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In the past, a lot of research has focused on using spirals and rings to confine concrete. Yet, the effect of using spirals to confine square cross sections is not well investigated. It would appea...

Timber–concrete composites (TCCs) take advantage of the properties of timber and concrete simultaneously. TCC slabs consist of timber beams or a timber deck, which resist tensile and bending stresses, connected through different types of shear connectors to an upper concrete slab, which withstands compressive stresses. The stiffness and strength of the slab are mostly defined by the properties of the connectors. To avoid the use of external materials that could be environmentally harmful, micro-notch connections were tested. These micro-notch connections are notches cut into timber elements and filled with wet concrete. The research focused on the influence of the gap between the micro-notches, the experimental configuration, the concrete composition and the concrete curing process on the shear strength of the connectors. The concrete compositions included ground granulated blast-furnace slag (GGBS) and superabsorbent polymer (SAP). These additives were used to evaluate their compliance with the shear strength of the TCC connections. GGBS was used to reduce the cement content in the concrete mix and SAP was used as a water-entraining agent to reduce the autogenous shrinkage of the concrete.

Antimicrobial peptides emerge as compounds that can alleviate the global health hazard of antimicrobial resistance, prompting a need for novel computational approaches to peptide generation. Here, we propose HydrAMP, a conditional variational autoencoder that learns lower-dimensional, continuous representation of peptides and captures their antimicrobial properties. The model disentangles the learnt representation of a peptide from its antimicrobial conditions and leverages parameter-controlled creativity. HydrAMP is the first model that is directly optimized for diverse tasks, including unconstrained and analogue generation and outperforms other approaches in these tasks. An additional preselection procedure based on ranking of generated peptides and molecular dynamics simulations increases experimental validation rate. Wet-lab experiments on five bacterial strains confirm high activity of nine peptides generated as analogues of clinically relevant prototypes, as well as six analogues of an inactive peptide. HydrAMP enables generation of diverse and potent peptides, making a step towards resolving the antimicrobial resistance crisis.

Ultrashort cationic lipopeptides (USCLs) and gemini cationic surfactants are classes of potent antimicrobials. Our recent study has shown that the branching and shortening of the fatty acids chains with the simultaneous addition of a hydrophobic N-terminal amino acid in USCLs result in compounds with enhanced selectivity. Here, this approach was introduced into arginine-rich gemini cationic surfactants. L-cystine diamide and L-lysine amide linkers were used as spacers. Antimicrobial activity against planktonic and biofilm cultures of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) strains and Candida sp. as well as hemolytic and cytotoxic activities were examined. Moreover, antimicrobial activity in the presence of human serum and the ability to form micelles were evaluated. Membrane permeabilization study, serum stability assay, and molecular dynamics were performed. Generally, critical aggregation concentration was linearly correlated with hydrophobicity. Gemini surfactants were more active than the parent USCLs, and they turned out to be selective antimicrobial agents with relatively low hemolytic and cytotoxic activities. Geminis with the L-cystine diamide spacer seem to be less cytotoxic than their L-lysine amide counterparts, but they exhibited lower antibiofilm and antimicrobial activities in serum. In some cases, geminis with branched fatty acid chains and N-terminal hydrophobic amino acid resides exhibited enhanced selectivity to pathogens over human cells.

Peptides and proteins constitute a large group of molecules that play multiple functions in living organisms. In conjunction with their important role in biological processes and advances in chemical approaches of synthesis, the interest in peptide-based drugs is still growing. As the side chains of amino acids can be basic, acidic, or neutral, the peptide drugs often occur in the form of salts with different counter-ions. This review focuses on the role of counter-ions in peptides. To date, over 60 peptide-based drugs have been approved by the FDA. Based on their area of application, biological activity, and results of preliminary tests they are characterized by different counter-ions. Moreover, the impact of counter-ions on structure, physicochemical properties, and drug formulation is analyzed. Additionally, the application of salts as mobile phase additives in chromatographic analyses and analytical techniques is highlighted.

The concept of transfer of genetic information as a practical clinical tool arose from the gene cloning technology developed during the 1970s. The existence of an excellent animal model — the Watanabe heritable hyperlipidaemic rabbit — permitted a series of preclinical experiments to verify the principles of gene therapy in familial hypercholesterolaemia. The main problem facing the gene therapist is how to get new genes into every tumour cell. The insertion of a foreign marker gene into cells from a tumour biopsy and the replacement of the marked cells into the patient prior to treatment can provide a sensitive new indicator of minimal residual disease after chemotherapy. Tumour necrosis factor genes have been inserted into tumour-infiltrating lymphocytes from patients with melanoma, and given systemically. The downregulation of abnormal oncogene expression has been shown to revert the malignant phenotype in a variety of tumour lines in vitro.

Objectivesthe aim of this study was to test Rutherford Health (RH) staff for the presence of SARS CoV-2 antibodies to reduce the risk of infection to cancer patients.SettingBetween 14 and 24 April 2020 we tested 161 staff at four locations: our cancer centres in Reading - Berkshire, Newport - S Wales, Liverpool - Merseyside, and Bedlington in Northumberland.ParticipantsTesting was available to all staff who were on site at the four locations named above at the time the study was carried out. 161 staff (80 men, 81 women) gave voluntary consent to have the tests and all testing gave rise to valid results.InterventionsWe used the South Korean test for antibodies to SARS CoV-2: Sugentech SGTi-flex COVID-19 IgM/IgG1. For each test, blood was collected and added to the sample well of the test cassette and buffer solution added. The test result was legible after 15 minutes. Outcome measures: The number of tests positive for the presence of antibodies was the primary outcome measure. The ratio of tests positive for the presence of IgM antibodies versus IgG antibodies was the secondary outcome measure.ResultsBetween 14 and 24 April 2020, 161 staff (age m = 43) were tested at four Rutherford Cancer Care centres that offer proton beam therapy, radiotherapy and chemotherapy. Out of 161, 12 samples (7.50%) tested positive of which 7 samples (4.35%) detected IgM only, 2 samples (1.24%) detected IgG only and 3 samples (1.86%) detected both IgM and IgG.ConclusionsThe low seroconversion rate in the sample population limits the current utility of the test as a way of reducing risk to vulnerable patient populations but longitudinal retesting will provide further data.Strengths and limitations of the studyThis is the first UK study on SARS CoV-2 antibody testing using the Sugentech SGTi-flex COVID-19 IgM/IgG in the workplace;This is the first UK study testing a population of cancer centre staff for SARS CoV-2 antibodies;This study builds on similar studies in other countries3-4, albeit with a smaller sample;Data on previous clinical symptoms is not included. We are in the process of revising consent paperwork for the test to include a question about previous symptoms like temperature, dry/persistent cough;Patient data is not included. We will consider testing patients once the pilot test with staff has reached conclusions about the efficacy and value of the test.

Despite ordinary Portland cement concrete presenting low performance in tension and a negative impact on the natural environment, it is the most used construction material. Researchers have noted that the usage of fibres as reinforcement and recycled aggregates, instead of natural ones, may minimize these issues. The concept of functionally graded material for new composite materials is proposed to address these problems. In this paper, five different concrete mixes were produced to analyse the potential of using functionally graded concretes (FGC) for sustainable structures. Their mechanical performance, a sustainable quality control method for these materials and their costs and embodied CO 2 were analyzed. The results show that FGC, even though showing a post-cracking flexural performance lower than conventional FRC, possesses high potential in terms of structural design based on Model Code 2010 specifications. The equations provided to use the Barcelona test to control the material, which is more environmentally friendly than the standardized beam test, may facilitate the introduction of FGC in the construction market. Finally, considering costs and embodied CO 2 , FGC presents a good prospect to be used as structural material for future sustainable concrete elements.

In view of an appreciable increase in resistance of Staphylococcus aureus to the conventional antibiotics, it is desired to develop new effective drugs. Antimicrobial peptides (AMPs) seem to be attractive candidates. In general, AMPs samples used for in vitro studies consist of a peptide, counter-ion, and water. The presence of the counter-ion could be significant as it affects peptide secondary structure and biological activity. The purpose of this study was to estimate the impact of counter-ion on antistaphylococcal activity of selected AMPs (CAMEL, citropin 1.1, LL-37, pexiganan, temporin A). To do this, three kinds of salts were prepared, namely, acetates, hydrochlorides, and trifluoroacetates. In addition, the hemolytic activity against human red blood cells (hRBCs) and cytotoxicity (HaCaT) were determined. The results indicate that there is a substantial difference between different salts, but the pattern is not consistent for the peptides. In general, the antistaphylococcal activity decreased in the order: CAMEL > temporin A > pexiganan > citropin 1.1 ≫ LL-37. The highest selectivity indexes were determined for CAMEL hydrochloride, pexiganan acetate, and temporin A trifluoroacetate. This study shows how important is to take into account the kind of counter-ions when designing novel peptide-based antimicrobials.

Glued-in rods offer an alternative method for creating structural timber connections however despite decades of research they have had limited implementation. The behaviour of glued-in rod connections in a framed structure was investigated. Nine partial frames were constructed of box sections connected with 12 mm diameter BFRP rods. A theoretical design approach was developed based on the optimum observed behaviour, where failure was located in the connection. For specimens with two embedded rods the theory predicted strength within 16% error of the experimental results. For specimens with two rods but gave an over-prediction of strength where three rods were used.

Increasing drug resistance of common pathogens urgently needs discovery of new effective molecules. Antimicrobial peptides are believed to be one of the possible solutions of this problem. One of the approaches for improvement of biological properties is reversion of the sequence (retro analog concept). This research is based on investigation of antimicrobial activity against Gram-positive, Gram-negative bacteria, and fungi, hemolysis of erythrocytes, interpretation of the circular dichroism spectra, measurement of counter-ion content, and assessment of the peptide hydrophobicity and self-assembly using reversed-phase chromatography. The experiments were conducted using the following peptides: aurein 1.2, CAMEL, citropin 1.1, omiganan, pexiganan, temporin A, and their retro analogs. Among the compounds studied, only retro omiganan showed an enhanced antimicrobial and a slightly increased hemolytic activity as compared to parent molecule. Moreover, retro pexiganan exhibited high activity towards Klebsiella pneumoniae, whereas pexiganan was in general more or equally active against the rest of tested microorganisms. Furthermore, the determined activity was closely related to the peptide hydrophobicity. In general, the reduced hemolytic activity correlates with lower antimicrobial activity. The tendency to self-association and helicity fraction in SDS seems to be correlated. The normalized RP-HPLC—temperature profiles of citropin 1.1 and aurein 1.2, revealed an enhanced tendency to self-association than that of their retro analogs.

The use of Fibre Reinforced Polymer (FRP) reinforcement has been shown to improve the short-term flexural behaviour of timber elements. This is particularly important when reinforced elements are subjected to a variable climate condition, which is known to accelerate long-term or creep behaviour. In this paper, both unreinforced and Basalt FRP reinforced beams are subjected to creep tests at a common maximum compressive stress of 8 MPa over a 75-week period. Results demonstrated a significant reduction in total creep deflection due to the FRP reinforcement. Using matched groups, experimentally measured total strain behaviour is decomposed into the elastic, viscoelastic, mechano-sorptive and swelling/shrinkage strain components. Analysis has shown that the mechano-sorptive component is similar in unreinforced and reinforced beams. The reduction in creep behaviour of the reinforced members was primarily due to the restrained swelling/shrinkage response of the reinforced beams and was independent of the mechano-sorptive effect. This finding demonstrates the positive influence of FRP reinforcement on the long-term behaviour of timber elements and indicates a potential to describe the long-term deflection performance of FRP reinforced elements from short-term swelling/shrinkage tests. This work has been carried out as part of the project ‘Innovation in Irish timber Usage’ (Project Ref. 11/C/207) funded by the Department of Agriculture, Food and the Marine of the Republic of Ireland under the FIRM/RSF/COFORD scheme. The authors would also like to thank ECC Ltd. (Earrai Coillte Chonnacht Teoranta) for supplying all the timber used in this project. The contribution of the technical staff of the College of Engineering and Informatics, NUIG, in particular, Peter Fahy, Colm Walsh and Gerard Hynes, is gratefully acknowledged. peer-reviewed 2021-09-25

Tests were conducted of the bonding shear strength of different bamboo configurations in terms of grain direction, adhesive, and clamping pressure. The bonding shear tests were carried out ...

Aimed at maximizing project value while reducing waste and cost, the lean construction (LC) approach was formally and successfully introduced to the architecture, engineering and construction (AEC) industry in 1993. Although LC has rapidly developed since that time, it was not applied to a Chinese construction project until 2005. However, due to insufficient knowledge and poor execution, this first attempt at lean construction in China was inadequate. The aim of this study was therefore to discover if the Chinese construction industry has since discovered how to use lean practices to maximize project value, shorten the project schedule, improve project quality, and reduce waste. This was achieved by conducting a case study of a LC project in Suzhou, China. The case study revealed that implementation of lean practices during the project, including Last Planner System (LPS), Kanban system, Just-In-Time (JIT), prefabrication, Internet of Things (IoT), quality and safety management, and continuous improvement, all contributed to the improvement of project performance. To supplement the case study and to provide insights on the differences between Chinese and international LC, interviews with project stakeholders and a questionnaire survey of global lean experts were conducted. Results indicated that interviewees and survey respondents both held the view that project waiting times and defects can be greatly reduced through the implementation of LC, and that improvement of construction workflow along with project productivity and quality were the two most valuable benefits of using lean practices; there was also a consensus that lack of trust and the abilities of stakeholders are the biggest challenges.

A fully coupled moisture-displacement finite element model has been developed to predict the viscoelastic, mechano-sorptive and swelling/shrinkage behaviour of FRP reinforced timber elements when stressed under long-term load and simultaneously subjected to changes in relative humidity. A DFLUX subroutine, to describe the changes in relative humidity with time, and a UMAT subroutine, implemented to describe the viscoelastic, mechano-sorptive and swelling/shrinkage behaviour, are presented. Additionally, an irrecoverable mechano-sorptive component is presented. This additional irrecoverable component occurs when the timber moisture content increases to a moisture content above levels previously attained. The model is found to be in agreement with experimentally determined deflection and strain results on both unreinforced and FRP reinforced beams subjected to constant and variable climates. This work has been carried out as part of the project entitled ‘Innovation in Irish timber Usage’ (project ref. 11/C/207) funded by the Department of Agriculture, Food and the Marine of the Republic of Ireland under the FIRM/RSF/COFORD scheme. The authors would also like to thank ECC Ltd. (Earrai Coillte Chonnacht Teoranta) for supplying all the timber used in this project. The contribution of the technical staff of the College of Engineering and Informatics, NUIG, in particular, Peter Fahy, Colm Walsh and Gerard Hynes, is acknowledged. peer-reviewed 2022-06-20

The use of fast-grown timber in the manufacture of engineered wood products is increasing; however, the fast growth rate results in a low-density timber that is susceptible to significant swelling and shrinkage deformations under changing moisture content. The current study focuses on the characterisation of the moisture diffusion and swelling/shrinkage of fast-grown Sitka spruce and the prediction of the moisture-induced strain development in Sitka spruce glulam beams under variable humidity cycles. Moisture content evolution and swelling/shrinkage coefficients were measured and the longitudinal swelling/shrinkage was found to be significantly greater than for slow-grown timber. Sitka spruce glued-laminated beams were subjected to controlled relative humidity cycling for 52 weeks and the moisture distribution and moisture-induced strains were measured continuously. Coupled moisturedisplacement numerical models, incorporating the experimentally measured material parameters were developed. The effect of the glue-line was found to have an insignificant effect on moisture transport, however, the material orientation greatly influenced the predicted moisture-induced strain. Accurately mapping the material orientation produced significantly better predictions of the experimental results over the 52-week period. Keywords: Adsorption, This work has been carried out as part of the project entitled ‘Innovation in Irish timber Usage’ (project ref. 11/C/207) funded by the Department of Agriculture, Food and the Marine of the Republic of Ireland under the FIRM/RSF/COFORD scheme. The authors would also like to thank ECC Ltd. (Earrai Coillte Chonnacht Teoranta) for supplying all the timber used in this project. The contribution of the technical staff of the College of Engineering and Informatics, NUIG, in particular, Peter Fahy, Colm Walsh and Gerrard Hynes, is acknowledged peer-reviewed

An unexpected side-reaction took place during the synthesis of quaternary ammonium salts with O-triflyl derivatives of 1,4:3,6-dianhydrohexitols and tertiary alkylamines. The products were identified as tertiary amine derivatives of 1,4:3,6-dianhydrohexitol and tetraalkylammonium triflate. It was found that formation of the products was the consequence of the methyl group migration from QAS formed to the amine present in excess in the reaction mixture. Such reaction is a case of transquaternization, in which the exchange of the methyl group between two amines occurs.

An investigation was carried out to examine the effect of flexural reinforcement on the long-term behaviour of timber beams. Creep tests, utilising statistically matched groups, were performed under Service Class 1 conditions on reinforced and unreinforced beams loaded to a common maximum compressive stress of 8 MPa. As flexural reinforcement resulted in a reduction in the timber tensile stresses, the viscoelastic tensile strains in the reinforced members were found to be significantly lower than in the unreinforced beams. It was found that the viscoelastic relative creep deflection was governed by the stress level in the timber and the reinforcement had an insignificant effect. It is concluded that current creep modification factors in Eurocode 5 may be suitable for the design of reinforced timber elements under Service Class 1 conditions. (C) 2018 Elsevier Ltd. All rights reserved. This work has been carried out as part of the project entitled ‘Innovation in Irish Timber Usage’ (project ref. 11/C/207) funded by the Department of Agriculture, Food and the Marine of the Republic of Ireland under the FIRM/RSF/COFORD scheme. The authors would also like to thank ECC Teo. (Earrai Coillte Chonnacht Teoranta) for supplying the timber used in this project. The contribution of the technical staff of the College of Engineering and Informatics, NUIG, in particular, Peter Fahy, Colm Walsh and Gerard Hynes, is acknowledged. peer-reviewed 2020-08-01

Karol Sikora is the Scientific Director of Medical Solutions Plc and Special Advisor to HCA International in the creation of the London Cancer Group – the largest UK cancer network outside the NHS in HCA’s six major London private hospitals. This includes the construction of a major new international cancer center for care, teaching and research in London at the Harley St clinic. He is Professor of Cancer Medicine and honorary Consultant Oncologist at Imperial College School of Medicine, Hammersmith Hospital, London.

Globally, biosimilars are expected to have a key role in improving patient access to biological therapies and addressing concerns regarding the escalating cost of health care. Indeed, in Europe, increased use of biologics and reduced drug prices have been observed after the introduction of biosimilars. Recently, several monoclonal antibody biosimilars of anticancer therapies have been approved, and numerous others are in various stages of clinical development. Biosimilars are authorized via a regulatory pathway separate from that used for generic drugs; they are also regulated separately from novel biologics. Biosimilar approval pathways in many major regulatory regions worldwide are, to a broad degree, scientifically aligned. However, owing to regional differences in health care priorities, policies, and resources, some important regulatory inconsistencies are evident. Acceptance of biosimilars by health care systems, health care professionals, and patients will be a key factor in the uptake of these therapies, and such regulatory variations could contribute to confusion and diminished confidence regarding the quality, efficacy, and reliability of these agents. Furthermore, the need for manufacturers to account for regulatory inconsistencies introduces inefficiencies and delays into biosimilar development programs. These issues should be addressed if biosimilars are to attain their maximal global potential. This review summarizes the evolution of the global biosimilar landscape and provides examples of inconsistencies between regulatory requirements in different regions. In addition, we review ongoing efforts to improve regulatory alignment and highlight the importance of education as a crucial factor in generating trust in, and acceptance of, biosimilars on a worldwide scale. Implications for Practice Biosimilars of monoclonal antibody anticancer therapies are beginning to emerge, and more are likely to become available for clinical use in the near future. The extent to which biosimilars can contribute to cancer care will depend on their level of acceptance by health care systems, health care professionals, and patients. A better understanding of the regulatory basis for the approval of biosimilars may enhance confidence and trust in these agents. In order to have informed discussions about treatment choices with their patients, oncologists should familiarize themselves with the biosimilar paradigm.

New, efficient, straightforward method of synthesizing quaternary diammonium salts of 1,4:3,6-dianhydro- l -iditol have been developed. This paper presents the synthesis and structural analysis of diammonium (gemini) salts, including their X-ray diffraction analysis, wherein the linking structure of nitrogen atoms consists of two fused furanoid rings. 1,4:3,6-dianhydro-2,5-di- O -triflyl- d -mannitol and four tertiary amines, i.e., 4-( N , N- dimethylamino)pyridine (DMAP), pyridine, trimethylamine and N , N- dimethyloctylamine, were used for the synthesis. All the syntheses were carried out under mild conditions by the direct nucleophilic displacement of the O -triflil group by the amine. Walden inversion of configuration at C2 and C5 atoms has occurred during the reaction, giving products with l - ido configuration. Furthermore, NMR and X-ray conformational analysis of 1,4:3,6-dianhydrohexitol residue was done. In most cases furanoid rings adopt the twisted conformation both in the crystal and in solution.

In view of the increasing interest in peptides in various market sectors, a stronger emphasis on topics related to their production has been seen. Fmoc-based solid phase peptide synthesis, although being fast and efficient, provides final products with significant amounts of trifluoroacetate ions in the form of either a counter-ion or an unbound impurity. Because of the proven toxicity towards cells and peptide activity inhibition, ion exchange to more biocompatible one is purposeful. Additionally, as most of the currently used counter-ion exchange techniques are time-consuming and burdened by peptide yield reduction risk, development of a new approach is still a sensible solution. In this study, we examined the potential of peptide counter-ion exchange using non-aqueous organic solvents saturated with HCl. Counter-ion exchange of a model peptide, citropin 1.1 (GLFDVIKKVASVIGGL-NH2), for each solvent was conducted through incubation with subsequent evaporation under reduced pressure, dissolution in water and lyophilization. Each exchange was performed four times and compared to a reference method—lyophilization of the peptide from an 0.1 M HCl solution. The results showed superior counter-ion exchange efficiency for most of the organic solutions in relation to the reference method. Moreover, HCl-saturated acetonitrile and tert-butanol provided a satisfying exchange level after just one repetition. Thus, those two organic solvents can be potentially introduced into routine peptide counter-ion exchange.

The paper is focused on identifi cation of micro-structural and mechanical alterations in porous matrices of Portland fl y ash cement mortar, during frost deterioration. An attempt is made to assess the effi ciency of superabsorbent polymer (SAP) ‘protection’ based on analysis of three SAP types with different water absorption/desorption capacities. Two different exposure regimes have been adopted in the study; the exposure to freeze/thaw cycles and the exposure to freeze/thaw with de-icing solution. In order to evaluate the effect of SAPs on the micro-structural features of deteriorating mortars comprehensive MIP and SEM analyses were performed. It has been found that SAPs with high water absorption capacities may prevent fl exural strength reduction caused by frost action. The limitation in micro-cracks propagation by SAP additions can be attributed to the higher tensile strength of ‘SAP pores’ walls, resulting from densifi cation of CSH gel. This is consistent with the fi nding of higher ‘breaking pressure’ for ‘SAP pores’. Nevertheless, it was shown that the additional exposure to salt ions reduces the initial resistance to less than one month. Desorption characteristics of SAPs may play a particularly important role in the case of very early exposure to F/T cycles. Too slow release of water does not suffi ciently facilitate densifi cation of structure prior frost action. Neither can it create a suitable network of air pockets for the expansion of ice and freezing water as in air-entrainers. This is particularly relevant to fl y ash cementitious composites due to delayed pozzolanic reaction.

The formation of pyridinium salts in the transformation of three O-isopropylidene-protected mesylates of furanoid sugar derivatives under pyridine action is considered at the B3LYP/6-31+G** computation level. All the structures were optimized in the gas phase, in chloroform and water. Activation barrier heights in the gas phase were also estimated at the B3LYP/6-311++G**, MPW1K/6-31+G** and MPW1K/6-311++G** levels. The conducted calculations, both in the gas phase (regardless of the computation level) and in solvents, revealed the barrier height increasing order as follows: 1 > 2 > 3 for the three reactions studied. The conformational behavior of the five-membered ring is discussed in the gas phase and in solvents. The fused dioxolane ring makes the furanoid ring less likely to undergo conformational changes. In the case of reaction 3, the furanoid ring shape does not change either in the gas phase or in solvents. All conformers are close to E0 or 0E.