A Dynamic Approach to Rhythm in Language: Toward a Temporal Phonology

It is proposed that the theory of dynamical systems offers appropriate tools to model many phonological aspects of both speech production and perception. A dynamic account of speech rhythm is shown to be useful for description of both Japanese mora timing and English timing in a phrase repetition task. This orientation contrasts fundamentally with the more familiar symbolic approach to phonology, in which time is modeled only with sequentially arrayed symbols. It is proposed that an adaptive oscillator offers a useful model for perceptual entrainment (or `locking in') to the temporal patterns of speech production. This helps to explain why speech is often perceived to be more regular than experimental measurements seem to justify. Because dynamic models deal with real time, they also help us understand how languages can differ in their temporal detail---contributing to foreign accents, for example. The fact that languages differ greatly in their temporal detail suggests that these effects are not mere motor universals, but that dynamical models are intrinsic components of the phonological characterization of language.Comment: 31 pages; compressed, uuencoded Postscrip

BIDding on cities: Applying the Business Improvement District model for urban sustainability

There is a growing expectation in the field of sustainable development that cities are the most suitable scale for addressing global environmental issues, particularly through their ability to mobilize local actors. Business improvement districts (BIDs) are a form of public-private partnership (PPP) in cities typically established by associations of private actors that aim to generate value in communities by jointly investing in physical improvements and local services. The model is gaining attention in Sweden, with one BID established in the Sofielund neighborhood of Malmö currently integrating sustainable development concepts into its core strategy to experiment with solutions for reducing socioeconomic inequalities and the area’s environmental impacts. Since BID Sofielund is seeking to learn new methods for incorporating sustainability and because the nexus between BIDs and sustainability has not been adequately addressed in the academic literature, this research utilizes an exploratory approach in a multiple-case study design focusing on BID Sofielund and four reference cases to investigate how BIDs engage with sustainability through the projects and processes they carry out and develops potential explanations for why they might choose to do so. By plotting BID activities in a sustainability framework, this study found that BIDs contribute to sustainable development through strategies including providing a platform for collaborative governance, promoting energy efficiency in buildings, investing in capital improvement projects that enhance public spaces, and filling gaps in social service provision. The study identified multiple contributors to why BIDs engage in sustainability and assembled a general framework consisting of both internal and external drivers that must be considered to fully understand BID sustainability activities, however more research is needed. From an academic standpoint, the knowledge produced furthers the discussion on BIDs in a sustainability context and it provides practical value for BID practitioners as they seek to measure performance in new ways and enhance their effectiveness through sustainability-driven strategies

SpxA1 and SpxA2 act coordinately to fine-tune stress responses and virulence in Streptococcus pyogenes

SpxA is a unique transcriptional regulator highly conserved among members of the phylum Firmicutes that binds RNA polymerase and can act as an antiactivator. Why some Firmicutes members have two highly similar SpxA paralogs is not understood. Here, we show that the SpxA paralogs of the pathogen Streptococcus pyogenes, SpxA1 and SpxA2, act coordinately to regulate virulence by fine-tuning toxin expression and stress resistance. Construction and analysis of mutants revealed that SpxA1− mutants were defective for growth under aerobic conditions, while SpxA2− mutants had severely attenuated responses to multiple stresses, including thermal and oxidative stresses. SpxA1− mutants had enhanced resistance to the cationic antimicrobial molecule polymyxin B, while SpxA2− mutants were more sensitive. In a murine model of soft tissue infection, a SpxA1− mutant was highly attenuated. In contrast, the highly stress-sensitive SpxA2− mutant was hypervirulent, exhibiting more extensive tissue damage and a greater bacterial burden than the wild-type strain. SpxA1− attenuation was associated with reduced expression of several toxins, including the SpeB cysteine protease. In contrast, SpxA2− hypervirulence correlated with toxin overexpression and could be suppressed to wild-type levels by deletion of speB. These data show that SpxA1 and SpxA2 have opposing roles in virulence and stress resistance, suggesting that they act coordinately to fine-tune toxin expression in response to stress. SpxA2− hypervirulence also shows that stress resistance is not always essential for S. pyogenes pathogenesis in soft tissue

Complete genome sequence of emm type 14 Streptococcus pyogenes strain HSC5

Streptococcus pyogenes causes a greater diversity of human disease than any other bacterial pathogen. Here, we present the complete genome sequence of the emm type 14 S. pyogenes strain HSC5. This strain is a robust producer of the cysteine protease SpeB and is capable of producing infection in several different animal models

Complete genome sequences of emm6 Streptococcus pyogenes JRS4 and parental strain D471

We report the complete genome assemblies of the group A Streptococcus pyogenes serotype emm6 strain D471 and its streptomycin-resistant derivative JRS4. Both of these well-studied laboratory strains have been extensively characterized over the past three decades and have been instrumental in the discovery of multiple aspects of streptococcal pathogenesis

An association between peptidoglycan synthesis and organization of the Streptococcus pyogenes ExPortal

The ExPortal of Streptococcus pyogenes is a focal microdomain of the cytoplasmic membrane that clusters the translocons of the general secretory pathway with accessory factors to facilitate the maturation of secreted polypeptides. While it is known that the ExPortal is enriched in anionic lipids, the mechanisms that organize the ExPortal are poorly understood. In the present study, we examined the role of the cell wall in organizing and maintaining the ExPortal. Removal of the cell wall resulted in a loss of ExPortal focal integrity accompanied by the circumferential redistribution of ExPortal lipid and protein components. A similar loss occurred upon treatment with gallidermin, a nonpermeabilizing lantibiotic that targets the lipid II precursor of peptidoglycan synthesis, and this treatment disrupted the secretion of several ExPortal substrates. Furthermore, several enzymes involved in the membrane-associated steps of lipid II synthesis, including MraY and MurN, were found to localize to a single discrete focus in the membrane that was coincident with the focal location of the secretory translocons and the anionic lipid microdomain. These data suggest that the ExPortal is associated with the site of peptidoglycan precursor synthesis and that peptidoglycan biogenesis influences ExPortal organization. These data add to an emerging literature indicating that cell wall biogenesis, cell division, and protein secretion are spatially coorganized processes

Streptococcus pyogenes polymyxin B-resistant mutants display enhanced exportal integrity

The ExPortal protein secretion organelle in Streptococcus pyogenes is an anionic phospholipid-containing membrane microdomain enriched in Sec translocons and postsecretion protein biogenesis factors. Polymyxin B binds to and disrupts ExPortal integrity, resulting in defective secretion of several toxins. To gain insight into factors that influence ExPortal organization, a genetic screen was conducted to select for spontaneous polymyxin B-resistant mutants displaying enhanced ExPortal integrity. Whole-genome resequencing of 25 resistant mutants revealed from one to four mutations per mutant genome clustered primarily within a core set of 10 gene groups. Construction of mutants with individual deletions or insertions demonstrated that 7 core genes confer resistance and enhanced ExPortal integrity through loss of function, while 3 were likely due to gain of function and/or combinatorial effects. Core resistance genes include a transcriptional regulator of lipid biosynthesis, several genes involved in nutrient acquisition, and a variety of genes involved in stress responses. Two members of the latter class also function as novel regulators of the secreted SpeB cysteine protease. Analysis of the most frequently isolated mutation, a single nucleotide deletion in a track of 9 consecutive adenine residues in pstS, encoding a component of a high-affinity P(i) transporter, suggests that this sequence functions as a molecular switch to facilitate stress adaptation. Together, these data suggest the existence of a membrane stress response that promotes enhanced ExPortal integrity and resistance to cationic antimicrobial peptides

Designing a Bike Trailer as an Alternative for Transportation and Distribution of Goods

This report explores the process taken and results of a project in creating a system of sustainable urban transportation. First, the problems facing cities with regards to transportation are identified and analyzed. A solution to these problems is then offered in the form of bike and bicycle trailer transportation. Research was then done to create designs of bicycle trailers to be utilized for businesses. An examination into the design process and evolution used in this project was also done to show why decisions were made with regards to the final design. The final designs, both general for a multitude of businesses and a specialized design for Higher Ground Farm. Ultimately, a framework for sustainable transportation was created by this project and analyzed by the report

Micro-RNA expression in cisplatin resistant germ cell tumor cell lines

<p>Abstract</p> <p>Background</p> <p>We compared microRNA expression patterns in three cisplatin resistant sublines derived from paternal cisplatin sensitive germ cell tumor cell lines in order to improve our understanding of the mechanisms of cisplatin resistance.</p> <p>Methods</p> <p>Three cisplatin resistant sublines (NTERA-2-R, NCCIT-R, 2102EP-R) showing 2.7-11.3-fold increase in drug resistance after intermittent exposure to increasing doses of cisplatin were compared to their parental counterparts, three well established relatively cisplatin sensitive germ cell tumor cell lines (NTERA-2, NCCIT, 2102EP). Cells were cultured and total RNA was isolated from all 6 cell lines in three independent experiments. RNA was converted into cDNA and quantitative RT-PCR was run using 384 well low density arrays covering almost all (738) known microRNA species of human origin.</p> <p>Results</p> <p>Altogether 72 of 738 (9.8%) microRNAs appeared differentially expressed between sensitive and resistant cell line pairs (NTERA-2R/NTERA-2 = 43, NCCIT-R/NCCIT = 53, 2102EP-R/2102EP = 15) of which 46.7-95.3% were up-regulated (NTERA-2R/NTERA-2 = 95.3%, NCCIT-R/NCCIT = 62.3%, 2102EP-R/2102EP = 46.7%). The number of genes showing differential expression in more than one of the cell line pairs was 34 between NTERA-2R/NTERA-2 (79%) and NCCIT-R/NCCIT (64%), and 3 and 4, respectively, between these two cell lines and 2102EP-R/2102EP (about 27%). Only the has-miR-10b involved in breast cancer invasion and metastasis and has-miR-512-3p appeared to be up-regulated (2-3-fold) in all three cell lines. The hsa-miR-371-373 cluster (counteracting cellular senescence and linked with differentiation potency), as well as hsa-miR-520c/-520h (inhibiting the tumor suppressor p21) were 3.9-16.3 fold up-regulated in two of the three cisplatin resistant cell lines. Several new micro-RNA species missing an annotation towards cisplatin resistance could be identified. These were hsa-miR-512-3p/-515/-517/-518/-525 (up to 8.1-fold up-regulated) and hsa-miR-99a/-100/-145 (up to 10-fold down-regulated).</p> <p>Conclusion</p> <p>Examining almost all known human micro-RNA species confirmed the miR-371-373 cluster as a promising target for explaining cisplatin resistance, potentially by counteracting wild-type P53 induced senescence or linking it with the potency to differentiate. Moreover, we describe for the first time an association of the up-regulation of micro-RNA species such as hsa-miR-512-3p/-515/-517/-518/-525 and down-regulation of hsa-miR-99a/-100/-145 with a cisplatin resistant phenotype in human germ cell tumors. Further functional analyses are warranted to gain insight into their role in drug resistance.</p