Henneguya sp. in yellowfin goby Acanthogobius flavimanus from the San Francisco Estuary.

Myxozoan spores were observed in yellowfin goby Acanthogobius flavimanus collected from Suisun Marsh, San Francisco Estuary (SFE). Although histopathological changes associated with the parasite were not observed, the spores formed plasmodia that partially blocked the gastric and intestinal mucosa and gut lumen and may affect the perfomance and survival of the yellowfin goby. Morphological features of the spores resembled Henneguya sp. and molecular analysis of the 18S ribosomal DNA (Domain III) confirmed close similarity to H. rhinogobii and H. pseudorhinogobii isolated from the Japanese freshwater goby. The yellowfin goby myxozoan however, is likely an undescribed species based on phylogenetic analysis and morphologic features. Detailed description of vegetative and spore stages are currently lacking for proposal to a new species of Henneguya. A specific PCR test was developed, which confirmed a 100% prevalence of the parasite among randomly collected gobies in group 1 (N = 30) and group 2 (N = 15) at termination of the study at one month in captivity. The myxozoan was also detected from 18 gobies (12%) that died in the first group within two weeks in captivity. Apparently healthy gobies that served as controls did not reveal the presence of the myxozoan by PCR. This study documents the occurrence of a potentially new species of myxozoan in the yellowfin goby and underscores the detection of a parasitic infection in an introduced fish in the SFE. Although the pathogenesis of the myxozoan was not assessed and the prevalence as reported here is restricted to a comparatively small collection site in Suisun slough, the reemergence, identification, and ecological relevance of the parasite on goby populations in the SFE may be investigated in the future using the specific diagnostic tool developed in this study

Enabling waste elimination, learning, and continuous improvement through standardization

Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering; in conjunction with the Leaders for Manufacturing Program at MIT, 2005.Includes bibliographical references (leaf 92).Many manufacturing companies have developed their own operating system, usually based upon the Toyota Production System, in an effort to improve productivity, quality, and profitability. Continuous improvement is a central theme to most operating systems. Typically large continuous improvement projects or kaizen bursts are used to improve processes. However, these often lead to variable and unsustainable results. A hypothesis is that a detailed standardization of processes will enable opportunities to be quickly revealed. Then a focus on incremental improvement through experimentation can lead to dramatic sustainable results. This thesis is based upon my experience at Mighty Motors in an attempt to gain a deeper understanding about standardization and continuous improvement. I obtained this understanding through direct observation by working with operators on the assembly line to standardize the process and make improvements. I developed the following conclusions: Focus on standardization to achieve sustainable continuous improvement. Without standardization, randomness and variability will hide the wastes and improvements will deteriorate.(cont.) Value the incremental improvement approach to continuous improvement. Through simple, common-sense, and low cost experimentation a great deal of process improvements can be made. Creating an organization that values standardization and continuous improvement is the hard part. This involves more than using a set of problem solving tools.by Mark E. Stover.S.M.M.B.A

Speech tested for Zipfian fit using rigorous statistical techniques

Zipf’s law describes the relationship between the frequencies of words in a corpus and their rank. Its most basic form is a simple series, indicating that the frequency of a word is inverselyproportional to its rank:1/2, 1/3, 1/4,...The past two decades have seen the emergence of usage-based and cognitive approaches to language study. A key observation of these approaches, along with the importance of frequency, is that speech differs in substantial and structural ways from writing. Yet, except for a few older analyses performed on very small corpora, most studies of Zipf’s law have been done on written corpora. Further, a judgement of Zifianness in much of this work is based on loose and informal criteria.  In fact, sophisticated statistical techniques have been developed for curve fitting in recent years in the mathematics and physics literature. These include the use of the Kolmogorov-Smirnov statistic, along with maximum likelihood estimation to generate p-values and the use of the complementary error function for normal distributions. The latter helps determine if a corpus, failing a Zipfian fit, might be better described by another distribution. In this paper, we will:Show that three corpora of recorded speech follow a power law distribution using rigorous statis- tical techniques: Buckeye, Santa Barbara, MiCaseDescribe preliminary results showing that the techniques outlined in this paper may be useful in the diagnoses of those conditions that can include disordered speech.Explain how to do the analyses described in this paper.Explain how to download and use the R/Python code we have written and packaged as the Zipf Tool Ki

Operon conservation and the evolution of trans-splicing in the phylum Nematoda

The nematode Caenorhabditis elegans is unique among model animals in that many of its genes are cotranscribed as polycistronic pre-mRNAs from operons. The mechanism by which these operonic transcripts are resolved into mature mRNAs includes trans-splicing to a family of SL2-like spliced leader exons. SL2-like spliced leaders are distinct from SL1, the major spliced leader in C. elegans and other nematode species. We surveyed five additional nematode species, representing three of the five major clades of the phylum Nematoda, for the presence of operons and the use of trans-spliced leaders in resolution of polycistronic pre-mRNAs. Conserved operons were found in Pristionchus pacificus, Nippostrongylus brasiliensis, Strongyloides ratti, Brugia malayi, and Ascaris suum. In nematodes closely related to the rhabditine C. elegans, a related family of SL2-like spliced leaders is used for operonic transcript resolution. However, in the tylenchine S. ratti operonic transcripts are resolved using a family of spliced leaders related to SL1. Non-operonic genes in S. ratti may also receive these SL1 variants. In the spirurine nematodes B. malayi and A. suum operonic transcripts are resolved using SL1. Mapping these phenotypes onto the robust molecular phylogeny for the Nematoda suggests that operons evolved before SL2-like spliced leaders, which are an evolutionary invention of the rhabditine lineage

Expression and function of Dlx genes in the osteoblast lineage

AbstractOur laboratory and others have shown that overexpression of Dlx5 stimulates osteoblast differentiation. Dlx5−/−/Dlx6−/− mice have more severe craniofacial and limb defects than Dlx5−/−, some of which are potentially due to defects in osteoblast maturation. We wished to investigate the degree to which other Dlx genes compensate for the lack of Dlx5, thus allowing normal development of the majority of skeletal elements in Dlx5−/− mice. Dlx gene expression in cells from different stages of the osteoblast lineage isolated by FACS sorting showed that Dlx2, Dlx5 and Dlx6 are expressed most strongly in less mature osteoblasts, whereas Dlx3 is very highly expressed in differentiated osteoblasts and osteocytes. In situ hybridization and Northern blot analysis demonstrated the presence of endogenous Dlx3 mRNA within osteoblasts and osteocytes. Dlx3 strongly upregulates osteoblastic markers with a potency comparable to Dlx5. Cloned chick or mouse Dlx6 showed stimulatory effects on osteoblast differentiation. Our results suggest that Dlx2 and Dlx6 have the potential to stimulate osteoblastic differentiation and may compensate for the absence of Dlx5 to produce relatively normal osteoblastic differentiation in Dlx5 knockout mice, while Dlx3 may play a distinct role in late stage osteoblast differentiation and osteocyte function

Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6′,7′-Dihydrospiro[Piperidine-4,4′-Thieno[3,2-c]Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-ca​rboxamide(THPP) and N-benzyl-6′,7′-dihydrospiro[piperidine-4,​4′-thieno[3,2-c]pyran](Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This ‘genetic phenotype’ was further confirmed by a ‘chemical phenotype’, whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice

Ensuring the Involvement of Children in the Evaluation of New Tuberculosis Treatment Regimens

William Burman and colleagues review the barriers to involving children in studies of new tuberculosis treatments and recommend strategies for overcoming these barriers

Ending AIDS as a public health threat by 2030: Time to reset targets for 2025.

Paul De Lay and co-authors introduce a Collection on the design of targets for ending the AIDS epidemic