Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs

Head and neck cancers (HNCs) comprise a heterogeneous group of tumors that extend from the oral cavity to the upper gastrointestinal tract. The principal etiologic factors for oral tumors include tobacco smoking and alcohol consumption, while human papillomavirus (HPV) infections have been accused of a high incidence of pharyngeal tumors. Accordingly, HPV detection has been extensively used to categorize carcinomas of the head and neck. The diverse nature of HNC highlights the necessity for novel, sensitive, and precise biomarkers for the prompt diagnosis of the disease, its successful monitoring, and the timely prognosis of patient clinical outcomes. In this context, the identification of certain microRNAs (miRNAs) and/or the detection of alterations in their expression patterns, in a variety of somatic fluids and tissues, could serve as valuable biomarkers for precision oncology. In the present review, we summarize some of the most frequently studied miRNAs (including miR-21, -375, -99, -34a, -200, -31, -125a/b, -196a/b, -9, -181a, -155, -146a, -23a, -16, -29, and let-7), their role as biomarkers, and their implication in HNC pathogenesis. Moreover, we designate the potential of given miRNAs and miRNA signatures as novel diagnostic and prognostic tools for successful patient stratification. Finally, we discuss the currently ongoing clinical trials that aim to identify the diagnostic, prognostic, or therapeutic utility of miRNAs in HNC.     

Dietary fiber suspensions from olive mill wastewater as potential fat replacements in meatballs

A dietary fiber containing material, named as alcohol insoluble residue (AIR), was recovered from the olive mill wastewater (OMW). It was separated into different fractions (water soluble and insoluble AIR) and characterized with regard to fiber and ion content. Dynamic rheological tests of the water soluble fraction (WSAIR) were conducted in order to examine its gelling ability. Thereafter, AIR as well as WSAIR were utilized as fat replacement in meatballs together or separately with carrot and starch and compared with regard to the total, water and fat loss or oil uptake during frying of the meatballs. Results indicated that AIR could not be considered as a potential fat replacement in meatballs due to the restricted water holding ability. Nevertheless, WSAIR could be utilized together with carrot fibers as additive in low fat meatballs, since it was able to improve the cooking properties of the product, by restricting the oil uptake and thereby giving rise to meatballs with sustained reduced fat content.     

Spatial dynamics and agglomeration forces in the external EU periphery

The countries belonging to the European Neighborhood Policy (ENP) of the EU are characterized by significant socioeconomic transformations and—more recently—by disconcerting instances of social and political turmoil. This comes to add to social and economic pressures applied to these countries under their process of market liberalization and economic integration, instigated at least in part by the very ENP process. In those conditions, questions of spatial cohesion and thus of regional convergence and divergence become increasingly salient, as the elimination of (social and) spatial imbalances is both a precondition for the legitimacy and successful implementation of the reforms aiming at market liberalization and economic integration and a core objective of such reforms. In this paper, we examine the spatial dynamics of population growth in the ENP countries prior to the recent destabilization in the region, using two complementary approaches—an analysis of the impact of agglomeration on growth and an analysis of club formation in population concentrations (convergence–divergence). We find that, on the whole, the ENPCs South space was characterized in recent years by evidence of regional convergence in the sense that population concentrations were becoming more diffused across regions; while the ENPCs East exhibited stronger and more consistent evidence of regional divergence (increased concentration of population). These findings suggest that agglomeration and cumulative causation forces are more strongly in operation in the more advanced, at least in terms of EU relations, countries of the ENP East, where also the “pull” factor of the EU economy is stronger.     

The effects of changes in the traffic scene during overtaking

Overtaking maneuvers were studied in real traffic, by comparing cases where a change in the opposite traffic occurred during the overtaking maneuver i.e., appearance of an oncoming car, with cases where no change occurred during the maneuver i.e., either an already apparent oncoming car or no oncoming car. In total 45 naturally occurring cases of overtaking were analysed. By examining the time headways (TH) between the overtaking car and the other cars involved, at the end of the maneuver, a significant correlation was found between the TH to opposite traffic and the TH rear to the overtaken car. In cases where a change in the opposite traffic occurred and the proximity to opposite traffic was below a critical TH (<4 s) the appearance of a new-oncoming car caused the overtakers to actively press, both longitudinally and laterally, close to the overtaken car. In cases of overtaking where no change in the opposite traffic occurred, the TH rear to the overtaking vehicle was unaffected by the TH to the opposite traffic. Interestingly, in comparing cases where an oncoming car appeared during overtaking with cases where an oncoming car was apparent from the start of the maneuver both the TH to the opposite traffic and the duration of the maneuver were not found to be significantly different. It is suggested that drivers were probably expecting to be confronted with an oncoming car during the overtaking. However, the decreased available time to disambiguate this situation leads the overtaking driver to limit the rear safety margin of the vehicle being overtaken. The appropriateness of this practice, in terms of safety, remains questionable.     

Effect of medium molecular weight xanthan gum in rheology and stability of oil‐in‐water emulsion stabilized with legume proteins

Xanthan gum is a water‐soluble extracellular polysaccharide that has gained widespread commercial use because of its strong pseudoplasticity and tolerance to high ionic strength, which bring unique rheological properties to solutions. This study compares and evaluates the emulsifying properties of oil‐in‐water (30:70 v/v) emulsions stabilized with lupin and soya protein isolates and medium molecular weight xanthan gum. The protein was obtained by an isoelectric precipitation method and the polysaccharide was produced by Xanthomonas campestris ATCC 1395 in batch culture in a laboratory fermenter (LBG medium) without pH control. The addition of xanthan gum in the emulsion formulation enhances emulsion stability through the phenomenon of thermodynamic incompatibility with the legume protein, resulting in an increase of the adsorbed protein at the interface. The emulsion stability is also enhanced by a network structure built by the polysaccharide in the bulk phase. Copyright © 2005 Society of Chemical Industry     

Evaluation of Insulin-Like Activity of Novel Zinc Metal–Organics toward Adipogenesis Signaling

Diabetes mellitus is a debilitating disease, plaguing a significant number of people around the globe. Attempts to develop new drugs on well-defined atoxic metalloforms, which are capable of influencing fundamental cellular processes overcoming insulin resistance, has triggered an upsurge in molecular research linked to zinc metallodrugs. To that end, meticulous efforts were launched toward the design and synthesis of materials with insulin mimetic potential. Henceforth, trigonelline and N-(2-hydroxyethyl)-iminodiacetic acid (HeidaH₂) were selected as organic substrates seeking binding to zinc (Zn(II)), with new crystalline compounds characterized by elemental analysis, FT-IR, X-rays, thermogravimetry (TGA), luminescence, NMR, and ESI-MS spectrometry. Physicochemical characterization was followed by in vitro biochemical experiments, in which three out of the five zinc compounds emerged as atoxic, exhibiting bio-activity profiles reflecting enhanced adipogenic potential. Concurrently, well-defined qualitative–quantitative experiments provided links to genetic loci responsible for the observed effects, thereby unraveling their key involvement in signaling pathways in adipocyte tissue and insulin mimetic behavior. The collective results (a) signify the quintessential role of molecular studies in unearthing unknown facets of pathophysiological events in diabetes mellitus II, (b) reflect the close associations of properly configured molecular zincoforms to well-defined biological profiles, and (c) set the stage for further physicochemical-based development of efficient zinc antidiabetic metallodrugs.     

Advances in De Novo Drug Design: From Conventional to Machine Learning Methods

De novo drug design is a computational approach that generates novel molecular structures from atomic building blocks with no a priori relationships. Conventional methods include structure-based and ligand-based design, which depend on the properties of the active site of a biological target or its known active binders, respectively. Artificial intelligence, including ma-chine learning, is an emerging field that has positively impacted the drug discovery process. Deep reinforcement learning is a subdivision of machine learning that combines artificial neural networks with reinforcement-learning architectures. This method has successfully been em-ployed to develop novel de novo drug design approaches using a variety of artificial networks including recurrent neural networks, convolutional neural networks, generative adversarial networks, and autoencoders. This review article summarizes advances in de novo drug design, from conventional growth algorithms to advanced machine-learning methodologies and high-lights hot topics for further development.     

Identifying Research Priorities for the further development and deployment of Solar Photovoltaics

Solar Photovoltaics (PV) is considered a highly competitive technology supporting the transition towards a low-carbon energy system. However, increased shares of its deployment have caused a set of mainly regulatory and financial challenges which require solutions. This paper identifies key research challenges for the further development and deployment of Solar PV, aiming to bridge the gap between expressed market needs and scientific research inquiries. The findings revealed a heterogeneous landscape of Research Priorities and Research Needs focused around the issues of renewable energy sources’ variability, the impacts of curtailment, material (re-)use and module efficiency, synergies with the cooling/heating sector, quality criteria and standardisation, as well as new support schemes and business models. These findings can be taken up by academic institutions or technology associations to shape further directions for research. Finally, a list of implications to guide potential end-users involved in the field of policy and practice is provided.     

Determining the principles of tunnel support based on the engineering geological behaviour types: example of a tunnel in tectonically disturbed heterogeneous rock in Serbia

A methodology for designing a tunnel support system according to the actual ground conditions and the critical behaviour types is analysed in this paper. The methodology is justified with the principles of the New Austrian Tunnelling Method that incorporates the top heading and bench method. The role of the geological material and its implication in tunnel design, reinforced with advances in site investigation methods, cannot be based solely on the development of the geotechnical classification systems and the consequent quantification of the rock masses. Support requirements for rock masses with equal classification ratings can be different. The procedure presented in this study cannot bypass the geological and/or in situ characteristics dictating or influencing the tunnel behaviour compared with a standardised classification that could miss the specifics and particularities of and around a tunnel section. The step-by-step procedure is applied in a tunnel excavated in tectonically disturbed heterogeneous flysch sediments in Serbia. The complex structure of these materials, resulting from their depositional and tectonic history that includes severe faulting and folding, presents a challenge to geologists and engineers. The possible ground types are evaluated, and then, combined with the factors of the tunnel geometry, the primary stress condition, and the water conditions, several behaviour types are considered. These classified behaviour types, followed by the suitable mechanical properties that are required for effective tunnel engineering design, are the basis for the numerical design of the appropriate primary support measures to achieve stable tunnel conditions. The twin-tube, two-lane highway tunnel was successfully constructed without significant problems.