Polymorphisms in Calpastatin and mu-Calpain Genes Are Associated with Beef Iron Content

The objective of this study was to assess the association of markers in the calpastatin and mu-calpain loci with iron in beef cattle muscle. The population consisted of 259 cross-bred steers from Beefmaster, Brangus, Bonsmara, Romosinuano, Hereford and Angus sires. Total iron and heme iron concentrations were measured. Markers in the calpastatin (referred to as CAST) and mu-calpain (referred to asCAPN4751) genes were used to assess their association with iron levels. The mean and standard error for iron and heme iron content in the population was 35.6 ± 1.3 μg and 27.1 ± 1.4 μg respectively. Significant associations (P \u3c 0.01) of markers were observed for both iron and heme iron content. For CAST, animals with the CC genotype had higher levels of iron and heme iron in longissimus dorsi muscle. ForCAPN4751, individuals with the TT genotype had higher concentrations of iron and heme iron than did animals with the CC and CT genotypes. Genotypes known to be associated with tougher meat were associated with higher levels of iron concentration

Conductivity of dielectric and thermal atom-wall interaction

We compare the experimental data of the first measurement of a temperature dependence of the Casimir-Polder force by Obrecht et al. [Phys. Rev. Lett. {\bf 98}, 063201 (2007)] with the theory taking into account small, but physically real, static conductivity of the dielectric substrate. The theory is found to be inconsistent with the data. The conclusion is drawn that the conductivity of dielectric materials should not be included in the model of the dielectric response in the Lifshitz theory. This conclusion obtained from the long separation measurement is consistent with related but different results obtained for semiconductors and metals at short separations.Comment: 4 pages, 2 figures; page size is correcte

Skeletal Recovery Following Long-Duration Spaceflight Missions as Determined by Preflight and Postflight DXA Scans of 45 Crew Members

Introduction: The loss of bone mineral in astronauts during spaceflight has been investigated throughout the more than 40 years of bone research in space. Consequently, it is a medical requirement at NASA that changes in bone mass be monitored in crew members by measurements of bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA). This report is the first to evaluate medical data to address the recovery of bone mineral that is lost during spaceflight. Methods: DXA scans are performed before and after flight in astronauts who serve on long-duration missions (4-6 months) to ensure that medical standards for flight certification are met, to evaluate the effects of spaceflight and to monitor the restoration to preflight BMD status after return to Earth. Through cooperative agreements with the Russian Space Agency, the Bone and Mineral Lab at NASA Johnson Space Center (Houston, TX), also had access to BMD data from cosmonauts who had flown on long-duration missions yielding data from a total of 45 individual crew members. Changes in BMD (between 56 different sets of pre- and postflight measurements) were plotted as a function of time (days after landing); plotted data were fitted to an exponential mathematical model that determined i) BMD change at day 0 after landing and ii) the number of days after which 50% of the lost bone was recovered ("Recovery Half-Life"). These fits were performed for BMD of the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. Results: In sum, averaged losses of bone mineral after spaceflight ranged between 2-9% for sites in the axial and appendicular skeleton. The fitted postflight BMD values predicted a 50% recovery of bone loss for all sites within 9 months

The trade off between diversity and quality for multi-objective workforce scheduling

In this paper we investigate and compare multi-objective and weighted single objective approaches to a real world workforce scheduling problem. For this difficult problem we consider the trade off in solution quality versus population diversity, for different sets of fixed objective weights. Our real-world workforce scheduling problem consists of assigning resources with the appropriate skills to geographically dispersed task locations while satisfying time window constraints. The problem is NP-Hard and contains the Resource Constrained Project Scheduling Problem (RCPSP) as a sub problem. We investigate a genetic algorithm and serial schedule generation scheme together with various multi-objective approaches. We show that multi-objective genetic algorithms can create solutions whose fitness is within 2% of genetic algorithms using weighted sum objectives even though the multi-objective approaches know nothing of the weights. The result is highly significant for complex real-world problems where objective weights are seldom known in advance since it suggests that a multi-objective approach can generate a solution close to the user preferred one without having knowledge of user preferences

Adaptation of the Skeletal System during Long-duration Spaceflight

This review will highlight evidence from crew members flown on space missions greater than 90 days to suggest that the adaptations of the skeletal system to mechanical unloading may predispose crew members to an accelerated onset of osteoporosis after return to Earth. By definition, osteoporosis is a skeletal disorder - characterized by low bone mineral density and structural deterioration - that reduces the ability of bones to resist fracture under the loading of normal daily activities. Involutional or agerelated osteoporosis is readily recognized as a syndrome afflicting the elderly population because of the insipid and asymptomatic nature of bone loss that does not typically manifest as fractures until after age approximately 60. It is not the thesis of this review to suggest that spaceflight-induced bone loss is similar to bone loss induced by metabolic bone disease; rather this review draws parallels between the rapid and earlier loss in females that occurs with menopause and the rapid bone loss in middle-aged crew members that occurs with spaceflight unloading and how the cumulative effects of spaceflight and ageing could be detrimental, particularly if skeletal effects are totally or partially irreversible. In brief, this report will provide detailed evidence that long-duration crew members, exposed to the weightlessness of space for the typical long-duration (4-6 months) mission on Mir or the International Space Station -- 1. Display bone resorption that is aggressive, that targets normally weight-bearing skeletal sites, that is uncoupled to bone formation and that results in areal BMD deficits that can range between 6-20% of preflight BMD; 2. Display compartment-specific declines in volumetric BMD in the proximal femur (a skeletal site of clinical interest) that significantly reduces its compressive and bending strength and which may account for the loss in hip bone strength (i.e., force to failure); 3. Recover BMD over a post-flight time period that exceeds spaceflight exposure but for which the restoration of whole bone strength remains an open issue and may involve structural alteration; and 4. Display risk factors for bone loss -- such as the negative calcium balance and down-regulated calcium-regulating hormones in response to bone atrophy -- that can be compounded by the constraints of conducting mission operations (inability to provide essential nutrients and vitamins). The full characterization of the skeletal response to mechanical unloading in space is not complete. In particular, countermeasures used to date have been inadequate and it is not yet known whether more appropriate countermeasures can prevent the changes in bone that have been found in previous flights, knowledge gaps related to the effects of prolonged (greater than or equal to 6 months) space exposure and to partial gravity environments are substantial, and longitudinal measurements on crew members after spaceflight are required to assess the full impact on skeletal recovery

Salt-inducible kinases (SIKs) regulate TGFβ-mediated transcriptional and apoptotic responses

The signalling pathways initiated by members of the transforming growth factor-β (TGFβ) family of cytokines control many metazoan cellular processes, including proliferation and differentiation, epithelial-mesenchymal transition (EMT) and apoptosis. TGFβ signalling is therefore strictly regulated to ensure appropriate context-dependent physiological responses. In an attempt to identify novel regulatory components of the TGFβ signalling pathway, we performed a pharmacological screen by using a cell line engineered to report the endogenous transcription of the TGFβ-responsive target gene PAI-1. The screen revealed that small molecule inhibitors of salt-inducible kinases (SIKs) attenuate TGFβ-mediated transcription of PAI-1 without affecting receptor-mediated SMAD phosphorylation, SMAD complex formation or nuclear translocation. We provide evidence that genetic inactivation of SIK isoforms also attenuates TGFβ-dependent transcriptional responses. Pharmacological inhibition of SIKs by using multiple small-molecule inhibitors potentiated apoptotic cell death induced by TGFβ stimulation. Our data therefore provide evidence for a novel function of SIKs in modulating TGFβ-mediated transcriptional and cellular responses.</p

Role of the ubiquitin system and tumor viruses in AIDS-related cancer

Tumor viruses are linked to approximately 20% of human malignancies worldwide. This review focuses on examples of human oncogenic viruses that manipulate the ubiquitin system in a subset of viral malignancies; those associated with AIDS. The viruses include Kaposi's sarcoma herpesvirus, Epstein-Barr virus and human papilloma virus, which are causally linked to Kaposi's sarcoma, certain B-cell lymphomas and cervical cancer, respectively. We discuss the molecular mechanisms by which these viruses subvert the ubiquitin system and potential viral targets for anti-cancer therapy from the perspective of this system

Project Selection and Process Plan Design for Alternative IME 143/144 Final Project

Hundreds of students each year enroll in IME 143 or IME 144, freshman-level machining classes, and complete an air motor to demonstrate the skills they have acquired on a variety of manufacturing processes. The air motor, however is useful only as a teaching tool in the classroom; once the students bring them home, the air motor becomes little more than a trophy at best. With the capabilities of the machining lab, a final project can be developed that can have a benefit to people in need while maintaining educational value. This project details a process plan for a manual water pump. The pump can be donated for use in developing countries where access to clean water is still in desperate need. The process for manufacturing the water pump had to be deconstructed into specific machining processes and balanced appropriately between the machines available to the classes. The machining lab has a number of different machines that enable students to use 14 different processes. Unlike a production environment, all processes have to be used and balanced to make use of lab time. This often meant using sub-optimal processes and/or procedures. The critical benchmark for implementing the water pump into the curriculum is the cost. Students in IME 143/144 pay lab fees, which cover the cost of materials for the quarter. The fees are $10 for IME 143 and$50 for IME 144. Based on rough estimates from these lab fees, the actual cost of the air motor is between $10 and$20. As designed currently, the water pump has a material cost of about $30. However, this project is larger and more complex. It is recommended that one pump be made for every two students bringing the per student cost to about$15, within the cost range of the air motor

Do Multinationals or Domestic Firms Face Higher Effective Tax Rates?

To our knowledge, this paper provides the most comprehensive analysis of firm-level corporate income tax expenses to date. We use publicly available financial statement information to estimate firm-level effective tax rates (ETRs) for 10,642 corporations from 85 countries from 1988 to 2007. We find that multinationals and domestic-only companies face similar ETRs. We also find that, on average, ETRs declined by seven percentage points or 20% over the period. German, Japanese, Australian and Canadian decreases were large. American, British, and French declines were more modest. Nonetheless, because ETRs were falling worldwide, the ordinal rank from high-tax countries to low-tax countries changed little. Japanese firms always faced the highest ETRs. ETRs for tax havens and countries from the Middle East and Asia (ignoring Japan) were always lower than those for the U.S. and European countries. These findings should provide some empirical underpinning for ongoing policy debates about the taxation of multinational profits.

Hypoxia induces a phase transition within a kinase signaling network in cancer cells

Hypoxia is a near-universal feature of cancer, promoting glycolysis, cellular proliferation, and angiogenesis. The molecular mechanisms of hypoxic signaling have been intensively studied, but the impact of changes in oxygen partial pressure (pO2) on the state of signaling networks is less clear. In a glioblastoma multiforme (GBM) cancer cell model, we examined the response of signaling networks to targeted pathway inhibition between 21% and 1% pO_2. We used a microchip technology that facilitates quantification of a panel of functional proteins from statistical numbers of single cells. We find that near 1.5% pO_2, the signaling network associated with mammalian target of rapamycin (mTOR) complex 1 (mTORC1)—a critical component of hypoxic signaling and a compelling cancer drug target—is deregulated in a manner such that it will be unresponsive to mTOR kinase inhibitors near 1.5% pO2, but will respond at higher or lower pO_2 values. These predictions were validated through experiments on bulk GBM cell line cultures and on neurosphere cultures of a human-origin GBM xenograft tumor. We attempt to understand this behavior through the use of a quantitative version of Le Chatelier’s principle, as well as through a steady-state kinetic model of protein interactions, both of which indicate that hypoxia can influence mTORC1 signaling as a switch. The Le Chatelier approach also indicates that this switch may be thought of as a type of phase transition. Our analysis indicates that certain biologically complex cell behaviors may be understood using fundamental, thermodynamics-motivated principles