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Coping with frequent unexpected events requires an organizational culture that allows the project manager to exercise a great amount of flexibility. The authors' studies, employing experiential data collected from more than 150 successful project managers affiliated with more than 20 organizations, indicate that today's successful project managers cope with unexpected events by a combination of the traditional and agile approaches, assuming four roles. Developing collaboration requires project managers to be people-oriented. Integrating planning and review with learning requires them to be information-oriented. Preventing major disruptions requires them to be action-oriented. Finally, maintaining forward momentum, which is pursued throughout a project, requires them to adopt all three orientations.

A finite expansion of the exponential map for a \\(N\\times N\\) matrix is presented. The method uses the Cayley-Hamilton theorem for writing the higher matrix powers in terms of the first N-1 ones. The resulting sums over the corresponding coefficients are rational functions of the eigenvalues of the matrix.

Welcome to the Academy of Program and Project Leadership (APPL) and ASK Magazine. APPL helps NASA managers and project teams accomplish today's missions and meet tomorrow's challenges by providing performance enhancement services and tools, supporting career development programs, sponsoring knowledge sharing events and publications, and creating opportunities for project management collaboration with universities, professional associations, industry partners and other government agencies. ASK Magazine grew out of APPL's Knowledge Sharing Initiative. The stories that appear in ASK are written by the 'best of the best' project managers, primarily from NASA, but also from other government agencies and industry. These stories contain genuine nuggets of knowledge and wisdom that are transferable across projects. Who better than a project manager to help another project manager address a critical issue on a project? Big projects, smaLl projects-they're ali here in ASK. Stories in this issue include: Earthly Considerations on Mars, Getting Politically Active, Stumping for the Project, Grins & Giggles: The Launch Pad to High Performance, Transfer Wisdom Workshops: Coming to a NASA Center Near You, Project Management: The Television Show, Lessons Learned Again and Again and Again, Implementation Reviews, ASK Talks with Dr. Michael Hecht, and What Is This Fourth Dimension?.

A study was conducted to assess the extent of influence of uncertainty on the accomplishment of planned project objectives through examining planning outcomes and attempts to pinpoint the factors having the greatest influence on the outcome. Data were collected from a questionnaire mailed to 400 top US construction firms, to which 72 replied. The questionnaire proposed a model project with 4 fixed and 8 variable characteristics grouped under 3 main project dimensions -- project complexity, project uncertainty, and attitudes toward planning. The results showed that, when moving from average to complex or uncertain situations, planned project objectives were affected considerably. However, a majority of the respondents felt that simple or certain situations had no effect on planning outcomes. Factors regarded as most influential were percentage of completion of design and construction experience. Factors having a strong influence were labor supply, weather predictability, and attitudes toward planning.

Mori's theory of extremal rays and minimal models has breathed new life into the classification problem in algebraic geometry. In this thesis, we investigate the behavior of minimal varieties under deformation. First, we show the preservation of minimality under an arbitrary smooth, projective deformation. Then, using results of Kodaira, Horikawa, Mori, and Kollar, we deduce the deformation invariance of plurigenera under small projective deformations. Along the way, we establish the basepoint free theorem for smooth minimal varieties, and discuss briefly the problem of computing bounds for effective non-vanishing. Lastly, we also make conjectures for both Kahler varieties and higher dimensional varieties, based on the results for both surfaces and three-folds.

The Arctic has the highest warming rates on Earth. Glaciated fjord ecosystems, which are hotspots of carbon cycling and burial, are extremely sensitive to this warming. Glaciers are important for the transport of iron from land to sea and supply this essential nutrient to phytoplankton in high-latitude marine ecosystems. However, up to 95% of the glacially-sourced iron settles to sediments close to the glacial source. Our data show that while 0.6–12% of the total glacially-sourced iron is potentially bioavailable, biogeochemical cycling in Arctic fjord sediments converts the glacially-derived iron into more labile phases, generating up to a 9-fold increase in the amount of potentially bioavailable iron. Arctic fjord sediments are thus an important source of potentially bioavailable iron. However, our data suggests that as glaciers retreat onto land the flux of iron to the sediment-water interface may be reduced. Glacial retreat therefore likely impacts iron cycling in coastal marine ecosystems. The impacts of a melting Arctic on the biogeochemistry of marine ecosystems are unknown. Here, the authors investigate glacial input of iron to Svalbard fjords finding that reworking of glacial iron in fjord sediment is important to make iron bioavailable, but could be susceptible to glacial retreat.

Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease accompanied by structural and contractile alterations. We identified a rare c.740C>T (p.T247M) mutation in ACTN2 , encoding α‐actinin 2 in a HCM patient, who presented with left ventricular hypertrophy, outflow tract obstruction, and atrial fibrillation. We generated patient‐derived human‐induced pluripotent stem cells (hiPSCs) and show that hiPSC‐derived cardiomyocytes and engineered heart tissues recapitulated several hallmarks of HCM, such as hypertrophy, myofibrillar disarray, hypercontractility, impaired relaxation, and higher myofilament Ca 2+ sensitivity, and also prolonged action potential duration and enhanced L‐type Ca 2+ current. The L‐type Ca 2+ channel blocker diltiazem reduced force amplitude, relaxation, and action potential duration to a greater extent in HCM than in isogenic control. We translated our findings to patient care and showed that diltiazem application ameliorated the prolonged QTc interval in HCM‐affected son and sister of the index patient. These data provide evidence for this ACTN2 mutation to be disease‐causing in cardiomyocytes, guiding clinical therapy in this HCM family. This study may serve as a proof‐of‐principle for the use of hiPSC for personalized treatment of cardiomyopathies. Synopsis Disease modeling of a rare ACTN2 mutation in iPSC‐derived cardiomyocytes & heart tissues engineering revealed typical features of hypertrophic cardiomyopathy & electrophysiological anomalies. Diltiazem reversed the in vitro phenotypes & guided clinical therapy in the family, reducing QTc intervals. Modeling hypertrophic cardiomyopathy (HCM) with patient‐ and isogenic control‐derived hiPSC‐cardiomyocytes revealed higher cell area, myofibrillar disarray and higher LTCC density in 2D, and hypercontractility, prolonged relaxation and action potentials in 3D. Prolonged action potentials in 3D associated with higher LTCC currents in 2D, matching prolonged QT intervals and monophasic action potentials in HCM‐affected family members. Diltiazem normalized the electro‐mechanical phenotype in vitro and guided clinical therapy in the HCM affected family, reducing QTc intervals. This study may serve as proof‐of‐principle for the use of hiPSC‐cardiomyocytes and CRISPR/Cas9 for personalized treatment of cardiomyopathies. Graphical Abstract Disease modeling of a rare ACTN2 mutation in iPSC‐derived cardiomyocytes & heart tissues engineering revealed typical features of hypertrophic cardiomyopathy & electrophysiological anomalies. Diltiazem reversed the in vitro phenotypes & guided clinical therapy in the family, reducing QTc intervals.

Invasive infections associated with non-typhoidal Salmonella (NTS) serovars Enteritidis (SE), Typhimurium (STm) and monophasic variant 1,4,[5],12:i:- are a major health problem in infants and young children in sub-Saharan Africa, and currently, there are no approved human NTS vaccines. NTS O-polysaccharides and flagellin proteins are protective antigens in animal models of invasive NTS infection. Conjugates of SE core and O-polysaccharide (COPS) chemically linked to SE flagellin have enhanced the anti-COPS immune response and protected mice against fatal challenge with a Malian SE blood isolate. We report herein the development of a STm glycoconjugate vaccine comprised of STm COPS conjugated to the homologous serovar phase 1 flagellin protein (FliC) with assessment of the role of COPS O-acetyls for functional immunity. Sun-type COPS conjugates linked through the polysaccharide reducing end to FliC were more immunogenic and protective in mice challenged with a Malian STm blood isolate than multipoint lattice conjugates (>95% vaccine efficacy [VE] versus 30-43% VE). Immunization with de-O-acetylated STm-COPS conjugated to CRM197 provided significant but reduced protection against STm challenge compared to mice immunized with native STm-COPS:CRM197 (63-74% VE versus 100% VE). Although OPS O-acetyls were highly immunogenic, post-vaccination sera that contained various O-acetyl epitope-specific antibody profiles displayed similar in vitro bactericidal activity when equivalent titers of anti-COPS IgG were assayed. In-silico molecular modeling further indicated that STm OPS forms a single dominant conformation, irrespective of O-acetylation, in which O-acetyls extend outward and are highly solvent exposed. These preclinical results establish important quality attributes for an STm vaccine that could be co-formulated with an SE-COPS:FliC glycoconjugate as a bivalent NTS vaccine for use in sub-Saharan Africa.