• 1H NMR quantification of spray dried and spray freeze-dried saccharide carriers in dry powder inhaler formulations

      Babenko, Mai; Peron, Jean-Marie R.; Kaialy, Waseem; Calabrese, Gianpiero; Alany, Raid; ElShaer, Amr (Elsevier, 2019-03-16)
      Quantitative analysis using proton NMR (1H qNMR) has been employed in various areas such as pharmaceutical analysis (e.g., dissolution study), vaccines, natural products analysis, metabolites, and macrolide antibiotics in agriculture industry. However, it is not routinely used in the quantification of saccharides in dry powder inhaler (DPI) formulations. The aim of this study was to develop a 1H NMR method for the quantification of saccharides employed in DPI formulations. Dry powders as DPI carriers were prepared by spray drying (SD) and spray freeze drying (SFD) using three saccharides: namely D-mannitol, D-sorbitol and D-(+)-sucrose. The calibration curves constructed for all three saccharides demonstrated linearity with R2 value of 1. The 1H qNMR method produced accurate (relative error %: 0.184-3.697) and precise data with high repeatability (RSD %: 0.517-3.126) within the calibration curve concentration range. The 1H qNMR method also demonstrated significant sensitivity with low values of limit of detection (0.058 mM for D-mannitol, 0.045 mM for D-(+)-sucrose, and 0.056 mM for D-sorbitol) and limit of quantitation (0.175 mM for D-mannitol, 0.135 mM for D-(+)-sucrose, and 0.168 mM for D-sorbitol). Pulmonary deposition via impaction experiments of the three saccharides was quantified using the developed method. It was found that SFD D-mannitol (68.99%) and SFD D-(+)-sucrose (66.62%) exhibited better delivered dose (total saccharide deposition in throat and all impactor stages) than SD D-mannitol (49.03%) and SD D-(+)-sucrose (57.70%) (p< 0.05). The developed 1H qNMR methodology can be routinely used as an analytical method to assess pulmonary deposition in impaction experiments of saccharides employed as carriers in DPI formulations.
    • 2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19

      Mallinger, Aurélie; Schiemann, Kai; Rink, Christian; Sejberg, Jimmy; Honey, Mark A.; Czodrowski, Paul; Stubbs, Mark; Poeschke, Oliver; Busch, Michael; Schneider, Richard; et al. (American Chemical Society, 2016-03-28)
      We demonstrate a designed scaffold-hop approach to the discovery of 2,8-disubstituted-1,6-naphthyridine- and 4,6-disubstituted-isoquinoline-based dual CDK8/19 ligands. Optimized compounds in both series exhibited rapid aldehyde oxidase-mediated metabolism, which could be abrogated by introduction of an amino substituent at C5 of the 1,6-naphthyridine scaffold or at C1 of the isoquinoline scaffold. Compounds 51 and 59 were progressed to in vivo pharmacokinetic studies, and 51 also demonstrated sustained inhibition of STAT1SER727 phosphorylation, a biomarker of CDK8 inhibition, in an SW620 colorectal carcinoma human tumor xenograft model following oral dosing.
    • 3D particle models for composite laminates with anisotropic elasticity

      Wan, L; Yang, D; Ismail, Y; Sheng, Y (Elsevier BV, 2018-05-25)
      © 2018 Elsevier Ltd This paper presents an assessment of three different particle based approaches for 3D modelling of fibre reinforced polymer (FRP) composite laminates with anisotropic elasticity, namely 3D Discrete Lattice model, 3D Hexagonal Close Packing model and Extended 2D Hexagonal and Square Packing model. These approaches are compared and evaluated against experimental results using a 0∘ ply lamina case. It has been confirmed that the Extended 2D Hexagonal and Square modelling approach in Discrete Element Method (DEM) is capable of modelling 3D composite laminates with better efficiency. Angle-ply lamina and two different laminates are modelled with the chosen particle approach. Good agreements between DEM, Finite Element and theoretical results prove the capability of this developed DEM approach for modelling the elastic behaviour of general FRP composite lamina and laminates.
    • 3D printed auxetic nasopharyngeal swabs for COVID-19 sample collection

      Arjunan, Arun; Zahid, Suhaib; Baroutaji, Ahmad; Robinson, John (Elsevier, 2020-11-12)
      The COVID-19 pandemic has resulted in worldwide shortages of nasopharyngeal swabs required for sample collection. While the shortages are becoming acute due to supply chain disruptions, the demand for testing has increased both as a prerequisite to lifting restrictions and in preparation for the second wave. One of the potential solutions to this crisis is the development of 3D printed nasopharyngeal swabs that behave like traditional swabs. However, the opportunity to digitally conceive and fabricate swabs allows for design improvements that can potentially reduce patient pain and discomfort. The study reports the progress that has been made on the development of auxetic nasopharyngeal swabs that can shrink under axial resistance. This allows the swab to navigate through the nasal cavity with significantly less stress on the surrounding tissues. This is achieved through systematically conceived negative Poisson's ratio (-ν) structures in a biocompatible material. Finite element (FE) and surrogate modelling techniques were employed to identify the most optimal swab shape that allows for the highest negative strain (-∊lat) under safe stress (σvon). The influence and interaction effects of the geometrical parameters on the swab's performance were also characterised. The research demonstrates a new viewpoint for the development of functional nasopharyngeal swabs that can be 3D printed to reduce patient discomfort. The methodology can be further exploited to address various challenges in biomedical devices and redistributed manufacturing.
    • 3D printed cobalt-chromium-molybdenum porous superalloy with superior antiviral activity

      Arjunan, Arun; Robinson, John; Baroutaji, Ahmad; Tuñón-Molina, Alberto; Martí, Miguel; Serrano-Aroca, Ángel (MDPI, 2021-11-24)
      COVID-19 pandemic and associated supply-chain disruptions emphasise the requirement for antimicrobial materials for on-demand manufacturing. Besides aerosol transmission, SARS-CoV-2 is also propagated through contact with virus-contaminated surfaces. As such, the development of effective biofunctional materials that can inactivate SARS-CoV-2 is critical for pandemic preparedness. Such materials will enable the rational development of antiviral devices with prolonged serviceability, reducing the environmental burden of disposable alternatives. This research reveals the novel use of Laser Powder Bed Fusion (LPBF) to 3D print porous Cobalt-Chromium-Molybdenum (Co-Cr-Mo) superalloy with potent antiviral activity (100% viral inactivation in 30 min). The porous material was rationally conceived using a multi-objective surrogate model featuring track thickness (tt) and pore diameter (ϕd) as responses. The regression analysis found the most significant parameters for Co-Cr-Mo track formation to be the interaction effects of scanning rate (Vs) and laser power (Pl) in the order PlVs>Vs>Pl. Contrastively, the pore diameter was found to be primarily driven by the hatch spacing (Sh). The study is the first to demonstrate the superior antiviral properties of 3D printed Co-Cr-Mo superalloy against an enveloped virus used as biosafe viral model of SARS-CoV-2. The material significantly outperforms the viral inactivation time of other broadly used antiviral metals such as copper and silver, as the material’s viral inactivation time was from 5 h to 30 min. As such, the study goes beyond the current state-of-the-art in antiviral alloys to provide extra protection to combat the SARS-CoV-2 viral spread. The evolving nature of the COVID-19 pandemic brings new and unpredictable challenges where on-demand 3D printing of antiviral materials can achieve rapid solutions while reducing the environmental impact of disposable devices
    • 3D-printed polyester-based prototypes for cosmetic applications—future directions at the forensic engineering of advanced polymeric materials

      Rydz, Joanna; Sikorska, Wanda; Musioł, Marta; Janeczek, Henryk; Włodarczyk, Jakub; Misiurska-Marczak, Marlena; Łeczycka, Justyna; Kowalczuk, Marek (MDPI, 2019-03-26)
      Knowledge of degradation and impairment phenomena of (bio)degradable polymeric materials under operating conditions, and thus the selection of test procedures and prediction of their behavior designates the scope and capabilities as well as possible limitations of both: the preparation of the final product and its durability. The main novelty and objective of this research was to determine the degradation pathways during testing of polylactide and polylactide/polyhydroxyalkanoate materials made with three-dimensional printing and the development of a new strategy for the comprehensive characterization of such complex systems including behavior during waste disposal. Prototype objects were subjected to tests for damage evolution performed under simulating operating conditions. The reference samples and the tested items were characterized by gel permeation chromatography and differential scanning calorimetry to determine changes in material properties. The studies showed that: polyhydroxyalkanoate component during accelerated aging and degradation in environments rich in microorganisms accelerated the degradation of the material; paraffin accelerates polylactide degradation and slows degradation of polyhydroxyalkanoate-based material; under the influence of an environment rich in enzymes, paraffin contamination accelerates biodegradation; under the influence of natural conditions, paraffin contamination slowed degradation; the processing conditions, in particular the printing orientation of individual parts of the container, influenced the material properties in its various regions, affecting the rate of degradation of individual parts.
    • A 140-year-old specimen from the southern Trans-Fly region of Papua New Guinea proves that the Eastern Brownsnake, Pseudonaja textilis, was not a wartime or post-war introduction (Serpentes, Elapidae, Hydrophiinae)

      O'Shea, Mark; Doria, Giuliano; Petri, Massimo; Kaiser, Hinrich (Museo Civico di Storia Naturelle, Genova, 2016-10-20)
      Abstract: The medically important Australian elapid Pseudonaja textilis was first documented for the island of New Guinea in the 1950s, when specimens from the northern coast of the Papuan Peninsula were collected and identified. It was initially believed that these snakes were from an invasive population that established post-World War II, a concept generally accepted over following decades. More recently molecular evidence and additional specimens, from West New Guinea and the southern coast of the Papuan Peninsula, have suggested that the New Guinea populations are indigenous. However, no pre-World War II specimens have been found to dismiss the human-mediated introduction argument. We here present the earliest known Papuan voucher specimen of P. textilis, a juvenile from collections housed in Genoa made by Luigi Maria D’Albertis in 1876 that pre-dates all other vouchers and the New Guinea Campaign (1942-1945) of World War II by 77 and 66 years, respectively. We also discuss the origins of P. textilis in New Guinea, the history of its discovery, and the Pleistocene routes of its invasion from Australia.
    • A 300-year record of sedimentation in a small tilled catena in Hungary based on δ13C, δ15N, and C/N distribution

      Jakab, Gergely; Hegyi, István; Fullen, Michael A.; Szabó, Judit; Zacháry, Dóra; Szalai, Zoltán (Springer, 2018-01-04)
      Purpose Soil erosion is one of the most serious hazards that endanger sustainable food production. Moreover, it has marked effects on soil organic carbon (SOC) with direct links to global warming. At the same time, soil organic matter (SOM) changes in composition and space could influence these processes. The aim of this study was to predict soil erosion and sedimentation volume and dynamics on a typical hilly cropland area of Hungary due to forest clearance in the early eighteenth century. Materials and methods Horizontal soil samples were taken along two parallel intensively cultivated complex convex-concave slopes from the eroded upper parts at mid-slope positions and from sedimentation in toe-slopes. Samples were measured for SOC, total nitrogen (TN) content, and SOMcompounds (δ13C, δ15N, and photometric indexes). They were compared to the horizons of an in situ non-eroded profile under continuous forest. On the depositional profile cores, soil depth prior to sedimentation was calculated by the determination of sediment thickness. Results and discussion Peaks of SOC in the sedimentation profiles indicated thicker initial profiles, while peaks in C/N ratio and δ13C distribution showed the original surface to be ~ 20 cm lower. Peaks of SOC were presumed to be the results of deposition of SOC-enriched soil from the upper slope transported by selective erosion of finer particles (silts and clays). Therefore, changes in δ13C values due to tillage and delivery would fingerprint the original surface much better under the sedimentation scenario than SOC content. Distribution of δ13C also suggests that the main sedimentation phase occurred immediately after forest clearance and before the start of intense cultivation with maize. Conclusions This highlights the role of relief in sheet erosion intensity compared to intensive cultivation. Patterns of δ13C indicate the original soil surface, even in profiles deposited as sediment centuries ago. The δ13C and C/N decrease in buried in situ profiles had the same tendency as recent forest soil, indicating constant SOM quality distribution after burial. Accordingly, microbiological activity, root uptake, and metabolism have not been effective enough to modify initial soil properties.
    • A closed-loop reciprocity calibration method for massive MIMO in terrestrial broadcasting systems

      Luo, Hua; Zhang, Yue; Huang, Li-Ke; Cosmas, John; Aggoun, Amar (IEEE, 2016-09-22)
      Massive multi-input multioutput (MIMO) is believed to be an effective technique for future terrestrial broadcasting systems. Reciprocity calibration is one of the major practical challenges for massive MIMO systems operating in time-division duplexing mode. A new closed-loop reciprocity calibration method is investigated in this paper which can support online calibration with a higher accuracy compared to the existing methods. In the first part of the proposed method, an optimized relative calibration is introduced using the same structure of traditional relative calibration, but with less impaired hardware in the reference radio chain. In the second part, a test device (TD)-based calibration is proposed which makes online calibration possible. An experiment setup is built for the measurement of the base station hardware impairments and TD-based calibration implementation. Simulation results and the error vector magnitude of UE received signal after calibration show that the performance of our proposed method is improved significantly compared to the existing relative calibration methods.
    • A comparative study of analytical methodologies to determine the soil organic matter content of Lithuanian Eutric Albeluvisols

      Jankauskas, Benediktas; Slepetiene, Alvyra; Jankauskiene, Genovaite; Fullen, Michael A.; Booth, Colin A. (2006)
      Large archive databases of soil organic matter (SOM) widely exist in Lithuania and the other countries of Central and Eastern Europe. Despite the demise of the former Soviet Union over 16 years ago, and Lithuania's integration as a full European Union state, difficulties of SOM data acceptance remain where these results are presented for publication in international journals, due to methodological differences between laboratory protocols. Therefore, the scientific pilot project ‘Carbon sequestration in Lithuanian soils’, supported by the Leverhulme Trust (U.K.), included an objective to correlate soil carbon methodologies, using Lithuanian Eutric Albeluvisols. A comparison of SOM content data acquired using five different analytical methods is reported. The research programme included a specific objective to correlate analytical methods for SOM analyses. A total of 92 Eutric Albeluvisol samples were collected from topsoil (0–0.2 m: Ap, n=36; Ah, n=10) and subsoil (0.2–0.4 m: Bt, n=46) horizons of 46 long-term experimental field plots at the Kaltinenai Research Station of the Lithuanian Institute of Agriculture. Each sample was then subsampled and analysed for SOM using dry combustion (by automatic elemental analyser), Walkley–Black (USDA), Tyurin photometrical, Tyurin titrimetrical and loss-on-ignition (LoI) methods (the later performed, in parallel, in both Lithuania and U.K. laboratories). Linear correlation and paired regression equations were calculated. Correlation coefficients between the sets of results varied between r=0.81–0.96 (from 0–0.2 m, n=46, P<0.001) and r=0.76–0.98 (from 0.2–0.4 m, n=46, P<0.001). Based on the strength and significance of these relationships, it is proposed that simple linear or more complex paired regression equations can be confidently employed to recalculate SOM data between various analytical methodologies. Future work will continue these investigations on other soil units and environments, hereby enhancing the database.
    • A comparative study of three-dimensional printing directions: The degradation and toxicological profile of a PLA/PHA blend

      Gonzalez Ausejo, Jennifer; Rydz, Joanna; Musioł, Marta; Sikorska, Wanda; Sobota, Michał; Włodarczyk, Jakub; Adamus, Grażyna; Janeczek, Henryk; Kwiecień, Iwona; Hercog, Anna; et al. (Elsevier, 2018-04-17)
      The use of biobased plastics is of great importance for many applications. Blending thermoplastic polylactide (PLA) with polyhydroxyalkanoate (PHA) enables the formulation of a more mechanically powerful material and this enables tailored biodegradation properties. In this study we demonstrate the 3D printing of a PLA/PHA blend as a potential candidate for biocompatible material applications. The filament for 3D printing consisted of PHA, which contains predominantly 3-hydroxybutyrate units and a small amount of 3-hydroxyvalerate units, as revealed by multistage mass spectrometry (ESI-MSn). This research found that the properties of 3D printed species before and during abiotic degradation are dependent on printing orientation. Furthermore, the 3D printed specimens exhibited good biocompatibility with HEK293 cells, indicating real promise as biological scaffolds for tissue engineering applications.
    • A Computationally-Efficient Numerical Model to Characterize the Noise Behavior of Metal-Framed Walls

      Arjunan, Arun; Wang, Chang; English, Martin; Stanford, Mark; Lister, Paul (MDPI AG, Basel, Switzerland, 2015-08-07)
      Architects, designers, and engineers are making great efforts to design acoustically-efficient metal-framed walls, minimizing acoustic bridging. Therefore, efficient simulation models to predict the acoustic insulation complying with ISO 10140 are needed at a design stage. In order to achieve this, a numerical model consisting of two fluid-filled reverberation chambers, partitioned using a metal-framed wall, is to be simulated at one-third-octaves. This produces a large simulation model consisting of several millions of nodes and elements. Therefore, efficient meshing procedures are necessary to obtain better solution times and to effectively utilise computational resources. Such models should also demonstrate effective Fluid-Structure Interaction (FSI) along with acoustic-fluid coupling to simulate a realistic scenario. In this contribution, the development of a finite element frequency-dependent mesh model that can characterize the sound insulation of metal-framed walls is presented. Preliminary results on the application of the proposed model to study the geometric contribution of stud frames on the overall acoustic performance of metal-framed walls are also presented. It is considered that the presented numerical model can be used to effectively visualize the noise behaviour of advanced materials and multi-material structures.
    • A critical review of the effective use of expert witnesses in construction disputes

      Charlson, Jennifer; Smalley, James (Sweet & Maxwell, 2014)
      Discusses the role and duties of expert witnesses in construction law disputes, and considers the issues of concern that have been raised about the quality of their evidence. Presents the findings of research exploring the views of legal and construction industry professionals on: (1) the level of control that clients have over expert witnesses; (2) experts' standards of objectivity; (3) their qualifications and training; (4) the future use of tribunal experts; (5) the impact of the Supreme Court judgment in Jones v Kaney removing experts' immunity; and (6) the cost of engaging experts.
    • A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell killing by enhancing the stability of NKG2D-ligand binding

      Zuo, Jianmin; Willcox, Carrie R; Mohammed, Fiyaz; Davey, Martin; Hunter, Stuart; Khan, Kabir; Antoun, Ayman; Katakia, Poonam; Croudace, Joanne; Inman, Charlotte; et al. (American Association for the Advancement of Science, 2017-05-30)
      NKG2D (natural killer group 2, member D) is an activating receptor found on the surface of immune cells, including natural killer (NK) cells, which regulates innate and adaptive immunity through recognition of the stress-induced ligands ULBP1 (UL16 binding protein 1) to ULBP6 and MICA/B. Similar to class I human leukocyte antigen (HLA), these NKG2D ligands have a major histocompatibility complex–like fold and exhibit pronounced polymorphism, which influences human disease susceptibility. However, whereas class I HLA polymorphisms occur predominantly in the α1α2 groove and affect antigen binding, the effects of most NKG2D ligand polymorphisms are unclear. We studied the molecular and functional consequences of the two major alleles of ULBP6, the most polymorphic ULBP gene, which are associated with autoimmunity and relapse after stem cell transplantation. Surface plasmon resonance and crystallography studies revealed that the arginine-to-leucine polymorphism within ULBP0602 affected the NKG2D-ULBP6 interaction by generating an energetic hotspot. This resulted in an NKG2D-ULBP0602 affinity of 15.5 nM, which is 10- to 1000-fold greater than the affinities of other ULBP-NKG2D interactions and limited NKG2D-mediated activation. In addition, soluble ULBP0602 exhibited high-affinity competitive binding for NKG2D and partially suppressed NKG2D-mediated activation of NK cells by other NKG2D ligands. These effects resulted in a decrease in a range of NKG2D-mediated effector functions. Our results reveal that ULBP polymorphisms affect the strength of human lymphocyte responses to cellular stress signals and may offer opportunities for therapeutic intervention.
    • A dynamic approach to urban road deposited sediment pollution monitoring (Marylebone Road, London, UK)

      Crosby, C.J.; Fullen, Michael A.; Booth, C.A.; Searle, D.E. (Elsevier, 2014-06)
      The use of mineral magnetic measurements (χLF, χARM and SIRM) as a potential pollution proxy using road deposited sediment (RDS) is explored as an alternative means of monitoring pollution on a busy city road. Comparison of sediment-related analytical data by correlation analysis between mineral magnetic, particle size and geochemical properties is reported. Mineral magnetic concentration parameters (χLF, χARM and SIRM) reveal significant (p < 0.001; n = 61) associations with PM1.0, PM2.5 and PM10. Significant associations were also found with mineral magnetic concentrations (χLF and SIRM) and specific concentrations of the elements Fe, Ni, Cu, Zn and Mn (p < 0.001; n = 61). Inter-geochemical correlation analysis found strong associations (p < 0.001; n = 61) between Fe, Ni, Cu, Zn and Mn and suggest anthropogenic enrichment influences. Low χFD% measurements imply an influence of multi-domain mineralogy, indicative of anthropogenic combustion processes. SEM micrographs also support this, as all samples contain Fe spherules indicative of vehicular combustion processes. This study advocates rapid and simple initial assessment of urban pollution episodes using mineral magnetic measurements as a dynamic explorative technology.
    • A Fast New Numerical Tool for Designing Pre-stressed Dies for Backward Extrusion: Part 1: Die Behaviour

      Bonnavand, F.; Bramley, Alan N.; Mynors, Diane J. (Professional Engineering Publishing, 2001)
      Prestressed die inserts are often used in the forging of axisymmetric parts. Their use enhances overall tool economy and can enhance the quality of the finished forging. The design of tooling that incorporates prestressed die inserts is, however, complex. The complexity arises from the interrelated phenomena that occur within the dies during the forging process. As a result, it is not possible to obtain an analytical expression for critical parameters such as die stresses and deflections. This paper shows the limitations of currently used design methods, and identifies, for the backward extrusion process, which physical phenomena should be taken into account when designing prestressed tooling. (Professional Engineering Publishing)
    • A fast new numerical tool for designing prestressed dies for backward extrusion: Part 2: numerical analysis

      Bonnavand, F.; Bramley, Alan N.; Mynors, Diane J. (Professional Engineering Publishing, 2001)
      The economics of forging requires tools to be designed to ensure maximum service life. Ideally, this should be achieved by determining the maximum equivalent stress experienced by tools during service. However, the determination of the maximum equivalent stress in the dies through numerical simulations is very time consuming. For the case of a backward extrusion process, this paper proposes a method for its determination that is based on an analytical function of the process parameters. This function was obtained by generating a database that includes the maximum equivalent stress for a large range of process parameters. This database was then modelled by a function determined through statistical analysis. (Professional Engineering Publishing)
    • A Finite Element Analysis of the Stress Intensity Resulting from Single-Edge Pre-Cracked Beam Loading Conditions

      Kibble, Kevin A.; Turner, D. (ASTM International, 2001)
      The single-edge precracked-beam (SEPB) fracture toughness method has been investigated using finite element methods to analyze the stress intensity (K1) resulting from variations in bridge span, punch length, and virtual crack length. A two-dimensional half-plane, semi-infinite model was used to approximate the stress intensity from a fit of the nodal displacements of a crack face under SEPB loading conditions. The finite element method models the crack in situ, using six-node triangular elements specified around a singular point that simulates the crack tip. The analysis reveals that for increasing virtual crack length (), the stress intensity increases to a maximum where / = 0. With further increasing virtual crack length, the stress intensity decreases. The inflection point differs for varying span and fixed punch length, and for varying punch lengths with fixed span. The resulting stress intensities per new ton force loading are presented in tabular and graphical form. The presented series of graphs can be used to explore variations in precracking parameters. This finite element analysis provides useful data for those developing or adopting the SEPB fracture toughness measurement technique.
    • A high-throughput synthetic platform enables the discovery of proteomimetic cell penetrating peptides and bioportides

      Jones, Sarah; Osman, Shaimaa; Howl, John (Springer-Verlag, 2018-02-19)
      Collectively, cell penetrating peptide (CPP) vectors and intrinsically active bioportides possess tremendous potential for drug delivery applications and the discrete modulation of intracellular targets including the sites of protein–protein interactions (PPIs). Such sequences are usually relatively short (< 25 AA), polycationic in nature and able to access the various intracellular compartments of eukaryotic cells without detrimental influences upon cellular biology. The high-throughput platform for bioportide discovery described herein exploits the discovery that many human proteins are an abundant source of potential CPP sequences which are reliably predicted using QSAR algorithms or other methods. Subsequently, microwave-enhanced solid phase peptides synthesis provides a high-throughput source of novel proteomimetic CPPs for screening purposes. By focussing upon cationic helical domains, often located within the molecular interfaces that facilitate PPIs, bioportides which act by a dominant-negative mechanism at such sites can be reliably identified within small number libraries of CPPs. Protocols that employ fluorescent peptides, routinely prepared by N-terminal acylation with carboxytetramethylrhodamine, further enable both the quantification of cellular uptake kinetics and the identification of specific site(s) of intracellular accretion. Chemical modifications of linear peptides, including strategies to promote and stabilise helicity, are compatible with the synthesis of second-generation bioportides with improved drug-like properties to further exploit the inherent selectivity of biologics.
    • A machine-learning approach to negation and speculation detection for sentiment analysis

      Cruz, Noa P.; Taboada, Maite; Mitkov, Ruslan; Department of Information Technology; University of Huelva; Huelva Spain; Department of Linguistics; Simon Fraser University; Vancouver Canada; Research Institute for Information and Language Processing; University of Wolverhampton; Wolverhampton UK (2015-05-13)
      Recognizing negative and speculative information is highly relevant for sentiment analysis. This paper presents a machine-learning approach to automatically detect this kind of information in the review domain. The resulting system works in two steps: in the first pass, negation/speculation cues are identified, and in the second phase the full scope of these cues is determined. The system is trained and evaluated on the Simon Fraser University Review corpus, which is extensively used in opinion mining. The results show how the proposed method outstrips the baseline by as much as roughly 20% in the negation cue detection and around 13% in the scope recognition, both in terms of F1. In speculation, the performance obtained in the cue prediction phase is close to that obtained by a human rater carrying out the same task. In the scope detection, the results are also promising and represent a substantial improvement on the baseline (up by roughly 10%). A detailed error analysis is also provided. The extrinsic evaluation shows that the correct identification of cues and scopes is vital for the task of sentiment analysis.