Coupling AFM,DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study

Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization challenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico-chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit^® RS PO and hydroxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm² h), and even the pH of the sample with Eudragit^® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile.     

Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis,Diagnosis and Therapy

Type 2 transglutaminase (TG2) is the main autoantigen in coeliac disease (CD), a widespread inflammatory enteropathy caused by the ingestion of gluten-containing cereals in genetically predisposed individuals. As a consequence, serum antibodies to TG2 represent a very useful marker in CD diagnosis. However, TG2 is also an important player in CD pathogenesis, for its ability to deamidate some Gln residues of gluten peptides, which become more immunogenic in CD intestinal mucosa. Given the importance of TG2 enzymatic activities in CD, several studies have sought to discover specific and potent inhibitors that could be employed in new therapeutical approaches for CD, as alternatives to a lifelong gluten-free diet. In this review, we summarise all the aspects regarding TG2 involvement in CD, including its enzymatic reactions in pathogenesis, the role of anti-TG2 antibodies in disease management, and the exploration of recent strategies to reduce deamidation or to use transamidation to detoxify gluten.     

Tracking Changes in the Spring Barley Gene Pool in Poland during 120 Years of Breeding

This study was undertaken to investigate the diversity and population structure of 83 spring barley (Hordeum vulgare L.) cultivars, which corresponded to 120 years of this crop’s breeding in Poland. The analysis was based on 11,655 DArTseq-derived SNPs evenly distributed across seven barley chromosomes. Five groups were assigned in the studied cultivars according to the period of their breeding. A decrease in observed heterozygosity within the groups was noted along with the progress in breeding, with a simultaneous increase in the inbreeding coefficient value. As a result of breeding, some of the unique allelic variation present in old cultivars was lost, but crosses with foreign materials also provided new alleles to the barley gene pool. It is important to mention that the above changes affected different chromosomes to varying degrees. The internal variability of the cultivars ranged from 0.011 to 0.236. Internal uniformity was lowest among the oldest cultivars, although some highly homogeneous ones were found among them. This is probably an effect of genetic drift or selection during their multiplications and regenerations in the period from breeding to the time of analysis. The population genetic structure of the studied group of cultivars appears to be quite complex. It was shown that their genetic makeup consists of as many as eleven distinct gene pools. The analysis also showed traces of directed selection on chromosomes 3H and 5H. Detailed data analysis confirmed the presence of duplicates for 11 cultivars. The performed research will allow both improvement of the management of barley genetic resources in the gene bank and the reuse of this rich and forgotten variability in breeding programs and research.     

Transition‐Metal Dichalcogenide NiTe2: An Ambient‐Stable Material for Catalysis and Nanoelectronics

By means of theory and experiments, the application capability of nickel ditelluride (NiTe₂) transition‐metal dichalcogenide in catalysis and nanoelectronics is assessed. The Te surface termination forms a TeO₂ skin in an oxygen environment. In ambient atmosphere, passivation is achieved in less than 30 min with the TeO₂ skin having a thickness of about 7 Å. NiTe₂ shows outstanding tolerance to CO exposure and stability in water environment, with subsequent good performance in both hydrogen and oxygen evolution reactions. NiTe₂‐based devices consistently demonstrate superb ambient stability over a timescale as long as one month. Specifically, NiTe₂ has been implemented in a device that exhibits both superior performance and environmental stability at frequencies above 40 GHz, with possible applications as a receiver beyond the cutoff frequency of a nanotransistor.     

Cryptanalysis of the Tillich�CZ��mor Hash Function

At CRYPTO ’94, Tillich and Zémor proposed a family of hash functions, based on computing a suitable matrix product in groups of the form SL₂(\mathbbF_2ⁿ)SL_{2}(\mathbb{F}_{2^{n}}). We show how to construct collisions between palindromic bit strings of length 2n+2 for Tillich and Zémor’s construction. The approach also yields collisions for related proposals by Petit et al. from ICECS ’08 and CT-RSA ’09.     

Outage analysis of selection diversity over Rayleigh fading channels with multiple co-channel interferers

In this paper an approach to the performance analysis of signal-to-interference (SIR) based selection combining (SC) operating over the Rayleigh fading channels experiencing an arbitrary number of multiple, Rayleigh co-channel interferers is presented. We have presented a general analysis of multibranch SC where each branch experiences an arbitrary number of multiple equal power co-channel interferers. Useful closed form expressions are derived for the probability density function (PDF) and cumulative distribution function (CDF) at the output of the combiner. Also an outage analysis is performed in order to show the effects of the number of multiple interferers, diversity order and input SIR unbalance to the system performances.     

Kitkaite NiTeSe,an Ambient-Stable Layered Dirac Semimetal with Low-Energy Type-II Fermions with Application Capabilities in Spintronics and Optoelectronics

The emergence of Dirac semimetals has stimulated growing attention, owing to the considerable technological potential arising from their peculiar exotic quantum transport related to their nontrivial topological states. Especially, materials showing type-II Dirac fermions afford novel device functionalities enabled by anisotropic optical and magnetotransport properties. Nevertheless, real technological implementation has remained elusive so far. Definitely, in most Dirac semimetals, the Dirac point lies deep below the Fermi level, limiting technological exploitation. Here, it is shown that kitkaite (NiTeSe) represents an ideal platform for type-II Dirac fermiology based on spin-resolved angle-resolved photoemission spectroscopy and density functional theory. Precisely, the existence of type-II bulk Dirac fermions is discovered in NiTeSe around the Fermi level and the presence of topological surface states with strong (≈50%) spin polarization. By means of surface-science experiments in near-ambient pressure conditions, chemical inertness towards ambient gases (oxygen and water) is also demonstrated. Correspondingly, NiTeSe-based devices without encapsulation afford long-term efficiency, as demonstrated by the direct implementation of a NiTeSe-based microwave receiver with a room-temperature photocurrent of 2.8 µA at 28 GHz and more than two orders of magnitude linear dynamic range. The findings are essential to bringing to fruition type-II Dirac fermions in photonics, spintronics, and optoelectronics.     

Genome-Wide Association Analysis and Genomic Prediction of Thyroglobulin Plasma Levels

Thyroglobulin (Tg) is an iodoglycoprotein produced by thyroid follicular cells which acts as an essential substrate for thyroid hormone synthesis. To date, only one genome-wide association study (GWAS) of plasma Tg levels has been performed by our research group. Utilizing recent advancements in computation and modeling, we apply a Bayesian approach to the probabilistic inference of the genetic architecture of Tg. We fitted a Bayesian sparse linear mixed model (BSLMM) and a frequentist linear mixed model (LMM) of 7,289,083 variants in 1096 healthy European-ancestry participants of the Croatian Biobank. Meta-analysis with two independent cohorts (total n = 2109) identified 83 genome-wide significant single nucleotide polymorphisms (SNPs) within the ST6GAL1 gene (p<5×10−8). BSLMM revealed additional association signals on chromosomes 1, 8, 10, and 14. For ST6GAL1 and the newly uncovered genes, we provide physiological and pathophysiological explanations of how their expression could be associated with variations in plasma Tg levels. We found that the SNP-heritability of Tg is 17% and that 52% of this variation is due to a small number of 16 variants that have a major effect on Tg levels. Our results suggest that the genetic architecture of plasma Tg is not polygenic, but influenced by a few genes with major effects.     

Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.     

The Impact of Sub-Millisecond Damage Fixation Kinetics on the In Vitro Sparing Effect at Ultra-High Dose Rate in UNIVERSE

The impact of the exact temporal pulse structure on the potential cell and tissue sparing of ultra-high dose-rate irradiation applied in FLASH studies has gained increasing attention. A previous version of our biophysical mechanistic model (UNIVERSE: UNIfied and VERSatile bio response Engine), based on the oxygen depletion hypothesis, has been extended in this work by considering oxygen-dependent damage fixation dynamics on the sub-milliseconds scale and introducing an explicit implementation of the temporal pulse structure. The model successfully reproduces in vitro experimental data on the fast kinetics of the oxygen effect in irradiated mammalian cells. The implemented changes result in a reduction in the assumed amount of oxygen depletion. Furthermore, its increase towards conventional dose-rates is parameterized based on experimental data from the literature. A recalculation of previous benchmarks shows that the model retains its predictive power, while the assumed amount of depleted oxygen approaches measured values. The updated UNIVERSE could be used to investigate the impact of different combinations of pulse structure parameters (e.g., dose per pulse, pulse frequency, number of pulses, etc.), thereby aiding the optimization of potential clinical application and the development of suitable accelerators.