The First United States Microgravity Laboratory

The United States Microgravity Laboratory (USML-1) is one part of a science and technology program that will open NASA's next great era of discovery and establish the United States' leadership in space. A key component in the preparation for this new age of exploration, the USML-1 will fly in orbit for extended periods, providing greater opportunities for research in materials science, fluid dynamics, biotechnology, and combustion science. The major components of the USML-1 are the Crystal Growth Furnace, the Surface Tension Driven Convection Experiment (STDCE) Apparatus, and the Drop Physics Module. Other components of USML-1 include Astroculture, Generic Bioprocessing Apparatus, Extended Duration Orbiter Medical Project, Protein Crystal Growth, Space Acceleration Measurement System, Solid Surface Combustion Experiment, Zeolite Crystal Growth and Spacelab Glovebox provided by the European Space Agency

ATLAS 1: Encountering Planet Earth

Several NASA science programs examine the dynamic balance of sunlight, atmosphere, water, land, and life that governs Earth's environment. Among these is a series of Space Shuttle-Spacelab missions, named the Atmospheric Laboratory for Applications and Science (ATLAS). During the ATLAS missions, international teams of scientists representing many disciplines combine their expertise to seek answers to complex questions about the atmospheric and solar conditions that sustain life on Earth. The ATLAS program specifically investigates how Earth's middle atmosphere and upper atmospheres and climate are affected by both the Sun and by products of industrial and agricultural activities on Earth

First International Microgravity Laboratory

This colorful booklet presents capsule information on every aspect of the International Microgravity Laboratory (IML). As part of Spacelab, IML is divided into Life Science Experiments and Materials Science Experiments. Because the life and materials sciences use different Spacelab resources, they are logically paired on the IML missions. Life science investigations generally require significant crew involvement, and crew members often participate as test subjects or operators. Materials missions capitalize on these complementary experiments. International cooperation consists in participation by the European Space Agency, Canada, France, Germany, and Japan who are all partners in developing hardware and experiments of IML missions. IML experiments are crucial to future space ventures, like the development of Space Station Freedom, the establishment of lunar colonies, and the exploration of other planets. Principal investigators are identified for each experiment

Public Disclosure im Versicherungsmarkt : erste Erfahrungen mit dem Bericht über die Finanzlage

Die vorliegende Studie untersucht die ersten Erfahrungen mit der neuen Offenlegungspflicht (Public Disclosure) im Schweizer Versicherungsmarkt. Die gewonnenen Erkenntnisse lassen vermuten, dass sich die Resonanz für den Bericht über die Finanzlage unter den Versicherungsnehmern bis anhin in Grenzen hält. Aus Sicht vieler der befragten Versicherer übersteigen die Kosten den Nutzen und die Public Disclosure wird als Pflichtübung mit geringem Mehrwert wahrgenommen

Beta-HPV E6 Contributes To Skin Cancer by Hindering DNA Repair

<div><p>Recent work has explored a putative role for the E6 protein from some β-human papillomavirus genus (β-HPVs) in the development of non-melanoma skin cancers, specifically β-HPV 5 and 8 E6. Because these viruses are not required for tumor maintenance, they are hypothesized to act as co-factors that enhance the mutagenic capacity of UV-exposure by disrupting the repair of the resulting DNA damage. Supporting this proposal, we have previously demonstrated that UV damage signaling is hindered by β-HPV 5 and 8 E6 resulting in an increase in both thymine dimers and UV-induced double strand breaks (DSBs). Here we show that β-HPV 5 and 8 E6 further disrupt the repair of these DSBs and provide a mechanism for this attenuation. By binding and destabilizing a histone acetyltransferase, p300, β-HPV 5 and 8 E6 reduce the enrichment of the transcription factor at the promoter of two genes critical to the homology dependent repair of DSBs (BRCA1 and BRCA2). The resulting diminished BRCA1/2 transcription not only leads to lower protein levels but also curtails the ability of these proteins to form repair foci at DSBs. Using a GFP-based reporter, we confirm that this reduced foci formation leads to significantly diminished homology dependent repair of DSBs. By deleting the p300 binding domain of β-HPV 8 E6, we demonstrate that the loss of robust repair is dependent on viral-mediated degradation of p300 and confirm this observation using a combination of p300 mutants that are β-HPV 8 E6 destabilization resistant and p300 knock-out cells. In conclusion, this work establishes an expanded ability of β-HPV 5 and 8 E6 to attenuate UV damage repair, thus adding further support to the hypothesis that β-HPV infections play a role in skin cancer development by increasing the oncogenic potential of UV exposure.</p></div

Beta-HPV 5 and 8 E6 Promote p300 Degradation by Blocking AKT/p300 Association

The E6 oncoprotein from high-risk genus alpha human papillomaviruses (α-HPVs), such as HPV 16, has been well characterized with respect to the host-cell proteins it interacts with and corresponding signaling pathways that are disrupted due to these interactions. Less is known regarding the interacting partners of E6 from the genus beta papillomaviruses (β-HPVs); however, it is generally thought that β-HPV E6 proteins do not interact with many of the proteins known to bind to α-HPV E6. Here we identify p300 as a protein that interacts directly with E6 from both α- and β-HPV types. Importantly, this association appears much stronger with β-HPV types 5 and 8-E6 than with α-HPV type 16-E6 or β-HPV type 38-E6. We demonstrate that the enhanced association between 5/8-E6 and p300 leads to p300 degradation in a proteasomal-dependent but E6AP-independent manner. Rather, 5/8-E6 inhibit the association of AKT with p300, an event necessary to ensure p300 stability within the cell. Finally, we demonstrate that the decreased p300 protein levels concomitantly affect downstream signaling events, such as the expression of differentiation markers K1, K10 and Involucrin. Together, these results demonstrate a unique way in which β-HPV E6 proteins are able to affect host-cell signaling in a manner distinct from that of the α-HPVs

Linguistic and kinesthetic ability in preschool childen with a language impairment

This study investigated the relationship between linguistic and kinesthetic ability for children with and without speech and language impairments. The kinesthetic ability of children with speech and language impairments was of specific interest. The relationship between kinesthetic ability and learning was also examined. All subjects (18 males, 17 females) were enrolled in a Long Island Head Start program. Seventeen subjects had been found to display speech and language delays. Eighteen subjects had no identified impairments. The Torrance Test of Creativity in Action and Movement was used to measure one form of kinesthetic ability. It included three areas of creative movement: fluency, originality, and imagination. The Preschool Language Scale-3 was used to measure overall language ability. The manual expression subtest of the Illinois Test of Psycholinguistic Abilities was used as a measure of conceptual learning. There were no significant differences between male and female subjects on each aspect of kinesthetic ability. No significant relationships were revealed between linguistic and kinesthetic ability for all children with and without speech and language impairments. No significant relationships were revealed between kinesthetic ability and conceptual learning for children with and without speech and language impairments. There was a significant relationship demonstrated between one aspect of kinesthetic ability (imagination) and conceptual learning for all children. Last, there was no significant difference between children with and without speech and language impairments for kinesthetic ability. The results of this study suggested that creative movement was relatively independent from language ability. However, a specific aspect of creative movement, imagination, was related to concept knowledge for this specific population of preschool children. The results of this study suggested the need for educators to broaden their perspective of intelligence and how it is assessed. Children with speech and language delays would benefit from assessment tools and intervention strategies that include motor-based activities

The Proteasome and Myeloma-Associated Bone Disease

Bone disease is the hallmark of multiple myeloma (MM), a hematological malignancy characterized by osteolytic lesions due to a severe uncoupled and unbalanced bone remodeling with pronounced osteoblast suppression. Bone metastasis is also a frequent complication of solid tumors including advanced breast or prostate cancer. In the past years, the ubiquitinâ\u80\u93proteasome pathway has been proved critical in regulating the balance between bone formation and bone resorption. Proteasome inhibitors (PIs) are a new class of drugs, currently used in the treatment of MM, that affect both tumor cells and bone microenvironment. Particularly, PIs stimulate osteoblast differentiation by human mesenchymal stromal cells and increase bone regeneration in mice. Interestingly, in vitro data indicate that PIs block MM-induced osteoblast and osteocyte cell death by targeting both apoptosis and autophagy. The preclinical data are supported by the following effects observed in MM patients treated with PIs: increase of bone alkaline phosphatase levels, normalization of the markers of bone turnover, and reduction of the skeletal-related events. Moreover, the histomorphometric data indicate that the treatment with bortezomib stimulates osteoblast formation and maintains osteocyte viability in MM patients. This review updates the evidence on the effects of PIs on bone remodeling and on cancer-induced bone disease while focusing on MM bone disease

Mechanism of action of bortezomib and the new proteasome inhibitors on myeloma cells and the bone microenvironment: Impact on myeloma-induced alterations of bone remodeling

Multiple myeloma (MM) is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI) bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and osteoblast formation. It is also evident that bortezomib either inhibits osteoclast differentiation induced by the receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) or stimulates the osteoblast differentiation. Similarly, the new PIs including carfilzomib and ixazomib can inhibit bone resorption and stimulate the osteoblast differentiation. In a clinical setting, PIs restore the abnormal bone remodeling by normalizing the levels of bone turnover markers. In addition, a bone anabolic effect was described in responding MM patients treated with PIs, as demonstrated by the increase in the osteoblast number. This review summarizes the preclinical and clinical evidence on the effects of bortezomib and other new PIs on myeloma bone disease