Supplementary Medial Locking Plate Fixation Of Ludloff Osteotomy versus Sole Lag Screw Fixation: A Biomechanical evaluation

Background: The Ludloff oblique osteotomy is inherently unstable, which might lead to delayed union and loss of correction. Supplementary fixation to two lag screw fixation has been proposed. The hypothesis is that the osteotomy fixation constructs supplemented by a mini locking plate provide greater resistance to osteotomy gaping and loss of angular correction in response to cyclic loading. Methods: Twenty fourth generation composite 1st metatarsals were used and underwent a Ludloff osteotomy. They were divided in two fixation groups: two lag screws (Group A), and with a supplementary mini locking plate (Group B). Specimens were subjected to either monotonic loading up to failure or to fatigue (cyclic) tests and tracked using an optical system for 3D Digital Image Correlation. Findings: The osteotomy gap increased in size under maximum loading and was significantly greater in Group A throughout the test. This increase was observed very early in the loading process (within the first 1000 cycles). The most important finding though, was that with the specimens completely unloaded the residual gap increase was significantly greater in Group A after only 5000 cycles of loading up to the completion of the test. The lateral angle change under maximum loading was also significantly greater in Group A throughout the test, with that increase observed early in the loading process (5000 cycles). With the specimens completely unloaded the residual lateral angle change was also significantly greater in Group A at the completion of the test. Interpretation: Supplementary fixation with a mini locking plate of the Ludloff osteotomy provided greater resistance to osteotomy gaping and loss of angular correction compared to sole lag screws, in response to cyclic loading

Induction motors versus permanent magnet actuators for aerospace applications

This paper introduces a comparative study on the design of aerospace actuators concerning Induction Motor (IM) and Permanent Magnet Motor (PMM) technologies. In the analysis undertaken, the two candidate configurations are evaluated in terms of both their electromagnetic and thermal behavior in a combined manner. On a first step, the basic dimensioning of the actuators and their fundamental operational characteristics are determined via a time-stepping Finite Element (FE) analysis. The consideration of the thermal robustness of the proposed motor configurations is integrated in the design procedure, through the appropriate handling of their respective constraints. As a result, all comparisons are carried out on a common thermal evacuation basis. On a second step, a single objective optimization procedure is employed, considering several performance and efficiency indexes using appropriate weights. Manufacturing and construction related costs for both investigated topologies are considered employing specific penalty functions. The impact of the utilized materials is also examined. The resultant motor designs have been validated through manufactured prototypes illustrating their suitability for aerospace actuatio

Novel Hit Compounds as Putative Antifungals: The Case of Aspergillus fumigatus

The prevalence of invasive fungal infections has been dramatically increased as the size of the immunocompromised population worldwide has grown. Aspergillus fumigatus is characterized as one of the most widespread and ubiquitous fungal pathogens. Among antifungal drugs, azoles have been the most widely used category for the treatment of fungal infections. However, increasingly, azole-resistant strains constitute a major problem to be faced. Towards this direction, our study focused on the identification of compounds bearing novel structural motifs which may evolve as a new class of antifungals. To fulfil this scope, a combination of in silico techniques and in vitro assays were implemented. Specifically, a ligand-based pharmacophore model was created and served as a 3D search query to screen the ZINC chemical database. Additionally, molecular docking and molecular dynamics simulations were used to improve the reliability and accuracy of virtual screening results. In total, eight compounds, bearing completely different chemical scaffolds from the commercially available azoles, were proposed and their antifungal activity was evaluated using in vitro assays. Results indicated that all tested compounds exhibit antifungal activity, especially compounds 1, 2, and 4, which presented the most promising minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values and, therefore, could be subjected to further hit to lead optimization

Transcatheter Aortic Valve Implantation in Severe Left Ventricular Dysfunction: A Viable Option in a Patient With Low-Flow, Low-Gradient Critical Aortic Stenosis

Images are provided from a successful procedure of transcatheter aortic valve implantation (TAVI) in an elderly patient with symptomatic low-flow, low-gradient critical aortic stenosis, and associated severe left ventricular dysfunction, who had a very high-risk for surgery

Design of Linear and Cyclic Mutant Analogues of Dirucotide Peptide (MBP82–98) against Multiple Sclerosis: Conformational and Binding Studies to MHC Class II

Background: Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system. MS is a T cell-mediated disease characterized by the proliferation, infiltration, and attack of the myelin sheath by immune cells. Previous studies have shown that cyclization provides molecules with strict conformation that could modulate the immune system. Methods: In this study, we synthesized peptide analogues derived from the myelin basic protein (MBP)82⁻98 encephalitogenic sequence (dirucotide), the linear altered peptide ligand MBP82⁻98 (Ala91), and their cyclic counterparts. Results: The synthesized peptides were evaluated for their binding to human leukocyte antigen (HLA)-DR2 and HLA-DR4 alleles, with cyclic MBP82⁻98 being a strong binder with the HLA-DR2 allele and having lower affinity binding to the HLA-DR4 allele. In a further step, conformational analyses were performed using NMR spectroscopy in solution to describe the conformational space occupied by the functional amino acids of both linear and cyclic peptide analogues. This structural data, in combination with crystallographic data, were used to study the molecular basis of their interaction with HLA-DR2 and HLA-DR4 alleles. Conclusion: The cyclic and APL analogues of dirucotide are promising leads that should be further evaluated for their ability to alter T cell responses for therapeutic benefit against MS

Molecular epidemiology of SARS-CoV-2: the dominant role of arginine in mutations and infectivity

Background, Aims, Methods, Results, Conclusions: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global challenge due to its ability to mutate into variants that spread more rapidly than the wild-type virus. The molecular biology of this virus has been extensively studied and computational methods applied are an example paradigm for novel antiviral drug therapies. The rapid evolution of SARS-CoV-2 in the human population is driven, in part, by mutations in the receptor-binding domain (RBD) of the spike (S-) protein, some of which enable tighter binding to angiotensin-converting enzyme (ACE2). More stable RBD-ACE2 association is coupled with accelerated hydrolysis by proteases, such as furin, trypsin, and the Transmembrane Serine Protease 2 (TMPRSS2) that augment infection rates, while inhibition of the 3-chymotrypsin-like protease (3CLpro) can prevent the viral replication. Additionally, non-RBD and non-interfacial mutations may assist the S-protein in adopting thermodynamically favorable conformations for stronger binding. This study aimed to report variant distribution of SARS-CoV-2 across European Union (EU)/European Economic Area (EEA) countries and relate mutations with the driving forces that trigger infections. Variants’ distribution data for SARS-CoV-2 across EU/EEA countries were mined from the European Centre for Disease Prevention and Control (ECDC) based on the sequence or genotyping data that are deposited in the Global Science Initiative for providing genomic data (GISAID) and The European Surveillance System (TESSy) databases. Docking studies performed with AutoDock VINA revealed stabilizing interactions of putative antiviral drugs, e.g., selected anionic imidazole biphenyl tetrazoles, with the ACE2 receptor in the RBD-ACE2 complex. The driving forces of key mutations for Alpha, Beta, Gamma, Delta, Epsilon, Kappa, Lambda, and Omicron variants, which stabilize the RBD-ACE2 complex, were investigated by computational approaches. Arginine is the critical amino acid in the polybasic furin cleavage sites S1/S2 (681-PRRARS-686) S2′ (814-KRS-816). Critical mutations into arginine residues that were found in the delta variant (L452R, P681R) and may be responsible for the increased transmissibility and morbidity are also present in two widely spreading omicron variants, named BA.4.6 and BQ.1, where mutation R346T in the S-protein potentially contributes to neutralization escape. Arginine binders, such as Angiotensin Receptor Blockers (ARBs), could be a class of novel drugs for treating COVID-19

Representation and parsing of multiword expressions: Current trends

This book consists of contributions related to the definition, representation and parsing of MWEs. These reflect current trends in the representation and processing of MWEs. They cover various categories of MWEs such as verbal, adverbial and nominal MWEs, various linguistic frameworks (e.g. tree-based and unification-based grammars), various languages including English, French, Modern Greek, Hebrew, Norwegian), and various applications (namely MWE detection, parsing, automatic translation) using both symbolic and statistical approaches

Representation and parsing of multiword expressions: Current trends

This book consists of contributions related to the definition, representation and parsing of MWEs. These reflect current trends in the representation and processing of MWEs. They cover various categories of MWEs such as verbal, adverbial and nominal MWEs, various linguistic frameworks (e.g. tree-based and unification-based grammars), various languages including English, French, Modern Greek, Hebrew, Norwegian), and various applications (namely MWE detection, parsing, automatic translation) using both symbolic and statistical approaches

Representation and parsing of multiword expressions: Current trends

This book consists of contributions related to the definition, representation and parsing of MWEs. These reflect current trends in the representation and processing of MWEs. They cover various categories of MWEs such as verbal, adverbial and nominal MWEs, various linguistic frameworks (e.g. tree-based and unification-based grammars), various languages including English, French, Modern Greek, Hebrew, Norwegian), and various applications (namely MWE detection, parsing, automatic translation) using both symbolic and statistical approaches

Representation and parsing of multiword expressions: Current trends

This book consists of contributions related to the definition, representation and parsing of MWEs. These reflect current trends in the representation and processing of MWEs. They cover various categories of MWEs such as verbal, adverbial and nominal MWEs, various linguistic frameworks (e.g. tree-based and unification-based grammars), various languages including English, French, Modern Greek, Hebrew, Norwegian), and various applications (namely MWE detection, parsing, automatic translation) using both symbolic and statistical approaches