Synergistic growth factor microenvironments

Growth factors (GF) are remarkably powerful signalling molecules that orchestrate developmental biology. GFs are currently used in medjcal applications with limited success but it is clear that if their potential can be harnessed for biomedicine then they could underpin the discipline of regenerative medicine. However, while we understand that biology uses cell-secreted growth factors tethered to the ECM, biologists typically employ GFs in soluble format at high concentrations. When used in vivo, this causes off-target, unwanted effects, which severely limits their use. There is a vast amount of literature dealing with material systems that control the delivery of GFs. However, it was soon observed that GFs could be more effectively presented bound to surfaces from a solid-phase state rather than in soluble form, recapitulating the way the extracellular matrix (ECM) binds GFs. In parallel, evidence was found that within the ECM, GFs can actually work in cooperation with integrins and that this produced ehnaced GF signalling due to the crosstalk between both receptors. Recently this knowledge was used to engineer microenvironments that target simultaneous integrin and GF receptor engagement seeking to maximise GF effects in vitro (e.g. in terms of stem cell differentiation) but also tissue repair in vivo (e.g. bone regeneration and wound healing). This feature article introduces the concept of synergistic GF/integrin signalling and then introduces GF delivery systems that were key in the development of more advanced synergistic growth factor microenvironments

Designing stem cell niches for differentiation and self-renewal

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche. Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro. In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries

Current approaches for modulation of the nanoscale interface in the regulation of cell behavior

Regulation of cell behavior in response to nanoscale features has been the focus of much research in recent years and the successful generation of nanoscale features capable of mimicking the natural nanoscale interface has been of great interest in the field of biomaterials research. In this review, we discuss relevant nanofabrication techniques and how they are combined with bioengineering applications to mimic the natural extracellular matrix (ECM) and create valuable nanoscale interfaces

Multi-epoch Sub-arcsecond [Fe II] Spectroimaging of the DG Tau Outflows with NIFS. II. On the Nature of the Bipolar Outflow Asymmetry

The origin of bipolar outflow asymmetry in young stellar objects (YSOs) remains poorly understood. It may be due to an intrinsically asymmetric outflow launch mechanism, or it may be caused by the effects of the ambient medium surrounding the YSO. Answering this question is an important step in understanding outflow launching. We have investigated the bipolar outflows driven by the T Tauri star DG Tauri on scales of hundreds of AU, using the Near-infrared Integral Field Spectrograph (NIFS) on Gemini North. The approaching outflow consists of a well-collimated jet, nested within a lower-velocity disc wind. The receding outflow is composed of a single-component bubble-like structure. We analyse the kinemat- ics of the receding outflow using kinetic models, and determine that it is a quasi-stationary bubble with an expanding internal velocity field. We propose that this bubble forms because the receding counterjet from DG Tau is obstructed by a clumpy ambient medium above the circumstellar disc surface, based on similarities between this structure and those found in the modeling of active galactic nuclei outflows. We find evidence of interaction between the obscured counterjet and clumpy ambient material, which we attribute to the large molecular envelope around the DG Tau system. An analytical model of a momentum-driven bubble is shown to be consistent with our interpretation. We conclude that the bipolar outflow from DG Tau is intrinsically symmetric, and the observed asymmetries are due to environmental effects. This mechanism can potentially be used to explain the observed bipolar asymmetries in other YSO outflows.Comment: 16 pages, 10 figures, accepted for publication in MNRA

Electrospun fibrinogen-PLA nanofibres for vascular tissue engineering

Here we report on the development of a new type of hybrid fibrinogen–polylactic acid (FBG–PLA) nanofibres (NFs) with improved stiffness, combining the good mechanical properties of PLA with the excellent cell recognition properties of native FBG. We were particularly interested in the dorsal and ventral cell response to the nanofibres' organization (random or aligned), using human umbilical endothelial cells (HUVECs) as a model system. Upon ventral contact with random NFs, the cells developed a stellate-like morphology with multiple projections. The well-developed focal adhesion complexes suggested a successful cellular interaction. However, time-lapse analysis shows significantly lowered cell movements, resulting in the cells traversing a relatively short distance in multiple directions. Conversely, an elongated cell shape and significantly increased cell mobility were observed in aligned NFs. To follow the dorsal cell response, artificial wounds were created on confluent cell layers previously grown on glass slides and covered with either random or aligned NFs. Time-lapse analysis showed significantly faster wound coverage (within 12 h) of HUVECs on aligned samples vs. almost absent directional migration on random ones. However, nitric oxide (NO) release shows that endothelial cells possess lowered functionality on aligned NFs compared to random ones, where significantly higher NO production was found. Collectively, our studies show that randomly organized NFs could support the endothelization of implants while aligned NFs would rather direct cell locomotion for guided neovascularization

Radial and vertical angular momentum transport in protostellar discs

Angular momentum in protostellar discs can be transported either radially, through turbulence induced by the magnetorotational instability (MRI), or vertically, through the torque exerted by a large-scale magnetic field. We present a model of steady-state discs where these two mechanisms operate at the same radius and derive approximate criteria for their occurrence in an ambipolar diffusion dominated disc. We obtain "weak field'' solutions - which we associate with the MRI channel modes in a stratified disc - and transform them into accretion solutions with predominantly radial angular-momentum transport by implementing a turbulent-stress prescription based on published results of numerical simulations. We also analyze "intermediate field strength'' solutions in which both radial and vertical transport operate at the same radial location. Our results suggest, however, that this overlap is unlikely to occur in real discs.Comment: 5 pages, 2 figures, 1 table, aastex.cls. Accepted for publication in Astrophysics & Space Scienc

Aviation Depot Maintenance Throughput Optimization

NPS NRP Executive SummaryAviation Depot Maintenance Throughput OptimizationN8 - Integration of Capabilities & ResourcesThis research is supported by funding from the Naval Postgraduate School, Naval Research Program (PE 0605853N/2098). https://nps.edu/nrpChief of Naval Operations (CNO)Approved for public release. Distribution is unlimited.

Turbulent mixing layers in supersonic protostellar outflows, with application to DG Tauri

Turbulent entrainment processes may play an important role in the outflows from young stellar objects at all stages of their evolution. In particular, lateral entrainment of ambient material by high-velocity, well-collimated protostellar jets may be the cause of the multiple emission-line velocity components observed in the microjet-scale outflows driven by classical T Tauri stars. Intermediate-velocity outflow components may be emitted by a turbulent, shock- excited mixing layer along the boundaries of the jet. We present a formalism for describing such a mixing layer based on Reynolds decomposition of quantities measuring fundamental properties of the gas. In this model, the molecular wind from large disc radii provides a continual supply of material for entrainment. We calculate the total stress profile in the mixing layer, which allows us to estimate the dissipation of turbulent energy, and hence the luminosity of the layer. We utilize MAPPINGS IV shock models to determine the fraction of total emission that occurs in [Fe II] 1.644 {\mu}m line emission in order to facilitate comparison to previous observations of the young stellar object DG Tauri. Our model accurately estimates the luminosity and changes in mass outflow rate of the intermediate-velocity component of the DG Tau approaching outflow. Therefore, we propose that this component represents a turbulent mixing layer surrounding the well-collimated jet in this object. Finally, we compare and contrast our model to previous work in the field.Comment: 18 pages, 13 figures, accepted for publication in MNRA

Nanoimaging of Organic Charge Retention Effects: Implications for Nonvolatile Memory, Neuromorphic Computing, and High Dielectric Breakdown Devices

While a large variety of organic and molecular materials have been found to exhibit charge memory effects, the underlying mechanism is not well-understood, which hinders rational device design. Here, we study the charge retention mechanism of a nanoscale memory system, an organic monolayer on a silicon substrate, with Au nanoparticles on top serving as the electrical contact. Combining scanning probe imaging/manipulation and density functional simulations, we observe stable charge retention effects in the system and attributed it to polaron effects at the amine functional groups. Our findings can pave the way for applications in nonvolatile memory, neuromorphic computing, and high dielectric breakdown devices

Neural signatures of cognitive flexibility and reward sensitivity following nicotinic receptor stimulation in dependent smokers : a randomized trial

IMPORTANCE Withdrawal from nicotine is an important contributor to smoking relapse. Understanding how reward-based decision making is affected by abstinence and by pharmacotherapies such as nicotine replacement therapy and varenicline tartrate may aid cessation treatment. OBJECTIVE To independently assess the effects of nicotine dependence and stimulation of the nicotinic acetylcholine receptor on the ability to interpret valence information (reward sensitivity) and subsequently alter behavior as reward contingencies change (cognitive flexibility) in a probabilistic reversal learning task. DESIGN, SETTING, AND PARTICIPANTS Nicotine-dependent smokers and nonsmokers completed a probabilistic reversal learning task during acquisition of functional magnetic resonance imaging (fMRI) in a 2-drug, double-blind placebo-controlled crossover design conducted from January 21, 2009, to September 29, 2011. Smokers were abstinent from cigarette smoking for 12 hours for all sessions. In a fully Latin square fashion, participants in both groups underwent MRI twice while receiving varenicline and twice while receiving a placebo pill, wearing either a nicotine or a placebo patch. Imaging analysis was performed from June 15, 2015, to August 10, 2016. MAIN OUTCOME AND MEASURES A well-established computational model captured effects of smoking status and administration of nicotine and varenicline on probabilistic reversal learning choice behavior. Neural effects of smoking status, nicotine, and varenicline were tested for on MRI contrasts that captured reward sensitivity and cognitive flexibility. RESULTS The study included 24 nicotine-dependent smokers (12 women and 12 men; mean [SD] age, 35.8 [9.9] years) and 20 nonsmokers (10 women and 10 men; mean [SD] age, 30.4 [7.2] years). Computational modeling indicated that abstinent smokers were biased toward response shifting and that their decisions were less sensitive to the available evidence, suggesting increased impulsivity during withdrawal. These behavioral impairments were mitigated with nicotine and varenicline. Similarly, decreased mesocorticolimbic activity associated with cognitive flexibility in abstinent smokers was restored to the level of nonsmokers following stimulation of nicotinic acetylcholine receptors (familywise error-corrected P<.05). Conversely, neural signatures of decreased reward sensitivity in smokers (vs nonsmokers; familywise error-corrected P<.05) in the dorsal striatum and anterior cingulate cortex were not mitigated by nicotine or varenicline. CONCLUSIONS AND RELEVANCE There was a double dissociation between the effects of chronic nicotine dependence on neural representations of reward sensitivity and acute effects of stimulation of nicotinic acetylcholine receptors on behavioral and neural signatures of cognitive flexibility in smokers. These chronic and acute pharmacologic effects were observed in overlapping mesocorticolimbic regions, suggesting that available pharmacotherapies may alleviate deficits in the same circuitry for certain mental computations but not for others