Integrated Calendar

We showed years ago by fusing two differentiated cell types in stable non-dividing heterokaryons that “terminally” differentiated human cells could be reprogrammed. The balance of regulators was critical in determining the direction of differentiation. We are now enlisting natural mechanisms to tip the balance of regulators and derive new mammalian cell sources for regenerative medicine: (1) by using heterokaryons to identify crucial early regulators of reprogramming to pluripotency (iPS); (2) by altering telomerase activity; (3) by mimicking cues of adult stem cell niches; and (4) by dedifferentiation like newts. Our experimental systems offer a means to explore regulatory networks. Elucidation of the logic underlying nuclear reprogramming via molecular timelapse snapshots (the “Kineticon) is revealing discrete steps in pathways of dedifferentiation and redifferentiation. These approaches provide fundamental mechanistic insights and are revealing common principles of nuclear reprogramming. The generation of novel cell sources should enable new clinical applications of cell therapies for regenerative medicine.

All animals sleep, or do they? This question remains controversial. If sleep is truly universal to the animal kingdom then even the simplest model animal should sleep, and may offer valuable clues regarding the origin and core function of sleep. The nematode Caenorhabditis elegans develops through four larval stages before it reaches adulthood. At the transition between stages and before it molts, i.e., synthesizes a new exoskeleton and sheds the old one, it exhibits a quiescent state termed lethargus. In a seminal paper in 2008, David Raizen has demonstrated that lethargus bears several similarities to sleep. The talk will focus on behavioral aspects of lethargus and establishing C. elegans as a model system for sleep. Examples of behavioral dynamics associated with lethargus include the nematode’s hockey stick-like posture and its hypothesized functionality, non-Markovian locomotion/quiescence dynamics (micro-homeostasis), responses to external stimuli that exhibit sensory gating, and the onset and timing of quiet wakefulness. As time permits, neurophysiological and genetic aspects of worm-sleep will be briefly discussed.

Solids brought in contact with an electrolyte spontaneously acquire surface charge, e.g. via ionization/dissociation of surface groups. A
balance between electrostatic forces and diffusion leads to the formation of a screening (Debye) layer where counter-ions are in excess and
co-ions are in deficit; the Debye length, on which space-charge density decays towards the electro-neutral bulk, is typically no more than a
few tens of nanometers. When exposed to an external electric field, the Debye layer is sheared in response to Coulomb body forces acting on
the charged liquid. On a scale much larger than the Debye length, this effect is manifested as "electro-osmotic slip". Thus, a freely suspended
micron-sized particle will migrate electrophoretically in response to the effective slip distribution induced over its surface — notwithstanding
the net electro-neutrality of the particle considered together with the Debye layer surrounding it.
From a modeling point of view, mutual coupling between ionic transport, electrostatics, surface chemistry, and hydrodynamics leads to a
mathematical formulation which is highly nonlinear. Moreover, the extreme scale disparity associated with the thin-Debye-layer limit hinders
the application of standard numerical methods. Ever since the intuitive derivation of the time-honored Smoluchowski slip condition (the
domain of validity of which is not always evident), most analyses have employed various linearizations tantamount to assuming weak applied
fields or small surface-charge densities. In many cases of practical interest, however, these assumptions are simply inadequate. In this talk, I
will describe how a simplified coarse-grained model – valid for arbitrary surface charge density and field strength – can be systematically
derived by exploiting the above-mentioned scale disparity. Approximate analyses of these models, complemented by numerical simulations on
the macroscale, will also be presented. These allow for an intuitive grasp along with quantitative predictions. Finally, the electrophoretic
migration of drops and bubbles will be considered following a similar thin-Debye-layer methodology. A unique mechanism for electrokinetic
flow is unraveled in the case of a gas bubble thereby resolving a long-lasting paradox.
Joint work with Ehud Yariv and Itzchak Frankel.

Hypnosis was the first Western form of psychotherapy, yet it remains underutilized in part because of insufficient understanding of its neural basis. Hypnosis involves highly focused attention, coupled with dissociation of aspects of awareness, relatively automatic response to social cues, and an enhanced ability to modulate perception. New evidence regarding this sensory processing ability will be presented, including studies employing event-related potentials, PET and fMRI. Our recent resting state fMRI data demonstrate functional connectivity between the executive control and salience networks among high but not low hypnotizable individuals. This hypnotic ability to modulate perception has clear clinical application, especially in pain and anxiety control. Randomized clinical trials that we have conducted demonstrate the efficacy of hypnosis in reducing pain, anxiety, somatic complications, and procedure duration during radiological interventions.

There has been remarkable progress in asymmetric catalysis since the inception of the field three decades ago and, chiefly, over the last decade. Because of this, asymmetric catalysis now provides chemical researchers in both academia and industry with the means to directly access useful enantiomerically enriched compounds. With advances in technology (i.e. high throughput screening), the identification of an asymmetric catalyst that promotes a transformation in high enantiomeric excess has been expedited. However, the approach to catalyst identification remains mainly empirical, wherein evaluation of a significant number of ligands, often structurally unrelated, is required to develop a mature chiral catalyst. Therefore, the central goal of our program is focused on developing general methods that facilitate the rapid design and optimization of new asymmetric catalysts for challenging, synthetically useful transformations. The lecture will focus on our recent efforts to evaluate structure-enantioselectivity relationships as a function of ligand structure to facilitate catalyst design and optimization. A particular focus will be on classic physical organic mechanistic tools in combination with multi-dimensional statistical approaches.

Olfaction researchers at all levels are ultimately trying to solve the same problem, namely a transform across three spaces: from the physicochemical space of odor molecules, through the brain space of neural activity, and on to the space of odor perception and its ensuing behavioral decisions. To solve these transforms, one has to be able to measure each one of these spaces independently. As each of these three spaces is apparently of very high dimensionality, we applied principal components analysis (PCA) to data in each of these three domains. We observed that the functional dimensionality of these spaces was significantly lower than their apparent dimensionality. Moreover, the key axis (PC1) was correlated across domains. In other words, the key axis of olfactory perception was correlated with the key axis of odorant structure, and both of these were correlated with the key axis of neural activity in the olfactory system across species. These correlations allowed us to construct a modest but significant predictive framework across domains. In other words, we could now look at the structure of a novel molecule, and predict modest but significant aspects of its perception and ensuing neural activity across species. Beyond this predictive framework, our approach has several implications regarding sensory phenomena within a metric space. For example, it implies a point of sensory convergence where all olfactory mixtures should smell the same. We call this point "olfactory white". Our metric approach also implies points (odors) that are at the upper and lower boundaries of this metric space, and should therefore be odorless. We call these points "infra smell" and "ultra smell". In this talk I will consider the implications of this approach, as well as its potential shortcomings, and their possible solutions.