Presenting Distributive Laws

Distributive laws of a monad T over a functor F are categorical tools for specifying algebra-coalgebra interaction. They proved to be important for solving systems of corecursive equations, for the specification of well-behaved structural operational semantics and, more recently, also for enhancements of the bisimulation proof method. If T is a free monad, then such distributive laws correspond to simple natural transformations. However, when T is not free it can be rather difficult to prove the defining axioms of a distributive law. In this paper we describe how to obtain a distributive law for a monad with an equational presentation from a distributive law for the underlying free monad. We apply this result to show the equivalence between two different representations of context-free languages

Sclerostin does not play a major role in the pathogenesis of skeletal complications in type 2 diabetes mellitus

In contrast to previously reported elevations in serum sclerostin levels in diabetic patients, the present study shows that the impaired bone microarchitecture and cellular turnover associated with type 2 diabetes mellitus (T2DM)-like conditions in ZDF rats are not correlated with changes in serum and bone sclerostin expression. INTRODUCTION: T2DM is associated with impaired skeletal structure and a higher prevalence of bone fractures. Sclerostin, a negative regulator of bone formation, is elevated in serum of diabetic patients. We aimed to relate changes in bone architecture and cellular activities to sclerostin production in the Zucker diabetic fatty (ZDF) rat. METHODS: Bone density and architecture were measured by micro-CT and bone remodelling by histomorphometry in tibiae and femurs of 14-week-old male ZDF rats and lean Zucker controls (n = 6/group). RESULTS: ZDF rats showed lower trabecular bone mineral density and bone mass compared to controls, due to decreases in bone volume and thickness, along with impaired bone connectivity and cortical bone geometry. Bone remodelling was impaired in diabetic rats, demonstrated by decreased bone formation rate and increased percentage of tartrate-resistant acid phosphatase-positive osteoclastic surfaces. Serum sclerostin levels (ELISA) were higher in ZDF compared to lean rats at 9 weeks (+40 %, p < 0.01), but this difference disappeared as their glucose control deteriorated and by week 14, ZDF rats had lower sclerostin levels than control rats (-44 %, p < 0.0001). Bone sclerostin mRNA (qPCR) and protein (immunohistochemistry) were similar in ZDF, and lean rats at 14 weeks and genotype did not affect the number of empty osteocytic lacunae in cortical and trabecular bone. CONCLUSION: T2DM results in impaired skeletal architecture through altered remodelling pathways, but despite altered serum levels, it does not appear that sclerostin contributes to the deleterious effect of T2DM in rat bone

Parallel plate model for trabecular bone exhibits volume fraction-dependent bias

Unbiased stereological methods were used in conjunction with microcomputed tomographic (micro-CT) scans of human and animal bone to investigate errors created when the parallel plate model was used to calculate morphometric parameters. Bone samples were obtained from the human proximal tibia, canine distal femur, rat tail, and pig spine and scanned in a micro-CT scanner. Trabecular thickness, trabecular spacing, and trabecular number were calculated using the parallel plate model. Direct thickness, and spacing and connectivity density were calculated using unbiased three-dimensional methods. Both thickness and spacing calculated using the plate model were well correlated to the direct three-dimensional measures (r(2) = 0. 77-0.92). The correlation between trabecular number and connectivity density varied greatly (r(2) = 0.41-0.94). Whereas trabecular thickness was consistently underestimated using the plate model, trabecular spacing was underestimated at low volume fractions and overestimated at high volume fractions. Use of the plate model resulted in a volume-dependent bias in measures of thickness and spacing (p < 0.001). This was a result of the fact that samples of low volume fraction were much more "rod-like" than those of the higher volume fraction. Our findings indicate that the plate model provides biased results, especially when populations with different volume fractions are compared. Therefore, we recommend direct thickness measures when three-dimensional data sets are available

Structural changes during water-mediated amorphization of semiconducting two-dimensional thiostannates

Owing to their combined open-framework structures and semiconducting properties, two-dimensional thio­stannates show great potential for catalytic and sensing applications. One such class of crystalline materials consists of porous polymeric [Sn$_3$S$_7$$^{2−}$]n sheets with molecular cations embedded in-between. The compounds are denoted R-SnS-1, where R is the cation. Dependent on the cation, some R-SnS-1 thio­stannates transition into amorphous phases upon dispersion in water. Knowledge about the fundamental chemical properties of the thio­stannates, including their water stability and the nature of the amorphous products, has not yet been established. This paper presents a time-resolved study of the transition from the crystalline to the amorphous phase of two violet-light absorbing thio­stannates, i.e. AEPz-SnS-1 [AEPz = 1-(2-amino­ethyl)­piperazine] and trenH-SnS-1 [tren = tris­(2-amino­ethyl)­amine]. X-ray total scattering data and pair distribution function analysis reveal no change in the local intralayer coordination during the amorphization. However, a rapid decrease in the crystalline domain sizes upon suspension in water is demonstrated. Although scanning electron microscopy shows no significant decrease of the micrometre-sized particles, transmission electron microscopy reveals the formation of small particles (∼200–400 nm) in addition to the larger particles. The amorphization is associated with disorder of the thio­stannate nanosheet stacking. For example, an average decrease in the interlayer distance (from 19.0 to 15.6 Å) is connected to the substantial loss of the organic components as shown by elemental analysis and X-ray photoelectron spectroscopy. Despite the structural changes, the light absorption properties of the amorphisized R-SnS-1 compounds remain intact, which is encouraging for future water-based applications of such materials

Produktorienteret miljøindsats i landbrugssektoren - forudsætninger

For at styrke den produktorienterede miljøindsats i landbruget nedsatte Miljøstyrelsen primo 2003 et produktkædepanel for landbrugsområdet. Panelets primære mål er at fremme udvikling og afsætning af landbrugsprodukter, der set i et livscyklusperspektiv ("fra jord til jord") er mindre miljøbelastende end tilsvarende traditionelle produkter. Som fundament for panelets arbejde er udarbejdet denne rapport, som beskriver de eksisterende forudsætninger for en produktorienteret indsats i sektoren - i form af en kortlægning af relevante projekter/tiltag. Denne rapport har dannet udgangspunkt for udarbejdelsen af et såkaldt fremsyn på området, som er publiceret særskilt. Fremsynet og information om panelets arbejde i øvrigt kan fås på www.produktpanel-landbrug.dk. En produktorienteret indsats vil altid være et supplement til de eksisterende overordnede reguleringer af samfundets adfærd, forbrug og udledninger. Vi vil stadig i fremtiden opleve berettiget miljøarbejde, der tager udgangspunkt i en konkret produktion eller proces eller i ønsket om at reducere en arealbelastning. Med produktorientering følger en anderledes og mere nuanceret opfattelse af, hvad der er "godt og dårligt" for miljøet, hvilke områder, der skal prioriteres i fødevaresektorens miljøindsats, og hvad miljøarbejdet kan omfatte i alle led i fødevarernes produktkæde. Et produktorienteret miljøarbejde stiller krav til og udfordrer alle aktører i produktkæderne. Der skal ikke alene udveksles og håndteres oplysninger om produktets miljøpåvirkning bagud og fremad i produktkæden, men der skal også ageres på baggrund af de erkendelser, denne udveksling af oplysninger giver anledning til. Helhedsorienteringen skaber også muligheder for at synliggøre og dokumentere valg undervejs i produktkæden. Produktorientering giver dermed en enestående mulighed for aktører/virksomheder for at dokumentere adfærd og valg overfor aftagere (herunder forbrugeren). Også for landbrugs- og gartnerierhvervet er produktorienteringen en udfordring. En kvalificeret diskussion af muligheder og perspektiver i produktorienteringen i landbrugserhvervet er derfor langt fra kun et spørgsmål om værktøjer, opgørelsesmetoder og mulighederne for afsætning af miljødokumenterede varer. Produktorienteringen er i langt højere grad den ramme, hvori f.eks. nedenstående spørgsmål kan diskuteres: Hvilke langsigtede scenarier for landbrugserhvervet er tænkelige? Hvilke strategier kan anlægges for erhvervsudvikling, forskning, kompetenceudvikling etc. for bedst muligt at sigte på de mest attraktive scenarier? Hvordan bringes aktørerne i spil, og hvordan skal ansvar fordeles? De hidtidige erfaringer med produktorientering viser, at en væsentlig forudsætning for succes er åbenhed og kommunikation i produktkæderne

Identification of CD8+ T Cell Epitopes in the West Nile Virus Polyprotein by Reverse-Immunology Using NetCTL

West Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies.In a reverse-immunology approach, we used bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients. We identified 26 new CD8(+) T cell epitopes, which we propose are restricted by 11 different HLA class I alleles. Aiming for optimal coverage of human populations, we suggest that 11 of these new WNV epitopes would be sufficient to cover from 48% to 93% of ethnic populations in various areas of the World.The 26 identified CD8(+) T cell epitopes contribute to our knowledge of the immune response against WNV infection and greatly extend the list of known WNV CD8(+) T cell epitopes. A polytope incorporating these and other epitopes could possibly serve as the basis for a WNV vaccine

Current concepts in osteogenesis imperfecta:bone structure, biomechanics and medical management

The majority of patients with osteogenesis imperfecta (OI) have mutations in the COL1A1 or COL1A2 gene, which has consequences for the composition of the bone matrix and bone architecture. The mutations result in overmodified collagen molecules, thinner collagen fibres and hypermineralization of bone tissue at a bone matrix level. Trabecular bone in OI is characterized by a lower trabecular number and connectivity as well as a lower trabecular thickness and volumetric bone mass. Cortical bone shows a decreased cortical thickness with less mechanical anisotropy and an increased pore percentage as a result of increased osteocyte lacunae and vascular porosity. Most OI patients have mutations at different locations in the COL1 gene. Disease severity in OI is probably partly determined by the nature of the primary collagen defect and its location with respect to the C-terminus of the collagen protein. The overall bone biomechanics result in a relatively weak and brittle structure. Since this is a result of all of the above-mentioned factors as well as their interactions, there is - considerable variation between patients, and accurate prediction on bone strength in the individual patient with OI is difficult. Current treatment of OI focuses on adequate vitamin-D levels and interventions in the bone turnover cycle with bisphosphonates. Bisphosphonates increase bone mineral density, but the evidence on improvement of clinical status remains limited. Effects of newer drugs such as antibodies against RANKL and sclerostin are currently under investigation. This paper was written under the guidance of the Study Group Genetics and Metabolic Diseases of the European Paediatric Orthopaedic Society