Publications

Local mechanical cues can affect crucial fate decisions of living cells. Transepithelial stress has been discussed in the context of epithelial monolayers, but the lack of appropriate experimental systems leads current studies to approximate it simply as an in-plane stress. To evaluate possible contribution of force vectors acting in other directions, double epithelium in a 3D-printed "GeminiChip" containing a sessile and a pendant channel is reconstituted. Intriguingly, the sessile epithelia is prone to apoptotic cell extrusion upon crowding, whereas the pendant counterpart favors live cell delamination. Transcriptome analyses show upregulation of RhoA, BMP2, and hypoxia-signaling genes in the pendant epithelium, consistent with the onset of an epithelial-mesenchymal transition program. HepG2 microtumor spheroids also display differential spreading patterns in the sessile and pendant configuration. Using this multilayered GeminiChip, these results uncover a progressive yet critical role of perpendicular force vectors in collective cell behaviors and point at fundamental importance of these forces in the biology of cancer.

Mixing of polystyrene resin in solid phase synthesis is performed using shaking or gentle agitation of the reaction vessel to avoid breaking the brittle beads. These mixing strategies result in poor diffusion to and into the beads. Using a large excess of reagents is the common way to compensate for these deficiencies. We used fast overhead stirring for performing coupling reactions on the solid support. We show that fast overhead stirring enhances the efficiency of amide bond formation on solid support compared to the state-of-the-art mixing method while preserving the integrity of the beads. We found that fast over overhead stirring minimizes the effect of decomposition of the activated species by increasing the diffusion dependent coupling reaction. This allows to decrease the excess of reagents used for the multi-step synthesis of peptides, thus, provides greener and more sustainable alternative for peptide synthesis on solid support.

Online Social Networking Sites (SNSs) are immensely popular, especially among adolescents. Activity on these sites leaves digital footprints, which may be used to study online behavioral correlates of adolescent psychological distress and to, ultimately, improve detection and intervention efforts. In the present work, we explore the digital footprints of adolescent depression, social rejection, and victimization of bullying on Facebook. Two consecutive studies were conducted among Israeli adolescents (N = 86 and N = 162). We collected a range of Facebook activity features, as well as self-report measurements of depression, social rejection, and victimization of bullying. Findings from Study 1 demonstrate that explicit distress references in Facebook postings (e.g., "Life sucks, I want to die") predict depression among adolescents, but that such explicit distress references are rare. In Study 2, we applied a bottom-up research methodology along with the previous top-down, theory driven approach. Study 2 demonstrates that less explicit features of Facebook behavior predict social rejection and victimization of bullying. These features include 'posts by others', 'check-ins', 'gothic and dark content', 'other people in pictures', and 'positive attitudes towards others'. The potential, promises and limitations of using digital Facebook footprints for the detection of adolescent psychological distress are discussed.

Peptides are very common recognition entities that are usually attached to surfaces using multistep processes. These processes require modification of the native peptides and of the substrates. Using functional groups in native peptides for their assembly on surfaces without affecting their biological activity can facilitate the preparation of biosensors. Herein, we present a simple single-step formation of native oxytocin monolayer on gold surface. These surfaces were characterized by atomic force spectroscopy, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy. We took advantage of the native disulfide bridge of the oxytocin for anchoring the peptide to the Au surface, while preserving the metal-ion binding properties. Self-assembled oxytocin monolayer was used by electrochemical impedance spectroscopy for metal-ion sensing leading to subnanomolar sensitivities for zinc or copper ions.

Peptides are very common recognition entities that are usually attached to surfaces using multistep processes. These processes require modification of the native peptides and of the substrates. Using functional groups in native peptides for their assembly on surfaces without affecting their biological activity can facilitate the preparation of biosensors. Herein, we present a simple single-step formation of native oxytocin monolayer on gold surface. These surfaces were characterized by atomic force spectroscopy, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy. We took advantage of the native disulfide bridge of the oxytocin for anchoring the peptide to the Au surface, while preserving the metal-ion binding properties. Self-assembled oxytocin monolayer was used by electrochemical impedance spectroscopy for metal-ion sensing leading to subnanomolar sensitivities for zinc or copper ions.

Peptides are very common recognition entities that are usually attached to surfaces using multistep processes. These processes require modification of the native peptides and of the substrates. Using functional groups in native peptides for their assembly on surfaces without affecting their biological activity can facilitate the preparation of biosensors. Herein, we present a simple single-step formation of native oxytocin monolayer on gold surface. These surfaces were characterized by atomic force spectroscopy, spectroscopic ellipsometry, and X-ray photoelectron spectroscopy. We took advantage of the native disulfide bridge of the oxytocin for anchoring the peptide to the Au surface, while preserving the metal-ion binding properties. Self-assembled oxytocin monolayer was used by electrochemical impedance spectroscopy for metal-ion sensing leading to subnanomolar sensitivities for zinc or copper ions.

Directed-assembly by standing surface acoustic waves (SSAWs) only requires an acoustic contrast between particles and their surrounding medium. It is therefore highly attractive as this requirement is fulfilled by almost all dispersed systems. Previous studies utilizing SSAWs demonstrated mainly reversible microstructure arrangements from nanoparticles. The surface chem. of colloids dramatically influences their tendency to aggregate and sinter; therefore, it should be possible to form permanent microstructures with intimate contact between nanoparticles by controlling this property. Dispersed silver nanoparticles in a microfluidic channel were exposed to SSAWs and reversibly accumulated at the pressure nodes. We show that addition of chloride ions that remove the polyacrylic capping of the nanoparticles trigger their sintering and the formation of stable conducting silver microstructures. Moreover, if the destabilizing ions are added prior to nanoparticle assembly while continuously streaming the dispersion through the acoustic aperture, the induced aggregation leads to formation of significantly thinner microstructures, which are (for the first time) unlimited in length by the acoustic apparatus This new approach overcomes the discrepancy between the need for organic dispersants to prevent unwanted aggregation in the dispersion, and the end product's requirement for intimate contact between the colloidal particles.

The cellular functions of arrestins are determined in part by the pattern of phosphorylation on the G protein-coupled receptors (GPCRs) to which arrestins bind. Despite high-resolution structural data of arrestins bound to phosphorylated receptor C-termini, the functional role of each phosphorylation site remains obscure. Here, we employed a library of synthetic phosphopeptide analogues of the GPCR rhodopsin C-terminus and determined the ability of these peptides to bind and activate arrestins using a variety of biochemical and biophysical methods. We further characterized how these peptides modulated the conformation of arrestin-1 by nuclear magnetic resonance (NMR). Our results indicate that the particular phosphorylation sites can be grouped into different functional classes: ‘key sites’ required for arrestin binding and activation, an ‘inhibitory site’ that abrogates arrestin binding, and ‘modulator sites’ that influence the global conformation of arrestin. These functional motifs allow a better understanding of how different GPCR phosphorylation patterns might control how arrestin functions in the cell.

This monograph deals with spatially dependent nonstationary time series in a way accessible to both time series econometricians wanting to understand spatial econometics, and spatial econometricians lacking a grounding in time series analysis. After charting key concepts in both time series and spatial econometrics, the book discusses how the spatial connectivity matrix can be estimated using spatial panel data instead of assuming it to be exogenously fixed. This is followed by a discussion of spatial nonstationarity in spatial cross-section data, and a full exposition of non-stationarity in both single and multi-equation contexts, including the estimation and simulation of spatial vector autoregression (VAR) models and spatial error correction (ECM)  models. 
The book reviews the literature on panel unit root tests and panel cointegration tests for spatially independent data, and for data that are strongly spatially dependent. It provides for the first time critical values for panel unit root tests and panel cointegration tests when the spatial panel data are weakly or spatially dependent. 
The volume concludes with a discussion of incorporating strong and weak spatial dependence in non-stationary panel data models. All discussions are accompanied by empirical  testing based on a spatial panel data of house prices in Israel.