Physical Characterization and In Vitro Toxicity Test of PDMS Synthesized from Low-Grade D4 Monomer as a Vitreous Substitute in the Human Eyes

Polydimethylsiloxane (PDMS) is one of the most superior materials and has been used as a substitute for vitreous humor in the human eye. In previous research, we have succeeded in producing PDMS with low and medium viscosity using octamethylcyclotetrasiloxane (D4) monomer with a low grade of 96%. Both have good physical properties and are comparable to commercial product PDMS and PDMS synthesized using D4 monomer with a high grade of 98%. An improvement of the synthesis process is needed to ensure that PDMS synthesized from a low-grade D4 monomer under specific synthesis conditions can repeatedly produce high-quality PDMS. Apart from good physical properties, the PDMS as a substitute for vitreous humor must also be safe and not cause other disturbances to the eyes. Here, we reported the process of synthesizing and characterizing the physical properties of low- and medium-viscosity PDMS using a low-grade D4 monomer. We also reported for the first time the in vitro toxicity test using the Hen’s Egg Test Chorioallantoic Membrane (HET-CAM) test method. We have succeeded in obtaining PDMS with viscosities of 1.15 Pa.s, 1.17 Pa.s, and 1.81 Pa.s. All samples have good physical properties such as refractive index, surface tension, and functional groups that are similar to commercial PDMS. The HET-CAM test results showed that all samples did not show signs of irritation indicating that samples were non-toxic. From the results of this study, it can be concluded that PDMS synthesized from a low-grade D4 monomer under specific synthesis conditions by the ROP method is very safe and has the potential to be developed as a substitute for vitreous humor in human eyes.

Guide RNA acrobatics: positioning consecutive uridines for pseudouridylation by H/ACA pseudouridylation loops with dual guide capacity

Site-specific pseudouridylation of human ribosomal and spliceosomal RNAs is directed by H/ACA guide RNAs composed of two hairpins carrying internal pseudouridylation guide loops. The distal “antisense” sequences of the pseudouridylation loop base-pair with the target RNA to position two unpaired target nucleotides 5′-UN-3′, including the 5′ substrate U, under the base of the distal stem topping the guide loop. Therefore, each pseudouridylation loop is expected to direct synthesis of a single pseudouridine (Ψ) in the target sequence. However, in this study, genetic depletion and restoration and RNA mutational analyses demonstrate that at least four human H/ACA RNAs (SNORA53, SNORA57, SCARNA8, and SCARNA1) carry pseudouridylation loops supporting efficient and specific synthesis of two consecutive pseudouridines (ΨΨ or ΨNΨ) in the 28S (Ψ3747/Ψ3749), 18S (Ψ1045/Ψ1046), and U2 (Ψ43/Ψ44 and Ψ89/Ψ91) RNAs, respectively. In order to position two substrate Us for pseudouridylation, the dual guide loops form alternative base-pairing interactions with their target RNAs. This remarkable structural flexibility of dual pseudouridylation loops provides an unexpected versatility for RNA-directed pseudouridylation without compromising its efficiency and accuracy. Besides supporting synthesis of at least 6% of human ribosomal and spliceosomal Ψs, evidence indicates that dual pseudouridylation loops also participate in pseudouridylation of yeast and archaeal rRNAs.

Site-Specific Synthesis of N4-Acetylcytidine in RNA Reveals Physiological Duplex Stabilization

N4-acetylcytidine (ac4C) is a post-transcriptional modification of RNA that is conserved across all domains of life. All characterized sites of ac4C in eukaryotic RNA occur in the central nucleotide of a CCG consensus sequence. However, the thermodynamic consequences of cytidine acetylation in this context have never been assessed due to its challenging synthesis. Here we report the synthesis and biophysical characterization of ac4C in its endogenous eukaryotic sequence context. First, we develop a synthetic route to homogenous RNAs containing electrophilic acetyl groups. Next, we use thermal denaturation to interrogate the effects of ac4C on duplex stability and mismatch discrimination in a native sequence found in human ribosomal RNA. Finally, we demonstrate the ability of this chemistry to incorporate ac4C into the complex modification landscape of human tRNA, and use duplex melting combined with sequence analysis to highlight a potentially unique enforcing role for ac4C in this setting. By enabling the analysis of nucleic acid acetylation in its physiological sequence context, these studies establish a chemical foundation for understanding the function of a universally-conserved nucleobase in biology and disease.

Program Synthesis as Dependency Quantified Formula Modulo Theory

Given a specification φ(X, Y ) over inputs X and output Y and defined over a background theory T, the problem of program synthesis is to design a program f such that Y = f (X), satisfies the specification φ. Over the past decade, syntax-guided synthesis (SyGuS) has emerged as a dominant approach to program synthesis where in addition to the specification φ, the end-user also specifies a grammar L to aid the underlying synthesis engine. This paper investigates the feasibility of synthesis techniques without grammar, a sub-class defined as T constrained synthesis. We show that T-constrained synthesis can be reduced to DQF(T),i.e., to the problem of finding a witness of a dependency quantified formula modulo theory. When the underlying theory is the theory of bitvectors, the corresponding DQF problem can be further reduced to Dependency Quantified Boolean Formulas (DQBF). We rely on the progress in DQBF solving to design DQBF-based synthesizers that outperform the domain-specific program synthesis techniques; thereby positioning DQBF as a core representation language for program synthesis. Our empirical analysis shows that T-constrained synthesis can achieve significantly better performance than syntax-guided approaches. Furthermore, the general-purpose DQBF solvers perform on par with domain-specific synthesis techniques.

Tuneable local order in thermoelectric crystals

Although crystalline solids are characterized by their periodic structures, some are only periodic on average and deviate on a local scale. Such disordered crystals with distinct local structures have unique properties arising from both collective and localized behaviour. Different local orderings can exist with identical average structures, making their differences hidden to Bragg diffraction methods. Using high-quality single-crystal X-ray diffuse scattering the local order in thermoelectric half-Heusler Nb1−x CoSb is investigated, for which different local orderings are observed. It is shown that the vacancy distribution follows a vacancy repulsion model and the crystal composition is found always to be close to x = 1/6 irrespective of nominal sample composition. However, the specific synthesis method controls the local order and thereby the thermoelectric properties thus providing a new frontier for tuning material properties.

“Lithuanian Athens”. Ludwik Janowski’s versions of the history of Vilnius University

The subject of this article is scientific reflection about the works on the history of Vilnius University had written in the first two decades of the twentieth century by the cultural historian, Ludwik Janowski (1878-1921), who was associated with the scientific community in Kiev and Krakow, and in 1919-1921 he was a professor at The Stefan Batory University in Vilnius. Janowski’s interest on the history of Vilnius University was a kind of a research passion all his life. Though he failed to write a historiographic synthesis that it has been planning. In his works he tried to correct and supplement the research on the history of Vilnius University. His studies and books compose a specific synthesis in fragments, which shows in a multi-variant narrative the most important stages and factors in the development of this great center of science and culture.