Noncooperative algorithms in self-assembly

We show the first non-trivial positive algorithmic results (i.e. programs whose output is larger than their size), in a model of self-assembly that has so far resisted many attempts of formal analysis or programming: the planar non-cooperative variant of Winfree's abstract Tile Assembly Model. This model has been the center of several open problems and conjectures in the last fifteen years, and the first fully general results on its computational power were only proven recently (SODA 2014). These results, as well as ours, exemplify the intricate connections between computation and geometry that can occur in self-assembly. In this model, tiles can stick to an existing assembly as soon as one of their sides matches the existing assembly. This feature contrasts with the general cooperative model, where it can be required that tiles match on \emph{several} of their sides in order to bind. In order to describe our algorithms, we also introduce a generalization of regular expressions called Baggins expressions. Finally, we compare this model to other automata-theoretic models.Comment: A few bug fixes and typo correction

Comparative functional genomics and the bovine macrophage response to strains of the Mycobacterium genus

Mycobacterial infections are major causes of morbidity and mortality in cattle and are also potential zoonotic agents with implications for human health. Despite the implementation of comprehensive animal surveillance programs, many mycobacterial diseases have remained recalcitrant to eradication in several industrialized countries. Two major mycobacterial pathogens of cattle are Mycobacterium bovis and Mycobacterium avium subspecies paratuberculosis (MAP), the causative agents of bovine tuberculosis (BTB) and Johne's disease (JD), respectively. BTB is a chronic, granulomatous disease of the respiratory tract that is spread via aerosol transmission, while JD is a chronic granulomatous disease of the intestines that is transmitted via the fecal-oral route. Although these diseases exhibit differential tissue tropism and distinct complex etiologies, both M. bovis and MAP infect, reside, and replicate in host macrophages - the key host innate immune cell that encounters mycobacterial pathogens after initial exposure and mediates the subsequent immune response. The persistence of M. bovis and MAP in macrophages relies on a diverse series of immunomodulatory mechanisms, including the inhibition of phagosome maturation and apoptosis, generation of cytokine-induced necrosis enabling dissemination of infection through the host, local pathology, and ultimately shedding of the pathogen. Here, we review the bovine macrophage response to infection with M. bovis and MAP. In particular, we describe how recent advances in functional genomics are shedding light on the host macrophage-pathogen interactions that underlie different mycobacterial diseases. To illustrate this, we present new analyses of previously published bovine macrophage transcriptomics data following in vitro infection with virulent M. bovis, the attenuated vaccine strain M. bovis BCG, and MAP, and discuss our findings with respect to the differing etiologies of BTB and JD

GOexpress: an R/Bioconductor package for the identification and visualisation of robust gene ontology signatures through supervised learning of gene expression data

Background: Identification of gene expression profiles that differentiate experimental groups is critical for discovery and analysis of key molecular pathways and also for selection of robust diagnostic or prognostic biomarkers. While integration of differential expression statistics has been used to refine gene set enrichment analyses, such approaches are typically limited to single gene lists resulting from simple two-group comparisons or time-series analyses. In contrast, functional class scoring and machine learning approaches provide powerful alternative methods to leverage molecular measurements for pathway analyses, and to compare continuous and multi-level categorical factors. Results: We introduce GOexpress, a software package for scoring and summarising the capacity of gene ontology features to simultaneously classify samples from multiple experimental groups. GOexpress integrates normalised gene expression data (e.g., from microarray and RNA-seq experiments) and phenotypic information of individual samples with gene ontology annotations to derive a ranking of genes and gene ontology terms using a supervised learning approach. The default random forest algorithm allows interactions between all experimental factors, and competitive scoring of expressed genes to evaluate their relative importance in classifying predefined groups of samples. Conclusions: GOexpress enables rapid identification and visualisation of ontology-related gene panels that robustly classify groups of samples and supports both categorical (e.g., infection status, treatment) and continuous (e.g., time-series, drug concentrations) experimental factors. The use of standard Bioconductor extension packages and publicly available gene ontology annotations facilitates straightforward integration of GOexpress within existing computational biology pipelines.Department of Agriculture, Food and the MarineEuropean Commission - Seventh Framework Programme (FP7)Science Foundation IrelandUniversity College Dubli

Uitdagings vir vergelykende opvoedkunde: alles vir almal en verstaan van die ander

Challenges for comparative education: everything for everybody and understanding of the other. This article explores the challenges and unique contribution of comparative education in the present age of global vs local (i.e. national or communal) agendas, perspectives and priorities. The thesis is that comparative education's sensitivity to the interrelationships between national context and education renders it in a valuable and irreplaceable position with respect to the task of reflecting on the consequences of universalistic trends on education systems and with respect to the assessment of the possibilities and dangers of taking over educational practices from other educational systems. In the education of educators as professionals, comparative education, with its characteristic focus on the education system, on societal-education interrelationships, and its impact on the individual has a unique contribution to make towards teachers' critical understanding of the linkage between global discourses and local narrative and the way it is shaping both the education system and the identity of learners. South African Journal of Education Vol.23(4) 2003: 307-31

Chemical Constituents, Anticancer and Anti-Proliferative Potential of Limonium Species: A Systematic Review

Limonium species represent a source of bioactive compounds that have been widely used in folk medicine. This study aimed to synthesize the anticancer and anti-proliferative potential of Limonium species through a systematic review. Searches were performed in the electronic databases PubMed/MEDLINE, Scopus, and Scielo and via a manual search. In vivo or in vitro studies that evaluated the anticancer or anti-proliferative effect of at least one Limonium species were included. In total, 942 studies were identified, with 33 articles read in full and 17 studies included for qualitative synthesis. Of these, 14 (82.35%) refer to in vitro assays, one (5.88%) was in vivo, and two (11.76%) were designed as in vitro and in vivo assays. Different extracts and isolated compounds from Limonium species were evaluated through cytotoxic analysis against various cancer cells lines (especially hepatocellular carcinoma-HepG2; n = 7, 41.18%). Limonium tetragonum was the most evaluated species. The possible cellular mechanism involved in the anticancer activity of some Limonium species included the inhibition of enzymatic activities and expression of matrix metalloproteinases (MMPs), which suggested anti-metastatic effects, anti-melanogenic activity, cell proliferation inhibition pathways, and antioxidant and immunomodulatory effects. The results reinforce the potential of Limonium species as a source for the discovery and development of new potential cytotoxic and anticancer agents. However, further studies and improvements in experimental designs are needed to better demonstrate the mechanism of action of all of these compounds

RNA-seq transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis

Bovine tuberculosis, caused by infection with Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including gene expression microarrays and RNA-sequencing (RNA-seq), has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analyzed the peripheral blood leukocyte (PBL) transcriptome of eight natural M. bovis-infected and eight age- and sex-matched non-infected control Holstein-Friesian animals using RNA-seq. In addition, we compared gene expression profiles generated using RNA-seq with those previously generated using the high-density Affymetrix(®) GeneChip(®) Bovine Genome Array platform from the same PBL-extracted RNA. A total of 3,250 differentially expressed (DE) annotated genes were detected in the M. bovis-infected samples relative to the controls (adjusted P-value ≤0.05), with the number of genes displaying decreased relative expression (1,671) exceeding those with increased relative expression (1,579). Ingenuity(®) Systems Pathway Analysis (IPA) of all DE genes revealed enrichment for genes with immune function. Notably, transcriptional suppression was observed among several of the top-ranking canonical pathways including Leukocyte Extravasation Signaling. Comparative platform analysis demonstrated that RNA-seq detected a larger number of annotated DE genes (3,250) relative to the microarray (1,398), of which 917 genes were common to both technologies and displayed the same direction of expression. Finally, we show that RNA-seq had an increased dynamic range compared to the microarray for estimating differential gene expression

The Identification and Localization of the Abelson Oncoprotein in Zebrafish, (Danio rerio)

The ubiquitously expressed Abelson oncoprotein (Abl) has multiple molecular functions, which affect homeostasis and cytoskeletal structuring of the cell. Mutation of the Abl gene is the causal event in several types of leukemia and is linked to the progression of certain lung and breast cancers. Despite extensive literature documenting the protein’s function in humans and the recent explosion of cancer research using zebrafish, no research to date has investigated the existence of an Abl ortholog in Danio rerio. We have sequenced a cDNA clone from D. rerio that demonstrates high identity to other vertebrate Abl proteins. In addition, we have investigated expression of the abl gene and abl protein during early embryonic development by in situ hybridization and immunohistochemistry. Expression of the gene and protein begins at 12 hours post fertilization and correlates to areas of nervous system development within the head and hematopoietic differentiation within the posterior blood island. These results suggest that the putative zebrafish abelson homolog has multiple functions in early development, aiding in the differentiation of the central nervous system and also facilitating the differentiation of hematopoietic stem cells in the posterior blood island

Telomere length as a biomarker for stress in Eastern bluebird nestlings (Sialia sialis) reared in urban habitats

Eastern bluebirds (Sialia sialis) are often found in urban areas and have seemingly adapted to the changing conditions, however, an often-overlooked potential threat for urban dwellers is anthropogenic stress or human-induced environmental stressors. Anthropogenic stressors may initiate a physiological cascade which leads to oxidative damage, including telomere loss. The intricate relationship between stress (physiological and oxidative stress) and telomere length (TL) has led to the utilization of TL as an index for stress. I hypothesized that Eastern bluebird nestlings developing in more urbanized settings experience higher levels of stress. Moreover, I predicted that urban nestlings have shorter telomeres than rural nestlings. This is in line with previous studies that found an association between stress exposure and shortened telomeres in other urban-raised birds. In this study, I used telomere length (TL) as a biomarker for stress in bluebird nestlings reared in an urban-rural gradient. I measured the relative telomere length (TL) of 35 nestlings reared in urban (17) and rural (18) habitats located in Carroll County, GA using quantitative "real-time" PCR (qPCR). The technique involves the measurement of amplified target (T) telomere sequences relative to a reference single copy gene (S); GAPDH was chosen as the single copy gene due to its conserved nature in all passerines. I found that urban nestlings have shorter telomeres as demonstrated by their lower mean T/S ratios when compared to those of rural nestlings. Therefore, the results of this study suggest that urban-reared Eastern bluebird nestlings are, in fact, stressed and incur a greater physiological cost than their rural counterparts. Future studies could explore the physiological processes behind the reduction of TL in Eastern bluebird nestlings by measuring the release of glucocorticoid stress hormones (e.g. CORT) in tandem with TL

Whole-transcriptome, high-throughput RNA sequence analysis of the bovine macrophage response to Mycobacterium bovis infection in vitro

BACKGROUND: Mycobacterium bovis, the causative agent of bovine tuberculosis, is an intracellular pathogen that can persist inside host macrophages during infection via a diverse range of mechanisms that subvert the host immune response. In the current study, we have analysed and compared the transcriptomes of M. bovis-infected monocyte-derived macrophages (MDM) purified from six Holstein-Friesian females with the transcriptomes of non-infected control MDM from the same animals over a 24 h period using strand-specific RNA sequencing (RNA-seq). In addition, we compare gene expression profiles generated using RNA-seq with those previously generated by us using the high-density Affymetrix® GeneChip® Bovine Genome Array platform from the same MDM-extracted RNA. RESULTS: A mean of 7.2 million reads from each MDM sample mapped uniquely and unambiguously to single Bos taurus reference genome locations. Analysis of these mapped reads showed 2,584 genes (1,392 upregulated; 1,192 downregulated) and 757 putative natural antisense transcripts (558 upregulated; 119 downregulated) that were differentially expressed based on sense and antisense strand data, respectively (adjusted P-value ≤ 0.05). Of the differentially expressed genes, 694 were common to both the sense and antisense data sets, with the direction of expression (i.e. up- or downregulation) positively correlated for 693 genes and negatively correlated for the remaining gene. Gene ontology analysis of the differentially expressed genes revealed an enrichment of immune, apoptotic and cell signalling genes. Notably, the number of differentially expressed genes identified from RNA-seq sense strand analysis was greater than the number of differentially expressed genes detected from microarray analysis (2,584 genes versus 2,015 genes). Furthermore, our data reveal a greater dynamic range in the detection and quantification of gene transcripts for RNA-seq compared to microarray technology. CONCLUSIONS: This study highlights the value of RNA-seq in identifying novel immunomodulatory mechanisms that underlie host-mycobacterial pathogen interactions during infection, including possible complex post-transcriptional regulation of host gene expression involving antisense RNA

Gender and the grotesque in the short fiction of Joyce Carol Oates

This thesis is a study of five works of short fiction by author Joyce Carol Oates. One story, “Where Are You Going, Where Have You Been,” is one of her best-known and often criticized, while the other four, “Haunted,” “The Premonition,” and “Extenuating Circumstances” are part of a lesser-known collection entitled Haunted: Tales of the Grotesque. The similarity running through all four stories is Oates’ use of the grotesque image in her depiction of violence, and the implications about gender roles found therein. Oates’ work is famous for its attention to violence perpetrated by men upon women, and the first story includes such. However, in the other three stories, the aggressor is female, and her action seems to represent an inability to achieve or a frustration with the feminine role; her violence is a grotesque inversion of idealized femininity. The aim of this thesis is to explore Oates’ treatment of gender and violence using elements of the grotesque. While much criticism of Oates suggests that she uses grotesque violence to bemoan the victimization of women, my contention is that her treatment of gender reveals that, regardless of sex, individuals who strive to conform to the prescribed gender roles society presents to them are grotesque and problematic