A Model for Enveloping Space Station Logistics Requirements

Since the inception of the Space Station customer Logistics study, it became apparent that a modeling process was needed to provide insight into the many sensitivities and relationships which exist among the numerous variables which impact Space Station Customer Accommodations and Logistics Support Requirements with regard to their associated design requirements. such a model would provide the necessary and timely support to the Space Station designers and planners during the program\u27s early development. This paper will address the current design and operations of the Space Station in particular the Manufacturing and Technology Laboratory (MTL) which is the primary focus of the study and the model. Typical experiments planned for the MTL will be addressed as well as their on-orbit operational and logistical requirements. A detailed description of the model developed under the study along with some of its many applications for scoping Space Station Logistics Requirements will be presented

Technology Development Missions Concept Definition Study TDMX 2066 Large Inflatable/ Rigidized Structures

The advent of the Space Station will require the development and advancement of many new technologies. One of which is the development of Inflatable/ Rigidized Structures. This paper addresses the concept definition, feasibility and requirements for a Large Inflatable/Rigidized Hangar for Payload Servicing on the Space Station. Inflatable/Rigidized Structure Technology has existed for .many years, but applications of this technology to Space Based Elements has only begun during the past decade. Inflatable/Rigidized Structures offer a variety of benefits and applications to the Space Station, key of which is their low weight and volume requirements for transfer to the Station. A 60X40 foot foam hangar can be packaged and shipped in a specialized container approximately 46 m3 and will provide 3200 m3 of usable working/storage space. Previous studies have produced tremendous success in the area of design, fabrication and development of such Inflatable/Rigidized Structures as: a Spacelab transfer tunnel, module airlocks, platforms, large storage hangars, interconnect tunnels, and lunar habitation modules. This paper will address the technology issues/advancements which must be meet, the requirements for accommodations on the Space Station, such as crew and equipment requirements to assemble the hangar at the Station. Pre-launch ground requirements will also be addresses, which include new advanced packaging techniques for Rigidized structures. Typical Ground and On-orbit scenarios will be provided. Finally a preliminary evolutionary plan will be presented which indicates the major experiment development phases from ground based prototypes to full scale Stat-ion deployment

Radiographic closure time of appendicular growth plates in the Icelandic horse

<p>Abstract</p> <p>Background</p> <p>The Icelandic horse is a pristine breed of horse which has a pure gene pool established more than a thousand years ago, and is approximately the same size as living and extinct wild breeds of horses. This study was performed to compare the length of the skeletal growth period of the "primitive" Icelandic horse relative to that reported for large horse breeds developed over the recent centuries. This information would provide practical guidance to owners and veterinarians as to when the skeleton is mature enough to commence training, and would be potentially interesting to those scientists investigating the pathogenesis of osteochondrosis. Interestingly, osteochondrosis has not been documented in the Icelandic horse.</p> <p>Methods</p> <p>The radiographic closure time of the appendicular growth plates was studied in 64 young Icelandic horses. The results were compared with previously published closure times reported for other, larger horse breeds. The radiographs were also examined for any signs of developmental orthopaedic diseases. In order to describe further the growth pattern of the Icelandic horse, the total serum alkaline phosphatase (ALP) activity was determined and the height at the withers was measured.</p> <p>Results</p> <p>Most of the examined growth plates were fully closed at the age of approximately three years. The horses reached adult height at this age; however ALP activity was still mildly increased over baseline values. The growth plates in the digits were the first to close at 8.1 to 8.5 months of age, and those in the regions of the distal radius (27.4 to 32.0 months), tuber olecrani (31.5 to 32.2 months), and the stifle (27.0 to 40.1 months) were the last to close. No horse was found to have osteochondrosis type lesions in the neighbouring joints of the evaluated growth plates.</p> <p>Conclusion</p> <p>The Icelandic horse appears to have similar radiographic closure times for most of the growth plates of its limbs as reported for large new breeds of horses developed during the past few centuries. It thus appears that different breeding goals and the intensity of breeding have not altered the length of the growth period in horses. Instead, it can be assumed that the pristine and relatively small Icelandic horse has a slower rate of growth. The appendicular skeleton of Icelandic horses has completed its bone growth in length at approximately 3 years of age, and therefore may be able to enter training at this time.</p

Protein-Protein Interactions within Late Pre-40S Ribosomes

Ribosome assembly in eukaryotic organisms requires more than 200 assembly factors to facilitate and coordinate rRNA transcription, processing, and folding with the binding of the ribosomal proteins. Many of these assembly factors bind and dissociate at defined times giving rise to discrete assembly intermediates, some of which have been partially characterized with regards to their protein and RNA composition. Here, we have analyzed the protein-protein interactions between the seven assembly factors bound to late cytoplasmic pre-40S ribosomes using recombinant proteins in binding assays. Our data show that these factors form two modules: one comprising Enp1 and the export adaptor Ltv1 near the beak structure, and the second comprising the kinase Rio2, the nuclease Nob1, and a regulatory RNA binding protein Dim2/Pno1 on the front of the head. The GTPase-like Tsr1 and the universally conserved methylase Dim1 are also peripherally connected to this second module. Additionally, in an effort to further define the locations for these essential proteins, we have analyzed the interactions between these assembly factors and six ribosomal proteins: Rps0, Rps3, Rps5, Rps14, Rps15 and Rps29. Together, these results and previous RNA-protein crosslinking data allow us to propose a model for the binding sites of these seven assembly factors. Furthermore, our data show that the essential kinase Rio2 is located at the center of the pre-ribosomal particle and interacts, directly or indirectly, with every other assembly factor, as well as three ribosomal proteins required for cytoplasmic 40S maturation. These data suggest that Rio2 could play a central role in regulating cytoplasmic maturation steps

FLT3 mutations in canine acute lymphocytic leukemia

<p>Abstract</p> <p>Background</p> <p>FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, and a poorer prognosis. A better understanding of the molecular consequences of FLT3 activation would allow improved therapeutic strategies in these patients. Canine lymphoproliferative diseases, including lymphoma and acute leukemias, share evolutionarily conserved chromosomal aberrations and exhibit conserved mutations within key oncogenes when compared to their human counterparts. A small percentage of canine acute lymphocytic leukemias (ALL) also exhibit <it>FLT3 </it>ITD mutations.</p> <p>Methods</p> <p>We molecularly characterized <it>FLT3 </it>mutations in two dogs and one cell line, by DNA sequencing, gene expression analysis via quantitative real-time PCR, and sensitivity to the FLT3 inhibitor lestaurtinib via <it>in vitro </it>proliferation assays. FLT 3 and downstream mediators of FLT3 activation were assessed by Western blotting.</p> <p>Results</p> <p>The canine B-cell leukemia cell line, GL-1, and neoplastic cells from 2/7 dogs diagnosed cytologically with ALL were found to have <it>FLT3 </it>ITD mutations and <it>FLT3 </it>mRNA up-regulation. Lestaurtinib, a small molecule FLT3 inhibitor, significantly inhibited the growth of GL-1 cells, while not affecting the growth of two other canine lymphoid cell lines without the <it>FLT3 </it>mutation. Finally, western blots were used to confirm the conserved downstream mediators of <it>FLT3 </it>activating mutations.</p> <p>Conclusions</p> <p>These results show that ALL and FLT3 biology is conserved between canine and human patients, supporting the notion that canine ALL, in conjunction with the GL-1 cell line, will be useful in the development of a relevant large animal model to aid in the study of human FLT3 mutant leukemias.</p

Rational Extension of the Ribosome Biogenesis Pathway Using Network-Guided Genetics

Gene networks are an efficient route for associating candidate genes with biological processes. Here, networks are used to discover more than 15 new genes for ribosomal subunit maturation, rRNA processing, and ribosomal export from the nucleus

A Downstream CpG Island Controls Transcript Initiation and Elongation and the Methylation State of the Imprinted Airn Macro ncRNA Promoter

A CpG island (CGI) lies at the 5′ end of the Airn macro non-protein-coding (nc) RNA that represses the flanking Igf2r promoter in cis on paternally inherited chromosomes. In addition to being modified on maternally inherited chromosomes by a DNA methylation imprint, the Airn CGI shows two unusual organization features: its position immediately downstream of the Airn promoter and transcription start site and a series of tandem direct repeats (TDRs) occupying its second half. The physical separation of the Airn promoter from the CGI provides a model to investigate if the CGI plays distinct transcriptional and epigenetic roles. We used homologous recombination to generate embryonic stem cells carrying deletions at the endogenous locus of the entire CGI or just the TDRs. The deleted Airn alleles were analyzed by using an ES cell imprinting model that recapitulates the onset of Igf2r imprinted expression in embryonic development or by using knock-out mice. The results show that the CGI is required for efficient Airn initiation and to maintain the unmethylated state of the Airn promoter, which are both necessary for Igf2r repression on the paternal chromosome. The TDRs occupying the second half of the CGI play a minor role in Airn transcriptional elongation or processivity, but are essential for methylation on the maternal Airn promoter that is necessary for Igf2r to be expressed from this chromosome. Together the data indicate the existence of a class of regulatory CGIs in the mammalian genome that act downstream of the promoter and transcription start

Epigenetic Regulation of a Murine Retrotransposon by a Dual Histone Modification Mark

Large fractions of eukaryotic genomes contain repetitive sequences of which the vast majority is derived from transposable elements (TEs). In order to inactivate those potentially harmful elements, host organisms silence TEs via methylation of transposon DNA and packaging into chromatin associated with repressive histone marks. The contribution of individual histone modifications in this process is not completely resolved. Therefore, we aimed to define the role of reversible histone acetylation, a modification commonly associated with transcriptional activity, in transcriptional regulation of murine TEs. We surveyed histone acetylation patterns and expression levels of ten different murine TEs in mouse fibroblasts with altered histone acetylation levels, which was achieved via chemical HDAC inhibition with trichostatin A (TSA), or genetic inactivation of the major deacetylase HDAC1. We found that one LTR retrotransposon family encompassing virus-like 30S elements (VL30) showed significant histone H3 hyperacetylation and strong transcriptional activation in response to TSA treatment. Analysis of VL30 transcripts revealed that increased VL30 transcription is due to enhanced expression of a limited number of genomic elements, with one locus being particularly responsive to HDAC inhibition. Importantly, transcriptional induction of VL30 was entirely dependent on the activation of MAP kinase pathways, resulting in serine 10 phosphorylation at histone H3. Stimulation of MAP kinase cascades together with HDAC inhibition led to simultaneous phosphorylation and acetylation (phosphoacetylation) of histone H3 at the VL30 regulatory region. The presence of the phosphoacetylation mark at VL30 LTRs was linked with full transcriptional activation of the mobile element. Our data indicate that the activity of different TEs is controlled by distinct chromatin modifications. We show that activation of a specific mobile element is linked to a dual epigenetic mark and propose a model whereby phosphoacetylation of histone H3 is crucial for full transcriptional activation of VL30 elements