Progenitor cells in auricular cartilage demonstrate promising cartilage regenerative potential in 3D hydrogel culture

The reconstruction of auricular deformities is a very challenging surgical procedure that could benefit from a tissue engineering approach. Nevertheless, a major obstacle is presented by the acquisition of sufficient amounts of autologous cells to create a cartilage construct the size of the human ear. Extensively expanded chondrocytes are unable to retain their phenotype, while bone marrow-derived mesenchymal stromal cells (MSC) show endochondral terminal differentiation by formation of a calcified matrix. The identification of tissue-specific progenitor cells in auricular cartilage, which can be expanded to high numbers without loss of cartilage phenotype, has great prospects for cartilage regeneration of larger constructs. This study investigates the largely unexplored potential of auricular progenitor cells for cartilage tissue engineering in 3D hydrogels

New product entry success : an examination of variable, dimensional and model evolution

This thesis examines the evolution of antecedents, dimensions and initial screening models which discriminate between new product success and failure. It advances on previous empirical new product success/failure comparative studies by developing a discrete simulation procedure in which participating new product managers supply judgements retrospectively on new product strategies and orientations for two distinct time periods in the new product program: (1) the initial screening stage and (2) a period approximately 1 year after market entry. Unique linear regression functions are derived for each event and offer different, but complimentary, temporally appropriate sets of determining factors. Model predictive accuracy ascends over time and conditional process moderators alter success factors at both time periods. Whilst the work validates and synthesises much from the new product development literature, is exposes probable measurement timing error when single retrospective models assess success dimension rank at the initial screen. Six of seven hypotheses are accepted and demonstrate that: 1. Many antecedents of success and measures of objective attainment are perceived by NPD (new product development) managers to differ significantly over time. 2. Reactive strategy, NPD multigenerational history and a superior product are the most important dimensions of success through one year post launch. 3. Current linear screening models constructed using retrospective methods produce average prescriptive dimensions which exhibit measurement timing error when used at the initial screen. 4. Success dimensions evolve from somewhat deterministic to more stochastic over time with model forecasting accuracy rising as launch approaches based on better data availability. 5. Product market PiLC (the life expectancy of an introduction before modification is necessary calculated in years and months) and its order of entry and level of innovation alter aggregate success model accuracy and dimension rank. 6. Proper initial dimensional alignment and intra-process realignment based on changing environments is critical to a successful project through one year post launch. The work cautions practitioners not to wait for better models to be developed but immediately: (1) benchmark reasons for their current product market success, failure and kill historical "batting average"; (2) enhance and/or replace contributing/offending processes and systems based on these history lessons; (3) choose or reject aggregate or conditional success/failure models based on team forecasting ability; (4) concentrate on the selected model's time specific dimensions of success and (5) provide/reserve adequate resources to adapt strategically over time to both internal and external antecedent changes in the NPD environment. Finally, it recommends new research into temporal, conditional and strategic tradeoffs in internal and external antecedents/dimensions of success. Best results should come from using both linear and curvilinear methods to validate more complex yet statistically elegant NPD simulations

Psr1p interacts with SUN/sad1p and EB1/mal3p to establish the bipolar spindle

Regular Abstracts - Sunday Poster Presentations: no. 382During mitosis, interpolar microtubules from two spindle pole bodies (SPBs) interdigitate to create an antiparallel microtubule array for accommodating numerous regulatory proteins. Among these proteins, the kinesin-5 cut7p/Eg5 is the key player responsible for sliding apart antiparallel microtubules and thus helps in establishing the bipolar spindle. At the onset of mitosis, two SPBs are adjacent to one another with most microtubules running nearly parallel toward the nuclear envelope, creating an unfavorable microtubule configuration for the kinesin-5 kinesins. Therefore, how the cell organizes the antiparallel microtubule array in the first place at mitotic onset remains enigmatic. Here, we show that a novel protein psrp1p localizes to the SPB and plays a key role in organizing the antiparallel microtubule array. The absence of psr1+ leads to a transient monopolar spindle and massive chromosome loss. Further functional characterization demonstrates that psr1p is recruited to the SPB through interaction with the conserved SUN protein sad1p and that psr1p physically interacts with the conserved microtubule plus tip protein mal3p/EB1. These results suggest a model that psr1p serves as a linking protein between sad1p/SUN and mal3p/EB1 to allow microtubule plus ends to be coupled to the SPBs for organization of an antiparallel microtubule array. Thus, we conclude that psr1p is involved in organizing the antiparallel microtubule array in the first place at mitosis onset by interaction with SUN/sad1p and EB1/mal3p, thereby establishing the bipolar spindle.postprin

Removal of antagonistic spindle forces can rescue metaphase spindle length and reduce chromosome segregation defects

Regular Abstracts - Tuesday Poster Presentations: no. 1925Metaphase describes a phase of mitosis where chromosomes are attached and oriented on the bipolar spindle for subsequent segregation at anaphase. In diverse cell types, the metaphase spindle is maintained at a relatively constant length. Metaphase spindle length is proposed to be regulated by a balance of pushing and pulling forces generated by distinct sets of spindle microtubules and their interactions with motors and microtubule-associated proteins (MAPs). Spindle length appears important for chromosome segregation fidelity, as cells with shorter or longer than normal metaphase spindles, generated through deletion or inhibition of individual mitotic motors or MAPs, showed chromosome segregation defects. To test the force balance model of spindle length control and its effect on chromosome segregation, we applied fast microfluidic temperature-control with live-cell imaging to monitor the effect of switching off different combinations of antagonistic forces in the fission yeast metaphase spindle. We show that spindle midzone proteins kinesin-5 cut7p and microtubule bundler ase1p contribute to outward pushing forces, and spindle kinetochore proteins kinesin-8 klp5/6p and dam1p contribute to inward pulling forces. Removing these proteins individually led to aberrant metaphase spindle length and chromosome segregation defects. Removing these proteins in antagonistic combination rescued the defective spindle length and, in some combinations, also partially rescued chromosome segregation defects. Our results stress the importance of proper chromosome-to-microtubule attachment over spindle length regulation for proper chromosome segregation.postprin

Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists

New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes

Sonic interactions in virtual environments

This book tackles the design of 3D spatial interactions in an audio-centered and audio-first perspective, providing the fundamental notions related to the creation and evaluation of immersive sonic experiences. The key elements that enhance the sensation of place in a virtual environment (VE) are: Immersive audio: the computational aspects of the acoustical-space properties of Virutal Reality (VR) technologies Sonic interaction: the human-computer interplay through auditory feedback in VE VR systems: naturally support multimodal integration, impacting different application domains Sonic Interactions in Virtual Environments will feature state-of-the-art research on real-time auralization, sonic interaction design in VR, quality of the experience in multimodal scenarios, and applications. Contributors and editors include interdisciplinary experts from the fields of computer science, engineering, acoustics, psychology, design, humanities, and beyond. Their mission is to shape an emerging new field of study at the intersection of sonic interaction design and immersive media, embracing an archipelago of existing research spread in different audio communities and to increase among the VR communities, researchers, and practitioners, the awareness of the importance of sonic elements when designing immersive environments