Millions of people suffer from different types of skin diseases worldwide. In the last decade, the development of nanocarriers has been the focus of the pharmaceutical and cosmetic industries to enhance the performance of their products, and to meet consumers’ demands. Several delivery systems have been developed to improve the efficiency and minimize possible side effects. In this study, retinyl palmitate and Dead Sea water loaded nanoemulsions were developed as carriers to treat skin conditions such as photoaging, psoriasis, or atopic dermatitis. Toxicity profiles were carried out by means of viability, cell membrane asymmetry study, evaluation of oxidative stress induction (reactive oxygen species), and inflammation via cytokines production with a human keratinocyte cell line (HaCaT) and a mouse embryo fibroblasts cell line (BALB/3T3). Results showed that loaded nanoemulsions were found to be non-cytotoxic under the conditions of the study. Furthermore, no oxidative stress induction was observed. Likewise, an efficacy test of these loaded nanoemulsions was also tested on human skin organ cultures, before and after ultraviolet B light treatment. Viability and caspase-3 production assessment, in response to the exposure of skin explants to the loaded nanoemulsions, indicated non-toxic effects on human skin in culture, both with and without ultraviolet B irradiation. Further the ability of loaded nanoemulsions to protect the skin against ultraviolet B damage was assessed on skin explants reducing significantly the apoptotic activation after ultraviolet B irradiation. Our promising results indicate that the developed loaded nanoemulsions may represent a topical drug delivery system to be used as an alternative treatment for recurrent skin diseases.
Trehalose is a naturally occurring disaccharide known to remarkably stabilize biomacromolecules in the biologically active state. The stabilizing effect is typically observed over a large concentration range and affects many macromolecules including proteins, lipids, and DNA. Of special interest is the transition from aqueous solution to the dense and highly concentrated glassy state of trehalose that has been implicated in bioadaptation of different organisms toward desiccation stress. Although several mechanisms have been suggested to link the structure of the low water content glass with its action as an exceptional stabilizer, studies are ongoing to resolve which are most pertinent. Specifically, the role that hydrogen bonding plays in the formation of the glass is not well resolved. Here we model aqueous trehalose mixtures over a wide concentration range, using molecular dynamics simulations with two available force fields. Both force fields indicate glass transition temperatures and osmotic pressures that are close to experimental values, particularly at high trehalose contents. We develop and employ a methodology that allows us to analyze the thermodynamics of hydrogen bonds in simulations at different water contents and temperatures. Remarkably, this analysis is able to link the liquid to glass transition with changes in hydrogen bond characteristics. Most notably, the onset of the glassy state can be quantitatively related to the transition from weakly to strongly correlated hydrogen bonds. Our findings should help resolve the properties of the glass and the mechanisms of its formation in the presence of added macromolecules.
Free-space quantum key distribution is gaining increasing interest as a leading platform for long range quantum communication. However, the sensitivity of quantum correlations to scattering induced by turbulent atmospheric links limits the performance of such systems. Recently, a method for compensating for the scattering of entangled photons was demonstrated, allowing for real-time optimization of their quantum correlations. In this Letter, we demonstrate the use of wavefront shaping for compensating for the scattering of non-collinear and non-degenerate entangled photons. These results demonstrate the applicability of wavefront shaping schemes for protocols utilizing the large bandwidth and emission angle of the entangled photons.
This article explores the Facebook unfriending of users from a majority group by members of a minority group, focusing on Palestinian and Jewish citizens of Israel. Indeed, this is the first study to focus on power differentials among Facebook users in the context of unfriending. The article thus adds depth to our understanding of unfriending, while also shedding light on the experience of social media use from the perspective of an oppressed minority. Based on semi-structured in-depth interviews with 20 ’48 Palestinians (Palestinian citizens of Israel), we present various triggers for unfriending (mainly, encounters with racism and surveillance), and show that Palestinians’ stories of unfriending Jewish Israelis are sometimes about punching up, and sometimes about stepping away. However, while unfriending is broadly considered an apt response to abuse, it also distances Palestinians from centers of power in Israel. This suggests an important way in which social media reproduce inequality.
The work of writers in exile is generally expected to display the theme of nostalgia and the techniques of defamiliarization. It is seldom noted that the experience of a young emigrant is sometimes characterized by bouts of overwhelming poignant happiness, of joy yielded by the senses in response to the natural or even urban scenes. This happiness, against the background of a near-sublime self-sufficiency, is a distinctive feature of Nabokov’s experience of the twenties, despite the painful blows that he received; it is a recurrent theme in his poetry, fiction, and letters. By the late 1930s, for a variety of personal and political reasons, the waves of joy become rare. Instead, Nabokov’s other capacities deepen and gain further development, a modified axiology partly replacing the youthful happiness or compensating for the infrequency of its returns. This paper is devoted to the shift of emphases in Nabokov’s poetics and his thematic concerns after he could no longer base his eschatology on a recurrent experience of joyful oneness with the world.
Heavy precipitation events (HPEs) can lead to natural hazards (e.g. floods and debris flows) and contribute to water resources. Spatiotemporal rainfall patterns govern the hydrological, geomorphological, and societal effects of HPEs. Thus, a correct characterisation and prediction of rainfall patterns is crucial for coping with these events. Information from rain gauges is generally limited due to the sparseness of the networks, especially in the presence of sharp climatic gradients. Forecasting HPEs depends on the ability of weather models to generate credible rainfall patterns. This paper characterises rainfall patterns during HPEs based on high-resolution weather radar data and evaluates the performance of a high-resolution, convection-permitting Weather Research and Forecasting (WRF) model in simulating these patterns. We identified 41 HPEs in the eastern Mediterranean from a 24-year radar record using local thresholds based on quantiles for different durations, classified these events into two synoptic systems, and ran model simulations for them. For most durations, HPEs near the coastline were characterised by the highest rain intensities; however, for short durations, the highest rain intensities were found for the inland desert. During the rainy season, the rain field's centre of mass progresses from the sea inland. Rainfall during HPEs is highly localised in both space (less than a 10 km decorrelation distance) and time (less than 5 min). WRF model simulations were accurate in generating the structure and location of the rain fields in 39 out of 41 HPEs. However, they showed a positive bias relative to the radar estimates and exhibited errors in the spatial location of the heaviest precipitation. Our results indicate that convection-permitting model outputs can provide reliable climatological analyses of heavy precipitation patterns; conversely, flood forecasting requires the use of ensemble simulations to overcome the spatial location errors.
We develop a range-separated stochastic resolution of identity (RS-SRI) approach for the four-index electron repulsion integrals, where the larger terms (above a predefined threshold) are treated using a deterministic RI and the remaining terms are treated using a SRI. The approach is implemented within a second-order Green’s function formalism with an improved O(N3) scaling with the size of the basis set, N. Moreover, the RS approach greatly reduces the statistical error compared to the full stochastic version [T. Y. Takeshita et al., J. Chem. Phys. 151, 044114 (2019)], resulting in computational speedups of ground and excited state energies of nearly two orders of magnitude, as demonstrated for hydrogen dimer chains and water clusters.
Cyclic peptide-peptoid hybrids possess improved stability and selectivity over linear peptides and are thus better drug candidates. However, their synthesis is far from trivial and is usually difficult to automate. Here we describe a new rapid and efficient approach for the synthesis of click-based cyclic peptide-peptoid hybrids. Our methodology is based on a combination between easily synthesized building blocks, automated microwave assisted solid phase synthesis and bioorthogonal click cyclization. We proved the concept of this method using the INS peptide, which we have previously shown to activate the HIV-1 integrase enzyme. This strategy enabled the rapid synthesis and biophysical evaluation of a library of cyclic peptide-peptoid hybrids derived from HIV-1 integrase in high yield and purity. The new cyclic hybrids showed improved biological activity and were significantly more stable than the original linear INS peptide.
Quantum technologies hold great promise for revolutionizing photonic applications such as cryptography. Yet, their implementation in real-world scenarios is challenging, mostly because of sensitivity of quantum correlations to scattering. Recent developments in optimizing the shape of single photons introduce new ways to control entangled photons. Nevertheless, shaping single photons in real time remains a challenge due to the weak associated signals, which are too noisy for optimization processes. Here, we overcome this challenge and control scattering of entangled photons by shaping the classical laser beam that stimulates their creation. We discover that because the classical beam and the entangled photons follow the same path, the strong classical signal can be used for optimizing the weak quantum signal. We show that this approach can increase the length of free-space turbulent quantum links by up to two orders of magnitude, opening the door for using wavefront shaping for quantum communications.
This study examines the role of digital media within the Ultra-Orthodox Jewish community in Israel, a conservative closed community, whose leadership is unable or unwilling to control the effects of digital media on the rank-and-file. Over the past decade, digital media have played an important role for challenging authoritarian rule around the globe. Especially in ideological communities sustained by strict taboos, digital media hold the potential to subvert hegemonic discourses. In this study, we make use of an incident that forced Israel’s Ultra-Orthodox community to address its long-standing taboo and hateful attitudes toward LGBT and Queer issues. In July 2015, an Ultra-Orthodox community member attacked participants of the Jerusalem Gay Pride Parade, murdering one and wounding six. While traditional community media attempted to ignore the event, two major Ultra-Orthodox news websites fell outside the control exercised by the community leadership, and enabled subversive discussions within the Ultra-Orthodox community. Through a process of negotiating the meaning of the attack, these discussions resulted in a reframing of the boundaries of the community, breaking a path for further contestation and debate. Using grounded theory analysis, this article contributes to a better understanding of the role of digital media in enabling contestation and challenging established power structures within authoritarian closed communities.
This study examines the role of digital media within the Ultra-Orthodox Jewish community in Israel, a conservative closed community, whose leadership is unable or unwilling to control the effects of digital media on the rank-and-file. Over the past decade, digital media have played an important role for challenging authoritarian rule around the globe. Especially in ideological communities sustained by strict taboos, digital media hold the potential to subvert hegemonic discourses. In this study, we make use of an incident that forced Israel’s Ultra-Orthodox community to address its long-standing taboo and hateful attitudes toward LGBT and Queer issues. In July 2015, an Ultra-Orthodox community member attacked participants of the Jerusalem Gay Pride Parade, murdering one and wounding six. While traditional community media attempted to ignore the event, two major Ultra-Orthodox news websites fell outside the control exercised by the community leadership, and enabled subversive discussions within the Ultra-Orthodox community. Through a process of negotiating the meaning of the attack, these discussions resulted in a reframing of the boundaries of the community, breaking a path for further contestation and debate. Using grounded theory analysis, this article contributes to a better understanding of the role of digital media in enabling contestation and challenging established power structures within authoritarian closed communities.
