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Target-based approaches have traditionally been used in the search for new anti-infective molecules. Target selection process, a critical step in Drug Discovery, identifies targets that are essential to establish or maintain the infection, tractable to be susceptible for inhibition, selective towards their human ortholog and amenable for large scale purification and high throughput screening. The work presented herein validates the Plasmodium falciparum mRNA 5’ triphosphatase (PfPRT1), the first enzymatic step to cap parasite nuclear mRNAs, as a candidate target for the development of new antimalarial compounds. mRNA capping is essential to maintain the integrity and stability of the messengers, allowing their translation. PfPRT1 has been identified as a member of the tunnel, metal dependent mRNA 5′ triphosphatase family which differs structurally and mechanistically from human metal independent mRNA 5′ triphosphatase. In the present study the essentiality of PfPRT1 was confirmed and molecular biology tools and methods for target purification, enzymatic assessment and target engagement were developed, with the goal of running a future high throughput screening to discover PfPRT1 inhibitors.

This study aims to impact the responsible management practices of factories in the Ready-Made Garment (RMG) sector in Bangladesh. Collaborative research with our main partner - the BGMEA University for Fashion and Technology (BUFT) - on responsible management has contributed to the embedding of ethical practices in the RMG sector. More specifically, in a first stage of this program, the collaborative knowledge development is ingrained in the degree and executive education programs of BUFT - impacting about a quarter of the professionals entering the RMG sector in Bangladesh - and has informed the practices and policies of professional bodies, such as BGMEA in Bangladesh, MODINT in the Netherlands and the International Apparel Federation (IAF). Furthermore, in a second stage of this program, research on sustainability hot spots in the RMG value chain has influenced decision-making of the European Committee in relation to their sustainability policies. It substantially advanced the understanding of how European non-development policies and regulations aimed at private and public market actors contribute to or undermine sustainable development policies. The project delivered practical tools and innovative regulatory reform proposals with substantial potential for greater policy-coherence for development, thereby contributing to an integral approach focusing on a shift towards responsibility.

The impact case enhances the understanding of socio-legal research that contemplates the development of novel legal company forms which serve the well-being of humans and nature equally. Introducing novel company law forms for social change regards research in the field of social entrepreneurship and law, such as the development of tailor-made legislation for social enterprises in the Netherlands. Current legal forms for companies in the Netherlands do not support types of social entrepreneurial activity. Our research influenced directly the regulatory-making process of the novel forthcoming company law entity named the Besloten Vennootschap maatschappelijk (BVm), i.e., the private limited company with societal purpose which is about to be introduced in the Dutch company legislation. Particularly, our research team: (i) formulated key indicators for the BVm, which were accepted by the government in 2020 and will form the basis for new legislation which is currently being drafted; (ii) generated multiple academic studies, publications, seminars and conferences, as well as a PhD dissertation about the topic; (iii) supported many social enterprises in finding suitable legal forms (through educational programs, network sessions and collaboration with company and tax law experts).

The selection of the optimal methodology for the 3D geometric documentation of cultural heritage is a subject of high concern in contemporary scientific research. As a matter of fact, it requires a multi-source data acquisition process and the fusion of datasets from different sensors. This paper aims to demonstrate the workflow for the proper implementation and integration of geodetic, photogrammetric and laser scanning techniques so that high-quality photorealistic 3D models and other documentation products can be generated for a complicated, large-dimensional architectural monument and its surroundings. As a case study, we present the monitoring of the Mehmet Bey Mosque, which is a landmark in the city of Serres and a significant remaining sample of the Ottoman architecture in Greece. The surveying campaign was conducted in the context of the 2022–2023 annual workshop of the Interdepartmental Program of Postgraduate Studies “Protection Conservation and Restoration of Cultural Monuments” of the Aristotle University of Thessaloniki, and it served as a geometric background for interdisciplinary cooperation and decision-making on the monument restoration process. The results of our study encourage the fusion of terrestrial laser scanning and photogrammetric datasets for the 3D modeling of the mosque, as they supplement each other as regards geometry and texture.

The outer segments (OS) of rod and cone photoreceptor cells are specialized sensory cilia that contain hundreds of opsin-loaded stacked membrane disks that enable phototransduction. The biogenesis of these disks is initiated at the OS base, but the driving force has been debated. Here, we studied the function of the protein encoded by the photoreceptor-specific gene C2orf71, which is mutated in inherited retinal dystrophy (RP54). We demonstrate that C2orf71/PCARE (photoreceptor cilium actin regulator) can interact with the Arp2/3 complex activator WASF3, and efficiently recruits it to the primary cilium. Ectopic coexpression of PCARE and WASF3 in ciliated cells results in the remarkable expansion of the ciliary tip. This process was disrupted by small interfering RNA (siRNA)-based down-regulation of an actin regulator, by pharmacological inhibition of actin polymerization, and by the expression of PCARE harboring a retinal dystrophy-associated missense mutation. Using human retinal organoids and mouse retina, we observed that a similar actin dynamics-driven process is operational at the base of the photoreceptor OS where the PCARE module and actin colocalize, but which is abrogated in Pcare-/- mice. The observation that several proteins involved in retinal ciliopathies are translocated to these expansions renders it a potential common denominator in the pathomechanisms of these hereditary disorders. Together, our work suggests that PCARE is an actin-associated protein that interacts with WASF3 to regulate the actin-driven expansion of the ciliary membrane at the initiation of new outer segment disk formation.

Abstract Background Genetic mutations in beta-glucocerebrosidase (GBA) represent the major genetic risk factor for Parkinson’s disease (PD). GBA participates in both the endo-lysosomal pathway and the immune response, two important mechanisms involved in the pathogenesis of PD. However, modifiers of GBA penetrance have not yet been fully elucidated. Methods We characterized the transcriptomic profiles of circulating monocytes in a population of patients with PD and healthy controls (CTRL) with and without GBA variants (n = 23 PD/GBA, 13 CTRL/GBA, 56 PD, 66 CTRL) and whole blood (n = 616 PD, 362 CTRL, 127 PD/GBA, 165 CTRL/GBA). Differential expression analysis, pathway enrichment analysis, and outlier detection were performed. Ultrastructural characterization of isolated CD14+ monocytes in the four groups was also performed through electron microscopy. Results We observed hundreds of differentially expressed genes and dysregulated pathways when comparing manifesting and non-manifesting GBA mutation carriers. Specifically, when compared to idiopathic PD, PD/GBA showed dysregulation in genes involved in alpha-synuclein degradation, aging and amyloid processing. Gene-based outlier analysis confirmed the involvement of lysosomal, membrane trafficking, and mitochondrial processing in manifesting compared to non-manifesting GBA-carriers, as also observed at the ultrastructural levels. Transcriptomic results were only partially replicated in an independent cohort of whole blood samples, suggesting cell-type specific changes. Conclusions Overall, our transcriptomic analysis of primary monocytes identified gene targets and biological processes that can help in understanding the pathogenic mechanisms associated with GBA mutations in the context of PD.

Highly-sensitive and stable ozone and hydrogen sensing elements were fabricated based on well-crystalline rounded cube-shaped CsPbBr3 microcrystals, synthesized by a facile solution process performed under ambient conditions. It is shown that such elements demonstrate enhanced room temperature gas sensing ability compared to the previously reported metal halide and oxide-based ones. Electrical measurements performed on these sensing components revealed high sensitivity to ultra-low ozone and hydrogen concentrations, namely 4 ppb and 1 ppm respectively, as well as a remarkable repeatability, even after a few months of storage in ambient conditions. Both ozone and hydrogen sensors were self-activated, as they did not require the use of UV or heating external stimuli to operate, and exhibited fast detection and short restoration times. All such attractive properties along with the simple fabrication process could provide an easy, efficient and low-cost technology for the realization of future gas sensing devices.

Aims: There is evidence that morbidly obese patients have more intra- and postoperative complications and poorer outcomes when undergoing total hip arthroplasty (THA) with the direct anterior approach (DAA). The aim of this study was to determine the efficacy of DAA for THA, and compare the complications and outcomes of morbidly obese patients with nonobese patients. Methods: Morbidly obese patients (n = 86), with BMI ≥ 40 kg/m2 who underwent DAA THA at our institution between September 2010 and December 2017, were matched to 172 patients with BMI < 30 kg/m2. Data regarding demographics, set-up and operating time, blood loss, radiological assessment, Harris Hip Score (HHS), International Hip Outcome Tool (12-items), reoperation rate, and complications at two years postoperatively were retrospectively analyzed. Results: No significant differences in blood loss, intra- and postoperative complications, or implant position were observed between the two groups. Superficial wound infection rate was higher in the obese group (8.1%) compared to the nonobese group (1.2%) (p = 0.007) and relative risk of reoperation was 2.59 (95% confidence interval 0.68 to 9.91). One periprosthetic joint infection was reported in the obese group. Set-up time in the operating table and mean operating time were higher in morbidly obese patients. Functional outcomes and patient-related outcome measurements were superior in the obese group (mean increase of HHS was 52.19 (SD 5.95) vs 45.1 (SD 4.42); p < 0.001), and mean increase of International Hip Outcome Tool (12-items) was 56.8 (SD 8.88) versus 55.2 (SD 5.85); p = 0.041). Conclusion: Our results suggest that THA in morbidly obese patients can be safely and effectively performed via the DAA by experienced surgeons. Cite this article: Bone Jt Open 2022;3(1):4–11.

The increased penetration of renewables and the variable behavior of solar irradiation makes the energy storage important for overcoming several stability issues that arise in the power network. The current paper examines the design and stability analysis of a grid-connected residential photovoltaic (PV) system with battery–supercapacitor hybrid energy storage. The battery and supercapacitor packs are connected to the common 400 V DC-bus in a fully active parallel configuration through two bidirectional DC–DC converters, hence they have different voltage levels and their power flow is controlled separately. A detailed small-signal stability analysis is considered for the design of the current controllers for the bidirectional converters of the battery and supercapacitor. An important contribution here is that a detailed stability analysis is performed for both the boost and the buck mode of operation for the battery and supercapacitor converters, resulting in more accurate tuning of the controllers. Moreover, the small-signal stability analysis of the voltage source inverter (VSI) is considered in order to design the DC-bus voltage controller, where a reference output current is obtained using a phase-locked loop (PLL) for grid synchronization. The proposed model is developed and simulated in the MATLAB/Simulink software environment, based on mathematical analysis and average modeling. The simulation results verify the dynamic performance of the proposed model, through several rapid changes in PV generation and in load demand. Also, the model works properly and responds extremely fast during different mode transitions, exhibiting a very fast DC-bus voltage regulation with a very small ripple voltage (a maximum of ± 0.625%). Finally, the supercapacitor handles the rapid changes occurring within 0.2 s, hence this can relieve the battery stress and extend the battery lifetime.

IntroductionOrganizational culture determines the ability of companies to adapt, transform, and innovate, thereby directly affecting their profitability and competitiveness. However, the same applies to the public sector since, now more than ever, it has to be agile in order to shield its society and economy against modern challenges (such as COVID-19, climate change, and digitalization). This article uses the case of Greece as an example to present the need for change in organizational culture to unlock its development and growth potential through transformation, adaptation, and innovation. To support our argument, we combine the findings of the international literature regarding the relationship between organizational culture and the aforementioned elements, as well as empirical evidence from Greece.MethodsIn particular, we assess organizational culture pertaining to the major sector reforms that took place in Greece, as a result of the recent economic and financial crisis, by presenting and evaluating comparative empirical findings on the characteristics of the prevailing and desired future organizational culture.Results and discussionExamining and comparing the results of previous studies in Greece that used the Organizational Culture Assessment Instrument (OCAI) questionnaire survey in both private (such as banking and telecoms) and public sectors (such as social security, public revenues authority, and hospitals), two interesting results arise: (i) there is a clear distinction between the public sector and the private sector, with the former being mainly characterized by “hierarchy culture,” while the latter by “market culture” and (ii) in both sectors and all industries/services, the desire to prevail in future organizational culture is the “clan culture.” These findings are of immense importance as organizational culture issues play a key role in formulating future strategic plans, enabling the development of key sectors of the Greek economy and enhancing effective governance and social services. Concisely, our results draw useful conclusions for policy implications and academics, implying that there is an emergent need for organizational transformation in both private and public sectors in Greece, which can be achieved through new innovative methods of organization and operation, creating a new more agile, adaptive, and innovative culture.

Recent improvements in low-altitude remote sensors and image processing analysis can be utilised to support archaeological research. Over the last decade, the increased use of remote sensing sensors and their products for archaeological science and cultural heritage studies has been reported in the literature. Therefore, different spatial and spectral analysis datasets have been applied to recognise archaeological remains or map environmental changes over time. Recently, more thorough object detection approaches have been adopted by researchers for the automated detection of surface ceramics. In this study, we applied several supervised machine learning classifiers using red-green-blue (RGB) and multispectral high-resolution drone imageries over a simulated archaeological area to evaluate their performance towards semi-automatic surface ceramic detection. The overall results indicated that low-altitude remote sensing sensors and advanced image processing techniques can be innovative in archaeological research. Nevertheless, the study results also pointed out existing research limitations in the detection of surface ceramics, which affect the detection accuracy. The development of a novel, robust methodology aimed to address the “accuracy paradox” of imbalanced data samples for optimising archaeological surface ceramic detection. At the same time, this study attempted to fill a gap in the literature by blending AI methodologies for non-uniformly distributed classes. Indeed, detecting surface ceramics using RGB or multi-spectral drone imageries should be reconsidered as an ‘imbalanced data distribution’ problem. To address this paradox, novel approaches need to be developed.

Purpose: This study is part of the first systematic program in the Republic of Cyprus examining the prevalence of traumatic brain injury (TBI) in children, teenagers, and university students. The study incorporated the Greek Version of the Brain Injury Screening Questionnaire (BISQ-G) as the primary tool to identify students with TBI. Methods: The BISQ-G was sent out to 2,800 families of children (aged 6-18 years) attending rural and urban elementary and secondary schools from varied socioeconomic backgrounds. Nine hundred forty-four questionnaires (33.8%) were returned. In addition to school-aged children, 322 university students (aged 17-25 years) were recruited from 3 universities and completed the BISQ-G. Results: Analyses indicated that 5.8% elementary, 9.7% secondary, and 22.7% university students had symptoms consistent with TBI. Several participants reported more than 1 TBI. Etiology of TBI was similar in all 3 groups and included sports, biking, and falls. Factor analyses yielded a 7-factor structure for the BISQ-G. Discussion/Conclusions: The BISQ-G is a valid tool for the identification of individuals with a prior history of TBI. Causes and symptoms of TBI were similar to those reported in the international literature. The article concludes with suggestions for TBI management in the schools.