In this book Professor Holmes discusses some of the evidence relating to one of the most baffling problems yet recognized by biologists-the factors involved in the regulation of growth and form. A wide range of possible influences, from enzymes to cellular competition, is considered. Numerous experiments and theories are described, with or without bibliographic citation. There is a list of references for each chapter and an index. The subject from a scientific standpoint is an exceedingly difficult one, for the reason that very little indeed is understood regarding such phenomena as differentiation. It follows that the problem offers fine opportunities for intellectual jousting by mechanists and vitalists, that hypotheses and theories must often be the weapons of choice, and philosophy the armor. Professor Holmes gives us a good seat from which to watch the combats, explains clearly what is going on, and occasionally slips away to enter the lists himself. This stereoscopic atlas of anatomy was designed as an aid in teaching neuro-anatomy for beginning medical students and as a review for physicians taking Board examinations in Psychiatry and Neurology. Each plate consists of a pair of stereoscopic photographs and a labelled diagram of the important parts seen in the photograph. Perhaps in this day of scarcity of materials, particularly of human brains hardened for dissection, photographs of this kind conceivably can be used as a substitute. Successive stages of dissection are presented in such a fashion that, used in conjunction with the dissecting manual, a student should be able to identify most of the important components of the nervous system without much outside help. The area covered is limited to the gross features of the brain and brain stem and perhaps necessarily does not deal with any of the microscopic structure. So much more can be learned from the dissection of the actual brain that it is doubtful if this atlas would be useful except where brains are not available. A good deal of effort has been spent on the preparation of this atlas, with moderately successful results.

The Integrative Action of the Nervous System.

The orderly migration of various white blood cell types to inflammatory sites is a highly regulated process that involves a diversity of adhesion and signaling molecules. This cellular influx is initiated by relatively low affinity interactions that allow for leukocytes to roll along the vascular surfa ce. This rolling phe­ nomenon is mediated by adhesive interactions between lectin containing ad­ hesion molecules, termed selectins, on both the vascular endothelium and leukocytes, and car bohydrate ligands immobilized on mucin-like scaffolds. This adhesion allows for a rapid recognition of various cell types under the conditions of vascular flow, with the result that inflammatory cells are spe­

Interactions and the initiation of the inflammatory response

The large Trp gene family encodes transient receptor potential (TRP) proteins that form novel cation-selective ion channels. In mammals, 28 Trp channel genes have been identified. TRP proteins exhibit diverse permeation and gating properties and are involved in a plethora of physiologic functions with a strong impact on cellular sensing and signaling pathways. Indeed, mutations in human genes encoding TRP channels, the so-called "TRP channelopathies," are responsible for a number of hereditary diseases that affect the musculoskeletal, cardiovascular, genitourinary, and nervous systems. This review gives an overview of the functional properties of mammalian TRP channels, describes their roles in acquired and hereditary diseases, and discusses their potential as drug targets for therapeutic intervention.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

Leukocyte adhesion through L-selectin to peripheral node addressin (PNAd, also known as MECA-79 antigen), an L-selectin ligand expressed on high endothelial venules, has been shown to require a minimum level of fluid shear stress to sustain rolling interactions (Finger, E.B., K.D. Puri, R. Alon, M.B. Lawrence, V.H. von Andrian, and T.A. Springer. 1996. Nature (Lond.). 379:266–269). Here, we show that fluid shear above a threshold of 0.5 dyn/cm2 wall shear stress significantly enhances HL-60 myelocyte rolling on P- and E-selectin at site densities of 200/μm2 and below. In addition, gravitational force is sufficient to detach HL60 cells from P- and E-selectin substrates in the absence, but not in the presence, of flow. It appears that fluid shear–induced torque is critical for the maintenance of leukocyte rolling. K562 cells transfected with P-selectin glycoprotein ligand-1, a ligand for P-selectin, showed a similar reduction in rolling on P-selectin as the wall shear stress was lowered below 0.5 dyn/cm2. Similarly, 300.19 cells transfected with L-selectin failed to roll on PNAd below this level of wall shear stress, indicating that the requirement for minimum levels of shear force is not cell type specific. Rolling of leukocytes mediated by the selectins could be reinitiated within seconds by increasing the level of wall shear stress, suggesting that fluid shear did not modulate receptor avidity. Intravital microscopy of cremaster muscle venules indicated that the leukocyte rolling flux fraction was reduced at blood centerline velocities less than 1 mm/s in a model in which rolling is mediated by L- and P-selectin. Similar observations were made in L-selectin–deficient mice in which leukocyte rolling is entirely P-selectin dependent. Leukocyte adhesion through all three selectins appears to be significantly enhanced by a threshold level of fluid shear stress.

Threshold levels of fluid shear promote leukocyte adhesion through selectins (CD62L,P,E)

Manufacturing of hydrogel biomaterials with controlled mechanical properties for tissue engineering applications.

Spontaneous emergence of ordered and complex structures from simple building units is a ubiquitous phenomenon in nature in a wide range of the scales [1,2]. For example, water molecules crystallize into snowflakes, nucleotides self-assemble into DNAs, and sands pile into ripple or stripe patterns in desert. This natural creation mode represents a smarter strategy and a higher efficiency than many human approaches that build an architecture piece by piece. Recently, assembly of microscale materials has drawn increasing attention due to great demands in engineering architectures/systems in the fields including bottom-up tissue engineering [3], microelectromechanical systems [4] and microphotonics [5]. Of particular interest is tissue engineering, where organization of cells and cell microcarriers into repeating units with well-defined 3D architectures that mimic native tissues is significant for the resulting tissue-specific functions [6]. Previous microscale technologies have their own unique advantages in creating various structures from microscale materials. However, these existing technologies have limitations such as unaffordable time budgets for assembling large number of building units (e.g., bioprinting [7], micro-robotic assembly [8]), incapability for reconfiguring final structure after the mold is created (e.g., micromolding [9], microscale templated assembly based on solid molds [10,11]), limited types or complexity in resulting structures/geometrics (e.g., magnetic assembly [10,12], electrostatic assembly [13], capillary assembly [14], molecular recognition [15]).

Here, we report a versatile bottom-up method that enables efficient generation of diverse structures from microscale materials in a reconfigurable and biocompatible way. We explore the topography of liquid surface established by standing waves serves as a template for directed assembly of large number (~106) of microscale materials into diverse sets of ordered, symmetric structures. This liquid-based template can be dynamically reconfigured in a few seconds (< 5 s), and the assembly on the template can be achieved in a scalable and parallel manner. We illustrate broad applicability of this approach by assembling diverse materials sized from 10 μm to 2 mm including soft matter, rigid bodies, mammalian cells, cell spheroids and cell-seeded microcarrier beads into structures ranging in area from 100 mm2 to 10,000 mm2. In addition, we show that the assembled structures can be immobilized by chemical- and photo-crosslinking for the subsequent applications.

Microscale assembly directed by liquid-based template.

Structure evolution and gasification characteristic analysis on co-pyrolysis char from lignocellulosic biomass and two ranks of coal: Effect of wheat straw

The deformation of a compound capsule (an elastic capsule with a smaller capsule inside) in simple shear flow is studied by using three-dimensional numerical simulations based on a front tracking method. The inner and outer capsules are concentric and initially spherical. Skalak et al.’s constitutive law is employed for the mechanics of both the inner and outer membranes. Our results concerning the deformation of homogeneous capsules (i.e. capsules without the inner capsules) are quantitatively in agreement with the predictions of previous numerical simulations and perturbation theories. Compared to homogeneous capsules, compound capsules exhibit smaller deformation. The deformations of both the inner and outer capsules are significantly affected by the capillary numbers of the inner and outer membranes and the volume ratio of the inner to the outer capsule. When the inner capsule is small, it presents smaller deformation than the outer capsule. However, when the inner capsule is sufficiently large, it can present larger deformation than the outer capsule, even if the inner membrane has much lower capillary number than the outer membrane. The underlying mechanisms are discussed: (i) the inner capsule is deformed by rotational flow with lower rate of strain rather than by simple shear flow that deforms the outer capsule, and thus the inner capsule exhibits smaller deformation; and (ii) when the inner and outer membranes are sufficiently close (i.e. the inner capsule is sufficiently large), the hydrodynamic interaction between the two membranes becomes significant, which is found to inhibit the deformation of the outer capsule but to promote the deformation of the inner capsule.

Deformation of spherical compound capsules in simple shear flow

Physicochemical structure and gasification reactivity of co-pyrolysis char from two kinds of coal blended with lignocellulosic biomass: Effects of the carboxymethylcellulose sodium

Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not “equally sensitive” to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices.

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Zhengyuan Luo

Papers

Microscale assembly directed by liquid-based template.

Structure evolution and gasification characteristic analysis on co-pyrolysis char from lignocellulosic biomass and two ranks of coal: Effect of wheat straw

Deformation of spherical compound capsules in simple shear flow

Physicochemical structure and gasification reactivity of co-pyrolysis char from two kinds of coal blended with lignocellulosic biomass: Effects of the carboxymethylcellulose sodium

Fluid mechanics in dentinal microtubules provides mechanistic insights into the difference between hot and cold dental pain.