Optimized cross-slot flow geometry for microfluidic extension rheometry

A precision-machined cross-slot flow geometry with a shape that has been optimized by numerical simulation of the fluid kinematics is fabricated and used to measure the extensional viscosity of a dilute polymer solution. Full-field birefringence microscopy is used to monitor the evolution and growth of macromolecular anisotropy along the stagnation point streamline, and we observe the formation of a strong and uniform birefringent strand when the dimensionless flow strength exceeds a critical Weissenberg number Wicrit 0:5. Birefringence and bulk pressure drop measurements provide self consistent estimates of the planar extensional viscosity of the fluid over a wide range of deformation rates (26 s1 "_ 435 s1) and are also in close agreement with numerical simulations performed by using a finitely extensible nonlinear elastic dumbbell model

Intravital Imaging of the Mouse Thymus using 2-Photon Microscopy

Two-photon Microscopy (TPM) provides image acquisition in deep areas inside tissues and organs. In combination with the development of new stereotactic tools and surgical procedures, TPM becomes a powerful technique to identify "niches" inside organs and to document cellular "behaviors" in live animals. While intravital imaging provides information that best resembles the real cellular behavior inside the organ, it is both more laborious and technically demanding in terms of required equipment/procedures than alternative ex vivo imaging acquisition. Thus, we describe a surgical procedure and novel "stereotactic" organ holder that allows us to follow the movements of Foxp3+ cells within the thymus

Instabilities in stagnation point flows of polymer solutions

A recently developed microfluidic device, the optimized shape cross-slot extensional rheometer or OSCER [S. J. Haward, M. S. N. Oliveira, M. A. Alves, and G. H. McKinley, “Optimized cross-slot flow geometry for microfluidic extensional rheometry,” Phys. Rev. Lett.109, 128301 (Year: 2012)10.1103/PhysRevLett.109.128301], is used to investigate the stability of viscoelastic polymer solutions in an idealized planar stagnation point flow. Aqueous polymer solutions, consisting of poly(ethylene oxide) and of hyaluronic acid with various molecular weights and concentrations, are formulated in order to provide fluids with a wide range of rheological properties. Semi-dilute solutions of high molecular weight polymers provide highly viscoelastic fluids with long relaxation times, which achieve a high Weissenberg number (Wi) at flow rates for which the Reynolds number (Re) remains low; hence the elasticity number El = Wi/Re is high. Lower concentration solutions of moderate molecular weight polymers provide only weakly viscoelastic fluids in which inertia remains important and El is relatively low. Flow birefringence observations are used to visualize the nature of flow instabilities in the fluids as the volumetric flow rate through the OSCER device is steadily incremented. At low Wi and Re, all of the fluids display a steady, symmetric, and uniform “birefringent strand” of highly oriented polymer molecules aligned along the outflowing symmetry axis of the test geometry, indicating the stability of the flow field under such conditions. In fluids of El > 1, we observe steady elastic flow asymmetries beyond a critical Weissenberg number,Wi [subscript crit], that are similar in character to those already reported in standard cross-slot geometries [e.g., P. E. Arratia, C. C. Thomas, J. Diorio, and J. P. Gollub, “Elastic instabilities of polymer solutions in cross-channel flow,” Phys. Rev. Lett.96, 144502 (Year: 2006)10.1103/PhysRevLett.96.144502]. However, in fluids with El < 1 we observe a sequence of time-dependent inertio-elastic instabilities beyond a critical Reynolds number, Re[subscript crit], characterized by high frequency spatiotemporal oscillations of the birefringent strand. By plotting the critical limits of stability for the various fluids in the Wi-Re operating space, we are able to construct a stability diagram delineating the distinct steady symmetric, steady asymmetric and inertio-elastic flow regimes in this idealized planar elongational flow device.European Commission. Marie Curie Actions (FP7-PEOPLE-2011-IIF Grant 298220)United States. National Aeronautics and Space Administration (Microgravity Fluid Sciences (Code UG) Grant NNX09AV99G

The Single-Particle Spectral Function of 16O^{16}{\rm O}

The influence of short-range correlations on the $p$-wave single-particle spectral function in $^{16}{\rm O}$ is studied as a function of energy. This influence, which is represented by the admixture of high-momentum components, is found to be small in the $p$-shell quasihole wave functions. It is therefore unlikely that studies of quasihole momentum distributions using the $(e,e'p)$ reaction will reveal a significant contribution of high momentum components. Instead, high-momentum components become increasingly more dominant at higher excitation energy. The above observations are consistent with the energy distribution of high-momentum components in nuclear matter.Comment: 5 pages, RevTeX, 3 figure

Chromatin establishes an immature version of neuronal protocadherin selection during the naive-to-primed conversion of pluripotent stem cells.

In the mammalian genome, the clustered protocadherin (cPCDH) locus provides a paradigm for stochastic gene expression with the potential to generate a unique cPCDH combination in every neuron. Here we report a chromatin-based mechanism that emerges during the transition from the naive to the primed states of cell pluripotency and reduces, by orders of magnitude, the combinatorial potential in the human cPCDH locus. This mechanism selectively increases the frequency of stochastic selection of a small subset of cPCDH genes after neuronal differentiation in monolayers, 10-month-old cortical organoids and engrafted cells in the spinal cords of rats. Signs of these frequent selections can be observed in the brain throughout fetal development and disappear after birth, except in conditions of delayed maturation such as Down's syndrome. We therefore propose that a pattern of limited cPCDH-gene expression diversity is maintained while human neurons still retain fetal-like levels of maturation

Integrin activation - the importance of a positive feedback

Integrins mediate cell adhesion and are essential receptors for the development and functioning of multicellular organisms. Integrin activation is known to require both ligand and talin binding and to correlate with cluster formation but the activation mechanism and precise roles of these processes are not yet resolved. Here mathematical modeling, with known experimental parameters, is used to show that the binding of a stabilizing factor, such as talin, is alone insufficient to enable ligand-dependent integrin activation for all observed conditions; an additional positive feedback is required.Comment: in press in Bulletin of Mathematical Biolog

Protein sequence and structure: Is one more fundamental than the other?

We argue that protein native state structures reside in a novel "phase" of matter which confers on proteins their many amazing characteristics. This phase arises from the common features of all globular proteins and is characterized by a sequence-independent free energy landscape with relatively few low energy minima with funnel-like character. The choice of a sequence that fits well into one of these predetermined structures facilitates rapid and cooperative folding. Our model calculations show that this novel phase facilitates the formation of an efficient route for sequence design starting from random peptides.Comment: 7 pages, 4 figures, to appear in J. Stat. Phy

IL-6/STAT3 promotes regeneration of airway ciliated cells from basal stem cells

The airways of the lungs are lined by ciliated and secretory epithelial cells important for mucociliary clearance. When these cells are damaged or lost, they are replaced by the differentiation of basal stem cells. Little is known about how this repair is orchestrated by signaling pathways in the epithelium and underlying stroma. We present evidence using cultured airway cells and genetic manipulation of a mouse model of airway repair that the cytokine IL-6 promotes the differentiation of ciliated vs. secretory cells. This process involves direct Stat3 regulation of genes controlling both cell fate (Notch1) and the differentiation of multiciliated cells (Multicilin and forkhead box protein J1). Moreover, the major producer of IL-6 appears to be mesenchymal cells in the stroma rather than immune cells

Momentum and Energy Distributions of Nucleons in Finite Nuclei due to Short-Range Correlations

The influence of short-range correlations on the momentum and energy distribution of nucleons in nuclei is evaluated assuming a realistic meson-exchange potential for the nucleon-nucleon interaction. Using the Green-function approach the calculations are performed directly for the finite nucleus $^{16}$O avoiding the local density approximation and its reference to studies of infinite nuclear matter. The nucleon-nucleon correlations induced by the short-range and tensor components of the interaction yield an enhancement of the momentum distribution at high momenta as compared to the Hartree-Fock description. These high-momentum components should be observed mainly in nucleon knockout reactions like $(e,e'p)$ leaving the final nucleus in a state of high excitation energy. Our analysis also demonstrates that non-negligible contributions to the momentum distribution should be found in partial waves which are unoccupied in the simple shell-model. The treatment of correlations beyond the Brueckner-Hartree-Fock approximation also yields an improvement for the calculated ground-state properties.Comment: 12 pages RevTeX, 7 figures postscript files appende

Momentum Distribution in Nuclear Matter and Finite Nuclei

A simple method is presented to evaluate the effects of short-range correlations on the momentum distribution of nucleons in nuclear matter within the framework of the Green's function approach. The method provides a very efficient representation of the single-particle Green's function for a correlated system. The reliability of this method is established by comparing its results to those obtained in more elaborate calculations. The sensitivity of the momentum distribution on the nucleon-nucleon interaction and the nuclear density is studied. The momentum distributions of nucleons in finite nuclei are derived from those in nuclear matter using a local-density approximation. These results are compared to those obtained directly for light nuclei like $^{16}O$.Comment: 17 pages REVTeX, 10 figures ps files adde