Challenges, Volume 9, Issue 1 (June 2018) – 25 articles

The development of the chassis for the hydrogen fuel cell powered car has been involved in the designing and manufacturing aspects, while taking into consideration the mass, strength, stiffness, centre of gravity (COG), and manufacturing cost requirements. Towards this direction, a chassis design is proposed employing a space frame structure and constructed by an aluminium alloy with great strength. The structural design has been derived through the lightweight engineering approaches in conjunction with the part consolidation, Design for Assembly (DFA) and Design for Manufacture methods. Moreover, it has been performed in compliance with the safety regulations of the Shell Eco Marathon racing competition. The material’s principal characteristics are the great strength, the low mass, as well as the great workability, machinability, and weldability. Following the national and global environmental issues, the recyclable characteristics of the aluminium alloy are an extra asset. Furthermore, the existence of aluminium alloy manufacturers around the fabricating area provides low cost supply and fast delivery benefits. The integration of the fuel cell powered vehicle is obtained through the designing and the manufacturing processes of the chassis and the parts fitted on the chassis. The manufacturing procedures are described thoroughly; mainly consisting of the cutting and welding processes and the assembling of the parts that are fitted on the chassis. Additionally, the proper welding parameters for the custom chassis design are investigated and are selected after deductive reasoning. The quality control of the weld joints is conducted by non-destructive methods (NDT) ensuring the required structural properties of the welds. A combination of the selected material, the specific type of the chassis, and the manufacturing processes lead to construction simplicity in a low manufacturing cost by using the existing laboratory equipment. Furthermore, the designing and manufacturing parameters lead to a stiff with a low centre of gravity, and the most lightweight chassis of the urban concept category at the Shell Eco Marathon race. Full article

Poly-ADP-ribosylation is a post-translational modification that occurs in multicellular organisms, including plants and some lower unicellular eukaryotes. The founding member of the PARP family is PARP1. To date, 17 members of the PARP family have been identified, which differ from each other in terms of domain organization, transmodification targets, cellular localization, and biological functions. In recent years, considering structural and biochemical features of the different members of the PARP family, a new classification has been proposed. Thus, enzymes firstly classified as PARP are now named diphtheria-toxin-like ARTs, abbreviated to ARTDs, in accordance with the prototype bacterial toxin that their structural aspects resemble, with numbers indicating the different proteins of the family. The 17 human ARTD enzymes can be divided on the basis of their catalytic activity into polymerases (ARTD1–6), mono-ADP-ribosyl-transferases (ARTD7–17), and the inactive ARTD13. In recent years, ADP-ribosylation was intensively studied, and research was dominated by studies focusing on the role of this modification and its implication on various cellular processes. The aim of this review is to provide a general overview of the ARTD enzymes, with a special focus on mono-ARTDs. Full article

PolyADP-ribosylation is a post-translational modification that plays key roles in cellular physiological functions and DNA damage responses. PolyADP-ribosylation is finely and dynamically regulated by various enzymes and factors involved in the synthesis and degradation of poly(ADP-ribose) (PAR). To better understand the function of polyADP-ribosylation, it is necessary to quantify and monitor the change of the in vivo level of PAR, the product of polyADP-ribosylation, which is rapidly turning over and kept in quite low level in cells or in organs. Recent developments of potent inhibitors of polyADP-ribosylation is expected to kill BRCA1/2-mutated breast cancer cells and ovarian cancer cells (synthetic lethality). To know the efficacy of these inhibitors in vivo, it is necessary to develop highly sensitive and reproducible methods to know PAR levels within cells or organs. However there have been several difficulties in measuring the physiologically low level of PAR without artefacts. Our experiments recently clarified that the method of sample preparation is very important in addition to the sensitivity and specificity. From reviewing the literature, including ours, we would like to emphasize the importance of the procedures of sample preparation for the assay, in addition to the sensitivity by comparing the reported PAR levels in vivo. Full article

Protein ADP-ribosylation is a reversible post-translational modification of cellular proteins that is catalysed by enzymes that transfer one (mono) or several (poly) units of ADP-ribose from β-NAD⁺ to a specific amino acid of the target protein. The most studied member of the ADP-ribosyltransferase family is PARP1 (also known as ADP-ribosyltransferase diphtheria toxin-like 1, ARTD1), which is directly activated by DNA strand breaks and is involved in DNA damage repair, chromatin remodelling and transcriptional regulation. Much less is known about the further 16 members of this family. Among these, ARTD10/PARP10 has been previously characterised as a mono-ADP-ribosyltransferase with a role in cell proliferation and in NF-kB signalling. In the present study, we identified the glycolytic enzyme GAPDH as an interactor and a novel cellular target for ARTD10/PARP10. Moreover, we detected the co-localisation of GAPDH and ARTD10/PARP10 in well-defined cytosolic bodies, which we show here to be membrane-free, rounded structures using immunogold labelling and electron microscopy. Using the cognitive binding module macro domain to visualise ADP-ribosylated proteins by immunofluorescence microscopy in cells over-expressing the ARTD10/PARP10 enzyme, we show that the staining of the ARTD10/PARP10-dependent cytosolic bodies was lost when the cells were treated with compounds that inhibit ARTD10/PARP10, either by directly inhibiting the enzyme or by reducing the cellular NAD⁺ levels. In parallel, the same treatment affected the co-localisation of GAPDH and ARTD10/PARP10, as GAPDH disappeared from the cytosolic cell bodies, which indicates that its presence there depends on the catalytic activity of ARTD10/PARP10. In line with this, in cells over-expressing the ARTD10/PARP10 catalytic domain alone, which we show here to form stress granules, GAPDH was recruited into stress granules. These data identify ARTD10/PARP10 as the enzyme that modifies and recruits GAPDH into cytosolic structures. Full article

The complexity of urban challenges obliges us to seek smarter paths for urban development and increase our awareness of urban dynamics in a more holistic manner. Stemming from the discipline of architecture and urban planning, this concept paper outlines an idea of a cybernetic urban management for anticipatory governance of smart cities. A cybernetic system absorbs information from different sources, such as buildings that are aware of their energy efficiency, a city aware of its traffic flows, and citizens who are aware of the affordances of urban life. Defined as context-aware cyber-physical social systems, smart cities of the future are planned and managed with increasing awareness of the manifoldness of physical, experiential, and virtual life. The benefits of a cybernetic urban management could, for instance, be related to dynamic service network planning with a real-time view to service network efficiency. This in turn could lead to better services for citizens, resource efficiency, and better allocation of financial resources. Cybernetic management and smart city production necessitates a shared view of urban processes that is not dedicated only for the eyes of a few experts but is widely accessible and supports information exchange and dialogue among city authorities, decision-makers, and citizens. Full article

Value engineering (VE) and function analysis (FA) are technological tools for the functional enhancement and cost reduction of engineering projects. They also help to overcome mental inertia by acknowledging the voice of the customer in complicated systems. Antenna engineering, providing electromagnetic remote links, is an important area in engineering science, with a large number of innovative concepts. However, managing innovative ideas to improve performance, reliability, quality, safety, and reduce life cycle costs, is still a work in progress. This research was designed to apply VE and FA as frameworks for innovative ideas in antenna systems, especially with regard to imaging and radar systems. FA diagrams free a designers’ mind from tools to instead focus on purpose, which can help them to obtain better ideas for solutions to problems. It was identified that there were several options available for functionality enhancement and cost reduction. The required functionalities of the components of antenna systems, and their advantages and limitations were indicated. In addition, it was identified that some of the advantages and limitations appeared for combinations of the components. Alternative methods for applications, such as polarization conversion and the separation of outgoing and incoming electromagnetic waves, were studied. Circular polarization (CP) is important for two-way communication, since left-handed circularly polarized waves usually return with right-handed CP from targets. Therefore, various methods for producing CP were discussed, such as metamaterial-based linear to circular polarization converters and waveguide polarizers. Also, potential extra applications for these systems were explained. Two examples were: (1) merging multiple systems with different operating frequencies using multiband components; and (2) applying a feeding system for multiple reflectors using surfaces that reflect half of the wave and transmit the other half. Consequently, it was identified that the clearance of existing functions, prioritization of customers, identification of system bottlenecks requiring innovative methods, and better communication between users and designers, were the key benefits of VE and FA. Full article

Many researchers consider chronic fatigue syndrome (CFS) to be a synonym of Myalgic Encephalomyelitis (ME). However, the case criteria of ME and CFS define two distinct clinical entities. Although some patients will meet both case criteria, other patients can meet the diagnosis of ME and not fulfil the case criteria for CFS, while the diagnosis of CFS is largely insufficient to be qualified as a ME patient. ME is a neuromuscular disease with distinctive muscular symptoms, including prolonged muscle weakness after exertion, and neurological signs implicating cerebral dysfunction, including cognitive impairment and sensory symptoms. The only mandatory symptom of CFS is chronic fatigue. Chronic fatigue must be accompanied by at least four out of eight nonspecific symptoms: substantial impairment in short-term memory or concentration, a sore throat, tender lymph nodes, muscle pain, multijoint pain, a new type of headaches, unrefreshing sleep, and postexertional “malaise” lasting more than 24 h. So, regardless whether the name ME is appropriate or not, ME is not synonymous to CFS. That is not a matter of opinion, but a matter of definition. Due to the definitions of ME and CFS, “ME/CFS” does not exist and cannot be replaced by a new clinical entity (SEID: Systemic Exertion Intolerance Disease), as recently suggested. Full article

This paper builds a link between isolated domains within the arts and sciences, specifically between music and psychiatry. An analogous model is presented that associates heavy metal music with bipolar disorder, a form of mental illness. Metal music consists of a variety of subgenres with distinct manifestations of song, rhythm, instrumentation, and vocal structure. These manifestations are analogous to the symptomatology of bipolar disorder, specifically the recurrent episodes of (hypo)mania and depression. Examples of songs are given which show these analogies. Besides creating a subjective link between apparently unconnected knowledge domains, these analogies could play a heuristic role in clinical applications and education about the disorder and mental illnesses at large. Full article

With the rapid development of new nanomaterials, it was recognized early that together with their beneficial properties, nanomaterials may pose a risk to human health and the environment. Evidence has accumulated over the last twenty years in support of oxidative stress as a broad mechanistic concept to explain the interaction of engineered nanoparticles with biological substances. As oxidative stress as a physiological response was recognized in redox biology, its wide-ranging use in nanotoxicology has exposed new challenges and limitations. In this commentary, we review certain oxidative stress concepts and their relevance to nanotoxicology. Full article

Soundscape research is attracting an ever-increasing worldwide interest from different disciplines and stakeholders. This brief commentary paper aims at offering some insights into the new directions this research (and practice) field will likely go, in the near future. For this purpose, eleven early-career soundscape researchers and practitioners were approached and asked to provide a response to the question “What are the current priorities and challenges for soundscape research?” Five recurring themes were identified in the participants’ statements. A major concern of the interviewed sample is the need to bridge the academic and practice sides of the soundscape community, in order to better position this discipline in the broader framework of (urban) sound planning and design. Full article

Herbal drugs have been widely used throughout the course of history. Traditional knowledge based on religious beliefs and/or experience has been transmitted orally between generations. First attempts to provide scientific evidence came in the 19th century when potent compounds were first isolated. Since then, modern pharmacology theory has been assumed by phytotherapy. Scientists have tried to elucidate the molecular mechanism of each compound and, for a pharmacological indication, propose an effective and secure dose. Stepwise, clinical trials confirm the benefits of herbal drug use in therapeutics, especially for chronic diseases. However, herbal drugs exert pleiotropic effects, and there is still a need for a complete, rational, and widely accepted theory that can explain phytotherapy efficacy. The “-omics” might help with this matter. Studies of modification in the gene expression profile, the metabolome, and the physiopathological state after the administration of a herbal extract could provide relevant information that verifies herbal therapies. Full article

Mobility is one of the most difficult domains of the smart city to face. In fact, most large cities in the world are still facing urban mobility problems, especially traffic congestion. Particularly, in Jakarta, Indonesia, traffic congestion is a major issue that negatively affects productivity and the overall living quality of the citizens. Along with the development of the information communication and technology (ICT), the transportation domain in Jakarta has formed a digital transportation ecosystem, shown by the emergence of innovative digital-based transportation services. In line with this current condition, this paper hopes to contribute to the improvement of urban traffic in Jakarta by proposing research directions to govern the digital transportation ecosystem within a smart city framework. The significance of the research directions is reviewed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology in a systematic review of previous studies. Ultimately, the research directions proposed in this paper lead to the necessity for an architectural perspective and relevant big data analytical tools to improve the digital transportation ecosystem in Jakarta. Full article

The term planetary health, popularized in the 1980s and 1990s, was born out of necessity; although the term was used by many diverse groups, it was consistently used to underscore that human health is coupled to the health of natural systems within the Earth’s biosphere. The interrelated challenges of climate change, massive biodiversity losses, environmental degradation, grotesque socioeconomic inequalities, conflicts, and a crisis of non-communicable diseases are, mildly stated, daunting. Despite ‘doomsday’ scenarios, there is plenty of room for hope and optimism in planetary health. All over planet Earth, humans are making efforts at the macro, meso and micro scales to promote the health of civilization with the ingredients of hope—agency and pathway thinking; we propose that planetary health requires a greater commitment to understanding hope at the personal and collective levels. Prioritizing hope as an asset in planetary health necessitates deeper knowledge and discourse concerning the barriers to hope and the ways in which hope and the utopian impulse are corrupted; in particular, it requires examining the ways in which hope is leveraged by advantaged groups and political actors to maintain the status quo, or even promote retrograde visions completely at odds with planetary health. Viewing the Earth as a superorganism, with humans as the collective ‘nervous system’, may help with an understanding of the ways in which experience and emotions lead to behavioral responses that may, or may not be, in the best interest of planetary health. We argue that the success of planetary health solutions is predicated on a more sophisticated understanding of the psychology of prevention and intervention at all scales. Full article

Worldwide, fires kill 300,000 people every year. The fire season is usually recognized to be in the warmer periods of the year. Recent research has, however, demonstrated that the colder season also has major challenges regarding severe fires, especially in inhabited (heated) wood-based structures in cold-climate areas. Knowledge about the effect of dry cellulose-based materials on fire development, indoor and outdoor, is a motivation for monitoring possible changes in potential fire behavior and associated fire risk. The effect of wind in spreading fires to neighboring structures points towards using weather forecasts as information on potential fire spread behavior. As modern weather forecasts include temperature and relative humidity predictions, there may already be sufficient information available to develop a structural fire danger rating system. Such a system may include the following steps: (1) Record weather forecasts and actual temperature and relative humidity inside and outside selected structures; (2) Develop a meteorology-data-based model to predict indoor relative humidity levels; (3) Perform controlled drying chamber experiments involving typical hygroscopic fire fuel; (4) Compare the results to the recorded values in selected structures; and (5) Develop the risk model involving the results from drying chamber experiments, weather forecasts, and separation between structures. Knowledge about the structures at risk and their use is also important. The benefits of an automated fire danger rating system would be that the society can better plan for potentially severe cold-climate fires and thereby limit the negative impacts of such fires. Full article

The blue-green pigment known as xylindein that is produced by species in the Chlorociboria genus is under heavy investigation for its potential in textile dyes, wood dyes, and solar cells. Xylindein has not yet been synthesized, and while its production can be stimulated under laboratory conditions, it is also plentiful in downed, decayed wood in forested lands. Unfortunately, little is known about the wood preference and forest type preference for this genus, especially outside New Zealand. To map the genus would be a massive undertaking, and herein a method by which citizen scientists could contribute to the distribution map of Chlorociboria species is proposed. The initial trial of this method found untrained participants successfully identified Chlorociboria stained wood in each instance, regardless of forest type. This simple, easy identification and classification system should be well received by citizen-scientists and is the first step towards a global understanding of how xylindein production might be managed for across various ecosystems. Full article

The epidemic of socially-rooted, lifestyle-driven non-communicable diseases (NCDs; also referred to as socially-transmitted conditions) has now overtaken infectious diseases as the leading cause of human mortality. Despite this reality, physician education, training and practice within industrialized nations is heavily slanted toward the biopharmaceutical (and away from the psychosocial) aspects of prevention and treatment. As we underscore, the current state of physician training and practical application of guidelines pertaining to lifestyle is paltry and untenable. However, the solution is not a few more hours of nutritional biochemistry to check off the curricula box. Physician readiness for the current NCD crisis will require a philosophical shift in medicine-at-large, including candidate pooling. Recent elections in the United States and Europe have cast a spotlight on the public health consequences of political authoritarianism. However, we highlight that authoritarianism—and its related facets of social dominance orientation and Machiavellianism—are not exclusive to political candidates. Here, we open a dialogue on authoritarianism in westernized medicine as a starting point in order to encourage the development of critical research and to explore its potential as a barrier to patient care. We suggest that authoritarianism and its prejudices act as a border wall to the World Health Organization’s broad vision of global health, cultural competency and patient autonomy. Moreover, the evidence reviewed here would suggest that in the context of the NCDs crisis, westernized medicine is long overdue a Flexner Report for the 21st Century. Full article

The United States (US) occupies the frontline of events in modern history of environmental reform. The federal government through the National Environmental Policy Act (NEPA) of 1970 has not only established an environmental policy template for other nations to emulate, but has also produced a viable tool for regulating environmental quality (EQ) and delivering environmental justice (EJ)—Environmental Impact Assessment (EIA). However, environmental history provides evidence that political process and special interests govern the attainment of the EJ goal by way of inadequate adherence to the NEPA provisions. Public participation (PP) is a principal requirement for achieving EJ and constitutes a pivotal determinant of EIA outcome. Effective delivery of EJ through EIA does require complete compliance with NEPA stipulations. Furthermore, the responsible agency’s resources in terms of both funding and commitment in allowing for the full representation of the opinions of residents within communities of concern (CoC) for environmental decision-making process are critically important. Public health research approach offers valuable tools towards achieving EJ goals. To approach this topic, first I provide a historical background on EIA and EJ from the standpoint of the NEPA. Second, I discuss the meaning and impediments of PP. Third, I examine two scenarios viz the Triassic Park Hazardous Waste Dump in Roswell, and the public hearing of the recent “controversial” oil and gas ordinance in Sandoval County, both in New Mexico. Finally, in the discussion part, I attempt to evaluate PP in both cases and suggest that none of the criteria seem to have been met in either case. I conclude that the Home State Rule designation of New Mexico State in terms of control over oil and gas activities places it at an advantage in benefitting from a fair PP. Full article

The complex interactions between empathy and vulnerability amongst those in helping professions/roles have been explored by practitioners and researchers across multiple disciplines for decades. While these explorations have spurred interest and awareness in the unique risks and protective factors of helping professions/roles, they have also resulted in myriad competing, overlapping, and/or parallel definitions, conceptualizations, terminology, and etiological attributions of adverse impacts of secondary exposure to others’ suffering. In this conceptual review, we will follow the historical origins of this phenomenon, beginning with the early 1900s with the First World War and the works of early psychiatric clinicians and moving toward recent advances in understanding etiology and conceptualization. Finally, we will provide support for the use and additional research of a proposed unifying and comprehensive conceptualization term: compassion stress injury (CSI), based on a mind-body and de-stigmatizing framework. Full article

The first evidence of an ADP-ribosylating activity in Archaea was obtained in Sulfolobus solfataricus(strain MT-4) where a poly(ADP-ribose) polymerase (PARP)-like thermoprotein, defined with the acronymous PARPSso, was found. Similarly to the eukaryotic counterparts PARPSso cleaves beta-nicotinamide adenine dinucleotide to synthesize oligomers of ADP-ribose; cross-reacts with polyclonal anti-PARP-1 catalytic site antibodies; binds DNA. The main differences rely on the molecular mass (46.5 kDa) and the thermophily of PARPSso which works at 80 °C. Despite the biochemical properties that allow correlating it to PARP enzymes, the N-terminal and partial amino acid sequences available suggest that PARPSso belongs to a different group of enzymes, the DING proteins, an item discussed in detail in this review.This finding makes PARPSso the first example of a DING protein in Archaea and extends the existence of DING proteins into all the biological kingdoms. PARPSsohas a cell peripheral localization, along with the edge of the cell membrane. The ADP-ribosylation reaction is reverted by a poly(ADP-ribose) glycohydrolase-like activity, able to use the eukaryotic poly(ADP-ribose) as a substrate too. Here we overview the research of (ADP-ribosyl)ation in Sulfolobus solfataricus in the past thirty years and discuss the features of PARPSso common with the canonical poly(ADP-ribose) polymerases, and the structure fitting with that of DING proteins. Full article

I illustrate the effects of both contingency and constraints on the body-mass scaling of metabolic rate by analyzing the significantly different influences of ambient temperature (T_a) on metabolic scaling in ectothermic versus endothermic animals. Interspecific comparisons show that increasing T_a results in decreasing metabolic scaling slopes in ectotherms, but increasing slopes in endotherms, a pattern uniquely predicted by the metabolic-level boundaries hypothesis, as amended to include effects of the scaling of thermal conductance in endotherms outside their thermoneutral zone. No other published theoretical model explicitly predicts this striking variation in metabolic scaling, which I explain in terms of contingent effects of T_a and thermoregulatory strategy in the context of physical and geometric constraints related to the scaling of surface area, volume, and heat flow across surfaces. My analysis shows that theoretical models focused on an ideal 3/4-power law, as explained by a single universally applicable mechanism, are clearly inadequate for explaining the diversity and environmental sensitivity of metabolic scaling. An important challenge is to develop a theory of metabolic scaling that recognizes the contingent effects of multiple mechanisms that are modulated by several extrinsic and intrinsic factors within specified constraints. Full article

NAD⁺ has emerged as a crucial element in both bioenergetic and signaling pathways since it acts as a key regulator of cellular and organism homeostasis. NAD⁺ is a coenzyme in redox reactions, a donor of adenosine diphosphate-ribose (ADPr) moieties in ADP-ribosylation reactions, a substrate for sirtuins, a group of histone deacetylase enzymes that use NAD⁺ to remove acetyl groups from proteins; NAD⁺ is also a precursor of cyclic ADP-ribose, a second messenger in Ca⁺⁺ release and signaling, and of diadenosine tetraphosphate (Ap4A) and oligoadenylates (oligo2′-5′A), two immune response activating compounds. In the biological systems considered in this review, NAD⁺ is mostly consumed in ADP-ribose (ADPr) transfer reactions. In this review the roles of these chemical products are discussed in biological systems, such as in animals, plants, fungi and bacteria. In the review, two types of ADP-ribosylating enzymes are introduced as well as the pathways to restore the NAD⁺ pools in these systems. Full article

For over 30 years, immortalized lung cells have enabled researchers to elucidate lung-pathogen molecular interactions. However, over the last five years, numerous commercial companies are now providing affordable, ready-to-use primary lung cells for use in research laboratories. Despite advances in primary cell culture, studies using immortalized lung cells still dominate the recent scientific literature. In this review, we highlight recent influenza and anthrax studies using in vitro primary lung tissue models and how these models are providing better predictive outcomes for when extrapolated to in vivo observations. By focusing on one virus (influenza) and one bacterium (Bacillus anthracis), it is the intent that these primary lung cell culture observations may translate into more useful studies for other related viral and bacterial lung pathogens of interest. Full article