Keratin 6a marks mammary bipotential progenitor cells that can give rise to a unique tumor model resembling human normal-like breast cancer.

Progenitor cells are considered an important cell of origin of human malignancies. However, there has not been any single gene that can define mammary bipotential progenitor cells, and as such it has not been possible to use genetic methods to introduce oncogenic alterations into these cells in vivo to study tumorigenesis from them. Keratin 6a is expressed in a subset of mammary luminal epithelial cells and body cells of terminal end buds. By generating transgenic mice using the Keratin 6a (K6a) gene promoter to express tumor virus A (tva), which encodes the receptor for avian leukosis virus subgroup A (ALV/A), we provide direct evidence that K6a(+) cells are bipotential progenitor cells, and the first demonstration of a non-basal location for some biopotential progenitor cells. These K6a(+) cells were readily induced to form mammary tumors by intraductal injection of RCAS (an ALV/A-derived vector) carrying the gene encoding the polyoma middle T antigen. Tumors in this K6a-tva line were papillary and resembled the normal breast-like subtype of human breast cancer. This is the first model of this subtype of human tumors and thus may be useful for preclinical testing of targeted therapy for patients with normal-like breast cancer. These observations also provide direct in vivo evidence for the hypothesis that the cell of origin affects mammary tumor phenotypes

Intersecting black branes in strong gravitational waves

We consider intersecting black branes with strong gravitational waves propagating along their worldvolume in the context of supergravity theories. Both near-horizon and space-filling gravitational wave modes are included in our ansatz. The equations of motion (originally, partial differential equations) are shown to reduce to ordinary differential equations, which include a Toda-like system. For special arrangements of intersecting black branes, the Toda-like system becomes integrable, permitting a more thorough analysis of the gravitational equations of motion.Comment: 17 pages; v2: cosmetic improvements, published versio

Transgenic tomato plants expressing cucumber mosaic virus coat protein and their resistance to CMV

English abstract: A chimeric gene containing a cloned cDNA of the coat protein (cp) of cucumber mosaic virus (CMV) was transferred into tomato cells, and 42 transgenic tomato plants have been produced by means of a novel leaf disk transformation with the help of a modified Ti plasmid of Agrobacterium tumefaciens. The results of DNA Southern bolt anaylsis confirmed that the CMV-cp gene was stably integrated into the genome of the transgenic plants. CMV coat protein was expressed in the plant cells tested by Western blot and Dot blot. it was shown that the transgenic plants of tomato were protected from infection by CMV. The rate of systematic infection of the virus is reduced or delayed compared with the control plants. The segregation of the R1 progeny of CMV resistance in a 3:1 ratio indicates a single insertion inherited in a Mendelian fashion

A computational method for genotype calling in family-based sequencing data

Background: As sequencing technologies can help researchers detect common and rare variants across the human genome in many individuals, it is known that jointly calling genotypes across multiple individuals based on linkage disequilibrium (LD) can facilitate the analysis of low to modest coverage sequence data. However, genotype-calling methods for family-based sequence data, particularly for complex families beyond parent-offspring trios, are still lacking. Results: In this study, first, we proposed an algorithm that considers both linkage disequilibrium (LD) patterns and familial transmission in nuclear and multi-generational families while retaining the computational efficiency. Second, we extended our method to incorporate external reference panels to analyze family-based sequence data with a small sample size. In simulation studies, we show that modeling multiple offspring can dramatically increase genotype calling accuracy and reduce phasing and Mendelian errors, especially at low to modest coverage. In addition, we show that using external panels can greatly facilitate genotype calling of sequencing data with a small number of individuals. We applied our method to a whole genome sequencing study of 1339 individuals at ~10X coverage from the Minnesota Center for Twin and Family Research. Conclusions: The aggregated results show that our methods significantly outperform existing ones that ignore family constraints or LD information. We anticipate that our method will be useful for many ongoing family-based sequencing projects. We have implemented our methods efficiently in a C++ program FamLDCaller, which is available from http://www.pitt.edu/~wec47/famldcaller.html

Importance Sampling for Objetive Funtion Estimations in Neural Detector Traing Driven by Genetic Algorithms

To train Neural Networks (NNs) in a supervised way, estimations of an objective function must be carried out. The value of this function decreases as the training progresses and so, the number of test observations necessary for an accurate estimation has to be increased. Consequently, the training computational cost is unaffordable for very low objective function value estimations, and the use of Importance Sampling (IS) techniques becomes convenient. The study of three different objective functions is considered, which implies the proposal of estimators of the objective function using IS techniques: the Mean-Square error, the Cross Entropy error and the Misclassification error criteria. The values of these functions are estimated by IS techniques, and the results are used to train NNs by the application of Genetic Algorithms. Results for a binary detection in Gaussian noise are provided. These results show the evolution of the parameters during the training and the performances of the proposed detectors in terms of error probability and Receiver Operating Characteristics curves. At the end of the study, the obtained results justify the convenience of using IS in the training

Deep level defect in Si-implanted GaN n +-p junction

The results of deep level transient spectroscopy (DLTS) experiments on GaN junctions, fabricated by silicon implantation, were discussed. An unusual appearance of a minority peak in the majority carrier DLTS spectra within the interfacial region of the junctions was observed. The presence of this minority peak suggested a high concentration of a deep level defect within the interfacial region.published_or_final_versio

Sliding charge density wave in manganites

The so-called stripe phase of the manganites is an important example of the complex behaviour of metal oxides, and has long been interpreted as the localisation of charge at atomic sites. Here, we demonstrate via resistance measurements on La_{0.50}Ca_{0.50}MnO_3 that this state is in fact a prototypical charge density wave (CDW) which undergoes collective transport. Dramatic resistance hysteresis effects and broadband noise properties are observed, both of which are typical of sliding CDW systems. Moreover, the high levels of disorder typical of manganites result in behaviour similar to that of well-known disordered CDW materials. Our discovery that the manganite superstructure is a CDW shows that unusual transport and structural properties do not require exotic physics, but can emerge when a well-understood phase (the CDW) coexists with disorder.Comment: 13 pages; 4 figure

Genome-wide analysis of the nucleotide binding site leucine-rich repeat genes of four orchids revealed extremely low numbers of disease resistance genes

Orchids are one of the most diverse flowering plant families, yet possibly maintain the smallest number of the nucleotide-binding site-leucine-rich repeat (NBS-LRR) type plant resistance (R) genes among the angiosperms. In this study, a genome-wide search in four orchid taxa identified 186 NBS-LRR genes. Furthermore, 214 NBS-LRR genes were identified from seven orchid transcriptomes. A phylogenetic analysis recovered 30 ancestral lineages (29 CNL and one RNL), far fewer than other angiosperm families. From the genetics aspect, the relatively low number of ancestral R genes is unlikely to explain the low number of R genes in orchids alone, as historical gene loss and scarce gene duplication has continuously occurred, which also contributes to the low number of R genes. Due to recent sharp expansions, Phalaenopsis equestris and Dendrobium catenatum having 52 and 115 genes, respectively, and exhibited an "early shrinking to recent expanding" evolutionary pattern, while Gastrodia elata and Apostasia shenzhenica both exhibit a "consistently shrinking" evolutionary pattern and have retained only five and 14 NBS-LRR genes, respectively. RNL genes remain in extremely low numbers with only one or two copies per genome. Notably, all of the orchid RNL genes belong to the ADR1 lineage. A separate lineage, NRG1, was entirely absent and was likely lost in the common ancestor of all monocots. All of the TNL genes were absent as well, coincident with the RNL NRG1 lineage, which supports the previously proposed notion that a potential functional association between the TNL and RNL NRG1 genes

Dialkyldithiophosphate Acids (HDDPs) as Effective Lubricants of Sol–Gel Titania Coatings in Technical Dry Friction Conditions

The goal of this study was the investigation of the effectiveness of dialkyldithiophosphate acids (HDDPs) films in improving the tribological properties of thin, sol– gel derived titania coatings. Amorphous, anatase, and rutile titania coatings were obtained using sol–gel dip–coating deposition after treatment at 100, 500, and 1,000 C, respectively. Titania coatings were then modified from the liquid phase by HDDPs acids having dodecyl-(C12), tetradecyl-(C14), and hexadecyl-(C16) alkyl chains deposited by dip–coating (DC) and Langmuir–Blodgett (LB) methods. The influence of the deposition procedure, the length of the HDDPs alkyl chain and the type of titania substrate on the surface morphology and tribological properties were studied. It was found, using wetting contact angle measurements, that these modifications of titania coatings decrease the surface free energy and increase its hydrophobicity. The surface topography imaged by Atomic force microscopy (AFM), exhibit island-like or agglomerate features for the DC deposition method, while smooth topographies were observed for LB depositions. Tribological tests were conducted by means of a microtribometer operating in the normal load range 30–100 mN. An enhancement of tribological properties was observed upon modification, as compared to unmodified titania