C-terminal fragments of parathyroid hormone-related protein,PTHrP-(107-111) and (107-139), and the N-terminal PTHrP-(1-40) fragment stimulate membrane-associated protein kinase C activity in rat spleen lymphocytes

Membrane-associated protein kinase C (PKC) activity in lymphocytes freshly isolated from rat spleen was stimulated by the C-terminal parathyroid hormonerelated protein fragments, PTHrP-(107–111) and PTHrP-(107–139), at concentrations from 10^?3 to 10⁴ pM. By contrast, the same concentrations of PTHrP-(120–139), Without the 107–111 TRSAW (-Thr-Arg-Ser-Ala-Trp-) sequence of the other C terminal fragments, did not stimulate spleen lymphocyte PKC. Low concentrations of the N-terminal PTHrP-(1–40) fragment also stimulated membrane-associated PKC activity in the spleen lymphocytes. These results suggest that PTHrP might be an important physiological regulator of the immune response. Published 1994 Wiley-Liss, Inc.     

Is it a good idea to train fillies and colts separately?

This study compared the physiological response to novel situations in sex-separated and sex-mixed groups of horses, as measured by heart rate (HR). The study evaluated the possibility of training horses in a mixed-sex system. The study included 41 Purebred Arabian 2?-year-olds during their first walk on an automated horse walker. Four groups, divided by manner of care and training, consisted of 10 colts and 10 fillies kept in separate stables and trained in separate male or female groups and 12 colts and 9 fillies kept in the same stable and trained together. The study measured HR when horses were at rest before exercise, while moving from stable to walker, during 30 min of exercise on walker, while moving from walker to stable, and at rest after exercise. Mean HR scores recorded from training on the walker were higher in sex-mixed groups. Results obtained while horses were moving from stable to walker, then from walker to stable, were significantly higher in the sex-mixed groups. The study did not recommend training young horses in sex-mixed groups.     

Linked Lists and the Method of Lights in Molecular Dynamics Simulation - Search for the Best Method of Forces Evaluation in Sequential MD Codes

Abstract

In this paper two methods of forces evaluation used in the MD codes are presented and compared against the classical linked lists algorithm [3,4] and its modified version [5]. The first algorithm, so called the method of lights is a sequential version of the CYBER 205 vector oriented code [6]. A new algorithm of forces evaluation is also proposed, which incorporates advantages of the method of lights and the linked lists technique.     

Integration of multiple types of genetic markers for neuroblastoma may contribute to improved prediction of the overall survival

Background

Modern experimental techniques deliver data sets containing profiles of tens of thousands of potential molecular and genetic markers that can be used to improve medical diagnostics. Previous studies performed with three different experimental methods for the same set of neuroblastoma patients create opportunity to examine whether augmenting gene expression profiles with information on copy number variation can lead to improved predictions of patients survival. We propose methodology based on comprehensive cross-validation protocol, that includes feature selection within cross-validation loop and classification using machine learning. We also test dependence of results on the feature selection process using four different feature selection methods.

Results

The models utilising features selected based on information entropy are slightly, but significantly, better than those using features obtained with t-test. The synergy between data on genetic variation and gene expression is possible, but not confirmed. A slight, but statistically significant, increase of the predictive power of machine learning models has been observed for models built on combined data sets. It was found while using both out of bag estimate and in cross-validation performed on a single set of variables. However, the improvement was smaller and non-significant when models were built within full cross-validation procedure that included feature selection within cross-validation loop. Good correlation between performance of the models in the internal and external cross-validation was observed, confirming the robustness of the proposed protocol and results.

Conclusions

We have developed a protocol for building predictive machine learning models. The protocol can provide robust estimates of the model performance on unseen data. It is particularly well-suited for small data sets. We have applied this protocol to develop prognostic models for neuroblastoma, using data on copy number variation and gene expression. We have shown that combining these two sources of information may increase the quality of the models. Nevertheless, the increase is small and larger samples are required to reduce noise and bias arising due to overfitting.

Reviewers

This article was reviewed by Lan Hu, Tim Beissbarth and Dimitar Vassilev.

     

Integer Interparticle Distances in Molecular Dynamics Simulation

The paper describes a sequential MD algorithm in which distances between particles are evaluated using fixed point arithmetics. Errors introduced by the method are estimated. Some simulation timings as well as fluctuations of the total energy are compared to the results obtained using floating point arithmetics.     

Parallel splitting solvers for the isogeometric analysis of the Cahn-Hilliard equation

Abstract

Modeling tumor growth in biological systems is a challenging problem with important consequences for diagnosis and treatment of various forms of cancer. This growth process requires large simulation complexity due to evolving biological and chemical processes in living tissue and interactions of cellular and vascular constituents in living organisms. Herein, we describe with a phase-field model, namely the Cahn-Hilliard equation the intricate interactions between the tumors and their host tissue. The spatial discretization uses highly-continuous isogeometric elements. For fast simulation of the time-dependent Cahn-Hilliard equation, we employ an alternating directions implicit methodology. Thus, we reduce the original problems to Kronecker products of 1?D matrices that can be factorized in a linear computational cost. The implementation enables parallel multi-core simulations and shows good scalability on shared-memory multi-core machines. Combined with the high accuracy of isogeometric elements, our method shows high efficiency in solving the Cahn-Hilliard equation on tensor-product meshes.     

An in vitro study of the interaction of heart mitochondria with troponin-bound Ca2+

Rat heart mitochondria are able to extract a large fraction of the Ca²⁺ tightly bound to rabbit skeletal muscle troponin, or to the 18.300 daltons, Ca²⁺ receptor fragment of the troponin molecule (TN-C). The amount of Ca²⁺ removed may reach 100% in the case of TN-C- but substantially less with intact troponin. The reaction is fairly rapid, often reaching completion in seconds, and is inhibited by uncouplers and by the classical inhibitor of Ca²⁺ transport in mitochondria, ruthenium red.     

Effects of heme oxygenase-1 on induction and development of chemically induced squamous cell carcinoma in mice

Heme oxygenase-1 (HO-1) is an antioxidative and cytoprotective enzyme, which may protect neoplastic cells against anticancer therapies, thereby promoting the progression of growing tumors. Our aim was to investigate the role of HO-1 in cancer induction. Experiments were performed in HO-1^+/+, HO-1^+/−, and HO-1^−/− mice subjected to chemical induction of squamous cell carcinoma with 7,12-dimethylbenz[a]anthracene and phorbol 12-myristate 13-acetate. Measurements of cytoprotective genes in the livers evidenced systemic oxidative stress in the mice of all the HO-1 genotypes. Carcinogen-induced lesions appeared earlier in HO-1^−/− and HO-1^+/− than in wild-type animals. They also contained much higher concentrations of vascular endothelial growth factor and keratinocyte chemoattractant, but lower levels of tumor necrosis factor-α and interleukin-12. Furthermore, tumors grew much larger in HO-1 knockouts than in the other groups, which was accompanied by an increased rate of animal mortality. However, pathomorphological analysis indicated that HO-1^−/− lesions were mainly large but benign papillomas. In contrast, in mice expressing HO-1, most lesions displayed dysplastic features and developed to invasive carcinoma. Thus, HO-1 may protect healthy tissues against carcinogen-induced injury, but in already growing tumors it seems to favor their progression toward more malignant forms.