On the axiomatic approach to the maximum entropy principle of inference

Recent axiomatic derivations of the maximum entropy principle from consistency conditions are critically examined. We show that proper application of consistency conditions alone allows a wider class of functionals, essentially of the form ∝ dx p(x)[p(x)/g(x)] s , for some real numbers, to be used for inductive inference and the commonly used form − ∝ dx p(x)ln[p(x)/g(x)] is only a particular case. The role of the prior densityg(x) is clarified. It is possible to regard it as a geometric factor, describing the coordinate system used and it does not represent information of the same kind as obtained by measurements on the system in the form of expectation values.

Novel conditional mouse models for targeted kidney research : Emphasis on the analysis of the biological function of nephrin

Nephrin is a transmembrane protein belonging to the immunoglobulin superfamily and is expressed primarily in the podocytes, which are highly differentiated epithelial cells needed for primary urine formation in the kidney. Mutations leading to nephrin loss abrogate podocyte morphology, and result in massive protein loss into urine and consequent early death in humans carrying specific mutations in this gene. The disease phenotype is closely replicated in respective mouse models. The purpose of this thesis was to generate novel inducible mouse-lines, which allow targeted gene deletion in a time and tissue-specific manner. A proof of principle model for succesful gene therapy for this disease was generated, which allowed podocyte specific transgene replacement to rescue gene deficient mice from perinatal lethality. Furthermore, the phenotypic consequences of nephrin restoration in the kidney and nephrin deficiency in the testis, brain and pancreas in rescued mice were investigated. A novel podocyte-specific construct was achieved by using standard cloning techniques to provide an inducible tool for in vitro and in vivo gene targeting. Using modified constructs and microinjection procedures two novel transgenic mouse-lines were generated. First, a mouse-line with doxycycline inducible expression of Cre recombinase that allows podocyte-specific gene deletion was generated. Second, a mouse-line with doxycycline inducible expression of rat nephrin, which allows podocyte-specific nephrin over-expression was made. Furthermore, it was possible to rescue nephrin deficient mice from perinatal lethality by cross-breeding them with a mouse-line with inducible rat nephrin expression that restored the missing endogenous nephrin only in the kidney after doxycycline treatment. The rescued mice were smaller, infertile, showed genital malformations and developed distinct histological abnormalities in the kidney with an altered molecular composition of the podocytes. Histological changes were also found in the testis, cerebellum and pancreas. The expression of another molecule with limited tissue expression, densin, was localized to the plasma membranes of Sertoli cells in the testis by immunofluorescence staining. Densin may be an essential adherens junction protein between Sertoli cells and developing germ cells and these junctions share similar protein assembly with kidney podocytes. This single, binary conditional construct serves as a cost- and time-efficient tool to increase the understanding of podocyte-specific key proteins in health and disease. The results verified a tightly controlled inducible podocyte-specific transgene expression in vitro and in vivo as expected. These novel mouse-lines with doxycycline inducible Cre recombinase and with rat nephrin expression will be useful for conditional gene targeting of essential podocyte proteins and to study in detail their functions in the adult mice. This is important for future diagnostic and pharmacologic development platforms.

Sensory Systems in Sawfishes. 2. The Lateral Line.

The lateral line system allows elasmobranchs to detect hydrodynamic movements in their close surroundings. We examined the distribution of pit organs and lateral line canals in 4 species of sawfish (Anoxypristis cuspidata, Pristis microdon, P. clavata and P. zijsron). Pit organs could only be located in A. cuspidata, which possesses elongated pits that are lined by dermal denticles. In all 4 pristid species, the lateral line canals are well developed and were separated into regions of pored and non-pored canals. In all species the tubules that extend from pored canals form extensive networks. In A. cuspidata, P. microdon and P. clavata, the lateral line canals on both the dorsal and ventral surfaces of the rostrum possess extensively branched and pored tubules. Based on this morphological observation, we hypothesized that these 3 species do not use their rostrum to search in the substrate for prey as previously assumed. Other batoids that possess lateral line canals adapted to perceive stimuli produced by infaunal prey possess non-pored lateral line canals, which also prevent the intrusion of substrate particles. However, this hypothesis remains to be tested behaviourally in pristids. Lateral line canals located between the mouth and the nostrils are non-pored in all 4 species of sawfish. Thus this region is hypothesized to perceive stimuli caused by direct contact with prey before ingestion. Lateral line canals that contain neuromasts are longest in P. microdon, but canals containing neuromasts along the rostrum are longest in A. cuspidata.

A study on the nature of the compound layer formed during the ion nitriding of En40B steel

Commercial-grade En40B steel has been ion nitrided in the temperature range 475–550°C in a 25%N2–75%H2 gas mixture. The nature of the compound layer formed was studied by the X-ray diffraction technique and optical metallography. It was observed that the structure of the compound layer gradually transforms from a predominantly epsilon (Porson) nitride to a predominantly γ′ nitride structure with increasing treatment time. Optical metallography studies on sections orthogonal to the nitrided surface showed that, after about 5 h of treatment, the thickness of the compound layer decreases with further increase in treatment time.

On the Transform Method of Solution of an External Crack Problem

The breakdown of the usual method of Fourier transforms in the problem of an external line crack in a thin infinite elastic plate is discovered and the correct solution of this problem is derived using the concept of a generalised Fourier transform of a type discussed first by Golecki [1] in connection with Flamant's problem.

Dasatinib, nilotinib and standard-dose imatinib for the first line treatment of chronic myeloid leukaemia: Systematic reviews and economic analyses

- Background Nilotinib and dasatinib are now being considered as alternative treatments to imatinib as a first-line treatment of chronic myeloid leukaemia (CML). - Objective This technology assessment reviews the available evidence for the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of Philadelphia chromosome-positive CML. - Data sources Databases [including MEDLINE (Ovid), EMBASE, Current Controlled Trials, ClinicalTrials.gov, the US Food and Drug Administration website and the European Medicines Agency website] were searched from search end date of the last technology appraisal report on this topic in October 2002 to September 2011. - Review methods A systematic review of clinical effectiveness and cost-effectiveness studies; a review of surrogate relationships with survival; a review and critique of manufacturer submissions; and a model-based economic analysis. - Results Two clinical trials (dasatinib vs imatinib and nilotinib vs imatinib) were included in the effectiveness review. Survival was not significantly different for dasatinib or nilotinib compared with imatinib with the 24-month follow-up data available. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were higher for patients receiving dasatinib than for those with imatinib for 12 months' follow-up (CCyR 83% vs 72%, p < 0.001; MMR 46% vs 28%, p < 0.0001). The rates of CCyR and MMR were higher for patients receiving nilotinib than for those receiving imatinib for 12 months' follow-up (CCyR 80% vs 65%, p < 0.001; MMR 44% vs 22%, p < 0.0001). An indirect comparison analysis showed no difference between dasatinib and nilotinib for CCyR or MMR rates for 12 months' follow-up (CCyR, odds ratio 1.09, 95% CI 0.61 to 1.92; MMR, odds ratio 1.28, 95% CI 0.77 to 2.16). There is observational association evidence from imatinib studies supporting the use of CCyR and MMR at 12 months as surrogates for overall all-cause survival and progression-free survival in patients with CML in chronic phase. In the cost-effectiveness modelling scenario, analyses were provided to reflect the extensive structural uncertainty and different approaches to estimating OS. First-line dasatinib is predicted to provide very poor value for money compared with first-line imatinib, with deterministic incremental cost-effectiveness ratios (ICERs) of between £256,000 and £450,000 per quality-adjusted life-year (QALY). Conversely, first-line nilotinib provided favourable ICERs at the willingness-to-pay threshold of £20,000-30,000 per QALY. - Limitations Immaturity of empirical trial data relative to life expectancy, forcing either reliance on surrogate relationships or cumulative survival/treatment duration assumptions. - Conclusions From the two trials available, dasatinib and nilotinib have a statistically significant advantage compared with imatinib as measured by MMR or CCyR. Taking into account the treatment pathways for patients with CML, i.e. assuming the use of second-line nilotinib, first-line nilotinib appears to be more cost-effective than first-line imatinib. Dasatinib was not cost-effective if decision thresholds of £20,000 per QALY or £30,000 per QALY were used, compared with imatinib and nilotinib. Uncertainty in the cost-effectiveness analysis would be substantially reduced with better and more UK-specific data on the incidence and cost of stem cell transplantation in patients with chronic CML. - Funding The Health Technology Assessment Programme of the National Institute for Health Research.

Critical review on the stability of illicit drugs in sewers and wastewater samples

Wastewater-based epidemiology (WBE) applies advanced analytical methods to quantify drug residues in wastewater with the aim to estimate illicit drug use at the population level. Transformation processes during transport in sewers (chemical and biological reactors) and storage of wastewater samples before analysis are expected to change concentrations of different drugs to varying degrees. Ignoring transformation for drugs with low to medium stability will lead to an unknown degree of systematic under- or overestimation of drug use, which should be avoided. This review aims to summarize the current knowledge related to the stability of commonly investigated drugs and, furthermore, suggest a more effective approach to future experiments. From over 100 WBE studies, around 50 mentioned the importance of stability and 24 included tests in wastewater. Most focused on in-sample stability (i.e., sample preparation, preservation and storage) and some extrapolated to in-sewer stability (i.e., during transport in real sewers). While consistent results were reported for rather stable compounds (e.g., MDMA and methamphetamine), a varying range of stability under different or similar conditions was observed for other compounds (e.g., cocaine, amphetamine and morphine). Wastewater composition can vary considerably over time, and different conditions prevail in different sewer systems. In summary, this indicates that more systematic studies are needed to: i) cover the range of possible conditions in sewers and ii) compare results more objectively. To facilitate the latter, we propose a set of parameters that should be reported for in-sewer stability experiments. Finally, a best practice of sample collection, preservation, and preparation before analysis is suggested in order to minimize transformation during these steps.

On the Geometry of Infinite-Dimensional Grassmannian Manifolds and Gauge Theory

This PhD Thesis is about certain infinite-dimensional Grassmannian manifolds that arise naturally in geometry, representation theory and mathematical physics. From the physics point of view one encounters these infinite-dimensional manifolds when trying to understand the second quantization of fermions. The many particle Hilbert space of the second quantized fermions is called the fermionic Fock space. A typical element of the fermionic Fock space can be thought to be a linear combination of the configurations m particles and n anti-particles . Geometrically the fermionic Fock space can be constructed as holomorphic sections of a certain (dual)determinant line bundle lying over the so called restricted Grassmannian manifold, which is a typical example of an infinite-dimensional Grassmannian manifold one encounters in QFT. The construction should be compared with its well-known finite-dimensional analogue, where one realizes an exterior power of a finite-dimensional vector space as the space of holomorphic sections of a determinant line bundle lying over a finite-dimensional Grassmannian manifold. The connection with infinite-dimensional representation theory stems from the fact that the restricted Grassmannian manifold is an infinite-dimensional homogeneous (Kähler) manifold, i.e. it is of the form G/H where G is a certain infinite-dimensional Lie group and H its subgroup. A central extension of G acts on the total space of the dual determinant line bundle and also on the space its holomorphic sections; thus G admits a (projective) representation on the fermionic Fock space. This construction also induces the so called basic representation for loop groups (of compact groups), which in turn are vitally important in string theory / conformal field theory. The Thesis consists of three chapters: the first chapter is an introduction to the backround material and the other two chapters are individually written research articles. The first article deals in a new way with the well-known question in Yang-Mills theory, when can one lift the action of the gauge transformation group on the space of connection one forms to the total space of the Fock bundle in a compatible way with the second quantized Dirac operator. In general there is an obstruction to this (called the Mickelsson-Faddeev anomaly) and various geometric interpretations for this anomaly, using such things as group extensions and bundle gerbes, have been given earlier. In this work we give a new geometric interpretation for the Faddeev-Mickelsson anomaly in terms of differentiable gerbes (certain sheaves of categories) and central extensions of Lie groupoids. The second research article deals with the question how to define a Dirac-like operator on the restricted Grassmannian manifold, which is an infinite-dimensional space and hence not in the landscape of standard Dirac operator theory. The construction relies heavily on infinite-dimensional representation theory and one of the most technically demanding challenges is to be able to introduce proper normal orderings for certain infinite sums of operators in such a way that all divergences will disappear and the infinite sum will make sense as a well-defined operator acting on a suitable Hilbert space of spinors. This research article was motivated by a more extensive ongoing project to construct twisted K-theory classes in Yang-Mills theory via a Dirac-like operator on the restricted Grassmannian manifold.

Now the real international fight begins for the Trans-Pacific Partnership

In Atlanta, the trade ministers of a dozen countries across the Pacific Rim announced that they had successfully reached a concluded agreement upon the Trans-Pacific Partnership. The debate over the TPP will now play out in legislatures across the Pacific Rim, where sentiment towards the deal is much more mixed. The ministers insisted: “After more than five years of intensive negotiations, we have come to an agreement that will support jobs, drive sustainable growth, foster inclusive development, and promote innovation across the Asia-Pacific region … The agreement achieves the goal we set forth of an ambitious, comprehensive, high standard and balanced agreement that will benefit our nation’s citizens … We expect this historic agreement to promote economic growth, support higher-paying jobs; enhance innovation, productivity and competitiveness; raise living standards; reduce poverty in our countries; and to promote transparency, good governance, and strong labor and environmental protections.” But there has been fierce criticism of the Trans-Pacific Partnership, because of both its secrecy and its substance. Nobel Laureate Professor Joseph Stiglitz has warned that the agreement is not about free trade, but about the protection of corporate monopolies. The intellectual property chapter provides for longer and stronger protection of intellectual property rights. The investment chapter provides foreign investors with the power to challenge governments under an investor-state dispute settlement (ISDS) regime. The environment chapter is weak and toothless, and seems to be little more than an exercise in greenwashing. The health annex — and many other parts of the agreement — strengthen the power of pharmaceutical companies and biotechnology developers. The text on state-owned enterprises raises concerns about public ownership of postal services, broadcasters and national broadband services.

On the orthogonality of suboptimum estimate in the combined estimation and control problem

By deriving the equations for an error analysis of modeling inaccuracies for the combined estimation and control problem, it is shown that the optimum estimation error is orthogonal to the actual suboptimum estimate.

On the orthogonality of suboptimum estimate in the combined estimation and control problem

By deriving the equations for an error analysis of modeling inaccuracies for the combined estimation and control problem, it is shown that the optimum estimation error is orthogonal to the actual suboptimum estimate.

On the definition of a small orifice

An attempt is made to draw a line of demarcation between small orifices and large orifices. It is proposed that an orifice can be considered 'small' if the discharge through it calculated on the small-orifice assumption differs from the exact discharge by less than half of one per cent. Using this criterion, it is shown that a circular or elliptic orifice can be deemed 'small' as long as the ratio of the depth of the orifice to the head causing the flow (measured from the center of the orifice to the liquid surface) is less than 0.8; a rectangular orifice can be deemed 'small' if the ratio is less than 0.7. A correction factor is suggested for the coefficient of discharge to account for the deviation from the exact discharge.

On the orthogonality of suboptimum estimate in the combined estimation and control problem

By deriving the equations for an error analysis of modeling inaccuracies for the combined estimation and control problem, it is shown that the optimum estimation error is orthogonal to the actual suboptimum estimate.

Studies on the Effects of Property Taxation, Rent Control and Housing Allowances

Tämä väitöskirja koostuu asuntomarkkinoiden taloustieteellistä analyysia esittelevästä johdantoluvusta ja kolmesta tutkimuksesta, joissa analysoidaan asuntomarkkinoihin vaikuttavia politiikkatoimenpiteitä. Luvussa 2 tutkitaan Suomen kiinteistöverojärjestelmän vaikutusta asuntorakentamiseen. Vuonna 2001 tehtiin uudistus, jonka myötä kunnat voivat verottaa rakentamatonta asuintonttia korkeammalla veroasteella kuin rakennettua tonttia. Maanomistajan rakentamispäätöksen teoreettisen mallin mukaan rakentamattoman tontin korotettu kiinteistöveron pitäisi nopeuttaa rakentamista, mutta toisaalta myös rakentamiseen investoitu rahamäärä saattaa muuttua. Asuintonttien kiinteistöverojen yleinen taso ei vaikuta maanomistajan käyttäytymiseen, sillä tontin verotusarvo ei riipu rakentamispäätöksestä. Vain rakentamattoman ja rakennetun tontin veroasteiden erolla on merkitystä. Empiiriset tulokset ovat sopusoinnussa teorian kanssa. Tulosten mukaan prosenttiyksikön nousu rakentamattoman ja rakennetun tontin veroasteiden erossa lisää omakotialoitusten määrää viidellä prosentilla lyhyellä aikavälillä. Luvussa 3 analysoidaan vuokrasääntelystä vuokralaisille aiheutuvia hyötyjä ja haittoja. Vuokrasäännellyissä asunnoissa asuvat kotitaloudet hyötyvät vuokrasääntelystä alhaisen vuokran muodossa. Heille saattaa kuitenkin koitua myös haittaa siitä, että toiveita vastaavan asunnon löytäminen on vuokrasääntelytilanteessa vaikeaa, koska vapaille asunnoille on suuri määrä ottajia. Vapaarahoitteisen vuokra-asuntokannan vuokrien sääntely purettiin Suomessa asteittain vuosina 1992–1995. Tutkimuksen empiiriset tulokset viittaavat siihen, että vuokrasääntelyn aiheuttamista suurista eroista halutun ja todellisen asuntokulutuksen välillä koituvat hyvinvointitappiot kumosivat merkittävän osan matalien vuokrien hyödyistä vuokralaisille. Luvussa 4 tutkitaan Suomen asumistukijärjestelmän kannustinvaikutuksia. Asumistuen määrää rajoittavat asunnon pinta-alalle ja neliövuokralle asetetut ylärajat. Neliövuokrarajoite voidaan tulkita asumisen laatua rajoittavana tekijänä. Tutkimuksen teoreettisessa osassa osoitetaan, että asumistukijärjestelmä luo vahvat kannustimet muuttaa asuntoihin, joissa pinta-ala- ja laaturajoitteet purevat. Empiiristen tulosten mukaan asumistukeen oikeutetut kotitaloudet eivät näytä reagoivan kannusteisiin. Tukeen oikeutettujen kotitalouksien asumisvalinnat suhteessa pinta-ala ja laaturajoitteisiin vastaavat muiden kotitalouksien valintoja ja asunnonvaihdon mahdollistama potentiaalinen asumistuen lisäys ei nosta muuttotodennäköisyyttä. Muuttamiseen liittyvät kustannukset ja vajavaiset tiedot tukijärjestelmästä saattavat selittää heikkoa reagointia asumistuen luomiin kannustimiin. Toinen mahdollinen selitys on asumistuen vajaakäyttö. Tutkimuksen mukaan vain 70–80 prosenttia asumistukeen oikeutetuista kotitalouksista nostaa tukea. Asumistuen hyödyntämisen todennäköisyys riippuu koulutustasosta, tuen määrästä ja tulo-odotuksista.