• T lymphocytes, multi-omic interactions and bronchopulmonary dysplasia

      Toldi, Gergely; Hummler, Helmut; Pillay, Thillagavathie (Frontiers Media, 2021-06-08)
      Bronchopulmonary dysplasia (BPD) remains a significant clinical challenge in neonatal medicine. BPD is clearly a multifactorial disease with numerous antenatal and postnatal components influencing lung development. Extremely immature infants are born in the late canalicular or early saccular stage and usually receive intensive care until the early alveolar stage of lung development, resulting in varying magnitudes of impairment of alveolar septation, lung fibrosis, and abnormal vascular development. The interactions between T lymphocytes, the genome and the epigenome, the microbiome and the metabolome, as well as nutrition and therapeutic interventions such as the exposure to oxygen, volutrauma, antibiotics, corticosteroids, caffeine and omeprazole, play an important role in pathogenesis and disease progression. While our general understanding of these interactions thanks to basic research is improving, this knowledge is yet to be translated into comprehensive prevention and clinical management strategies for the benefit of preterm infants developing BPD and later during infancy and childhood suffering from the disease itself and its sequelae. In this review, we summarise existing evidence on the interplay between T lymphocytes, lung multi-omics and currently used therapeutic interventions in BPD, and highlight avenues for potential future immunology related research in the field.
    • Tailoring the supramolecular structure of amphiphilic glycopolypeptide analogue toward liver targeted drug delivery systems

      Mohamed Wali, Aisha Roshan; Zhou, Jie; Ma, Shengnan; He, Yiyan; Yue, Dong; Tang, James Z; Gu, Zhongwei (Elsevier, 2017-04-07)
      Amphiphilic glycopolypeptide analogues have harboured great importance in the development of targeted drug delivery systems. In this study, lactosylated pullulan-graft-arginine dendrons (LP-g-G3P) was synthesized using Huisgen azide-alkyne 1,3-dipolar cycloaddition between lactosylated pullulan and generation 3 arginine dendrons bearing Pbf and Boc groups on the periphery. Hydrophilic lactosylated pullulan was selected for amphiphilic modification, aiming at specific lectin recognition. Macromolecular structure of LP-g-G3P combined alkyl, aromatic, and peptide dendritic hydrophobic moieties and was able to self-assemble spontaneously into core-shell nanoarchitectures with small particle sizes and low polydispersity in the aqueous media, which was confirmed by CAC, DLS and TEM. Furthermore, the polyaromatic anticancer drug (doxorubicin, DOX) was selectively encapsulated in the hydrophobic core through multiple interactions with the dendrons, including π-π interactions, hydrogen bonding and hydrophobic interactions. Such multiple interactions had the merits of enhanced drug loading capacity (16.89 ± 2.41%), good stability against dilution, and excellent sustained release property. The cell viability assay presented that LP-g-G3P nanoparticles had an excellent biocompatibility both in the normal and tumor cells. Moreover, LP-g-G3P/DOX nanoparticles could be effectively internalized into the hepatoma carcinoma cells and dramatically inhibited cell proliferation. Thus, this approach paves the way to develop amphiphilic and biofunctional glycopolypeptide-based drug delivery systems.
    • Tailoring the supramolecular structure of guanidinylated pullulan toward enhanced genetic photodynamic therapy

      Zhou, Jie; Mohamed Wali, Aisha Roshan; Ma, Shengnan; He, Yiyan; Yue, Dong; Tang, James Zhenggui; Gu, Zhongwei (ACS Publications, 2018-04-24)
      In the progress of designing a gene carrier system, what is urgently needed is a balance of excellent safety and satisfactory efficiency. Herein, a straightforward and versatile synthesis of a cationic guanidine-decorated dendronized pullulan (OGG3P) for efficient genetic photodynamic therapy was proposed. OGG3P was able to block the mobility of DNA from a weight ratio of 2. However, G3P lacking guanidine residues could not block DNA migration until at a weight ratio of 15, revealing guanidination could facilitate DNA condensation via specific guanidinium-phosphate interactions. A zeta potential plateau (∼+23 mV) of OGG3P complexes indicated the nonionic hydrophilic hydroxyl groups in pullulan might neutralize the excessive detrimental cationic charges. There was no obvious cytotoxicity and hemolysis, but also enhancement of transfection efficiency with regard to OGG3P in comparison with that of native G3P in Hela and HEK293T cells. More importantly, we found that the uptake efficiency in Hela cells between OGG3P and G3P complexes was not markedly different. However, guanidination caused changes in uptake pathway and led to macropinocytosis pathway, which may be a crucial reason for improved transfection efficiency. After introducing a therapeutic pKillerRed-mem plasmid, OGG3P complexes achieved significantly enhanced KillerRed protein expression and ROS production under irradiation. ROS-induced cancer cells proliferation suppression was also confirmed. This study highlights the guanidine-decorated dendronized pullulan could emerge as a reliable nonviral gene carrier to specifically deliver therapeutic genes.
    • Tangled skeins: a first report of non-captive mating behavior in the Southeast Asian Paradise Flying Snake (Reptilia: Squamata: Colubridae: Chrysopelea paradisi)

      Kaiser, Hinrich; Kim, Johnny; Worth, Heike; O'Shea, Mark (Threatened Taxa, 2016-02-26)
      We describe the courtship behavior of the Paradise Flying Snake, Chrysopelea paradisi, from a series of images taken near Sandakan, eastern Sabah, Borneo, Malaysia. During the episode observed, four males moved together with a female in various states of entanglement, traveling at ground level and into a series of bushes. The observations took place over the course of a 30-min period until the snakes were lost to view. Our report is the first direct observation of mating behavior in C. paradisi in the wild and provides another rare glimpse of the multi-male courtship in Southeast Asian colubrids.
    • Targeted sound attenuation capacity of 3D printed noise cancelling waveguides

      Arjunan, Arun (Elsevier, 2019-03-08)
      The study explores the creation of 3D printed sound cancelling waveguides that can be customised for selected frequencies as a function of geometry. The potential for attenuation in these waveguides is characterised through experimentally measured acoustic-absorption (α) and Transmission Loss (TL). This was done to evaluate the potential of geometry-controlled waveguides in the development of passive sound cancelling structures. Geometrically complex waveguides to exploit the Herschel–Quincke-Arjunan (HQA) waveguide model manufactured in Nylon-12 using Selective Laser Melting (SLM) are presented. The attenuation of the waveguides was compared to the bulk Nylon-12 materials to segregate the material-based influence. The results showed that the performance of HQA waveguides can be controlled as a function of length, diameter and waveguide-tortuosity. Accordingly, under right parameters significant improvement in α (0.96, 0.80, 0.61 and 0.98) and TL (65.59%, 30.15%, 53.36% and 95.28%) can be achieved at the design frequency. The proposed methodology can be used to develop customisable waveguides exploiting the principles of acoustic wave interference for a range of application including building walls, noise barriers and absorptive panels.
    • Targeting Aquaporin-4 subcellular localization to treat central nervous system edema

      Kitchen, P; Salman, MM; Halsey, AM; Clarke-Bland, C; MacDonald, JA; Ishida, H; Vogel, HJ; Almutiri, S; Logan, A; Kreida, S; et al. (Elsevier, 2020-05-14)
      © 2020 The Author(s) Swelling of the brain or spinal cord (CNS edema) affects millions of people every year. All potential pharmacological interventions have failed in clinical trials, meaning that symptom management is the only treatment option. The water channel protein aquaporin-4 (AQP4) is expressed in astrocytes and mediates water flux across the blood-brain and blood-spinal cord barriers. Here we show that AQP4 cell-surface abundance increases in response to hypoxia-induced cell swelling in a calmodulin-dependent manner. Calmodulin directly binds the AQP4 carboxyl terminus, causing a specific conformational change and driving AQP4 cell-surface localization. Inhibition of calmodulin in a rat spinal cord injury model with the licensed drug trifluoperazine inhibited AQP4 localization to the blood-spinal cord barrier, ablated CNS edema, and led to accelerated functional recovery compared with untreated animals. We propose that targeting the mechanism of calmodulin-mediated cell-surface localization of AQP4 is a viable strategy for development of CNS edema therapies.
    • Technical and commercial challenges of proton-exchange membrane (PEM) fuel cells

      Alaswad, A; Omran, A; Sodre, JR; Wilberforce, T; Pignatelli, G; Dassisti, M; Baroutaji, A; Olabi, AG (MDPI, 2020-12-29)
      This review critically evaluates the latest trends in fuel cell development for portable and stationary fuel cell applications and their integration into the automotive industry. Fast start-up, high efficiency, no toxic emissions into the atmosphere and good modularity are the key advantages of fuel cell applications. Despite the merits associated with fuel cells, the high cost of the technology remains a key factor impeding its widespread commercialization. Therefore, this review presents detailed information into the best operating conditions that yield maximum fuel cell performance. The paper recommends future research geared towards robust fuel cell geometry designs, as this determines the cell losses, and material characterization of the various cell components. When this is done properly, it will support a total reduction in the cost of the cell which in effect will reduce the total cost of the system. Despite the strides made by the fuel cell research community, there is a need for public sensitization as some people have reservations regarding the safety of the technology. This hurdle can be overcome if there is a well-documented risk assessment, which also needs to be considered in future research activities.
    • Technological and economic evaluation of conversion of potential flare gas to electricity in Nigeria

      Ojijiagwo, Emeka Nnanna; Oduoza, Chike F; Emekwuru, Nwabueze (Elsevier, 2018-06-11)
      Globally, over 100 billion cubic metres (BCM) of gas is flared annually and linked to an annual emission of 400 million tons of carbon dioxide. In Nigeria the annual gas production is valued at 33.21 BCM, out of which more than 50% of this volume is wasted through flaring, thereby emitting about 35 million tons of carbon dioxide. About 14.94 BCM of gas produced in Nigeria is used for a variety of activities including electricity generation. Despite this scenario, Nigeria is still unable to generate and distribute enough electricity for the citizenry. This paper therefore proposes the option to divert gas which is normally flared to generate electricity in Nigeria while minimising the associated environmental impacts. The research methodology was based on interviewing top level managers in an electricity generation company, and gas Production Company, as well as the researchers’ site observations within the two case companies. Results from this study showed that electricity generation could be improved from its current daily production rate of 4358 MW to about 12000 MW. This improvement comes from the use of 18.27 BCM of gas currently flared annually in Nigeria, which could potentially be diverted as fuel for 50 units of gas turbine with power output of 150 MW each, with an increase in daily electricity generation of 7500 MW. The study also incorporates an economic analysis for the option to generate electricity as aforementioned.
    • ‘Technologizing’ the postgraduate classroom

      Smith, Sara; Khechara, Martin (Pedagogic Research Institute and Observatory (PedRIO), 2016)
      The MSc Biomedical Science award like many other awards at Masters Level attracts students from a range of undergraduate studies as well as a large number of international students. Transition from undergraduate to postgraduate learner is challenging for most students. For those who have studied on generic UG courses or those with non-UK degrees, this transition is potentially more difficult, and students often struggle with the specialist context of this award. We describe an investigation which evaluated the use of two current technologies available to support learning and teaching to enhance the student experience and consequently engagement. Panopto software allows lectures to be captured by tutors and watched by students outside of taught sessions (flipped). This provides more time during class to focus upon application of knowledge, to address more complex topics, develop problem solving skills and for students to benefit from peer and tutor support during contact time. Socrative enables the use of instantaneous questioning and feedback of students’ responses using mobile devices. It provides the tutor with an insight into levels of understanding, as well as allowing students to evaluate their own progress. Evaluation and comparison of the non-traditional vs. traditional delivery was undertaken via questionnaires and focus group interviews with students. Analysis of the data illustrates that although the use of technology is identified as being a valuable addition to the learning environment, it is the relationships built in the safe space of group working tasks afforded by the technology that is most beneficial in aiding engagement. Indeed, many factors that influence student sense of belonging also in turn promote success; attainment and engagement and are identified as being enhanced by the approach used.
    • Telechelic Polyhydroxyalkanoates/Polyhydroxybutyrates (PHAs/PHBs)

      Kowalczuk, Marek; Alli, A.; Hazer, B.; Adamus, G. (CRC PRESS Taylor&Francis Group, 2017)
      Telechelic polymers have garnered a great deal of scientific interest due to their reactive chain-end functions. This comprehensive book compiles and details the basic principles of and cutting-edge research in telechelic polyesters, polycarbonates, and polyethers, ranging from synthesis to applications. It discusses general strategies toward telechelic polymers, centered on the fundamental aspects of polycondensation reactions, of cationic, anionic, coordination-insertion, and activated monomer mechanisms of the metal-, enzyme-, or otherwise organocatalyzed ring-opening polymerization of cyclic monomers, and of postpolymerization chemical modification methods of polymer precursors. All main classes of polymers are covered separately, comprising polyhydroxyalkanoates, poly(ε-caprolactone)s, poly(lactic acid)s, polylactides, polycarobnates, and polyethers, including synthetic approaches as well as some illustrative, up-to-date examples and uses. The book also addresses applications of hydroxyl, thiol, amino, or acrylate/methacrylate end-capped polymers as starting materials for the preparation of diverse polymer architectures ranging from block, graft, and star-shaped polymers and micelles to precursors for ATRP macroinitiators, polyurethane copolymers, shape-memory polymers, or nanosized drug delivery systems. The book will appeal to advanced undergraduate- and graduate-level students of polymer science; researchers in macromolecular science, especially those with an interest in functional and reactive polymers; and polymer chemists in academia and industry.
    • Temporal changes in soil temperature at the Hilton Experimental Site, Shropshire, UK (1982-2006): Evidence of a warming trend?

      Subedi, Madhu; Fullen, Michael A. (Informaworld (Taylor & Francis), 2009)
      Soil temperature variations at different depths at a research site over a 25-year period (1982-2006) are discussed. Based on a database of 11,498 individual soil temperature measurements in loamy sand (Bridgnorth series) soils, soil temperature at the Hilton Experimental Site in Shropshire, UK, significantly increased between 1982 and 2006. The surface soil (0 cm) warmed twice as fast (∼0.1°C year-1) as soil at 100 cm depth (∼0.05°C year-1) and thus implies progressively steeper thermal gradients with soil depth through time. The trend of increase in soil temperatures at 0 cm was generally greater in winter. These observations contribute to the growing corpus of evidence of global warming.
    • Temporal changes in soil temperature at Wolverhampton, UK and Hohe Warte, Vienna, Austria 1976–2010

      Webb, J; Amon, Barbara; Subedi, Madhu; Fullen, Michael A. (Royal Meteorological Society, 2017-09-11)
      Soil temperature is determined by the available heat energy that the soil absorbs, with solar radiation being the primary source (Brady and Weil, 1999). Chow et al. (2011) found that, in an urban environment, soil temperature is strongly correlated (R = 0.869) with the dry-bulb air temperature, whereas its dependence on relative humidity, precipitation, global solar radiation or wind speed was weak (R < 0.250 in all cases). Snow cover, irregular episodes of cloud cover and droughts may also influence soil temperatures. Snow cover can provide an effective insulation barrier that creates an observable lag in the thermal response of a soil relative to changing air temperature (Fullen and Smith, 1983; Mackiewicz, 2012). Soil temperature fluctuates when there is a change in the ratio of heat energy absorbed by soil to energy lost from soil. This dynamic ratio changes over time and space. Soil temperature variation in different layers is a result of complex processes. The correlation with air temperature generally decreases with depth (Liu et al., 2013). Study of temperature variation in different layers of soil is useful in understanding surface energy processes and regional environmental and climatic conditions (Hu and Feng, 2003). Soil temperature has great significance for the growth and hence productivity of agricultural crops (Kaspar and Bland, 1992; Wraith and Ferguson, 1994; Bollero et al., 1996; Hu and Buyanovsky, 2003) and forest plantations (Balisky and Burton, 1995). Moreover, soil temperature affects plant diseases, soil hydrology and the over-wintering of pathogens (Marshall and Holmes, 1979; Phillips et al., 1999; Pivonia et al., 2002). Generally, the growth and development of most annual crop plants cease at temperatures <6–10°C (Subedi and Fullen, 2009). Thus, soil temperatures below this range inhibit root growth. Soil temperatures at different soil depths between 5 and 60cm at a UK research site over 35 years (1976–2010) and at a site in Austria at 10cm over the same period are reported and discussed.
    • Tendon and ligament injuries in elite rugby: the potential genetic influence

      Brazier, Jon; Antrobus, Mark; Stebbings, Georgina K; Day, Stephen H; Heffernan, Shane M; Cross, Matthew J; Williams, Alun G (MDPI AG, 2019-06-04)
      This article reviews tendon and ligament injury incidence and severity within elite rugby union and rugby league. Furthermore, it discusses the biological makeup of tendons and ligaments and how genetic variation may influence this and predisposition to injury. Elite rugby has one of the highest reported injury incidences of any professional sport. This is likely due to a combination of well-established injury surveillance systems and the characteristics of the game, whereby high-impact body contact frequently occurs, in addition to the high intensity, multispeed and multidirectional nature of play. Some of the most severe of all these injuries are tendon and ligament/joint (non-bone), and therefore, potentially the most debilitating to a player and playing squad across a season or World Cup competition. The aetiology of these injuries is highly multi-factorial, with a growing body of evidence suggesting that some of the inter-individual variability in injury susceptibility may be due to genetic variation. However, little effort has been devoted to the study of genetic injury traits within rugby athletes. Due to a growing understanding of the molecular characteristics underpinning the aetiology of injury, investigating genetic variation within elite rugby is a viable and worthy proposition. Therefore, we propose several single nucleotide polymorphisms within candidate genes of interest; COL1A1, COL3A1, COL5A1, MIR608, MMP3, TIMP2, VEGFA, NID1 and COLGALT1 warrant further study within elite rugby and other invasion sports.
    • TensiStrength: Stress and relaxation magnitude detection for social media texts

      Thelwall, Mike (2016-07-12)
      Computer systems need to be able to react to stress in order to perform optimally on some tasks. This article describes TensiStrength, a system to detect the strength of stress and relaxation expressed in social media text messages. TensiStrength uses a lexical approach and a set of rules to detect direct and indirect expressions of stress or relaxation, particularly in the context of transportation. It is slightly more effective than a comparable sentiment analysis program, although their similar performances occur despite differences on almost half of the tweets gathered. The effectiveness of TensiStrength depends on the nature of the tweets classified, with tweets that are rich in stress-related terms being particularly problematic. Although generic machine learning methods can give better performance than TensiStrength overall, they exploit topic-related terms in a way that may be undesirable in practical applications and that may not work as well in more focused contexts. In conclusion, TensiStrength and generic machine learning approaches work well enough to be practical choices for intelligent applications that need to take advantage of stress information, and the decision about which to use depends on the nature of the texts analysed and the purpose of the task.
    • Terminal regions confer plasticity to the tetrameric assembly of human HspB2 and HspB3

      Clark, Alice R; Vree Egberts, Wilma; Kondrat, Frances DL; Hilton, Gillian R; Ray, Nicholas J; Cole, Ambrose R; Carver, John A; Benesch, Justin LP; Keep, Nicholas H; Boelens, Wilbert C; et al. (Elsevier, 2018-06-30)
      Heterogeneity in small heat shock proteins (sHsps) spans multiple spatiotemporal regimes—from fast fluctuations of part of the protein, to conformational variability of tertiary structure, plasticity of the interfaces, and polydispersity of the inter-converting, and co-assembling oligomers. This heterogeneity and dynamic nature of sHsps has significantly hindered their structural characterization. Atomic coordinates are particularly lacking for vertebrate sHsps, where most available structures are of extensively truncated homomers. sHsps play important roles in maintaining protein levels in the cell and therefore in organismal health and disease. HspB2 and HspB3 are vertebrate sHsps that are found co-assembled in neuromuscular cells, and variants thereof are associated with disease. Here, we present the structure of human HspB2/B3, which crystallized as a hetero-tetramer in a 3:1 ratio. In the HspB2/B3 tetramer, the four α-crystallin domains (ACDs) assemble into a flattened tetrahedron which is pierced by two non-intersecting approximate dyads. Assembly is mediated by flexible “nuts and bolts” involving IXI/V motifs from terminal regions filling ACD pockets. Parts of the N-terminal region bind in an unfolded conformation into the anti-parallel shared ACD dimer grooves. Tracts of the terminal regions are not resolved, most likely due to their disorder in the crystal lattice. This first structure of a full-length human sHsp heteromer reveals the heterogeneous interactions of the terminal regions and suggests a plasticity that is important for the cytoprotective functions of sHsps.
    • Testing for zero-modification relative to a negative-binomial distribution

      Wilson, Paul (International Statistical Modelling Society, 2018-07)
    • Text-Independent Speaker Identification Using Vowel Formants

      Almaadeed, Noor; Aggoun, Amar; Amira, Abbes (Springer US, 2015-05-05)
      Automatic speaker identification has become a challenging research problem due to its wide variety of applications. Neural networks and audio-visual identification systems can be very powerful, but they have limitations related to the number of speakers. The performance drops gradually as more and more users are registered with the system. This paper proposes a scalable algorithm for real-time text-independent speaker identification based on vowel recognition. Vowel formants are unique across different speakers and reflect the vocal tract information of a particular speaker. The contribution of this paper is the design of a scalable system based on vowel formant filters and a scoring scheme for classification of an unseen instance. Mel-Frequency Cepstral Coefficients (MFCC) and Linear Predictive Coding (LPC) have both been analysed for comparison to extract vowel formants by windowing the given signal. All formants are filtered by known formant frequencies to separate the vowel formants for further processing. The formant frequencies of each speaker are collected during the training phase. A test signal is also processed in the same way to find vowel formants and compare them with the saved vowel formants to identify the speaker for the current signal. A score-based scheme allows the speaker with the highest matching formants to own the current signal. This model requires less than 100 bytes of data to be saved for each speaker to be identified, and can identify the speaker within a second. Tests conducted on multiple databases show that this score-based scheme outperforms the back propagation neural network and Gaussian mixture models. Usually, the longer the speech files, the more significant were the improvements in accuracy.
    • The abject dream of neo-capital: Capitalist urbanism, architecture and endangered liveability of the Middle East’s modern cities

      Abdelmonem, Mohamed Gamal (Open House International, 2016-06-01)
      This article interrogates the notion of “New Capital” in the context of the hegemony of neoliberal urbanism in the Arab cities in the Middle East from historical, socio-economic and spatial perspectives. It reviews the historical narratives of new centres and districts in Cairo, Beirut and evolving capitalist urbanism and architecture in the Arabian Peninsula in search of elitist dream of neo-liberal urbanism. It offers a comprehensive analysis to the notions of neoLiberal ideology and urban policies, neoCapital city as catalyst for nation-building and neoCapitalist architecture as reproduction of clone structures of western models. The paper focuses its critical analysis on the aspects of liveability in the contemporary Arab City and its socio-spatial structures and everyday urban reality. It reports on urban narratives based on archival records, urban projects and investigation of governmental accounts to determine aspects of success and failure in projects of new capital cities and districts. It argues that cities are essentially social-spatial system in which hierarchy is a fundamental element, the lack of which determines abject failure of their anticipated vision.
    • The Aspergillus nidulans stress response transcription factor StzA is ascomycete-specific and shows species-specific polymorphisms in the C-terminal region.

      Chilton, Ian J.; Delaney, C. E,; Barham-Morris, J.; Fincham, Daron A.; Hooley, Paul; Whitehead, Michael P. (Elsevier, 2008)
      Orthologues of the Aspergillus nidulans gene stzA were identified and characterised in an additional 19 fungi. These orthologues were restricted to, and found within all the Pezizomycotina subphyla of the Ascomycota, for which data are available, but not the Saccharomycotina or Taphrinomycotina subphyla. Intron analysis indicated that both intron loss and gain have occurred in this gene. The orthologous proteins demonstrate considerable size variation (between 663 and 897 amino acids); with almost all this variability accounted for by a hyper-variable region that is carboxy terminal to the zinc finger region. The Hypocrea jecorina orthologue (ACE1) has the binding site 5'AGGCA. There is evidence of competition, or interaction, between the ACE1/StzA and AreA binding sites in promoters of stzA and its orthologues, as well as genes involved in the metabolism of amino acids. The A. nidulans and A. fumigatus cpcA promoters have seven potential ACE1/StzA binding sites, six of which are highly conserved in position. Two very closely positioned sites are conserved across 14 of the 19 fungi analysed. Potential CpcA binding sites (5'TGAC/GTCA) have been identified between -50 and -170bp of the ATG start in the promoters of 16 of the stzA orthologues.