The Fundamentals And Fun Of Electronic Teamwork For Students And Their Instructors

This paper reviews and integrates best practices for online teamwork for students and instructors from current and classical literature as well as the author’s own six years of online teaching experience (over 40 online courses). A qualitative reflection of six graduate and six undergraduate courses in management, human resource management and organizational development using student teams via the internet were used in this study. An updated model of Tuckman’s (1965) team development process is offered. Additional reflection on the use of confidential, student peer ratings are given. Samples of student feedback on the team experience in their courses are summarized along with lessons learned for the instructor and the student

Establishment of a Spaceport Network Architecture

Since the beginning of the space age, the main actors in space exploration have been governmental agencies, enabling a privileged access to space, but with very restricted and rare missions. The last decade has seen the rise of space tourism, and the founding of ambitious private space mining companies, showing the beginnings of a new exploration era, that is based on a more generalized and regular access to space and which is not limited to the Earth's vicinity. However, the cost of launching sufficient mass into orbit to sustain these inspiring challenges is prohibitive, and the necessary infrastructures to support these missions is still lacking. To provide easy and affordable access into orbital and deep space destinations, there is the need to create a network of spaceports via specific waypoint locations coupled with the use of natural resources, or In Situ Resource Utilization (ISRU), to provide a more economical solution. As part of the International Space University Space Studies Program 2012, the international and intercultural team of Operations and Service Infrastructure for Space (OASIS) proposes an interdisciplinary answer to the problem of economical space access and transportation. This paper presents a summary of a detailed report [1] of the different phases of a project for developing a network of spaceports throughout the Solar System in a timeframe of 50 years. The requirements, functions, critical technologies and mission architecture of this network of spaceports are outlined in a roadmap of the important steps and phases. The economic and financial aspects are emphasized in order to allow a sustainable development of the network in a public-private partnership via the formation of an International Spaceport Authority (ISPA). The approach includes engineering, scientific, financial, legal, policy, and societal aspects. Team OASIS intends to provide guidelines to make the development of space transportation via a spaceports logistics network feasible, and believes that this pioneering effort will revolutionize space exploration, science and commerce, ultimately contributing to permanently expand humanity into space

Vector Meson Photoproduction from the BFKL Equation II: Phenomenology

Diffractive vector meson photoproduction accompanied by proton dissociation is studied for large momentum transfer. The process is described by the non-forward BFKL equation which we use to compare to data collected at the HERA collider.Comment: 39 pages, 29 figure

Apollo Lightcraft Project

This second year of the NASA/USRA-sponsored Advanced Aeronautical Design effort focused on systems integration and analysis of the Apollo Lightcraft. This beam-powered, single-stage-to-orbit vehicle is envisioned as the shuttlecraft of the 21st century. The five person vehicle was inspired largely by the Apollo Command Module, then reconfigured to include a new front seat with dual cockpit controls for the pilot and co-pilot, while still retaining the 3-abreast crew accommodations in the rear seat. The gross liftoff mass is 5550 kg, of which 500 kg is the payload and 300 kg is the LH2 propellant. The round trip cost to orbit is projected to be three orders of magnitude lower than the current space shuttle orbiter. The advanced laser-driven 5-speed combined-cycle engine has shiftpoints at Mach 1, 5, 11 and 25+. The Apollo Lightcraft can climb into low Earth orbit in three minutes, or fly to any spot on the globe in less than 45 minutes. Detailed investigations of the Apollo Lightcraft Project this second year further evolved the propulsion system design, while focusing on the following areas: (1) man/machine interface; (2) flight control systems; (3) power beaming system architecture; (4) re-entry aerodynamics; (5) shroud structural dynamics; and (6) optimal trajectory analysis. The principal new findings are documented. Advanced design efforts for the next academic year (1988/1989) will center on a one meter+ diameter spacecraft: the Lightcraft Technology Demonstrator (LTD). Detailed engineering design and analyses, as well as critical proof-of-concept experiments, will be carried out on this small, near-term machine. As presently conceived, the LTD could be constructed using state of the art components derived from existing liquid chemical rocket engine technology, advanced composite materials, and high power laser optics

Serum Levels of Alpha-1 Antitrypsin following Vascular Limb or Intra-Muscular Delivery of AAV1 or AAV8 Gene Therapy Vectors in Rhesus Macaques

Alpha-one antitrypsin (AAT) deficiency is a genetic disease that results in both lung disease and potentially liver failure in affected patients. In un-affected people AAT is produced in the liver and secreted to act as an anti-protease (primarily counteracting the effects of neutrophil elastase) in the lung. On-going human clinical trials have focused on intra-muscular delivery of adeno-associated virus (AAV1) to patients. The goal of delivery to the muscle is to have the myocytes serve as bio-factories to produce normal AAT protein and secrete it into the blood where it can exert its normal function in the lung. In the last Phase II trial patients in the highest dose cohort were given 100 intra-muscular (IM) injections with serum AAT levels still below therapeutic thresholds. Previous work has shown that delivering AAV vector to the musculature of the limb via the vasculature, while blood flow is obstructed using a tourniquet, leads to wide-spread gene expression in myocytes. We hypothesize that local delivery via IM injection results in saturated AAT expression within the myocytes surrounding the injection sight and that a more widespread delivery would result in an overall increase in serum AAT levels with the same dose of AAV gene therapy vector due to production by a larger overall number of myocytes. We have been able to show that we can attain similar or slightly higher (573.0 ng/ml versus 562.5 ng/nl) serum AAT levels using a vascular delivery method in rhesus macaques when compared to IM delivery. These results have been obtained using AAV1. Animals receiving either AAV1 or AAV8 show a decrease in muscle immune cell infiltrates following intra-vascular delivery versus IM delivery, which may improve long-term expression. Serum AAT data from animals dosed using AAV8, a serotype shown to better target muscle following vascular delivery, are currently being processed

Associations of Prenatal Nicotine Exposure and the Dopamine Related Genes ANKK1 and DRD2 to Verbal Language

Language impairment (LI) and reading disability (RD) are common pediatric neurobehavioral disorders that frequently co-occur, suggesting they share etiological determinants. Recently, our group identified prenatal nicotine exposure as a factor for RD and poor reading performance. Using smoking questionnaire and language data from the Avon Longitudinal Study of Parents and Children, we first determined if this risk could be expanded to other communication disorders by evaluating whether prenatal nicotine exposure increases risk for LI and poor performance on language tasks. Prenatal nicotine exposure increased LI risk (OR = 1.60; p = 0.0305) in a dose-response fashion with low (OR = 1.25; p = 0.1202) and high (OR = 3.84; p = 0.0002) exposures. Next, hypothesizing that the effects of prenatal nicotine may also implicate genes that function in nicotine related pathways, we determined whether known nicotine dependence (ND) genes associate with performance on language tasks. We assessed the association of 33 variants previously implicated in ND with LI and language abilities, finding association between ANKK1/DRD2 and performance on language tasks (p≤0.0003). The associations of markers within ANKK1 were replicated in a separate LI case-control cohort (p<0.05). Our results show that smoking during pregnancy increases the risk for LI and poor performance on language tasks and that ANKK1/DRD2 contributes to language performance. More precisely, these findings suggest that prenatal environmental factors influence in utero development of neural circuits vital to language. Our association of ANKK1/DRD2 further implicates the role of nicotine-related pathways and dopamine signaling in language processing, particularly in comprehension and phonological memory

Sustained Expression with Partial Correction of Neutrophil Defects 5 Years After Intramuscular rAAV1 Gene Therapy for Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) deficiency is a common monogenic disorder resulting in emphysema, which is currently treated with weekly infusions of protein replacement. We previously reported achieving plasma wild-type (M) AAT concentrations at 2.5-3.8% of the therapeutic level at 1 year after intramuscular (IM) administration of 6×1012vg/kg of a recombinant adeno-associated virus serotype 1 (rAAV1)-AAT vector in AAT-deficient patients, with an associated regulatory T cell (Treg) response to AAV1 capsid epitopes in the absence of any exogenous immune suppression. Here, we report sustained expression at greater than 2% of the therapeutic level for 5 years after one-time treatment with rAAV1-AAT in an AAT-deficient patient from that study, with partial correction of neutrophil defects previously reported in AAT-deficient patients. There was also evidence of an active Treg response (FoxP3+, Helios+) and an exhausted cytotoxic T cell response (PD-1+, LAG-3+) to AAV1 capsid. These findings suggest that muscle-based AAT gene replacement is toleragenic and that very stable levels of M AAT may exert beneficial effects at lower concentrations than previously anticipated

Bridging from Intramuscular to Limb Perfusion Delivery of rAAV: Optimization in a Non-human Primate Study

Phase 1 and phase 2 gene therapy trials using intramuscular (IM) administration of a recombinant adeno-associated virus serotype 1 (rAAV1) for replacement of serum alpha-1 antitrypsin (AAT) deficiency have shown long-term (5-year) stable transgene expression at approximately 2% to 3% of therapeutic levels, arguing for the long-term viability of this approach to gene replacement of secreted serum protein deficiencies. However, achieving these levels required 100 IM injections to deliver 135 mL of vector, and further dose escalation is limited by the scalability of direct IM injection. To further advance the dose escalation, we sought to bridge the rAAV-AAT clinical development program to regional limb perfusion, comparing two methods previously established for gene therapy, peripheral venous limb perfusion (VLP) and an intra-arterial push and dwell (IAPD) using rAAV1 and rAAV8 in a non-human primate (rhesus macaque) study. The rhesus AAT transgene was used with a c-myc tag to enable quantification of transgene expression. 5 cohorts of animals were treated with rAAV1-IM, rAAV1-VLP, rAAV1-IAPD, rAAV8-VLP, and rAAV8-IAPD (n = 2-3), with a dose of 6 x 10(12) vg/kg. All methods were well tolerated clinically. Potency, as determined by serum levels of AAT, of rAAV1 by the VLP method was twice that observed with direct IM injection; 90 mug/mL with VLP versus 38 mug/mL with direct IM injection. There was an approximately 25-fold advantage in estimated vector genomes retained within the muscle tissue with VLP and a 5-fold improvement in the ratio of total vector genomes retained within muscle as compared with liver. The other methods were intermediate in the potency and retention of vector genomes. Examination of muscle enzyme (CK) levels indicated rAAV1-VLP to be equally safe as compared with IM injection, while the IAPD method showed significant CK elevation. Overall, rAAV1-VLP demonstrates higher potency per vector genome injected and a greater total vector retention within the muscle, as compared to IM injection, while enabling a much greater total dose to be delivered, with equivalent safety. These data provide the basis for continuation of the dose escalation of the rAAV1-AAT program in patients and bode well for rAAV-VLP as a platform for replacement of secreted proteins