been developed to improve the speech quality. The algorithm consists of enhancing the Shimmer and HNR parameters using Discrete Wavelet Transform (DWT) and Kalman Filtering. By taking advantage of the Wavelet Transform's special time-frequency properties, a corrective algorithm in the form of a wave is applied for the signal intervals in which the shimmer measurement goes beyond normal levels. Therefore, an atomized control of the signal peaks is carried out, having an effect on the normalization of the shimmer. Regarding Kalman filtering, it is proved that the noise obtained from an oesophageal voice during periods of silence is the most suitable. The speech enhancement has been measured using Multidimensional Voice Program tool (MDVP) [1].


Miguel Hernandez University of Elche, Spain. __________________________________________________________________________________________________________________ ABSTRACT The national golf organizations support the development of golf in their country and one of the signs of their success is the generation of elite professional golfers. In this paper, we analyze the emergence of elite professional golfers in eighteen European nations. The efficiency of these nations is measured through output-oriented Data Envelopment Analysis models. In particular, we propose variable and constant returns to scale radial models. The main purpose is to classify each of the nations as efficient or inefficient according to its ability to produce elite professional players and with regard to the inefficient ones, determine how far they have to go to achieve efficiency. We further propose a stepwise procedure for each inefficient nation that identifies a path towards the frontier with several intermediate points. The analysis of the results can be used by the nations for designing new strategies in order to improve their performance.


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Is there a link between asset prices and economic fundamentals? Many studies fail to find a convincing link and conclude that asset prices and economic fundamentals are disconnected. A famous example of the disconnect between exchange rates and macroeconomic fundamentals is presented in Meese and Rogoff (1983). The main success connecting asset prices to economic fundamentals is in very short periods immediately after macroeconomic announcements (e.g. Andersen et al., 2007). However, individual announcements are much less important in the medium term. The reason is that medium term returns are contaminated by other types of news (including economic news) unrelated to the news analyzed. Therefore simultaneously relating medium term asset returns to a large number of economic news announcements can provide means of mitigating contamination. This thesis provides evidence of a strong medium term relation between asset prices and economic fundamentals by using news aggregation and novel methods. While the literature documents that the link between asset prices and economic fundamentals, measured by R-squared, does not exceed eight percent, this thesis shows that the R-squared can be as high as 27 percent.


It is shown that the retarded potential for an extended source, whose density depends on the azimuthal angle T and the time t in the combination p-at only, has a discontinuous gradient at points within the source that lie on the cylindrical surface rp = c/ws, and that the radial component of this gradient diverges like (rp c/w)-I as rp o/c1+, where rp is the radial position of the observation point in cylindrical polar coordinates, c is the propagation speed of the waves described by the retarded potential, and o is a constant angular frequency. So, for an extended source moving on a curved path whose speed is in parts smaller and in parts greater than the speed of the disturbances it generates, there is a sudden and infinitely large change in the strength of the field across the surface (within the source) at which the speed of the source and the speed of the waves are equal. The divergence in the field strength does not arise from any long-term transfer of energy to the field; it occurs instantaneously and so is to be understood either as signifying the breakdown of the governing wave equation or as disallowing the type of source in question. Some implications of this non-elementary catastrophe in the contexts of gas-dynamics, electrodynamics and general relativity are also pointed out.


Parent-of-origin–dependent gene expression resulting from genomic imprinting plays an important role in modulating complex traits ranging from developmental processes to cognitive abilities and associated disorders. However, while gene-targeting techniques have allowed for the identification of imprinted loci, very little is known about the contribution of imprinting to quantitative variation in complex traits. Most studies, furthermore, assume a simple pattern of imprinting, resulting in either paternal or maternal gene expression; yet, more complex patterns of effects also exist. As a result, the distribution and number of different imprinting patterns across the genome remain largely unexplored. We address these unresolved issues using a genome-wide scan for imprinted quantitative trait loci (iQTL) affecting body weight and growth in mice using a novel three-generation design. We identified ten iQTL that display much more complex and diverse effect patterns than previously assumed, including four loci with effects similar to the callipyge mutation found in sheep. Three loci display a new phenotypic pattern that we refer to as bipolar dominance, where the two heterozygotes are different from each other while the two homozygotes are identical to each other. Our study furthermore detected a paternally expressed iQTL on Chromosome 7 in a region containing a known imprinting cluster with many paternally expressed genes. Surprisingly, the effects of the iQTL were mostly restricted to traits expressed after weaning. Our results imply that the quantitative effects of an imprinted allele at a locus depend both on its parent of origin and the allele it is paired with. Our findings also show that the imprinting pattern of a locus can be variable over ontogenetic time and, in contrast to current views, may often be stronger at later stages in life.


The purpose of this article is to debate the relationship between a convergent approach to the sciences and Scriptural authority. The thesis is that a multi-disciplinary convergent methodology may be beneficial in the current apologetical debate about the relevance of Scripture. This line of thought is also in compliance with the ideals of the protestant reformation. We will assess this view by investigating the possible consonance between scientific perspectives and theological confessions of what it means to be human. Subsequently the focus will shift to the impact consonance might have on the different interpretations of the creation narratives in Genesis. In conclusion, we will state the case for a convergent approach to the sciences, and the benefits with regard to Scriptural authority. Intradisciplinary and/or interdisciplinary implications: This study would not have been possible without extensive intradisciplinary and interdisciplinary research. The subject matter imposes on the researcher the necessity to make use of knowledge from across the theological spectrum. It compels the various subjects within the theological encyclopedia to take note of any new research and incorporate it. In addition, it dispels the myth that natural science and theology have little in common. From a holistic perspective on creation the need for continuous interaction between the sciences is imperative.


This paper will introduce the Creative CoCooking Patterns. This is a pattern language for a creative and collaborative cooking session. CoCooking is a word we have coined for this pattern language with the meaning "cooking together." When people eat today, in most cases there exists a large gap between the person who cooks and the person who eats. Based on Alexander's attempt to create a architectural process which allowed the families to join the architects in building their homes, CoCooking is our proposal as a new way of cooking that would solve many of the problems that today's cooking holds. The Kitchen Captain is a new kind of a professional that is similar to the Architect Builder proposed by alexander, which allows beginners to cook at their own decision but provides necessary help when needed. By recapturing cooking as a fun, social, and a creative process, CoCooking will make cooking a more easy and daily activity for all, become a method for team building and enhancing communication, and also would nurture people's fundamental creativity. The Creative CoCooking Patterns is a pattern language to actualize such a cooking session, and contains 34 patterns on effective cooking techniques, creating a warm atmosphere, and on nurturing creativity in the kitchen. The paper will introduce 6 patterns (Kitchen Captain, Small-Lot Dishwashing, Chat in the Kitchen, Kitchen Lessons, Menu Bind, and Leftover Producer) in full length, and then show the rest of the patterns as patlets.


Across the world, colonialism produced a substantial built legacy that in many cases continues to mark post-colonial urban landscapes. This theme issue addresses the ambivalences surrounding the position of colonial architecture as heritage in the present day, questioning the common assumption that architecture produced under colonial rule constitutes, by definition, a "dissonant heritage". Presenting cases that highlight the myriad ways in which colonial architecture is re-used, re-appropriated, embraced and at times contested, the contributions gathered here argue for the important role research in architectural history has to play not only in re-situating edifices in the historical contexts that produced them, but also in unpacking the contemporary narratives constructed or even "invented" about colonial built heritage.


With the characterization of the total genomes of Arabidopsis thaliana and Oryza sativa, several putative plasma membrane components have been identified. However, a lack of knowledge at the protein level, especially for hydrophobic proteins, have hampered analyses of physiological changes. To address whether protein complexes may be present in the native membrane, we subjected plasma membranes isolated from Spinacia oleracea leaves to blue-native polyacrylamide gel electrophoresis (BN-PAGE). BN-PAGE is well established in the separation of functional membrane protein complexes from mitochondria and chloroplasts, but a resolved protein complex pattern from PM of eukaryotic cells has previously not been reported. Using this method, protein complexes from Spinacia oleracea PM could be efficiently solubilized and separated, including the highly hydrophobic aquaporin (apparent molecular mass 230 kDa), a putative tetramer of H+-ATPase, and several less abundant complexes with apparent masses around or above 750 kDa. After denaturation and separation of the complexes into their subunits in a second dimension (SDS-PAGE), several of the complexes were identified as hydrophobic membrane proteins. Large amounts of protein (up to 1 mg) can be resolved in each lane, which suggests that the method could be used to study also low-abundance protein complexes, e.g. under different physiological conditions. (Less)


The speckle grain close to a diffuser medium carries information about the angles at which light is scattered. We propose the extension of a technique that allows obtaining the angular distribution of the scattered intensity in the far-field speckle pattern from the near-field speckle pattern produced by strong diffusers (whose roughness is greater than the illuminating wavelength). To illustrate this technique we applied it to the light scattered from ground glass diffusers. The experimental results are compared with those obtained by direct measurement of the angular distribution of the mean scattered intensity in the far field showing good agreement with each other. The advantages over the classical far-field methods are outlined.


Blueswarm is a 3D underwater collective that uses only local implicit vision-based coordination to self-organize. Many fish species gather by the thousands and swim in harmony with seemingly no effort. Large schools display a range of impressive collective behaviors, from simple shoaling to collective migration and from basic predator evasion to dynamic maneuvers such as bait balls and flash expansion. A wealth of experimental and theoretical work has shown that these complex three-dimensional (3D) behaviors can arise from visual observations of nearby neighbors, without explicit communication. By contrast, most underwater robot collectives rely on centralized, above-water, explicit communication and, as a result, exhibit limited coordination complexity. Here, we demonstrate 3D collective behaviors with a swarm of fish-inspired miniature underwater robots that use only implicit communication mediated through the production and sensing of blue light. We show that complex and dynamic 3D collective behaviors—synchrony, dispersion/aggregation, dynamic circle formation, and search-capture—can be achieved by sensing minimal, noisy impressions of neighbors, without any centralized intervention. Our results provide insights into the power of implicit coordination and are of interest for future underwater robots that display collective capabilities on par with fish schools for applications such as environmental monitoring and search in coral reefs and coastal environments.


Purpose

The purpose of this study is to explore the contributing barriers to corporate social and environmental responsibility (CSER) practices. In particular, this study focuses on non-managerial stakeholders' perceptions of the barriers to CSER practices in a developing country context. The study also investigates the current initiatives undertaken by the different stakeholders, such as government, non-governmental organisations (NGOs) and regulators.

Design/methodology/approach

The study takes a qualitative approach, undertaking semi-structured in-depth interviews with 26 participants from NGOs, the media, regulatory authorities, government departments, shareholders, trade union leaders and customers.

Findings

The views of stakeholder groups were analysed to identify the contributing barriers to CSER practices. The findings of the study reveal that corruption and politics, lack of coordination, lack of government initiatives and unsatisfactory implementation of laws are perceived as the major barriers that hinder CSER practices in Bangladesh. The study also found a lack of awareness amongst various stakeholder groups regarding the influential role CSER plays in promoting sustainable development. The current initiatives undertaken by various stakeholders to improve CSER practices were limited but growing.

Research Limitations/implications

The study utilises the stakeholder theory to examine the role of stakeholders, rather than managers, in relation to CSER practice in Bangladesh. The findings may provide impetus for mitigating CSER barriers in a developing country context.

Originality/value

This study is one of the few engagement-based studies to explore the non-managerial stakeholders' views on CSER in a developing country context.


This thesis investigates the related topics of speckle reduction and edge detection as applied to speckled ultrasonography. A strategy for the evaluation of speckle filters is presented. This includes their application to a large test set of both clinical and simulated images. Functional performance is measured by application of objective image quality metrics, and the relationship between these objective metrics and the subjective opinion of clinical experts is investigated. Finally a detailed analysis of the complexity of the filtering methods is performed to ascertain the computational requirements of the different filters. Edge detection is investigated using Gabor filters to perform orientation-specific multiscale decompositions. The effect of speckle is reduced in the Gabor transforms by MAP estimation. This involves modelling the statistics of the speckle Gabor transform as a combined Gaussian and symmetric α-stable distribution. A technique is proposed for the estimation of the parameters of this model, and its accuracy is demonstrated. Edge detection is achieved by finding the zero crossings of the even-symmetric Gabor coefficients. To suppress the zero crossings which do not correspond to images edges, two observed properties of the Gabor zero crossings are examined. These measurements are combined to form the final edge detector, which is shown to exceed the performance of other edge detectors for speckled imagery. A close relationship exists between edge detection and speckle removal, especially for the diffusion class of filters. The proposed zero crossing edge detector is accordingly incorporated into a tensor-valued diffusion scheme. The performance of this speckle filter is evaluated using the framework proposed in this thesis, and is found to exhibit excellent functional performance.


A number of microRNAs (miRs) have been identified as being involved in the regulation of anesthesia-induced cognitive impairment. The aim of the present study was to investigated the role and potential mechanism of miR-133b in isoflurane-induced learning and memory impairment. An animal model of isoflurane exposure was established using neonatal Sprague-Dawley rats. The rats were trained for Morris water maze (MWM) testing to assess their spatial learning and memory ability. Reverse transcription-quantitative polymerase chain reaction was used for the measurement of miR-133b expression in hippocampal tissues and primary hippocampal neuron cultures. Cell viability was assessed using a Cell Counting Kit-8 assay, and flow cytometric analysis was used to determine the rate of apoptosis. The MWM test results indicated that during the training period, the time required to locate the platform was significantly increased for rats exposed to isoflurane, and this increased time was reduced by the overexpression of miR-133b. The results of a probe trial indicated that isoflurane exposure increased escape latency and decreased the time spent in the platform area for isoflurane-treated rats; however, these effects were reversed by the injection of miR-133b agomir. The in vitro experiments demonstrated that the overexpression of miR-133b attenuated the reduction of neuronal cell viability induced by isoflurane, and inhibited the isoflurane-induced apoptosis of hippocampal neurons. In conclusion, the present study revealed that the overexpression of miR-133b attenuated isoflurane-induced learning and memory impairment in rats. Furthermore, miR-133b overexpression promoted the viability of hippocampal neurons and their resistance to apoptosis when exposed to isoflurane.


We propose a new discriminative learning framework, called soft margin feature extraction (SMFE), for jointly optimizing the parameters of transformation matrix for feature extraction and of hidden Markov models (HMMs) for acoustic modeling. SMFE extends our previous work of soft margin estimation (SME) to feature extraction. Tested on the TIDIGITS connected digit recognition task, the proposed approach achieves a string accuracy of 99.61%, much better than our previously reported SME results. To our knowledge, this is the first study on applying the margin-based method in joint optimization of feature extraction and acoustic modeling. The excellent performance of SMFE demonstrates the success of soft margin based method, which targets to obtain both high accuracy and good model generalization.


B cell lineage acute lymphoblastic leukemia (ALL) arises in virtually all cases from B cell precursors that are arrested at pre–B cell receptor–dependent stages. The Philadelphia chromosome–positive (Ph+) subtype of ALL accounts for 25–30% of cases of adult ALL, has the most unfavorable clinical outcome among all ALL subtypes and is defined by the oncogenic BCR-ABL1 kinase and deletions of the IKAROS gene in >80% of cases. Here, we demonstrate that the pre–B cell receptor functions as a tumor suppressor upstream of IKAROS through induction of cell cycle arrest in Ph+ ALL cells. Pre–B cell receptor–mediated cell cycle arrest in Ph+ ALL cells critically depends on IKAROS function, and is reversed by coexpression of the dominant-negative IKAROS splice variant IK6. IKAROS also promotes tumor suppression through cooperation with downstream molecules of the pre–B cell receptor signaling pathway, even if expression of the pre–B cell receptor itself is compromised. In this case, IKAROS redirects oncogenic BCR-ABL1 tyrosine kinase signaling from SRC kinase-activation to SLP65, which functions as a critical tumor suppressor downstream of the pre–B cell receptor. These findings provide a rationale for the surprisingly high frequency of IKAROS deletions in Ph+ ALL and identify IKAROS-mediated cell cycle exit as the endpoint of an emerging pathway of pre–B cell receptor–mediated tumor suppression.


Reproductive isolation is central to the speciation process, and cases where the strength of reproductive isolation varies geographically can inform our understanding of speciation mechanisms. Although generally treated as separate species, Black-capped chickadees (Poecile atricapillus) and Carolina chickadees (P. carolinensis) hybridize and undergo genetic introgression in many areas where they come into contact across the eastern United States and in the northern Appalachian Mountains. The Great Smoky Mountains harbor the last large breeding population of atricapillus in the southern Appalachians, isolated from the species' main range by nearly 200 km. This population is believed to be reproductively isolated from local carolinensis due to an unusual, behaviorally mediated elevational range gap, which forms during the breeding season and may function as an incipient reproductive isolating mechanism. We examined the effectiveness of this putative isolating mechanism by looking for genetic introgression from carolinensis in Great Smoky Mountain atricapillus. We characterized this population and parental controls genetically using hundreds of amplified fragment length polymorphism (AFLP) loci as well as mitochondrial DNA (mtDNA) sequence data from cytochrome-b. Great Smoky Mountain atricapillus have experienced nuclear genetic introgression from carolinensis, but at much lower levels than other populations near the hybrid zone to the north. No mitochondrial introgression was detected, in contrast to northern contact areas. Thus, the seasonal elevational range gap appears to have been effective in reducing gene flow between these closely related taxa.


In the absence of true regional data on changes in the acid/base status of lakes in the northeastern United States, we explore the possibility of using site-specific trends information from a judgment sample of lakes to assess the efficacy of the Clean Air Act Amendments. A meta-analytical technique is used to combine trends results from 44 Long-Term Monitoring (LTM) lakes in the Northeast for the period 1982–1994, with the goal of producing estimates of overall trends in the region. The lakes are subdivided into subpopulations (High ANC, Intermediate Till Drainage, Thin Till Drainage and Perched Seepage lakes) on the basis of their expected response to changes in acidic deposition, and they appear to represent the most acid-sensitive of these lake classes well. While the overall tendencies in the trends are as expected (e.g., most of the recovery is observed in the most sensitive subpopulations), there is significant trend heterogeneity among the lakes within most of the subpopulations; this heterogeneity prohibits the summarizing of trends at the regional level (i.e., for all of the Northeast). This heterogeneity is explained by differences in the responses of lakes in two subregions (Adirondacks vs. New England), and we present trends results separately for each subpopulation within these two subregions. All subpopulations in both subregions showed decreasing trends in sulfate concentrations, probably a reflection of decreasing trends in sulfur deposition in the region. Few trends in nitrate concentrations were observed. Recovery (as evidenced by increasing trends in acid-neutralizing capacity) was evident in Thin Till and Intermediate Till Drainage lakes in New England, but not in the Adirondacks. Most groups of lakes exhibited downward trends in base cations (Σ[Ca2+ + Mg2+ + Na+ + K+]); the magnitudes of these trends were always greater in Adirondack lakes than in similar New England lakes. This suggests that the depletion of soil cation pools in the Adirondacks may be responsible for some of the differences in recovery between Adirondack and New England lakes. While export of base cations may be the key difference producing different trends results in the two subregions, the site-specific nature of the trends, and their possible lack of regional representation, should be considered in interpreting the overall results.


ABSTRACT Previous research identifies the importance of feminist knowledge for improving gender equity, economic prosperity and social justice for all. However, there are difficulties in embedding feminist knowledge in higher education curricula. Across England, undergraduate sociology is a key site for acquiring feminist knowledge. In a study of four English sociology departments, Basil Bernstein's theoretical concepts and Madeleine Arnot's notion of gender codes frame an analysis indicating that sociology curricula in which feminist knowledge is strongly classified in separate modules is associated with more women being personally transformed. Men's engagement with feminist knowledge is low and it does not become more transformative when knowledge is strongly classified. Curriculum, pedagogy and gender codes are all possible contributors to these different relationships with feminist knowledge across the sample of 98 students.


We study how a negative labor market shock like job loss generates health spillovers in couples. Using administrative data of all workers and firms matched to mortality and patient records, we document that male job displacement increases the mortality risk for both the man and his partner. For every 10,000 displaced men, there are 27 additional deaths over a 5-year period rising to 115 additional deaths over two decades. Of those, 60% accrue to the displaced worker but 40% are due to excess spousal mortality. Deaths from cardiovascular diseases jump up and hospitalization records show more treatments for alcohol-related disorders and mental health issues. We also find a stunning gender asymmetry: while male job displacement generates large and persistent health effects, no such dire health consequences are observed after a woman loses her job. We explore three explanations for the observed health spillovers: risk sharing through spousal labor supply; earnings losses and the role of public insurance; and the influence of gender roles and family structure.


This article discusses the geographical flows of the global knowledge economy and their unstable and rapidly changing nature. We use the development of activities in ICT (information and communication technology) in India and its connections to Sweden to illustrate changes in international business. The article explores the ways in which transformations in geography and spatial relations, politics and management are causes and effects of rapid and profound transformations in the global economy. The transformations we illustrate provide reasons to reconsider the conventional idea of uneven power relations in the world, between the stronger "global North" and the weaker "global South". Firms based in the global South and in India develop their organizations and capabilities to compete for market share worldwide, and on the same basis as firms based in the global North.


Return correlations in the U.S. dollar and euro credit markets are systematically different on at least two dimensions: returns for normal day–to–day spread changes versus spread returns associated with extreme events; and spread returns for investment–grade versus speculative issuers. A large part of the return correlation is driven by extreme global events such as the 2001 terrorist attacks or the 2002 credit crisis ensuing on the Enron meltdown. Under more normal market conditions, euro and U.S. dollar credit markets are weakly linked, especially for highly rated debt. Returns on speculative debt issued by the same issuer in different markets tend to be highly correlated; this is less so for high–grade issuers. An immediate implication is that currency diversification is much more efficient than name diversification for high–grade debt. Conversely, high–yield portfolios benefit from name or even sector diversification more than they benefit from currency diversification. Risk models need to include currency–dependent factors, particularly for investment–grade instruments. The results provide some indication of the way to use global credit factors or factor return proxies to estimate credit risk in markets lacking much corporate bond data.


Effect size indices are indispensable for carrying out meta-analyses and can also be seen as an alternative for making decisions about the effectiveness of a treatment in an individual applied study. The desirable features of the procedures for quantifying the magnitude of intervention effect include educational/clinical meaningfulness, calculus easiness, insensitivity to autocorrelation, low false alarm, and low miss rates. Three effect size indices related to visual analysis are compared according to the aforementioned criteria. The comparison is made by means of data sets with known parameters: degree of serial dependence, presence or absence of general trend, and changes in level and/or in slope. The percent of nonoverlapping data showed the highest discrimination between data sets with and without intervention effect. In cases when autocorrelation or trend is present, the percentage of data points exceeding the median may be a better option to quantify the effectiveness of a psychological treatment.


OBJECTIVE
To assess the influence of socioeconomic, reproductive, and behavioral factors on the evolution of weight during pregnancy.

METHODS
Body weight was measured prospectively in a cohort of 215 healthy pregnant women attended to by a public prenatal service in the city of São Paulo, between 1997 and 1998. The criteria for inclusion were the following: aged 18 or older and with the beginning of prenatal care at a gestational age <or= 16 weeks. The relation between the independent variables and the evolution of weight during pregnancy was assessed by means of the multilevel hierarchical linear analysis, and subsequently analyzed by the maximum likelihood test.

RESULTS
In the multilevel analysis, the factors that were significantly associated to gestational weight gain were the following: initial BMI, level of education, marital status and parity. The equations thus obtained enabled to identify the individual effect of each of these characteristics: eutrophic initial BMI, level of education >or= 4 years, lack of partner, and primiparity cause increases of 3.0 kg, 1.9 kg, 2.3 kg and 2.4 kg in the total weight gain during pregnancy, respectively.

CONCLUSIONS
Initial BMI, level of education and parity are the maternal characteristics that, along with the marital status, must be taken into consideration in the development of strategies to promote adequate weight gain during pregnancy.


Introduction: Twin pregnancies, especially monochorionic placentations, are associated with a higher rate of maternal and foetal complications when compared to singleton pregnancies. The objective of this work was to describe the clinical characteristics and the maternal and foetal outcomes according to the type of placentation (monochorial or dichorial) of twin pregnancies delivered at Hospital Universitario de Santander (HUS), a level III institution located in Bucaramanga, Colombia. Materials and methods: Descriptive cohort study. The cohort consisted of patients delivered of a twin pregnancy between 2007 and 2011 at the HUS, a general referral hospital for the central-eastern region of the country. The assessment included gestational age at the time of initial presentation to the hospital, clinical findings during the initial assessment, delivery completion, and perinatal results. Descriptive analysis by chorionicity type. Results: A total of 248 women with a twin pregnancy during the study period were included. The mean gestational age on the first visit to the hospital was 34 weeks. On admission, 127 patients (51.2%) were diagnosed with a monochorionic  pregnancy, but only in two thirds of the cases was the prenatal chorionicity diagnosis consistent with the post-partum finding. IUGR was diagnosed more frequently in monochorionic than in dichorionic pregnancies (22.3% v. 7.5%) and abnormal Doppler findings were more frequent in monochorionic foetuses (7.8% v. 1.1%). Neonates > 24 of gestational age in monochorionic pregnancies weigh in average 109 gr (IC 95%: 34-184) less than dichorionic twins. Conclusions: The results of this study suggest a public health problem in this group of patients who come late for their prenatal visits and are late referrals to specialized centres, when there is already a limited ability to determine chorionicity. There is a need to develop care strategies in which twin pregnancies are included as a high-risk condition, and to ensure timely and adequate care provision in accordance with differential care guidelines for this group of pregnant women.


The etiology of most types of alopecia is not fully understood. Excessive use of hat is believed to be a cause of alopecia, but the possible involvement of altered micronutrients (essential elements and vitamins) levels in cap\scarf- induced alopecia has not been explored. This study is therefore embarked on to identify if alteration in micronutrients levels exists in subjects who may have cap\scarf- induced alopecia. Forty female subjects each, constituted the alopecia and control groups, and were selected by random sampling technique. Each subject has a history of prolonged use of cap\scarf of over a period of 10 years. Results show that ALT, AST, ALP, GGT, bilirubin and globulin are not significantly different in alopecia subjects compared with controls (p>0.05) whereas nutritional indices; albumin, total protein, Zn, Cu, vitamins A & E are significantly decreased (p 0.05). Renal indices; urea and creatinine are significantly increased in alopecia subjects compared with controls (p<0.05). The result of this study suggests that altered serum levels of micronutrients and total protein may exist in individuals who may have cap\scarf- induced alopecia.


In this paper we investigate the implications of providing a real-time messaging interface in a Web-based citizen science game. Our study draws on data from two weeks of chat messages and survey responses collected from Eyewire, a highly successful citizen science game which enables players to take part in scientific enquiries, within a semi-gamified environment. Our analysis reveals that real-time chat facilitates and supports players for several types of engagement; to collaboration on tasks, knowledge sharing, learning, socialising, supporting other in the community, and to help sustain long-term participation. Based on the analysis, we derive a set of design recommendations for citizen science platforms designers, focusing on the role of real-time chat on improving participation and performance.


The functional activity of integrin receptors on T cells is dynamically regulated so that T cells can alternate rapidly between adhesive and nonadhesive states. The CD7 Ag is one of several molecules on T cells that can transduce intracellular signals that rapidly up-regulate integrin-mediated adhesion. We demonstrate in this report that the signaling pathway that CD7 utilizes to regulate integrin activity involves the lipid kinase phosphatidylinositol 3-kinase (PI 3-K). CD7 stimulation of both Jurkat T cells and resting human peripheral blood CD4+ T cells results in rapid association and activation of PI 3-K with CD7. Phosphopeptide competition assays demonstrate that the association of CD7 with PI 3-K is dependent on tyrosine phosphorylation of the SH2 binding motif Tyr-Glu-Asp-Met (YEDM) in the CD7 cytoplasmic domain. A role for PI 3-K in the regulation of integrin function by CD7 is demonstrated by: 1) the ability of two structurally distinct PI 3-K inhibitors, wortmannin and LY294002, to inhibit CD7-mediated increases in beta1 integrin function of human T cells; and 2) inhibition of CD7-mediated activation of beta3 integrin function in human T cells by expression of a dominant negative form of the p85 subunit of PI 3-K. These results demonstrate that the CD7 Ag on human T cells is coupled to PI 3-K and that this association is relevant to CD7-mediated signaling events, specifically CD7-induced increases in integrin adhesiveness. Furthermore, these studies provide important new evidence implicating PI 3-K in the regulation of integrin adhesiveness by multiple cell surface signaling receptors.


The interaction of ionising radiation with polymers is described and the literature relating; to the effects on polypropylene is reviewed. Oxidative and free radical reactions are discussed with particular reference to post-irradiationeffects.Isotactic and atactic polypropylene were δ and electron irradiated to doses of up to 20 megarad. Irradiations weremainly made in air. A series of other polymers were also irradiated in a preliminary survey. Molar mass measurements are used to measure the radiationyield for chain scission G (s). Irradiation at room temperature causes significantly more chain scission than at 195K. Additional chain scission occurs on storage following irradiation at 195 K. Free radical concentrations are determined by electron spin resonance, and the decay rates measured. The radical formed in air is a peroxy radical and in vacuo is a hydrocarbon radical. At77K in vacuo the radical is -CH2 - C* (CH3) - CH2 - but additional radicals are produced on warning to room temperature. The effects of increasing tenparature on radicals formed in air are described. Electron spin resonance studies on atactic polypropylene,and isotactic polypropylene in hydrogen, sulphur dioxide and nitric oxide are reported.. The melting temperatures, spherulite growth rates, and isothermal crystallisation rates of irradiated polypropylene are compared to those of the non-irradiated polymer. Crystallisation is found to proceed with an Avrami integer n = 2. At a given crystallisation temperature, the overall crystallisation rate of irradiated polymer is less than the non-irradiated, but spherulite growth rates are identical. Thermogravimetric analysis is used to assess the thermal stability of irradiated polypropylene in nitrogen, air and oxygen. Hydroperoxide analysis is used to show that several molecules of oxygen are absorbed for each initial radical, and that hydroperoxides continue to be formed for a long period following irradiation. Possible solutions for minimising irradiation and post-irradiation degradation are suggested, together with some problems for further study.


Motivated by the problem of modeling nucleation in non-isothermal systems,
we consider the stochastic evolution of a coupled system of a lattice spin
variable $\sigma$ and a continuous variable $e$ (corresponding to the phase and
the energy density of a continuum system). The spin variables flip with rates
depending both on a Kac potential type interaction with the spins and on an
interaction with the $e$-field, which plays the role of the external field in
ferromagnetics but evolves by a diffusion equation with a forcing depending on
the spins.
 We analyze the mesoscopic limit, where space scales like the diverging
interaction range of the Kac potential, $\gamma^{-1},$ while time is not rescaled.
By writing $\sigma$ as random time change of a family of independent spins,
and thus reducing the problem to investigating integral equations parametrized
by independent random variables, we show that as $\gamma\to 0$ the average of
the spins over small cubes and the field $e$ converge in probability to the
solution of a system of nonlocal evolution equations which is similar to the
phase field equations. In some cases the convergence holds until times of order
${\log(\gamma^{-1})}.$


Cold hardiness evaluation is important for screening woody species in cold areas. We compared cold hardiness by estimating the 50% lethal temperature (LT50) using electrolyte leakage test (ELLT50) and triphenyltetrazolium chloride test (TTCLT50) for 26 woody species in the Bashang region of China. One-year-old shoots were collected in January and exposed to five subfreezing temperatures in a programmable temperature and humidity chamber. LT50 was estimated by fitting relative electrolyte leakage and percentage of dead tissue against test temperature. For all tested species, triphenyltetrazolium chloride (TTC) staining of the pith was weak and the cambium TTCLT50 was lower than the extreme minimum temperature (−37 °C) recorded in the region. The cambium TTCLT50 and the sd were lower than that for the phloem and xylem. The phloem TTCLT50 was lower than the xylem TTCLT50, and the two sds were similar. The ELLT50 showed no significant correlation with any TTCLT50. For most species, the ELLT50 was higher than the cambium and phloem TTCLT50 and was not significant different with the xylem TTCLT50. The ELLT50 showed higher sd than any tissue TTCLT50. Based on results obtained in this study, when choosing cold hardiness of single stem tissue as an indicator for screening woody species, the xylem should be considered first, followed by the phloem; the cambium and pith were unsuitable. The cold hardiness estimated by ELLT50 was more suitable as indicator for screening woody species than that of stem tissue in winter estimated by TTCLT50.


The groundwater contained in the alterites is one of the main sources of water supply for many households in the city of Yaounde and its surroundings. Information from the field and laboratory studies was compiled and analyzed in order to under-stand the hydrogeological context of this superficial aquifer. Preliminary results show a staged morphology of the alteration mantle (regolith) of Yaounde migmatitic representative of the polyphase character of alteration processes observed in all granito-gneissic formations of the world. This mantle has a multilayer system whose soil sets could have a different hydrodynamic functioning. The values of the hydraulic conductivity have a normal distribution and vary over four orders of magnitude, attesting the variability of the hydraulic conductivity of the soft materi-als. The hydrometric and piezometric characteristics indicate that the aquifer has highly heterogeneous zones that would be related to the morphostructural character of the region. The δ 18 O mean values of the rain ( − 2.47‰) and shallow groundwater ( − 2.57‰) are not significantly different. They indicate that the recharge of the shallow aquifer of Yaounde Precambrian basement is recent and is done directly by infiltration of precipitation without any notable change due to evaporation.


Social organization varies widely among herbivores, and the level of social organization in bison is widely debated. I hypothesized that when mother-daughter relationships are allowed to develop, bison form long-term associations. In my study, 25 treatment mothers were selected from a free-ranging herd and kept together with their calves, while 25 control females had their calves forcefully removed. Treatment mothers and offspring had by far the greatest number of associations with a greater percentage of individuals with a half weight index (HWI) > 0.50. The strongest associations (HWI > 0.31) were among treatment mothers and their offspring. Moreover, these associations persisted over multiple generations. Group coordination requires group decisions and these can vary between extremes. I hypothesized bison utilized both democratic and despotic decisions. I examined movement initiation and direction decisions following rest periods. For direction decisions older cows repeatedly made decisions despotically for the group; in 93% of the choices, group directions were within 95% confidence intervals. For movement initiation, bison used a more democratic decision-making process; group movements did not begin until an average of 47% of adult cows exited the group. Interestingly, the oldest females led this final post-rest movement behavior in 81% of the decisions. Presumably, living in properly functioning social groups has many benefits, including reduced stress. I hypothesized levels of stress was related to animal density. Consequently, yearling bison males were weaned and placed in either 1) tight confinement (TC), 2) loose (LC) confinement, or 3) free-ranging (FR, returned to herd). I measured fecal cortisol metabolites (FCM) as an index of stress. Fecal samples were collected in each group every 2 weeks from January to April 2009. Fecal cortisol levels were lowest for FR (23 ng/g DM), intermediate for LC (39 ng/g DM), and highest for TC (63 ng/g DM; P


Abstract. The European Location Framework (ELF) means a technical infrastructure which will deliver authoritative, interoperable geospatial reference data from all over Europe for analysing and understanding information connected to places and features. The ELF has been developed and set up through the ELF Project, which has been realized by a consortium of partners (public, private and academic organisations) since March 2013. Their number increased from thirty to forty in the year 2016, together with a project extension from 36 to 44 months. The project is co-funded by the European Commission's Competitiveness and Innovation Framework Programme (CIP) and will end in October 2016. In broad terms, the ELF Project will deliver a unique gateway to the authoritative reference geospatial information for Europe (harmonised pan-European maps, geographic and land information) sourced from the National Mapping and Cadastral Authorities (NMCAs) around Europe and including transparent licensing. This will be provided as an online ELF web service that will deliver an up-to-date topographic base map and also as view & download services for access to the ELF datasets. To develop and build up the ELF, NMCAs are accompanied and collaborate with several research & academia institutes, a standardisation body, system integrators, software developers and application providers. The harmonisation is in progress developing and triggering a number of geo-tools like edge-matching, generalisation, transformation and others. ELF will provide also some centralised tools like Geo Locator for searching location based on geographical names, addresses and administrative units, and GeoProduct Finder for discovering the available web-services and licensing them. ELF combines national reference geo-information through the ELF platform. ELF web services will be offered to users and application developers through open source (OSKARI) and proprietary (ArcGIS Online) cloud platforms. Recently, 29 NMCAs plus the EuroGeographics – their pan-European umbrella association, contribute to the ELF through an enrichment of data coverage. As a result, over 20 European countries will be covered with the ELF topo Base Map in 2016. Most countries will contribute also with other harmonized thematic data for viewing or down-loading. To overcome the heterogeneity of data resources and diversity of languages in tens of European countries, ELF builds on the existing INSPIRE rules and its own coordination and interoperability measures. ELF realisation empowers the implementation of INSPIRE in Europe and it complements related activities of European NMCAs, e.g. Czech Office for Surveying, Mapping and Cadastre (CUZK), which provides a large portfolio of spatial data/services and contributes significantly to the NSDI of Czech Republic. CUZK is also responsible for the Base Register of Territorial Identification, Addresses and Real Estates (RUIAN) – an important pillar of Czech e-Government. CUZK became an early-bird in implementing INSPIRE and it provides to the ELF a number of compliant datasets and web services. CUZK and the Polish NMCA (GUGiK) collaborate in the Central-European ELF Pilot (cluster) and test various cross-border prototypes. The presentation combines the national and crossborder view and experiences of CUZK and the European perspective of EuroGeographics.


Abstract The late–middle Eocene Gosport Sand of the United States Gulf Coastal Plain preserves a spectacularly dense accumulation of fossil mollusks in which shells appear unusually large in comparison to congeners in adjacent units. We use size-frequency distributions of common taxa drawn from bulk samples to quantify size differences between the Gosport Sand and the underlying Lisbon and overlying Moodys Branch Formations. In all but one of the twelve lineages examined, Gosport Sand individuals are larger than those in adjacent units. As taphonomic processes such as sorting or winnowing cannot account for observed differences, the larger body sizes in the Gosport Sand must have resulted from differences in life history. We used sclerochronology and stable isotope geochemistry to assess growth trajectories for twelve lineages common to the three formations. Isotope analyses of microsamples collected along the ontogenetic trajectory reveal seasonal temperature changes, providing a chronometer for growth. Size-age data indicate that, while life spans vary somewhat among the three units, Gosport Sand taxa almost universally grew faster than those in the two adjacent formations. While growth rate can be enhanced by several factors, we hypothesize that rates of primary production were higher during deposition of the Gosport Sand. Ba/Ca ratios along the growth trajectories of shell carbonate exhibit spikes in Gosport Sand mollusks that are indistinguishable from those observed in modern shells that accrete in high productivity settings.


This article addresses the role of the Church of Sweden in spiritual care for parishioners in their end-of-life phase. The frame of reference is a new geography of dying that implies that a majority of Swedes today, particularly older people, die in their local neighborhood of belonging, in fact in their parishes. Findings from a study of all parishes in two Swedish communities are presented that indicate support for dying parishioners is surprisingly uncommon, although most parishes offer support for the bereaved. A possible interpretation of these contrasting patterns is discussed. The findings indicate that divergent forms of care logic motivated the different types of support offered by the Church. Long-standing relationships with aging parishioners seemed to be at the heart of the matter.


A pulsed laser system is realized with graphene employed as a Q-switch. The graphene is exfoliated from its solution using an optical deposition and the optical tweezer effect. A fiber ferrule that already has the graphene deposited on it is inserted into an erbium-ytterbium laser (EYL) system with linear cavity configuration. We successfully demonstrate a pulsed EYL with a pulse duration of approximately 5.9 \mu s and a repetition rate of 20.0 kHz.


According to previous research, the junior-to-senior transition (JST) is decisive for athletes who want to reach the elite/professional sport level, it lasts for 2-4 years, and is known for its high dropout rate. The longitudinal study of the junior-to-senior transition process in Swedish club-based athletes conducted by the authors involved several lines of data analysis with this presentation focusing on the dynamics of athletes' junior-to-senior transition adjustment in relation to their personal characteristics. The study had five measurements conducted every six months using several instruments; these instruments measured the athletes' level of athletic identity, task- and ego orientation, self-esteem and adjustment in the transition process. The latent profile analysis identified three profiles (based on athletes personal characteristics; BIC = 771.11; entropy = 0.87; Parametric Bootstrapped likelihood ratio test = -356.07, p < 0.001). In the profile-1, athletes (34 males and 11 females) were characterized by high athletic identity, self-esteem, task orientation, and the JST motivation; they also had moderately high ego orientation. These athletes perceived to be 72 % adjusted at the first measurement, had a positive progression through the transition process, and at the fifth measurement perceived to be 83 % adjusted at the senior level. In the profile-2, athletes (30 males and 7 females) perceived themselves to have high self-esteem and the JST motivation, relatively high athletic identity and task orientation complemented by moderate ego orientation. They perceived themselves to be 66 % adjusted at the first measurement, had a positive progression through the transition process, and at the fifth measurement perceived themselves to be 73% adjusted. In the profile-3 athletes (9 males and 9 females) reported high self-esteem, relatively high task orientation, as well as moderate athletic identity, ego orientation and the JST motivation. These athletes perceived to be 62 % adjusted at the first measurement, had almost no progression through the transition process, and at the fifth measurement perceived themselves to be 64 % adjusted. These findings supported our hypothesis that athletes with different profiles of personal characteristics follow different pathways through the JST process. The JST pathways are going to be explored more in detail with the aim to understand transition variables contributing to the dynamics of perceived adjustment. Further this knowledge can be used in assisting athletes in the JST.


Deoxyribonucleic acid (DNA) methylation of promoter CpG (cytosine/guanine) islands is a process that inhibits the expression of genes through mechanisms that interfere with transcriptional initiation. Transcriptional silencing occurs when the 5′ flanking DNA region becomes heavily methylated, either allowing transcriptional repressor proteins to directly bind to the methylated DNA region or causing a conformational change in the DNA sequence. Thus, the downstream consequence of DNA methylation is to interfere with the binding and activational activity of specific transcription factors required for gene expression. The effect of DNA hypermethylation is therefore to inhibit or reduce the expression potential of a target gene. The role of methylation in cancer has been determined by association studies where the promoter regions of tumour suppressor genes have been found to be highly methylated. This is followed by gene silencing and an increase in tumour growth. Clinical interest in the treatment of tumours has gained increased impetus because recent evidence on the use of novel therapeutic agents suggests that DNA promoter methylation is potentially reversible. This may thus allow for the development of future therapeutic intervention.

Key Concepts:

Epigenetic methylation is a key mechanism that can inhibit or reduce gene expression in the absence of DNA sequence variations.

Aberrant DNA methylation may downregulate a gene as effectively as a pathological mutation.

CpG island methylation of tumour suppressor gene promoter regions is a mechanism responsible for silencing gene expression leading to tumour development.

Methylation of CpG islands can occur in regions of DNA that reside at great distances from a target gene but still lead to a reduction in gene expression.

Aberrant methylation of tumour suppressor genes is potentially reversible in tumours allowing for therapeutic intervention.

Keywords:

promoter;
epigenetic;
hypermethylation;
tumour suppressor;
carcinogenesis;
CpG island


Abstract: A Lagerstätte of Glyptocrinus decadactylus collected from the Upper Fairview Formation at Maysville, Kentucky, USA, yields new insights into the paleoautecology of camerate crinoids of the Late Ordovician. The Lagerstätte represents an autochthonous community composed of a single siltstone bed representing an obrution event and containing over 400 individual glyptocrinids that had colonized a slight topographic rise of relatively high energy within the deep subtidal zone. The high density of the crinoid community was accommodated by tiering, in which the crinoids presumably employed macroalgae (not preserved), occasionally bryozoans, and the columns of earlier-settled specimens as attachment sites; differing column lengths positioned the crinoids at various levels within the community. A further strategy for crowded conditions may have been small body size. Storm-induced turbidity flows led to the suspension of silts by a lofting plume that smothered the crinoids in their habitat. The densely packed crinoid-macroalgae assemblage may have baffled the sediment plume and induced deposition, facilitating burial. Some specimens apparently died shortly prior to burial, suggesting more than one earlier killing event, likely related to the storm that ultimately caused the obrution. Other specimens were killed by the obrution event and subjected to little or no subsequent scavenging or decay after burial, leading to excellent preservation.


Extant research on lean manufacturing has focused on the relationship between systemic inventory and performance. However, limited research, if any, has focused on dynamics between three main types of inventory – raw material, workin-process, and finished goods – and firm performance. Drawing on the interdependence framework and a sample of 1,286 firms representing 41,067 firm-quarter observations from 2000 to 2013, when considering two types of inventory efficiencies jointly, higher efficiency in the subsequent inventory type must be accompanied by lower efficiency in the previous inventory type. In other words, lower raw material inventory efficiency and higher work-in-process inventory efficiency, or lower work-in-process inventory efficiency and higher finished goods inventory efficiency are associated with higher performance. High performance is also realized only when inventory efficiency is increasing across all three inventory types. The findings show that pursuing efficiency in one type of inventory requires lower efficiency in the previous inventory stage, and benefits of lean manufacturing could only be realized when all three inventory efficiencies are simultaneously high.


Install, configure, and manage a robust Customer Relationship Management system using Siebel CRM Overview of Oracle Siebel CRM 8 Installation and Management Install and configure the Siebel CRM server and client software on Microsoft Windows and Linux Support development environments and migrate configurations with Application Deployment Manager Understand data security and manage user accounts with LDAP Manage multi-server and multi-language environments Written in an accessible readable style, this practical book will help you to successfully install and manage Siebel CRM The instructions in the book are valid for all versions 8.0, 8.1 and 8.2 alike In Detail Oracle's Siebel CRM is market-leading Customer Relationship Management software. Unmatched in functionality and scalability, Siebel enhances a company's sales performance, improves customer satisfaction, and provides a robust Customer Relationship Management system for an organization. This practical book offers a comprehensive understanding of Siebel CRM. It is your safe vessel for navigating the deep waters of Siebel installation and system management. This book is a complete exercise in installing and managing Oracle's Siebel CRM for your organization. You will understand the Siebel architecture and install it piece by piece. In easy-to-follow chapters, the book will guide you through the installation of Siebel server, client and third-party reporting software on Microsoft Windows and Linux, covering everything from the planning the process and software download to the installation and configuration tasks. After reading this book, you will feel fully prepared for setting up multiple servers and multi-lingual configurations. This book fosters your general understanding of the intricate features and functionality of Oracle Siebel CRM. In addition, you will learn how to support development environments and how to migrate configuration changes between environments using Application Deployment Manager. Another benefit of this book is that it teaches administrators how to establish system monitoring strategies to identify and avoid performance bottlenecks. When you have finished the book, you will feel prepared to install and manage Oracle's Siebel CRM in a real-world environment. In addition, you will know some tricks that even seasoned experts will envy. A pragmatic guide for effectively and efficiently implementing and managing Oracle's Siebel CRM What you will learn from this book Understand Siebel Web Architecture Plan and prepare Siebel CRM infrastructure Install and configure Siebel CRM software on Microsoft Windows and Linux Install and configure Siebel Charts and Oracle BI Publisher for Siebel Implement load balancing and support multi-language environments Manage the Siebel servers from the Siebel Web Client and the command line Implement LDAP authentication and Web Single-Sign-On Understand Siebel Access Control and Personalization Manage organizations, positions, and user accounts Install the Siebel Management Server infrastructure and use ADM to migrate configuration changes Monitor Siebel CRM environments for usage and performance Use Siebel Remote to support developers and mobile users Approach This book provides a practical, hands-on experience. Chapter by chapter, a Siebel CRM self-study environment is created which can be used to follow the examples described in the book to explore the Siebel functionality. The book ensures that you understand what you are doing and why you are doing it. It contains clear step-by-step instructions, explanatory tables, screenshots, and precise diagrams. Who this book is written for This book is for administrators who want to develop and strengthen their Siebel CRM skills in the areas of installation and system management. Whether you are a novice or a more experienced user, this book will teach you something new in many ways and by the end of the book, you will be ready to install and manage Siebel CRM in a real-world environment.


In past and present ecosystems, trophic interactions determine material and energy transfers among species, regulating population dynamics and community stability. Food web studies in past ecosystems are helpful to assess the persistence of ecosystem structure throughout geological times and to explore the existence of general principles of food web assembly. We determined and compared the trophic structure of two Devonian fish assemblages [(1) the Escuminac assemblage (ca. 380 Ma), Miguasha, eastern Canada and (2) the Lode assemblage (ca. 390 Ma), Straupe, Latvia] with a closer look at the Escuminac assemblage. Both localities are representative of Middle to Late Devonian aquatic vertebrate assemblages in terms of taxonomic richness (ca. 20 species), phylogenetic diversity (all major groups of lower vertebrates) and palaeoenvironment (palaeoestuaries). Fossil food web structures were assessed using different kinds of direct (i.e. digestive contents and bite marks in fossils) and indirect (e.g. ecomoiphological measurements, stratigraphic species co-occurrences) indicators. First, the relationships between predator and prey body size established for the Escuminac fishes are comparable to those of recent aquatic ecosystems, highlighting a consistency of aquatic food web structure across geological time. Second, non-metric dimensional scaling on ecomorphological variables and cluster analysis showed a common pattern of functional groups for both fish assemblages; top predators, predators, primary and secondary consumers were identified. We conclude that Devonian communities were organized in multiple trophic levels and that size-based feeding interactions were established early in vertebrate history.


Part One of this article provides a phenomenological and hedonic critique of the conception of the human – and thus the female – that underlies liberal legal feminism. Part Two presents a phenomenological critique of the conception of the human – and thus the female – which underlies radical feminist legal criticism. Again, I will argue that in both cases the theory does not pay enough attention to feminism: liberal feminist legal theory owes more to liberalism than to feminism and radical feminist legal theory owes more to radicalism than it does to feminism. Both models accept a depiction of human nature which is simply untrue of women. Thus, both accept, uncritically, a claimed correlation between objective condition and subjective reality, which, I will argue, is untrue to women. As a result, both groups fail to address the distinctive quality of women's subjective, hedonic lives, and the theories they have generated therefore have the potential to backfire – badly – against women's true interests. In the concluding section I will suggest an alternative normative model for feminist legal criticism which aims neither for choice nor equality, but directly for women's happiness, and a feminist legal theory which has as its critical focus the felt experience of women's subjective, hedonic lives. My substantive claim is that women's happiness or pleasure – as opposed to women's freedom or equality – should be the ideal toward which feminist legal criticism and reform should be pressed, and that women's misery, suffering and pain – as opposed to women's oppression or subordination – is the evil we should resist. I will argue that feminist legal theorists, in short, have paid too much attention to the ideals of equality and autonomy and not enough attention to the hedonistic ideals of happiness and pleasure, and that correlatively we have paid too much attention to the evils of subordination and oppression, and not enough attention to the hedonistic evils of suffering and pain. My methodological assumption is that the key to moral decision-making lies in our capacity to empathize with the pain of others, and thereby resist the source of it, and not in our capacity for abstraction, generalization, or reason. My strategic claim is directly entailed: the major obstacle to achieving the empathic understanding which is the key to significant moral commitment, including the commitment of the legal system to address the causes of women's suffering, is the striking difference between women's and men's internal lives, and more specifically, the different quality of our joys and sorrows. This obstacle can only be overcome through rich description of our internal hedonic lives.


ObjectiveIncreased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake. MethodsData were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from 45 movement disorders centers across the United States and Canada. A total of 1741 subjects with PD participated in the primary clinical study, and caffeine intake data were available for 1549 of these subjects. The association of caffeine intake with rate of progression of PD as measured by the change in the total Unified Parkinson Disease Rating Scale score and the interaction of this association with creatine intake were assessed. ResultsCaffeine intake was not associated with the rate of progression of PD in the main analysis, but higher caffeine intake was associated with significantly faster progression among subjects taking creatine. ConclusionsThis is the largest and longest study conducted to date that addresses the association of caffeine with the rate of progression of PD. These data indicate a potentially deleterious interaction between caffeine and creatine with respect to the rate of progression of PD.


The study of quantum chromodynamics (QCD) at finite temperature and density provides important contributions to the understanding of strong-interaction matter as it is present e.g. in nuclear matter and in neutron stars or as produced in heavy-ion collision experiments. Lattice QCD is a non-perturbative approach, where equations of motion for quarks and gluons are discretized on a finite space-time lattice. The method successfully describes the behavior of QCD in the vacuum and at finite temperature, however it cannot be applied to finite baryon density due to the fermion sign problem. Various QCD-like theories, that offer to draw conclusions about QCD, allow simulations also at finite densities.

In this work we investigate two-color QCD as a popular example of a QCD-like theory free from the sign problem with methods from lattice gauge theory. For the generation of gauge configurations with two dynamical quark flavors in the staggered formalism with the "rooting trick" we apply the Rational Hybrid Monte Carlo (RHMC) algorithm. We carry out essential preparatory work for future simulations at finite density.

As a start, we concentrate on the calculation of the effective potential for the Polyakov loop, which is an order parameter for the confinement-deconfinement transition, in dependence of the temperature and quark mass. It serves as an important input for effective models of QCD. We obtain the effective potential via the histogram method from local distributions of the Polyakov loop. To study the influence of dynamical quarks on gluonic observables, the simulations are performed with large quark masses and are compared to calculations in the pure gauge theory.

In the second part of the thesis we examine aspects of the chiral phase transition along the temperature axis. The symmetry group of chiral symmetry in two-color QCD is enlarged to SU(2 Nf). Discretized two-color QCD in the staggered formalism exhibits a chiral symmetry breaking pattern of U(2 Nf)->O(2 Nf), contrary to the continuum theory. We determine pseudo-critical couplings where Ferrenberg-Swendsen reweighting is applied for an improved extraction of the peak of the chiral susceptibility. In order to assess the universality class critical exponents are studied via the scaling behavior of the chiral condensate and the corresponding susceptibility. Simulations are performed at various small quark masses to obtain results in the chiral limit. By introducing an improved discretization of the gauge action we mitigate effects of an unphysical "bulk" phase, which appears as a discretization artifact at small values of the lattice coupling. Furthermore, an important step is the detailed investigation of finite volume effects, which become relevant at very small quark masses.

When temperature is varied using the coupling constant, also the underlying length and energy scale is modified. It is desirable to simulate along "lines of constant physics" (LCP) in parameter space. We thus have begun to calculate meson masses to determine LCP via the pion to rho meson mass ratio. Influence of the bulk phase at low lattice couplings and finite-volume effects at larger couplings however hamper their calculation.


Fibroblast growth factor (Fgf) signalling plays a crucial role in many developmental processes. Among the Fgf pathway ligands, Fgf9 (UniProt: P54130) has been demonstrated to participate in maturation of various organs and tissues including skeleton, testes, lung, heart, and eye. Here we establish a novel Fgf9 allele, discovered in a dominant N-ethyl-N-nitrosourea (ENU) screen for eye-size abnormalities using the optical low coherence interferometry technique. The underlying mouse mutant line Aca12 was originally identified because of its significantly reduced lens thickness. Linkage studies located Aca12 to chromosome 14 within a 3.6 Mb spanning interval containing the positional candidate genes Fgf9 (MGI: 104723), Gja3 (MGI: 95714), and Ift88 (MGI: 98715). While no sequence differences were found in Gja3 and Ift88, we identified an A→G missense mutation at cDNA position 770 of the Fgf9 gene leading to an Y162C amino acid exchange. In contrast to previously described Fgf9 mutants, Fgf9Y162C carriers were fully viable and did not reveal reduced body-size, male-to-female sexual reversal or skeletal malformations. The histological analysis of the retina as well as its basic functional characterization by electroretinography (ERG) did not show any abnormality. However, the analysis of head-tracking response of the Fgf9Y162C mutants in a virtual drum indicated a gene-dosage dependent vision loss of almost 50%. The smaller lenses in Fgf9Y162C suggested a role of Fgf9 during lens development. Histological investigations showed that lens growth retardation starts during embryogenesis and continues after birth. Young Fgf9Y162C lenses remained transparent but developed age-related cataracts. Taken together, Fgf9Y162C is a novel neomorphic allele that initiates microphakia and reduced vision without effects on organs and tissues outside the eye. Our data point to a role of Fgf9 signalling in primary and secondary lens fiber cell growth. The results underline the importance of allelic series to fully understand multiple functions of a gene.