Articles / Άρθρα

We demonstrate for the first time that 4H-1,2,6-thiadiazin-4-one (TDZ) can function as a chemotype for the design of ATP-competitive kinase inhibitors. Using insights from a co-crystal structure of a 3,5-bis(arylamino)-4H-1,2,6-thiadiazin-4-one bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2), several analogues were identified with micromolar activity through targeted displacement of bound water molecules in the active site. Since the TDZ analogues showed reduced promiscuity compared to their 2,4-dianilinopyrimidine counter parts, they represent starting points for development of highly selective kinase inhibitors.

The reaction of [Mn(O2CMe)2] · 4H2O with pdH2 (1,3-propanediol) or mpdH2 (2-methyl-1,3-propanediol) in the presence of NaN3 in MeCN/py (py = pyridine) results in the formation of two new one-dimensional coordination polymers composed of a [MnIII 6MnII 11(μ4-O)8(μ3-N3)4]25+ octahedral unit. The peripheral ligation is completed by pd2- (or mpd2-), acetate, pyridine and μ-1,3-N3 - ligands. The latter bridges each Mn17 unit to its neighboring one, resulting in the formation of the two 1-D coordination polymers. Variable-temperature dc magnetic susceptibility studies indicate the existence of predominantly ferromagnetic interactions and a resulting giant ground state spin within the Mn17 units and intermolecular antiferromagnetic exchange interactions between the neighboring Mn17 units that result in diamagnetic ground spin states for both polymeric compounds.

Objective: This review focuses on the presentation of the emerging technology of metabolomics, a promising tool for the detection of identifying the unrevealed biological pathways that lead to cardiac arrest. Data sources: The electronic bases of PubMed, Scopus, and EMBASE were searched. Research terms were identified using the MESH database and were combined thereafter. Initial search terms were "cardiac arrest", "cardiopulmonary resuscitation", "post-cardiac arrest syndrome" combined with "metabolomics". Results: Metabolomics allow the monitoring of hundreds of metabolites from tissues or body fluids and already influence research in the field of cardiac metabolism. This approach has elucidated several pathophysiological mechanisms and identified profiles of metabolic changes that can be used to follow the disease processes occurring in the peri-arrest period. This can be achieved through leveraging the strengths of unbiased metabolome-wide scans, which include thousands of final downstream products of gene transcription, enzyme activity and metabolic products of extraneously administered substances, in order to identify a metabolomic fingerprint associated with an increased risk of cardiac arrest. Conclusion: Although this technology is still under development, metabolomics is a promising tool for elucidating biological pathways and discovering clinical biomarkers, strengthening the efforts for optimizing both the prevention and treatment of cardiac arrest.

The crystal structure of the title compound, C9H 12O4S, was determined in order to investigate the effect of the eclipsed O atoms on the bond length of the vicinal quaternary C atoms. The two quaternary C atoms of the noradamantane skeleton and the two O atoms to which they are connected all located essentially in the same plane (maximum deviation = 0.01 Å), resulting in an eclipsed conformation of the C - O bonds. The C - C bond of the quaternary C atoms is 1.581 (3) Å, considerably longer than the other C - C bonds of the molecule due to the stretch of the cage structure.

The title compound, C18H24I2, has an adamantanoid structure with tetra-hedral cages having four C atoms lying on the same plane [(I-)C-C-C-C(-I) torsion angle = 0°]. The plane is extended by the two I atoms, each having a deviation of 1.0 (6) Å [C-C-C-I torsion angle = 178.9 (4)°]. The central C-C bond connecting the two quaternary carbons seems enlarged [1.593 (9) Å] in comparison to the corresponding bond in [2]diadamantane [1.554 (3) Å]. This is attributed to the presence of the electronegative I atoms, which affect inductively the C atoms of the four-C-atom plane, making the central C-C bond weaker.

Stille coupling of 3,5-bis(5-bromothien-2-yl)-4H-1,2,6-thiadiazin-4-one (10) with 2-(tri-n-butylstannyl)thiazole and Pd(Ph 3 P) 2 Cl 2 in PhMe, at ca. 110 ◦ C, for 2 h, gave 3,5-bis[5-(thiazol-2-yl)thien-2-yl]-4H-1,2,6-thiadiazin-4-one (9) in 81% yield. The latter is evaluated for its electronic properties.

Stille coupling of 5-chloro-4-oxo-4H-1,2,6-thiadiazin-3-yl trifluoromethanesulfonate (7) with tributyl(3-n-hexylthien-2-yl)stannane and Pd(Ph 3 P) 2 Cl 2 in PhMe at ca. 20 ◦ C, for 24 h gave 3-chloro-5-(3-n-hexylthien-2-yl)-4H-1,2,6-thiadiazin-4-one (9) with a 60% yield. The latter is a potentially useful building block for the synthesis of oligomeric and polymeric donors for organic photovoltaics.

Stille coupling of 5,5'-dichloro-4H,4‘H-[3,3'-bi(1,2,6-thiadiazine)]-4,4'-dione (8) with 9-decyl-3-[5-(tributylstannyl)thien-2-yl]-9H-carbazole and Pd(Ph3P)2Cl2 in PhMe, at ca. 110 °C, for 2 h, gave 5,5'-bis[5-(9-decyl-9H-carbazol-3-yl)thien-2-yl]-4H,4‘H-[3,3'-bi(1,2,6-thiadiazine)]-4,4'-dione (7) in 51% yield. The latter is investigated as an oligomer donor for organic photovoltaics.

This chapter investigates the Network Layer aspects that will characterize the merger of the cellular paradigm and the IoT architectures, in the context of the evolution towards 5G-and-beyond, including some promising emerging services as Unmanned Aerial Vehicles or Base Stations, and V2X communications.

Introduction: Dynamic image acquisition protocols are increasingly used in emission tomography for drug development and clinical research. As such, there is a need for computational phantoms to accurately describe both the spatial and temporal distribution of radiotracers, also accounting for periodic and non-periodic physiological processes occurring during data acquisition. Methods: A new 5D anthropomorphic digital phantom was developed based on a generic simulation platform, for accurate parametric imaging simulation studies in emission tomography. The phantom is based on high spatial and temporal information derived from real 4D MR data and a detailed multi-compartmental pharmacokinetic modelling simulator. Results: The proposed phantom is comprised of three spatial and two temporal dimensions, including periodic physiological processes due to respiratory motion and non-periodic functional processes due to tracer kinetics. Example applications are shown in parametric [18F]FDG and [15O]H2O PET imaging, successfully generating realistic macro- and micro-parametric maps. Conclusions: The envisaged applications of this digital phantom include the development and evaluation of motion correction and 4D image reconstruction algorithms in PET and SPECT, development of protocols and methods for tracer and drug development as well as new pharmacokinetic parameter estimation algorithms, amongst others. Although the simulation platform is primarily developed for generating dynamic phantoms for emission tomography studies, it can easily be extended to accommodate dynamic MR and CT imaging simulation protocols.

Small island states, due to their size, remoteness and dependence on foreign capital, are often susceptible to various global disruptions and crises. The effects of such crises can be chaotic, seriously damaging their economies and altering their systems. However, in the context of tourism crisis management, linear approaches are predominant overlooking the chaotic characteristics and transformations of the complex tourism system. In response, this research investigates the implications of the economic crisis and the interaction effects of unforeseen events, on Cypriot tourism through a chaos theory perspective. Based on semi-structured interviews, archival document analysis and a pertinent literature review, findings indicate that the evolution of Cyprus tourism was not a linear process, but instead iterative, characterised by interactions of several endogenous and exogenous events that have shaped its systemic transformation. The research reveals the lack of comprehensive policy responses to crises that would enable the sustainable tourism development of Cyprus. The paper concludes that it is imperative for small island states to understand holistically the interrelated dimensions of crises and therefore mitigate their detrimental consequences. To this end, tourism policy needs to realise that crises and sustainability are not linear processes but evolving systemic configurations that necessitate the preparedness of tourism policy-makers and stakeholders to anticipate change and swiftly respond.

A 15-year-old Asian male was referred to the department of oral and maxillofacial surgery at Tufts University School of Dental Medicine (TUSDM) for evaluation of a radiolucent lesion on the posterior left mandible. The patient was initially evaluated by his primary dentist for pain of two months' duration associated with teeth #17 and 18. Radiographic examination was performed and the panoramic radiograph revealed a radiolucent lesion involving the left mandibular body and ascending ramus, along with resorption of the roots of the predetermined teeth. Considering odontogenic infection, the patient was placed on antibiotics and referred to TUSDM for further evaluation and treatment.

Despite advances during the last 2 decades in every aspect of cardiovascular research (interventional cardiology, cardiopulmonary resuscitation, and so forth), Western societies still are plagued by the consequences of cardiovascular disease. Consequently the discovery of new regimens and therapeutic interventions is of utmost importance. Research using human subjects is associated with substantial methodologic and ethical considerations, and the quest for an appropriate animal model for the human cardiovascular system has led to swine. The porcine heart bears a close resemblance to the human heart in terms of its coronary circulation and hemodynamic similarities and offers ease of implementation of methods and devices from human healthcare facilities. A thorough comprehension of the anatomy and physiology of the porcine cardiovascular system should focus on differences between swine and humans as well as similarities. Understanding these differences and similarities is essential to extrapolating data appropriately and to addressing the social demand for the ethical use of animals in biomedical research.

To assess the oral health status of preschool children with neurodevelopmental disorders (NDD) in Greece and compare it to that, of healthy children of the same age. The sample consisted of 146 preschool children with NDD and movement limitations attending the rehabilitation centers of ELEPAP and 165 healthy children matched for age and maternal origin. Caries prevalence, dmft index, precavitated carious lesions (WSL) prevalence Visual Plaque Index (VPI), Restorative Index (RI), Mutans Streptococci (MS) levels, saliva buffer capacity, gingival hyperplasia, tooth wear and developmental dental defects were assessed. Data were analyzed using parametric and nonparametric tests (P ≤.05). The NDD group, compared to the healthy controls, had significantly lower caries prevalence (P <.001), dmft index (P <.001), VPI (P <.001) and MS levels (P = .027), significantly higher WSL prevalence (P <.001), and visited the dentist at an older age (P <.001). Significant determinants of WSL in the NDD group was the VPI (P = .009) and the presence of MS (P <.028). Preschool children with NDD had lower prevalence of manifested caries but higher prevalence of WSL. However, most oral health parameters need improvement for both groups indicating the need for proper early interventions especially in the NDD group.