2022
Jared Vicory, Herz, Christian , Allemang, David , Nam, Hannah H, Cianciulli, Alana , Vigil, Chad , Han, Ye , Lasso, Andras , Jolley, Matthew A, ו Paniagua, Beatriz . 2022.
“Statistical Shape Analysis Of The Tricuspid Valve In Hypoplastic Left Heart Sydrome”. Stat. Atlases Comput. Models Heart, 13131, Pp. 132–140.
תקציר Hypoplastic left heart syndrome (HLHS) is a congenital heart disease characterized by incomplete development of the left heart. Children with HLHS undergo a series of operations which result in the tricuspid valve (TV) becoming the only functional atrioventricular valve. Some of those patients develop tricuspid regurgitation which is associated with heart failure and death and necessitates further surgical intervention. Repair of the regurgitant TV, and understanding the connections between structure and function of this valve remains extremely challenging. Adult cardiac populations have used 3D echocardiography (3DE) combined with computational modeling to better understand cardiac conditions affecting the TV. However, these structure-function analyses rely on simplistic point-based techniques that do not capture the leaflet surface in detail, nor do they allow robust comparison of shapes across groups. We propose using statistical shape modeling and analysis of the TV using Spherical Harmonic Representation Point Distribution Models (SPHARM-PDM) in order to generate a reproducible representation, which in turn enables high dimensional low sample size statistical analysis techniques such as principal component analysis and distance weighted discrimination. Our initial results suggest that visualization of the differences in regurgitant vs. non-regurgitant valves can precisely locate populational structural differences as well as how an individual regurgitant valve differs from the mean shape of functional valves. We believe that these results will support the creation of modern image-based modeling tools, and ultimately increase the understanding of the relationship between valve structure and function needed to inform and improve surgical planning in HLHS.
The substitution reaction of phosphinates with a binaphthyloxy group at the phosphorus atom with lithium alkoxides proceeded with good to high efficiencies to give P-chirogenic phosphinates with a high enantiomeric ratio. As alcohols, primary, secondary, and tertiary alcohols could be used, and the use of tert-butyl alcohol yielded the products with a higher enantiomeric ratio. A substrate with two different alkyl groups on the phosphorus atom could also participate in the substitution reaction to give the corresponding products in good yields with excellent selectivity. The molecular structures of one of the substrates and the corresponding products, determined by X-ray analyses, proved that the substitution reaction at the phosphorus atom proceeded with inversion of the absolute configuration. The usefulness of the reaction was demonstrated by using it to prepare a drug candidate for Duchenne muscular dystrophy. Finally, thionation of the resulting phosphinates was carried out to form P-chirogenic phosphinothioates.
Sayantan Panda, Jozwiak, Adam , Sonawane, Prashant D. , Szymanski, Jedrzej , Kazachkova, Yana , Vainer, Andrii , Kilambi, Himabindu Vasuki , Almekias-Siegl, Efrat , Dikaya, Varvara , Bocobza, Samuel , Shohat, Hagai , Meir, Sagit , Wizler, Guy , Giri, Ashok P. , Schuurink, Robert , Weiss, David , Yasuor, Hagai , Kamble, Avinash , ו Aharoni, Asaph . 2022.
“Steroidal Alkaloids Defence Metabolism And Plant Growth Are Modulated By The Joint Action Of Gibberellin And Jasmonate Signalling”. New Phytologist, 233, 3, Pp. 1220-1237. doi:https://doi.org/10.1111/nph.17845.
Publisher's Version תקציר Summary Steroidal glycoalkaloids (SGAs) are protective metabolites constitutively produced by Solanaceae species. Genes and enzymes generating the vast structural diversity of SGAs have been largely identified. Yet, mechanisms of hormone pathways coordinating defence (jasmonate; JA) and growth (gibberellin; GA) controlling SGAs metabolism remain unclear. We used tomato to decipher the hormonal regulation of SGAs metabolism during growth vs defence tradeoff. This was performed by genetic and biochemical characterisation of different JA and GA pathways components, coupled with in vitro experiments to elucidate the crosstalk between these hormone pathways mediating SGAs metabolism. We discovered that reduced active JA results in decreased SGA production, while low levels of GA or its receptor led to elevated SGA accumulation. We showed that MYC1 and MYC2 transcription factors mediate the JA/GA crosstalk by transcriptional activation of SGA biosynthesis and GA catabolism genes. Furthermore, MYC1 and MYC2 transcriptionally regulate the GA signalling suppressor DELLA that by itself interferes in JA-mediated SGA control by modulating MYC activity through protein–protein interaction. Chemical and fungal pathogen treatments reinforced the concept of JA/GA crosstalk during SGA metabolism. These findings revealed the mechanism of JA/GA interplay in SGA biosynthesis to balance the cost of chemical defence with growth.
Johnny N. Naoum, Alshanski, Israel , Mayer, Guy , Strauss, Poriah , ו Hurevich, Mattan . 2022.
“Stirring Peptide Synthesis To A New Level Of Efficiency”. Organic Process Research & Development, 26, 1, Pp. 129-136. doi:10.1021/acs.oprd.1c00304.
תקציר
Accelerating solid-phase synthesis is crucial for accessing a large number of peptides in a short time. Since standard peptide synthesis is usually done under poor diffusion conditions with slow or no mixing of the solid support, acceleration of the process is achieved by applying a large excess of reagents. In this work, overhead stirring and heating were combined to provide accelerated solid-phase peptide synthesis without using an excess of reagent. A new setup that allows both heating and fast stirring was designed specifically for research laboratory-scale peptide synthesis. By increasing the diffusion of both reagents and beads in a narrow dimension reactor, solid-phase reactions were done in seconds and medium-size peptides were synthesized in minutes.
We review a suite of stochastic vector computational approaches for studying the electronic structure of extended condensed matter systems. These techniques help reduce algorithmic complexity, facilitate efficient parallelization, simplify computational tasks, accelerate calculations, and diminish memory requirements. While their scope is vast, we limit our study to ground-state and finite temperature density functional theory (DFT) and second-order perturbation theory. More advanced topics, such as quasiparticle (charge) and optical (neutral) excitations and higher-order processes, are covered elsewhere. We start by explaining how to use stochastic vectors in computations, characterizing the associated statistical errors. Next, we show how to estimate the electron density in DFT and discuss highly effective techniques to reduce statistical errors. Finally, we review the use of stochastic vector techniques for calculating correlation energies within the secondorder Møller-Plesset perturbation theory and its finite temperature variational form. Example calculation results are presented and used to demonstrate the efficacy of the methods.
The avian embryo has a remarkable ability that allows it to suspend its development during blastulation for a long time at low temperatures, and to resume normal development when incubated. This ability is used by poultry hatcheries to store eggs prior to incubation. We have previously found that this ability correlates with the temperature during storage; embryos recover much better following prolonged storage at 12°C rather than at 18°C. However, the molecular and cellular mechanisms underlying these differences are poorly understood. To successfully resume development following storage, the embryo has to shift from the blastulation phase to gastrulation. Several genes are known to partake in the blastulation-to-gastrulation transition under normal conditions, such as the pluripotency-related genes Inhibitor of DNA Binding 2 (ID2) and NANOG that are expressed during blastulation, and the gastrulation-regulating genes NODAL and Brachyury (TBXT). However, their expression and activity following storage is unknown. To elucidate the molecular mechanisms that initiate the ability to successfully transit from blastulation to gastrulation following storage, embryos were stored for 28 days at 12°C or 18°C, and were assessed either prior to incubation, 12, or 18 h of incubation at 37.8°C. Immediately following storage at 18°C group showed remarkable impaired morphology compared to the blastoderm of the 12°C group and of non-stored control embryos. Concurrently with these, expression of ID2 and NANOG was maintained following storage at 12°C similar to the control group, but was significantly reduced upon storage at 18°C. Nevertheless, when the 18°C-stored embryos were incubated, the morphology and the reduced genes were reverted to resemble those of the 12°C group. At variance, key gastrulation genes, NODAL and its downstream effector Brachyury (TBXT), which were similarly expressed in the control and the 12°C group, were not restored in the 18°C embryos following incubation. Notably, ectopic administration of Activin rescued NODAL and TBXT expression in the 18°C group, indicating that these embryos maintain the potential to initiate. Collectively, this study suggests a temperature-dependent mechanisms that direct the transition from blastulation to gastrulation. These mechanisms promote a successful developmental resumption following prolonged storage at low temperatures.
Although Alva Noë’s Strange Tools: Art and Human Nature (2015) makes no direct reference to Philip Pullman’s His Dark Materials trilogy (1995–2000), these otherwise dissimilar works share an astonishingly similar and current view of the mind: both Noë and Pullman construe cognition as embodied action that extends and reflects on its own possibilities through various instruments and technologies. For Noë, the key technology aiding this reaching of the mind is art; making and engaging with art is a self-reflexive endeavor that makes our activities available for closer examination and evaluation. By extension, works of speculative fiction could be read as illustrations of or investigations into speculative, imaginative cognition.
In case of Pullman’s trilogy, this is certainly true as it incorporates several explicit commentaries on John Keats’ notion of negative capability, which is closely linked to imagination and creative cognition. Moreover, Pullman illustrates his characters’ negative capabilities through very particular ”strange tools”: the Golden Compass, the Subtle Knife, and the Amber Spyglass. These imaginary instruments serve the dual purpose of, first, modifying affordances, i.e. the ways the characters can respond to their changing situations, and second, making these speculative cognitive processes more visible to the readers.
Ultimately, the analysis of the trilogy suggests that skillful speculation entails at least two subskills: first, the ability to see as full a range of actionable possibilities as possible and, second, the ability to choose and act on the most suitable one. In the 4E framework, which views the mind as embodied, extended and action-oriented, speculation and imagination could thus be defined as especially extensive and flexible use of affordances. As such, speculation is something that always oveflows the limits of narrative. Like other forms of art, narrative is merely a tool for modifying and highlighting the affordances at its disposal.
February 2022: Essi Varis, PhD, is currently working on her four-year postdoctoral research project, Metacognitive Magic Mirrors (2020–2024), which explores how different kinds of texts and images aid and illustrate imagination and speculation in arts and research alike. Funded by the Finnish Cultural Foundation, she is splitting her time between the Universities of Helsinki, Jyväskylä, and Oslo. In her doctoral dissertation (2019), Varis suggested a new theory of fictional characters as experiential Frankenstein’s monsters. In addition to cognitive literary theory and speculative fiction, her research interests revolve around graphic narratives, Japanese fiction and Gothic horror.
INTRODUCTION: Oral administration of cannabinoids is a convenient route of administration in many cases. To enhance the poor and variable bioavailability of cannabinoids, selected strategies utilizing proper delivery systems have been designed. Low solubility in the GI aqueous media is the first and most critical barrier. Thereafter, cannabinoids can reach the systemic blood circulation via the portal vein that is associated with significant hepatic first pass metabolism (FPM) or bypass it via lymphatic absorption. AREAS COVERED: The solubility obstacle of cannabinoids is mainly addressed with lipid-based formulations such as self-nanoemulsifying drug delivery systems (SNEDDS). Certain lipids are used to overcome the solubility issue. Surfactants and other additives in the formulation have additional impact on several barriers, including dictating the degree of lymphatic bioavailability and hepatic FPM. Gastro-retentive formulation is also plausible. EXPERT OPINION: Comparison of the role of the same SNEDDS formulation, cyclosporine vs. cannabinoids, when used to elevate the oral bioavailability of different compounds, is presented. It illustrates some similarities and major mechanistic differences obtained by the same SNEDDS. Thus, the different influence over the absorption pathway illuminates the importance of understanding the absorption mechanism and its barriers to properly select appropriate strategies to achieve enhanced oral bioavailability.
Yi-Teng Huang, Kavanagh, Seán R, Righetto, Marcello , Rusu, Marin , Levine, Igal , Unold, Thomas , Zelewski, Szymon J, Sneyd, Alexander J, Zhang, Kaiwen , Dai, Linjie , ו others, . 2022.
“Strong Absorption And Ultrafast Localisation In Nabis2 Nanocrystals With Slow Charge-Carrier Recombination”. Nature Communications, 13, Pp. 4960.
Background: Since (1-x)[Pb(Mg1/3Nb2/3)O3]-(x)PbTiO3 (PMN-PT) ceramic has a high dielectric constant and piezoelectric coefficient, it has been widely investigated for profound applications in electro-optical devices, sensors, multilayer capacitors and actuators. Objectives: The objective of this paper is to study the structural and electrical properties of 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (0.7PMN-0.3PT) ceramic to understand the biphasic structural nature using Rietveld Refinement. Also, it characterises the type of conduction process as well as the role of grain and grain boundary resistance in the material on the basis of electrical properties such as impedance and modulus to understand the relaxation process. Methods: 0.7PMN-0.3PT is synthesised by mixed oxide method using PbO, MgO, Nb2O5 and TiO2 as precursor materials. Results: The XRD data reveals the biphasic structure of the tetragonal phase with the space group of P4mm and the monoclinic phase with the space group of Pm. The complex impedance analysis clearly represents the effect of grain on the overall resistance and departs from normal Debye-type behaviour. Also, the resistance is found to decrease with temperature, thereby confirming the semiconducting nature of the sample. The presence of long as well as short-range mobility of charge carriers is confirmed from the modulus and impedance analysis. The influence of long-range motion is observed at high temperatures and of short-range motion at low temperatures. Conclusion: XRD analysis confirmed the biphasic structure of the M+T phase. The frequencydependent modulus and impedance spectroscopy show the presence of a relaxation effect in the ceramic which is found to increase with temperature. The Nyquist plot shows that the resistance is decreased with temperature, thereby confirming the NTCR behaviour in the studied sample.
C. Gorski, Riddle, R. , Toporik, H. , Da, Z. , Dobson, Z. , Williams, D. , ו Mazor, Y.. 2022.
“The Structure Of The Physcomitrium Patens Photosystem I Reveals A Unique Lhca2 Paralogue Replacing Lhca4”. Nature Plants, 8, Pp. 307–316. doi:10.1038/s41477-022-01099-w.
תקציר The moss Physcomitrium patens diverged from green algae shortly after the colonization of land by ancient plants. This colonization posed new environmental challenges, which drove evolutionary processes. The photosynthetic machinery of modern flowering plants is adapted to the high light conditions on land. Red-shifted Lhca4 antennae are present in the photosystem I light-harvesting complex of many green-lineage plants but absent in P. patens. The cryo-EM structure of the P. patens photosystem I light-harvesting complex I supercomplex (PSI–LHCI) at 2.8 Å reveals that Lhca4 is replaced by a unique Lhca2 paralogue in moss. This PSI–LHCI supercomplex also retains the PsaM subunit, present in Cyanobacteria and several algal species but lost in vascular plants, and the PsaO subunit responsible for binding light-harvesting complex II. The blue-shifted Lhca2 paralogue and chlorophyll b enrichment relative to flowering plants make the P. patens PSI–LHCI spectroscopically unique among other green-lineage supercomplexes. Overall, the structure represents an evolutionary intermediate PSI with the crescent-shaped LHCI common in vascular plants, and contains a unique Lhca2 paralogue that facilitates the moss’s adaptation to low-light niches.
Henri-Baptiste Marjault, Yang-Sung, Sohn , Zuo, Ke , Carloni, Paolo , Mittler, Ron , ו Nechushtai, Rachel . 2022.
“Structure-Based Screening Reveals A Ligand That Stabilizes The [2Fe-2S] Clusters Of Human Mitoneet And Reduces Ovarian Cancer Cell Proliferation”. The Journal Of Physical Chemistry B, 126, Pp. 9559–9565.
Convolutional neural networks (CNNs) offer significant advantages when used in various image classification tasks and computer vision applications. CNNs are increasingly deployed in environments from edge and Internet of Things (IoT) devices to high-end computational infrastructures, such as supercomputers, cloud computing, and data centers. The growing amount of data and the growth in their model size and computational complexity, however, introduce major computational challenges. Such challenges present entry barriers for IoT and edge devices as well as increase the operational expenses of large-scale computing systems. Thus, it has become essential to optimize CNN algorithms. In this paper, we introduce the S-VELCRO compression algorithm, which exploits value locality to trim filters in CNN models utilized for specialized tasks. S-VELCRO uses structured compression, which can save costs and reduce overhead compared with unstructured compression. The algorithm runs in two steps: a preprocessing step identifies the filters with a high degree of value locality, and a compression step trims the selected filters. As a result, S-VELCRO reduces the computational load of the channel activation function and avoids the convolution computation of the corresponding trimmed filters. Compared with typical CNN compression algorithms that run heavy back-propagation training computations, S-VELCRO has significantly fewer computational requirements. Our experimental analysis shows that S-VELCRO achieves a compression-saving ratio between 6% and 30%, with no degradation in accuracy for ResNet-18, MobileNet-V2, and GoogLeNet when used for specialized tasks.
The most well-known and widely cited literature in the multidisciplinary field of childhood studies has been undertaken by scholars based in the Global North, who have produced theoretical frameworks and conceptualisations about childhood frequently deployed by Northern and Southern scholars alike. These are often based on priorities developed in Northern academic institutions, sometimes in response to funding calls by grant-making agencies also based in the North. As a result, when Southern scholars contribute to the dominant childhood studies literature, a field of study in which the majority of well-known articles tend to be published in Northern-based Anglophone journals, their contributions stand mainly as empirical variations of mainstream Northern theories whose scholarship foregrounds theoretical and methodological frameworks designed with particular childhoods in mind. The resulting outcome is that Global South childhoods – in their plurality and diversity – do not contribute epistemically to the construction of a transnational childhood scientific discourse. This ultimately limits the quality of global childhood studies and hinders the development of more conceptually sophisticated, eventually divergent, theoretical frameworks that can account for multiplicity and diversity in childhoods. Therefore, this volume sought to explore locally driven perspectives of childhoods in diverse contexts in the South for the purpose of gaining insights into the knowledge that can be produced about Southern childhoods when research is driven by priorities, demands, and needs of locales in the Global South.
