A principled approach to programming with nested types in Haskell

Initial algebra semantics is one of the cornerstones of the theory of modern functional programming languages. For each inductive data type, it provides a Church encoding for that type, a build combinator which constructs data of that type, a fold combinator which encapsulates structured recursion over data of that type, and a fold/build rule which optimises modular programs by eliminating from them data constructed using the buildcombinator, and immediately consumed using the foldcombinator, for that type. It has long been thought that initial algebra semantics is not expressive enough to provide a similar foundation for programming with nested types in Haskell. Specifically, the standard folds derived from initial algebra semantics have been considered too weak to capture commonly occurring patterns of recursion over data of nested types in Haskell, and no build combinators or fold/build rules have until now been defined for nested types. This paper shows that standard folds are, in fact, sufficiently expressive for programming with nested types in Haskell. It also defines buildcombinators and fold/build fusion rules for nested types. It thus shows how initial algebra semantics provides a principled, expressive, and elegant foundation for programming with nested types in Haskell

Simulation of a particle-laden turbulent channel flow using an improved stochastic Lagrangian model

The purpose of this paper is to examine the Lagrangian stochastic modeling of the fluid velocity seen by inertial particles in a nonhomogeneous turbulent flow. A new Langevin-type model, compatible with the transport equation of the drift velocity in the limits of low and high particle inertia, is derived. It is also shown that some previously proposed stochastic models are not compatible with this transport equation in the limit of high particle inertia. The drift and diffusion parameters of these stochastic differential equations are then estimated using direct numerical simulation (DNS) data. It is observed that, contrary to the conventional modeling, they are highly space dependent and anisotropic. To investigate the performance of the present stochastic model, a comparison is made with DNS data as well as with two different stochastic models. A good prediction of the first and second order statistical moments of the particle and fluid seen velocities is obtained with the three models considered. Even for some components of the triple particle velocity correlations, an acceptable accordance is noticed. The performance of the three different models mainly diverges for the particle concentration and the drift velocity. The proposed model is seen to be the only one which succeeds in predicting the good evolution of these latter statistical quantities for the range of particle inertia studied

Measuring Endocytosis During Proliferative Cell Quiescence

Quiescence (also called "G0") is the state in which cells have exited the cell cycle but are capable to reenter as required. Though poorly understood, it represents one of the most prevalent cell states across all life. Many biologically important cell types reside in quiescence including mature hepatocytes, endothelial cells, and dormant adult stem cells. Furthermore, the quiescence program occurs in both short- and long-term varieties, depending on the physiological environments. A barrier slowing our understanding of quiescence has been a scarcity of available in vitro model systems to allow for the exploration of key regulatory pathways, such as endocytosis. Endocytosis, the internalization of extracellular material into the cell, is a fundamental and highly regulated process that impacts many cell biological functions. Accordingly, we have developed an in vitro model of deep quiescence in hTERT-immortalized RPE1 cells, combining both long-term contact inhibition and mitogen removal, to measure endocytosis. In addition, we present an analytical approach employing automated high-throughput microscopy and image analysis that yields high-content data allowing for meaningful and statistically robust interpretation. Importantly, the methods presented herein provide a suitable platform that can be easily adapted to investigate other regulatory processes across the cell cycle

Spontaneous Raman scattering for simultaneous measurements of in-cylinder species

A technique for multi-species mole fraction measurement in internal combustion engines is described. The technique is based on the spontaneous Raman scattering. It can simultaneously provide the mole fractions of several species of N-2, O-2, H2O, CO2 and fuel. Using the system, simultaneous measurement of air/fuel ratio and burnt residual gas are carried out during the mixture process in a Controlled Auto Ignition (CAI) combustion engine. The accuracy and consistency of the measured results were confirmed by the measured air fuel ratio using an exhaust gas analyzer and independently calculated mole fraction values. Measurement of species mole fractions during combustion process has also been demonstrated. It shows that the SRS can provide valuable data on this process in a CAI combustion engine

Evaluation of sedimentation rate methodology reveals an unusual pediatric subpopulation with lupus or lupus-like syndrome and hemolytic anemia

Purpose Sedimentaion rate is often used to manage pediatric patients with rheumatologic disease. Most management decisions are dependent on studies which have used Wintrobe or Westergren sedimentation rate methodologies. However, these methods suffer from the need for relatively large amounts of blood and long turn-around times. Determination of sedimentation rate using laser kinetic rate determination has allowed calibration to Westergren methods, low volume of blood needed for testing and very rapid results. We sought to compare the Wintrobe method to the ESR Stat method (kinetic method; HemaTechnologies, Lebanon NJ) to determine suitability of the ESR Stat method for patient testing. Go to: Methods We performed a prospective comparison between the traditional Wintrobe and ESR Stat sedimentation rates in consecutive pediatric patients at a tertiary care pediatric hospital. Wintrobe and ESR Stat sedimentation data was fitted using a logarithmic model. Outliers were defined as those samples with ESR Stat sedimentation rates greater than 80 mm/hr and Wintrobe sedimentation rates less than 30 mm/hr (normal or mildly elevated sedimentation rate). Retrospective chart review was performed on all patients undergoing testing. Go to: Results A total of 131 pediatric patients (with one patient undergoing repeat testing because of sedimentation rate discrepancy) were tested. Age range was 18 months to 34 years with 29% being male. A logarithmic model appeared to best fit the data (R2 = 0.7768) and is seen below. Of interest was the identification of four patients who had apparently normal or mildly elevated sedimentation rates by the Wintrobe method versus an extremely high (greater than 120 mm/hr) by the ESR Stat method. These patients were noted to have lupus or lupus-like syndrome and a history of hemolytic anemia. Non-outlier samples were from patients who did not this combination of disease morbidities. Figure 1 Go to: Conclusion Discrepancies in Wintrobe and ESR Stat sedimentation rates may identify a subgroup of with lupus (or lupus-like syndrome) and a history of hemolytic anemia. Careful consideration of methodology is needed when sedimentation rate testing is performed on pediatric lupus patients

Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy

Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no treatment. Both collagen and the giant sarcomeric protein titin determine diastolic function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as a therapeutic target. We adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain cardiac filling in diastole but also ameliorates cardiac atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced RBM20 activity partially normalized gene expression related to muscle development and fatty acid metabolism. The adaptation of cardiac growth was related to hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into hypertrophy signals. We provide a novel link between cardiac isoform expression and trophic signaling via FHLs and suggest cardiac splicing as a therapeutic target in diastolic dysfunction. KEY MESSAGE: Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction