Synapses are a key component of neural circuits, facilitating rapid and specific signalling between neurons. Synaptic engineering — the synthetic insertion of new synaptic connections into in vivo neural circuits — is an emerging approach for neural circuit interrogation. This approach is especially powerful for establishing causality in neural circuit structure–function relationships, for emulating synaptic plasticity and for exploring novel patterns of circuit connectivity. Contrary to other approaches for neural circuit manipulation, synaptic engineering targets specific connections between neurons and functions autonomously with no user-controlled external activation. Synaptic engineering has been successfully implemented in several systems and in different forms, including electrical synapses constructed from ectopically expressed connexin gap junction proteins, synthetic optical synapses composed of presynaptic photon-emitting luciferase coupled with postsynaptic light-gated channels, and artificial neuropeptide signalling pathways. This Perspective describes these different methods and how they have been applied, and examines how the field may advance.
Design and synthesis of orthogonally protected monosaccharide building blocks are crucial for the preparation of well-defined oligosaccharides in a stereo- and regiocontrolled manner. Selective introduction of protecting groups to partially protected monosaccharides is nontrivial due to the often unpredictable electronic, steric, and conformational effects of the substituents. Abolished reactivity toward a commonly used Lewis base-catalyzed acylation of O-2 was observed in conformationally restricted 4,6-O-benzylidene-3-O-Nap galactoside. Investigation of analogous systems, crystallographic characterization, and quantum chemical calculations highlighted the overlooked conformational and steric considerations, the combination of which produces a unique passivity of the 2-OH nucleophile. Evaluating the role of electrophile counterion and auxiliary base in the acylation of the sterically crowded and conformationally restricted galactoside system revealed an alternative Brønsted base-driven reaction pathway via nucleophilic activation. Insights gained from this model system were utilized to access the target galactoside intermediate within the envisioned synthetic route. The acylation strategy described herein can be implemented in future syntheses of key monomeric building blocks with unique protecting group hierarchies.Design and synthesis of orthogonally protected monosaccharide building blocks are crucial for the preparation of well-defined oligosaccharides in a stereo- and regiocontrolled manner. Selective introduction of protecting groups to partially protected monosaccharides is nontrivial due to the often unpredictable electronic, steric, and conformational effects of the substituents. Abolished reactivity toward a commonly used Lewis base-catalyzed acylation of O-2 was observed in conformationally restricted 4,6-O-benzylidene-3-O-Nap galactoside. Investigation of analogous systems, crystallographic characterization, and quantum chemical calculations highlighted the overlooked conformational and steric considerations, the combination of which produces a unique passivity of the 2-OH nucleophile. Evaluating the role of electrophile counterion and auxiliary base in the acylation of the sterically crowded and conformationally restricted galactoside system revealed an alternative Brønsted base-driven reaction pathway via nucleophilic activation. Insights gained from this model system were utilized to access the target galactoside intermediate within the envisioned synthetic route. The acylation strategy described herein can be implemented in future syntheses of key monomeric building blocks with unique protecting group hierarchies.
This article presents an upgrade of the ıt D}+ software [Ginsburg ıt et al.} (2019). ıt J. Appl. Cryst.} \bf 52, 219–242], expanding its hierarchical solution X-ray scattering modeling capabilities for fiber diffraction and single crystallographic orientations. This upgrade was carried out using the reciprocal grid algorithm [Ginsburg ıt et al.} (2016). ıt J. Chem. Inf. Model.} \bf 56, 1518–1527], providing ıt D}+ its computational strength. Furthermore, the extensive modifications made to the Python API of ıt D}+ are described, broadening the X-ray analysis performed with ıt D}+ to account for the effects of the instrument-resolution function and polydispersity. In addition, structure-factor and radial-distribution-function modules were added, taking into account the effects of thermal fluctuations and intermolecular interactions. Finally, numerical examples demonstrate the usage and potential of the added features.
To cope with stress induced by high salinity and hydrostatic pressure, some marine animals accumulate small organic solutes called osmolytes. Most notable among these osmolytes are the denaturant urea, and trimethylamine N-oxide (TMAO) that is known to stabilize proteins. Although their effects on proteins and nucleic acids have been extensively studied, osmolytes are less commonly studied in the context of lipids, which are a crucial component in many cellular processes. Here we resolve the mechanism for urea’s action on the forces acting between lipid membranes, in the presence and absence of TMAO. We find that unlike the way urea denatures proteins, and by contrast to TMAO, urea does not preferentially interact with net-neutral lipid membranes. Instead, urea modulates the interactions between membranes mainly by weakening the van der Waals attraction between bilayers. Interestingly, regardless of concentration, the effects of urea and TMAO appear to be additive to a large extent, so that the presence of one osmolyte hardly changes the interaction of the other with lipid. Weak non-additive effects are likely due to structural changes in the lipid membrane induced by the osmolytes. Finally, we comment on the potential role of osmolytes acting together in the modification of lipid adhesion and fusion.
Conflict points around the world involve government forces fighting terrorist groups. In this type of warfare, there is a danger that counterterrorist efforts may backfire, providing ammunition for additional cycles of violence. We study this issue focusing on selective and indiscriminate house demolitions employed by Israel during the Second Intifada. We exploit the temporal and spatial variation of this policy to assess its impact on Palestinians’ political views. We find that the civilian population does not react to punitive house demolitions, a selective form of counterterrorism. On the contrary, Palestinians are more likely to adopt more radical political opinions in response to precautionary house demolitions, an indiscriminate form of counterterrorism. We also show that political radicalization induced by indiscriminate counterterrorism leads to an increase in future terror attacks. Overall, our analysis provides explicit empirical support to the mechanism behind the positive correlation between indiscriminate counterterrorism and future levels of violence.
In Uncertainty by Design Limor Samimian-Darash presents cases of the use of scenario technology in the fields of security and emergency preparedness, energy, and health by analyzing scenario narratives and practices at the National Emergency Management Authority in Israel, the World Health Organization's Regional Office for Europe, and the World Energy Council.
Humankind has long struggled with the uncertainty of the future, with how to foresee the future, imagine alternatives, or prepare for and guard against undesirable eventualities. Scenario—or scenario planning—emerged in recent decades to become a widespread means through which states, large corporations, and local organizations imagine and prepare for the future.
The scenario technology cases examined in Uncertainty by Design provide a useful lens through which to view contemporary efforts to engage in an overall journey of discovering the future, along with the modality of governing involved in these endeavors to face future uncertainties. Collectively, they enable us to understand in depth how scenarios express a new governing modality.
This book sheds light on a technology for systematically thinking, envisioning, and preparing for future uncertainties: the scenario – an uncertainty-based technology that not only accepts the potential uncertainty of the future but also promotes uncertainty as a mode of observing and acting in the world. The book presents sociocultural perspectives and anthropological research on cases where the scenario has been used within the fields of security and emergency preparedness, energy, and health, analyzing and comparing scenario narratives and practices at Israel’s National Emergency Management Authority, the World Health Organization’s Regional Office for Europe, and the World Energy Council. Taken together, these cases provide a useful lens through which to view contemporary attempts to address future uncertainties with a new modality of governing here termed “uncertainty by design” – a mode of governing that is based on imagination, potentiality, and acceptance of the emergent and the unpredictable, but that is nonetheless a designed practice, one that has specific rules and systems for creating, narrating, and using the future stories that make up the scenario.
We describe a new process for fabricating chiral organosilica 3D complex structures by combining digital light processing 3D printing with a sol-gel polycondensation process. The fabricated low-density objects have a high surface area with hierarchical porosity based on micropores resulting from the materials’ design, and on macropores in the structure resulting from the 3D printing design. Thus, several 3D objects having complex shapes were printed by the polycondensation of 3-acryloxypropyltrimethoxysilane (APTMS) and chiral silane monomers that were obtained by reacting (1R,2R)-cyclohexane-1,2-diamine or (1S,2S)-cyclohexane-1,2-diamine with (3-Isocyanatopropyl)triethoxysilane. The dual-function monomer APTMS enabled both localized photopolymerization and polycondensation. Printed gyroids, cubes, and disk-shaped chiral monoliths successfully revealed the enantioselective adsorption of tryptophan enantiomers. It was found that the macroscopic shape of the monolith affects the adsorption performance and its enantioselectivity. High enantioselectivity was obtained when the objects were formed from a chiral silane synthesized from (1R,2R)-cyclohexane-1,2-diamine: L-tryptophan was adsorbed ∼10 fold higher than D-tryptophan. When the chiral object was fabricated using a chiral silane monomer prepared from (1S,2S)-cyclohexane-1,2-diamine, the enantioselectivity of the adsorption was reversed towards the D-tryptophan isomer. The new approach utilizes the 3D printing methodologies developed here for all-printed enantioselective separation columns; the printed macroporosity facilitates efficient flow, and the meso/microporous walls facilitate enantioselectivity.
4D printing is based on 3D printing of objects that can change their shape upon a proper triggering. Here, a novel approach is reported for fabricating programmable 3D printed objects composed of shape-memory polymers (SMPs) that are activated by light. The light activation of the movement and shape morphing are based on combining gold nanoparticles (AuNPs) as photothermal converters with acrylate-based printing compositions that form an SMP with tunable transition temperatures. The shape change of the printed objects is triggered by remote irradiation with a low-cost LED light at a wavelength specific to the surface plasmon resonance of the embedded AuNPs. The light is converted to heat which enables the shape transition when the temperature reaches the Tg of the polymer. Excellent SMP properties are achieved with shape fixity and recovery ratios over 95%. This material composition and triggering approach enable fabricating programmable light-activated 3D printed structures with a dual transition while tuning the concentration. Furthermore, numerical simulations performed by finite-element analysis result in the excellent prediction of the shape-memory recovery. The presented approach can be applied in remotely controlling morphing, mainly for applications in the fields of actuators and soft robotics.
In orienting themselves to the future, people form expectations not only on what will happen but also on how they will feel about possible future occurrences. So far, such affective forecasting – the prediction of future feelings – has been studied mainly from a psychological perspective. This study aims to show the importance of a socio-communicative perspective for understanding the predictors, manifestations, and consequences of affective forecasting, especially when collective futures are at stake. Using the case study of the 2019-2021 Israeli elections and a combination of a twelve-wave survey and twenty-five focus groups, we show how political affective forecasts are associated with socio-communicative factors, are used in social interactions, and drive political polarization and participation. We conclude with a discussion of the implications of our findings for future research on affective forecasting in communication studies.
Photons occupying multiple spatial modes hold a great promise for implementing high-dimensional quantum communication. We use spontaneous four-wave mixing to generate multimode photon pairs in a few-mode fiber. We show the photons are correlated in the fiber mode basis using an all-fiber mode sorter. Our demonstration offers an essential building block for realizing high-dimensional quantum protocols based on standard, commercially available fibers, in an all-fiber configuration.
