Commercial leases in the UK regions: business as usual?

PurposeThe purpose of this paper is to analyse the changing nature of commercial leases with specific reference to the landlord and tenant relationship, lease lengths and incentivisation in the post-recessionary UK property market.Design/methodology/approachThe research applies data analysis utilising the Estates Gazette Interactive database coupled with survey analysis conducted across three UK cities to investigate and compare the changing nature of the commercial property leasing market and the landlord and tenant relationship.FindingsThe empirical analysis highlights that recessionary conditions prevalent in the market from the 2007 global crisis has caused a reassessment of lease structures, leading to shorter lease terms and increased use of incentives, as tenants have been empowered to negotiate more flexible leases due to their stronger market position.Originality/valueThis paper builds upon previous research conducted back in 2005, investigating commercial leases in the market up-cycle. The recent volatility in the commercial property sector requires fresh insights and in-depth analysis of lease patterns, length and covenant strength, which is fundamental for investor decision-making. In addition, past research has tended to consider solely landlord or occupier perspectives, whereas this research offers new insight into the landlord–tenant lease negotiation process.</jats:sec

Establishing normative performance values of modified Star Excursion Balance Test (mSEBT) and Limb Symmetry Index (LSI) scores and their relationship to age in female adolescent footballers

Objectives: to establish normative performance values for the modified Star Excursion Balance Test and derived Limb Symmetry Index scores in non-injured female adolescent footballers, and identity if there is a relationship between the aforementioned metrics and ageDesign: single measure study design Setting: A single football club’s female regional talent and development teams Participants: Thirty-four uninjured female footballers, aged between 13 to 18 years.Main Outcome Measures: Modified Star Excursion Balance Test and derived Limb Symmetry Index scores.Results: There were no statistically significant differences between dominant and non-dominant leg distance scores in any of the modified Star Excursion Balance Test specific reach direction or composite scores. Across all age groups, mean dominant leg total distance scores ranged from 231.5 cm to 250.4 cm whilst non-dominant total distance scores ranged from 234.3 cm to 253.3 cm. Mean Limb Symmetry Index values ranged from 97.8% to 100.5%. Age accounted for approximately 8% of the variance within dominant, non-dominant total distance and Limb Symmetry Index scores.Conclusions: Our study has established normative performance values for the mSEBT and derived LSI scores in non-injured female adolescent footballers. Age had a very limited ability in accounting for the variance observed for composite scores in dominant, non-dominant and LSI based scores.</p

Biomimetic microfluidics

Through developments in 3D fabrication technologies in recent years, we can now build and characterize much more sophisticated 3D platforms than was previously possible. We can create regions of differing polarity and hydrophobicity, mix passive and binding behaviours, and regions of differing flexibility/rigidity, hardness/softness. In addition, we can integrate materials that can switch between these characteristics, enabling the creation of biomimetic microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and detection. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required for many applications, and what we can currently deliver [1]. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts represents a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realise biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-awareness/self-diagnosis of condition and self-repair capabilities to extend their useful lifetime [2]. In this contribution, I will present ideas and demonstrations of practical ways to begin building a biomimetic function toolbox that could form the basis of futuristic microfluidic systems. Examples will include chemotactic microvehicles that can collaborate to perform sophisticated functions at specific locations [3] and precision control of flow behaviour in channels using light [4]. Strategies for creating high resolution (sub-200 nm) 3D soft-polymer responsive structures will be discussed. References [1] F. Benito-Lopez, R. Byrne, A.M. Răduţă, N.E. Vrana, G. McGuinness, D. Diamond, Ionogel-based light-actuated valves for controlling liquid flow in micro-fluidic manifolds, Lab Chip. 10 (2010) 195–201. doi:10.1039/B914709H. [2] L. Florea, K. Wagner, P. Wagner, G.G. Wallace, F. Benito-Lopez, D.L. Officer, D. Diamond, Photo-Chemopropulsion - Light-Stimulated Movement of Microdroplets, Advanced Materials. 26 (2014) 7339–7345. doi:10.1002/adma.201403007. [3] W. Francis, C. Fay, L. Florea, D. Diamond, Self-propelled chemotactic ionic liquid droplets, Chem. Commun. 51 (2015) 2342–2344. doi:10.1039/C4CC09214G. [4] C. Delaney, P. McCluskey, S. Coleman, J. Whyte, N. Kent, D. Diamond, Precision control of flow rate in microfluidic channels using photoresponsive soft polymer actuators, Lab Chip. 17 (2017) 2013–2021. doi:10.1039/C7LC00368D

Bio-inspired systems: an exciting Vision for future autonomous biochemical sensing platforms

Through developments in 3D fabrication technologies in recent years, it is now possible to build and characterize much more sophisticated 3D platforms than was formerly the case. Regions of differing polarity, binding behaviour, flexibility/rigidity, can be incorporated into these fluidic systems. Furthermore, materials that can switch these characteristics can be incorporated, enabling the creation of microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and selective uptake and release of molecular targets. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required and what science can currently deliver for many challenging applications. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts appears to represent a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realising biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-awareness of condition and self-repair capabilities to extend their useful lifetime. In this lecture, I will present ideas and demonstrations of practical ways to begin building a bio-inspired functional toolbox that could form the basis of these futuristic biomimetic systems

Biomimetic microfluidics based on stimuli-responsive soft polymers

Through developments in 3D fabrication technologies in recent years, it is now possible to build and characterize much more sophisticated 3D platforms than was formerly the case. Regions of differing polarity, binding behaviour, flexibility/rigidity, can be incorporated into these fluidic systems. Furthermore, materials that can switch these characteristics can be incorporated, enabling the creation of microfluidic building blocks that exhibit switchable characteristics such as programmed microvehicle movement (chemotaxis), switchable binding and release, switchable soft polymer actuation (e.g. valving), and selective uptake and release of molecular targets. These building blocks can be in turn integrated into microfluidic systems with hitherto unsurpassed functionalities that can contribute to bridging the gap between what is required and what science can currently deliver for many challenging applications. The emerging transition from existing engineering-inspired 2D to bioinspired 3D fluidic concepts appears to represent a major turning point in the evolution of microfluidics. Implementation of these disruptive concepts may open the way to realising biochemical sensing systems with performance characteristics far beyond those of current devices. A key development will be the integration of biomimetic functions like self-awareness of condition and self-repair capabilities to extend their useful lifetime. In this contribution I will present ideas and demonstrations of practical ways to begin building a biomimetic function toolbox that could form the basis of these futuristic biomimetic systems

Natural HLA Class I Polymorphism Controls the Pathway of Antigen Presentation and Susceptibility to Viral Evasion

HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion

TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexnucleotide repeat expansion

Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA binding protein of 43kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n=14), with the major allele correlated with later age at death (p=0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n=75), again finding that the major allele associates with later age at death (p=0.016), as well as later age at onset (p=0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease

TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions

Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease