Gain-of-function haplotype in the epithelial calcium channel TRPV6 is a risk factor for renal calcium stone formation

The rate-limiting step of dietary calcium absorption in the intestine requires the brush border calcium entry channel TRPV6. The TRPV6 gene was completely sequenced in 170 renal calcium stone patients. The frequency of an ancestral TRPV6 haplotype consisting of three non-synonymous polymorphisms (C157R, M378V, M681T) was significantly higher (P = 0.039) in calcium stone formers (8.4%; derived = 502, ancestral = 46) compared to non-stone-forming individuals (5.4%; derived = 645, ancestral = 37). Mineral metabolism was investigated on four different calcium regimens: (i) free-choice diet, (ii) low calcium diet, (iii) fasting and (iv) after a 1 g oral calcium load. When patients homozygous for the derived haplotype were compared with heterozygous patients, no differences were found with respect to the plasma concentrations of 1,25-vitamin D, PTH and calcium, and the urinary excretion of calcium. In one stone-forming patient, the ancestral haplotype was found to be homozygous. This patient had absorptive hypercalciuria. We therefore expressed the ancestral protein (157R+378V+681T) in Xenopus oocytes and found a significantly enhanced calcium permeability when tested by a (45)Ca(2+) uptake assay (7.11 +/- 1.93 versus 3.61 +/- 1.01 pmol/min/oocyte for ancestral versus derived haplotype, P < 0.01). These results suggest that the ancestral gain-of-function haplotype in TRPV6 plays a role in calcium stone formation in certain forms of absorptive hypercalciuria.

Three dimensional finite element simulation of polymer melting and flow in a single-screw extruder : optimization of screw channel geometry

Single-screw extrusion is one of the widely used processing methods in plastics industry, which was the third largest manufacturing industry in the United States in 2007 [5]. In order to optimize the single-screw extrusion process, tremendous efforts have been devoted for development of accurate models in the last fifty years, especially for polymer melting in screw extruders. This has led to a good qualitative understanding of the melting process; however, quantitative predictions of melting from various models often have a large error in comparison to the experimental data. Thus, even nowadays, process parameters and the geometry of the extruder channel for the single-screw extrusion are determined by trial and error. Since new polymers are developed frequently, finding the optimum parameters to extrude these polymers by trial and error is costly and time consuming. In order to reduce the time and experimental work required for optimizing the process parameters and the geometry of the extruder channel for a given polymer, the main goal of this research was to perform a coordinated experimental and numerical investigation of melting in screw extrusion. In this work, a full three-dimensional finite element simulation of the two-phase flow in the melting and metering zones of a single-screw extruder was performed by solving the conservation equations for mass, momentum, and energy. The only attempt for such a three-dimensional simulation of melting in screw extruder was more than twenty years back. However, that work had only a limited success because of the capability of computers and mathematical algorithms available at that time. The dramatic improvement of computational power and mathematical knowledge now make it possible to run full 3-D simulations of two-phase flow in single-screw extruders on a desktop PC. In order to verify the numerical predictions from the full 3-D simulations of two-phase flow in single-screw extruders, a detailed experimental study was performed. This experimental study included Maddock screw-freezing experiments, Screw Simulator experiments and material characterization experiments. Maddock screw-freezing experiments were performed in order to visualize the melting profile along the single-screw extruder channel with different screw geometry configurations. These melting profiles were compared with the simulation results. Screw Simulator experiments were performed to collect the shear stress and melting flux data for various polymers. Cone and plate viscometer experiments were performed to obtain the shear viscosity data which is needed in the simulations. An optimization code was developed to optimize two screw geometry parameters, namely, screw lead (pitch) and depth in the metering section of a single-screw extruder, such that the output rate of the extruder was maximized without exceeding the maximum temperature value specified at the exit of the extruder. This optimization code used a mesh partitioning technique in order to obtain the flow domain. The simulations in this flow domain was performed using the code developed to simulate the two-phase flow in single-screw extruders.

Future value based single assignment program representations and optimizations

An optimizing compiler internal representation fundamentally affects the clarity, efficiency and feasibility of optimization algorithms employed by the compiler. Static Single Assignment (SSA) as a state-of-the-art program representation has great advantages though still can be improved. This dissertation explores the domain of single assignment beyond SSA, and presents two novel program representations: Future Gated Single Assignment (FGSA) and Recursive Future Predicated Form (RFPF). Both FGSA and RFPF embed control flow and data flow information, enabling efficient traversal program information and thus leading to better and simpler optimizations. We introduce future value concept, the designing base of both FGSA and RFPF, which permits a consumer instruction to be encountered before the producer of its source operand(s) in a control flow setting. We show that FGSA is efficiently computable by using a series T1/T2/TR transformation, yielding an expected linear time algorithm for combining together the construction of the pruned single assignment form and live analysis for both reducible and irreducible graphs. As a result, the approach results in an average reduction of 7.7%, with a maximum of 67% in the number of gating functions compared to the pruned SSA form on the SPEC2000 benchmark suite. We present a solid and near optimal framework to perform inverse transformation from single assignment programs. We demonstrate the importance of unrestricted code motion and present RFPF. We develop algorithms which enable instruction movement in acyclic, as well as cyclic regions, and show the ease to perform optimizations such as Partial Redundancy Elimination on RFPF.

Length of the annular regime for condensing flows inside a horizontal channel - the experimental determination of its values and its trends

The experiments observe and measure the length of the annular regime in fully condensing quasi-steady (steady-in-the-mean) flows of pure FC-72 vapor in a horizontal condenser (rectangular cross-section of 2 mm height, 15 mm width, and 1 m length). The sides and top of the duct are made of clear plastic that allows flow visualization. The experimental system in which this condenser is used is able to control and achieve different quasi-steady mass flow rates, inlet pressures, and wall cooling conditions (by adjustment of the temperature and flow rate of the cooling water flowing underneath the condensing-plate). The reported correlations and measurements for the annular length are also vital information for determining the length of the annular regime and proposing extended correlation (covering many vapors and a larger parameter set than the experimentally reported version here) by ongoing independent modeling and computational simulation approach.

Interrelation of peri-operative morbidity and ASA class assignment in patients undergoing gynaecological surgery

OBJECTIVE: The aim of this study was to estimate intra- and post-operative risk using the American Society of Anaesthesiologists (ASA) classification which is an important predictor of an intervention and of the entire operating programme. STUDY DESIGN: In this retrospective study, 4435 consecutive patients undergoing elective and emergency surgery at the Gynaecological Clinic of the University Hospital of Zurich were included. The ASA classification for pre-operative risk assessment was determined by an anaesthesiologist after a thorough physical examination. We observed several pre-, intra- and post-operative parameters, such as age, body-mass-index, duration of anaesthesia, duration of surgery, blood loss, duration of post-operative stay, complicated post-operative course, morbidity and mortality. The investigation of different risk factors was achieved by a multiple linear regression model for log-transformed duration of hospitalisation. RESULTS: Age and obesity were responsible for a higher ASA classification. ASA grade correlates with the duration of anaesthesia and the duration of the surgery itself. There was a significant difference in blood loss between ASA grades I (113+/-195 ml) and III (222+/-470 ml) and between classes II (176+/-432 ml) and III. The duration of post-operative hospitalisation could also be correlated with ASA class. ASA class I=1.7+/-3.0 days, ASA class II=3.6+/-4.3 days, ASA class III=6.8+/-8.2 days, and ASA class IV=6.2+/-3.9 days. The mean post-operative in-hospital stay was 2.5+/-4.0 days without complications, and 8.7+/-6.7 days with post-operative complications. Multiple linear regression model showed that not only the ASA classification contained an important information for the duration of hospitalisation. Parameters such as age, class of diagnosis, post-operative complications, etc. also have an influence on the duration of hospitalisation. CONCLUSION: This study shows that the ASA classification can be used as a good and early available predictor for the planning of an intervention in gynaecological surgery. The ASA classification helps the surgeon to assess the peri-operative risk profile of which important information can be derived for the planning of the operation programme.

Synthesis, Optical Resolution, and Configurational Assignment of Novel Axially Chiral Quateraryls

A one-pot, general synthesis of highly functionalized quateraryls through carbanion-induced, base-catalyzed ring transformation of 5,6-diaryl-2H-pyran-2-ones and core-substituted phenylacetones is delineated. These conversions were found to give diversely functionalized benzenes bearing peripheral aryl rings, some of which possess inherent atropisomerism. Exemplarily for one of the quateraryls, the optical resolution of the respective atropo-enantiomers by HPLC on a chiral phase and the assignment of their absolute axial configurations succeeded by LC-CD coupling in combination with semiempirical CNDO/S and TDDFT CD calculations. This synthetic approach offers – in a transition metal-free environment – high flexibility in the construction of quateraryls with the desired conformational freedom along the molecular axis, which may help in exploring and developing new potential ligands for asymmetric synthesis.

Multi-Channel-Learning (MCL)

Lerneinheiten müssen stark variierenden Anforderungen gerecht werden. Neben unterschiedlichen Lerntypen spielen vor allem auch die Umfeldbedingungen eine wesentliche Rolle, in denen Lernprozesse stattfinden. Faktoren wie z. B. die Tagesform führen letztlich dazu, dass nicht einmal für eine einzelne Person konstante Lernpräferenzen herrschen. Mit diesem Beitrag wird vorgeschlagen, zur Lösung des Problems einer Mehrkanalstrategie zu folgen. Allerdings sind spezifische Eigenschaften von Learning-Content-Systemen (LCS) notwendig, um ein sog. Multi-Channel-Learning (MCL) zu ermöglichen. Diese Eigenschaften werden im Beitrag anhand von Informationsmodellen beschrieben werden. Sie sollen als Referenzmodell dienen, das sowohl bei der Entwicklung als auch bei der Auswahl und Anpassung von LCS hilfreich sein kann. Das Referenzmodell wird deduktiv abgeleitet und anhand praktischer Anwendungen geprüft. Vorgestellt werden sowohl Anwendungs- als auch Organisationssysteme, die nach dem Modell realisiert worden sind. Auf dieser Grundlage kann schließlich eine Nutzenabschätzung des Modells für das Multi-Channel-Learnings vorgenommen werden.

Effect of calcium-channel blockers on calcium-phosphate metabolism in patients with end-stage renal disease

After EDTA-induced hypocalcaemia, healthy volunteers treated with diltiazem display more severe hyperparathyroidism than subjects on felodipine studied under identical conditions. Therefore patients with end-stage renal disease (ESRD) and severe secondary hyperparathyroidism might be particularly sensitive to this side-effect.

A Qualitative Study on the Adoption of Copyright Assignment Agreements (CAA) and Copyright License Agreements (CLA) within Selected FOSS Projects

Open source software projects are multi-collaborative works incorporating the contributions of numerous developers who, in spite of publishing their code under a public license such as GPL, Apache or BSD, retain the copyright in their contributions. Having multiple copyright-owners can make the steering of a project difficult, if not impossible, as there is no ultimate authority able to take decisions relating to the maintenance and use of the project. This predicament can be remedied by centring the dispersed copyrights in a single authority via contributor agreements. Whether to introduce contributor agreements, and if so in which form, is a pressing question for many emerging, but also for established projects. The current paper provides an insight into the ethos of different projects and their reason for adopting or rejecting particular contributor agreements. It further examines the exact set-up of the contributor agreements used and concludes that smart drafting can blur the difference between CAAs and CLAs to a considerable extent, manoeuvring them into a legal grey area. To avoid costly litigation to test the legal enforceability of individual clauses, this paper proposes the establishment of an international committee comprised of developers, product managers and lawyers interested in finding a common terminology that may serve as a foundation for every contributor agreement