Establishing design characteristics for the development of stab resistant Laser Sintered body armour

Stab resistant body armour had been used throughout history, with examples ranging from animal hide construction to the moulded Polycarbonate units typically used by United Kingdom (UK) Police Officers. Such protective articles have historically, and continue to present a number of issues which have shown to impair the operational performance of its wearer including but not exclusive to poor thermal regulation, large masses, and reduced manoeuvrability. A number of developments have been made in an attempt to minimise the effects of such issues. One potential solution yet to be fully explored is the utilisation of Additive Manufacturing (AM) technologies. In recent years the use of such manufacturing technologies, particularly Laser Sintering, has successfully demonstrated their suitability for a range of high performance applications ranging from Formula 1® to aerospace. Due to the fundamental additive nature of AM build processes, the utilisation of such technologies have facilitated the realisation of design concepts that are typically too expensive, difficult or impossible to create using traditional manufacturing processes. In order for AM technologies to be used for the generation of stab resistant body armour a number of historical issues and performance characteristics fundamental to ensure stab resistance is achieved must be satisfied. This body of research firstly evaluated the stab resistive performance of two of the most common materials suitable for Laser Sintering as highlighted by an initial review of AM technologies. Once an appropriate material had been highlighted it was used as the basis for further experimental testing. Such tests focussed on minimising the material thickness required to maintain an appropriate level of stab resistance within United Kingdom Home Office Scientific Development Branch (HOSDB) KR1-E1 requirement of 24 Joules of stab impact energy. Test results demonstrated that specimens manufactured from Duraform EX® required a minimum single layer thickness of 11.00 mm, and a dual layer total thickness of 9.00 mm to provide an appropriate level of stab protection within the HOSDB KR1-E1 standard. Coupled with the results generated from an investigation identifying the overlapping/imbricated assembly angle required to maintain an appropriate level of coverage across a scale structure, the stab resistant characteristics initially identified were used for the development of an imbricated scale-like assembly. Additional design features were also investigated to further minimise the total thickness of the final element design and corresponding assembled imbricated structure such features included angling strike surfaces and integrating a dual layered structure within individual elements. When the finalised imbricated assemblies were stab tested, they successfully demonstrated levels of stab resistance to the UK HOSDB KR1-E1 impact energy of 24 Joules

Computational Studies of Natural and Nonnatural Nucleic Acids: Formation and Repair of Thymine Dimers and Structure/Dynamics of GNA

Exposure of DNA to UV-light (260-320 nm) leads to the formation of two major photolesions between adjacent pyrimidine nucleobases, the cyclobutane pyrimidine dimer (CPD) and the (6-4) photoproduct (6-4PP). Both originate from an ultrafast [2 + 2] cycloaddition and the process leads to the covalent linking between the two bases. This damage produces stalling of DNA replication and transcription and causes errors in the genome leading to phenotypic display of skin cancer. Many species contain enzymes capable of repairing these photolesions, however, humans do not and must rely on nucleotide excision repair to replace the bases. DNA photolyase is an enzyme capable of binding to and repairing CPD photolesions. A redox active flavin cofactor (FADH-) found near the active site is capable of donating an electron into the CPD breaking orbital symmetry and leading to a breaking of the cyclobutane ring covalently linking the two bases. This repair mechanism is light dependant and highly efficient. As humans do not possess this enzyme, there is much interest in developing small molecules which can mimic DNA photolyase. Our group has developed an artificial photolyase which is capable to binding to CPDs in water effecting repair. The work here builds upon previous studies by testing this artificial photolyase on duplex DNA. (6-4) photolyase is an enzyme capable of repairing the 6-4PP. In contrast to the mechanism of CPD repair, little is known about mechanism employed by (6-4) photolyase. Much debate exists in the literature on what this mechanism is, however, each proposed mechanism is lacking in experimental evidence and support. In this work we use high level electronic structure methods to study the energetic landscape of the proposed mechanisms both in solution and in the (6-4) photolyase active site. By using these methods we conclude that none of the currently proposed mechanisms are energetically feasible and a new, two proton repair mechanism is proposed for the repair of 6-4PP. Much work has been done by scientists in modifying the nucleic backbone of nucleic acids. However, only a few unnatural nucleic acids are known to form stable duplexes. The newly discovered glycol nucleic acid (GNA) is perhaps the simplest backbone scheme capable of duplex formation. It consists of a phosphodiester backbone connected by repeating propylene glycol subunits and is completely acyclic. GNA forms duplexes far exceeding the thermal stabilities of DNA with melting temperatures Ì¢'¡è 20ÌÜÁC greater. Thermodynamic analysis shows that GNA duplex formation is entropically less penalizing than the same process in DNA and RNA. This is a counterintuitive notion considering the acyclic nature of the GNA backbone. This study uses molecular dynamics (MD) simulations to study the structure and dynamics of dsGNA and uncovers a coiling/ uncoiling mode which explains the decreased entropic penalty of annealing in comparison to natural nucleic acids. MD simulations are also used to study the arrangement of porphyrin base pairs incorporated into GNA and support the notion of a slipped cofacial geometry of adjacent porphyrin moieties which has been speculated from the experimental data

Guest Back-Folding: A Molecular Design Strategy That Produces a Deep-Red Fluorescent Host/Guest Pair with Picomolar Affinity in Water

One of the major goals of modern supramolecular chemistry, with important practical relevance in many technical fields, is the development of synthetic host/guest partners with ultrahigh affinity and selectivity in water. Currently, most association pairs exhibit micromolar affinity or weaker, and there are very few host/guest systems with Ka > 109 M–1, apparently due to a barrier imposed by enthalpy/entropy compensation. This present study investigated the threading of a water-soluble tetralactam cyclophane by a deep-red fluorescent squaraine guest with flanking polyethylene glycol chains, an association process that is dominated by a highly favorable enthalpic driving force. A squaraine structure was rationally designed to permit guest back-folding as a strategy to greatly expand the hydrophobic surface area that could be buried upon complexation. Guided by computational modeling, an increasing number of N-benzyl groups were appended to the squaraine core, so that, after threading, the aromatic rings could fold back and stack against the cyclophane periphery. The final design iteration exhibited an impressive combination of fluorescence and supramolecular properties, including ratiometric change in deep-red emission, picomolar affinity (Ka = 5.1 × 1010 M–1), and very rapid threading (kon = 7.9 × 107 M–1 s–1) in water at 25 °C. Similar excellent behavior was observed in serum solution. A tangible outcome of this study is a new cyclophane/squaraine association pair that will be a versatile platform for many different types of fluorescence-based imaging and diagnostics applications. From a broader perspective, guest back-folding of aromatic groups is a promising new supramolecular stabilization strategy to overcome enthalpy/entropy compensation and produce ultrahigh affinity [2]­pseudorotaxane complexes in water and biological media

Guest Back-Folding: A Molecular Design Strategy That Produces a Deep-Red Fluorescent Host/Guest Pair with Picomolar Affinity in Water

One of the major goals of modern supramolecular chemistry, with important practical relevance in many technical fields, is the development of synthetic host/guest partners with ultrahigh affinity and selectivity in water. Currently, most association pairs exhibit micromolar affinity or weaker, and there are very few host/guest systems with <i>K</i>_a > 10⁹ M^–1, apparently due to a barrier imposed by enthalpy/entropy compensation. This present study investigated the threading of a water-soluble tetralactam cyclophane by a deep-red fluorescent squaraine guest with flanking polyethylene glycol chains, an association process that is dominated by a highly favorable enthalpic driving force. A squaraine structure was rationally designed to permit guest back-folding as a strategy to greatly expand the hydrophobic surface area that could be buried upon complexation. Guided by computational modeling, an increasing number of <i>N</i>-benzyl groups were appended to the squaraine core, so that, after threading, the aromatic rings could fold back and stack against the cyclophane periphery. The final design iteration exhibited an impressive combination of fluorescence and supramolecular properties, including ratiometric change in deep-red emission, picomolar affinity (<i>K</i>_a = 5.1 × 10¹⁰ M^–1), and very rapid threading (<i>k</i>_on = 7.9 × 10⁷ M^–1 s^–1) in water at 25 °C. Similar excellent behavior was observed in serum solution. A tangible outcome of this study is a new cyclophane/squaraine association pair that will be a versatile platform for many different types of fluorescence-based imaging and diagnostics applications. From a broader perspective, guest back-folding of aromatic groups is a promising new supramolecular stabilization strategy to overcome enthalpy/entropy compensation and produce ultrahigh affinity [2]­pseudorotaxane complexes in water and biological media

Guest Back-Folding: A Molecular Design Strategy That Produces a Deep-Red Fluorescent Host/Guest Pair with Picomolar Affinity in Water

One of the major goals of modern supramolecular chemistry, with important practical relevance in many technical fields, is the development of synthetic host/guest partners with ultrahigh affinity and selectivity in water. Currently, most association pairs exhibit micromolar affinity or weaker, and there are very few host/guest systems with <i>K</i>_a > 10⁹ M^–1, apparently due to a barrier imposed by enthalpy/entropy compensation. This present study investigated the threading of a water-soluble tetralactam cyclophane by a deep-red fluorescent squaraine guest with flanking polyethylene glycol chains, an association process that is dominated by a highly favorable enthalpic driving force. A squaraine structure was rationally designed to permit guest back-folding as a strategy to greatly expand the hydrophobic surface area that could be buried upon complexation. Guided by computational modeling, an increasing number of <i>N</i>-benzyl groups were appended to the squaraine core, so that, after threading, the aromatic rings could fold back and stack against the cyclophane periphery. The final design iteration exhibited an impressive combination of fluorescence and supramolecular properties, including ratiometric change in deep-red emission, picomolar affinity (<i>K</i>_a = 5.1 × 10¹⁰ M^–1), and very rapid threading (<i>k</i>_on = 7.9 × 10⁷ M^–1 s^–1) in water at 25 °C. Similar excellent behavior was observed in serum solution. A tangible outcome of this study is a new cyclophane/squaraine association pair that will be a versatile platform for many different types of fluorescence-based imaging and diagnostics applications. From a broader perspective, guest back-folding of aromatic groups is a promising new supramolecular stabilization strategy to overcome enthalpy/entropy compensation and produce ultrahigh affinity [2]­pseudorotaxane complexes in water and biological media

Guest Back-Folding: A Molecular Design Strategy That Produces a Deep-Red Fluorescent Host/Guest Pair with Picomolar Affinity in Water

One of the major goals of modern supramolecular chemistry, with important practical relevance in many technical fields, is the development of synthetic host/guest partners with ultrahigh affinity and selectivity in water. Currently, most association pairs exhibit micromolar affinity or weaker, and there are very few host/guest systems with <i>K</i>_a > 10⁹ M^–1, apparently due to a barrier imposed by enthalpy/entropy compensation. This present study investigated the threading of a water-soluble tetralactam cyclophane by a deep-red fluorescent squaraine guest with flanking polyethylene glycol chains, an association process that is dominated by a highly favorable enthalpic driving force. A squaraine structure was rationally designed to permit guest back-folding as a strategy to greatly expand the hydrophobic surface area that could be buried upon complexation. Guided by computational modeling, an increasing number of <i>N</i>-benzyl groups were appended to the squaraine core, so that, after threading, the aromatic rings could fold back and stack against the cyclophane periphery. The final design iteration exhibited an impressive combination of fluorescence and supramolecular properties, including ratiometric change in deep-red emission, picomolar affinity (<i>K</i>_a = 5.1 × 10¹⁰ M^–1), and very rapid threading (<i>k</i>_on = 7.9 × 10⁷ M^–1 s^–1) in water at 25 °C. Similar excellent behavior was observed in serum solution. A tangible outcome of this study is a new cyclophane/squaraine association pair that will be a versatile platform for many different types of fluorescence-based imaging and diagnostics applications. From a broader perspective, guest back-folding of aromatic groups is a promising new supramolecular stabilization strategy to overcome enthalpy/entropy compensation and produce ultrahigh affinity [2]­pseudorotaxane complexes in water and biological media

Guest Back-Folding: A Molecular Design Strategy That Produces a Deep-Red Fluorescent Host/Guest Pair with Picomolar Affinity in Water

One of the major goals of modern supramolecular chemistry, with important practical relevance in many technical fields, is the development of synthetic host/guest partners with ultrahigh affinity and selectivity in water. Currently, most association pairs exhibit micromolar affinity or weaker, and there are very few host/guest systems with <i>K</i>_a > 10⁹ M^–1, apparently due to a barrier imposed by enthalpy/entropy compensation. This present study investigated the threading of a water-soluble tetralactam cyclophane by a deep-red fluorescent squaraine guest with flanking polyethylene glycol chains, an association process that is dominated by a highly favorable enthalpic driving force. A squaraine structure was rationally designed to permit guest back-folding as a strategy to greatly expand the hydrophobic surface area that could be buried upon complexation. Guided by computational modeling, an increasing number of <i>N</i>-benzyl groups were appended to the squaraine core, so that, after threading, the aromatic rings could fold back and stack against the cyclophane periphery. The final design iteration exhibited an impressive combination of fluorescence and supramolecular properties, including ratiometric change in deep-red emission, picomolar affinity (<i>K</i>_a = 5.1 × 10¹⁰ M^–1), and very rapid threading (<i>k</i>_on = 7.9 × 10⁷ M^–1 s^–1) in water at 25 °C. Similar excellent behavior was observed in serum solution. A tangible outcome of this study is a new cyclophane/squaraine association pair that will be a versatile platform for many different types of fluorescence-based imaging and diagnostics applications. From a broader perspective, guest back-folding of aromatic groups is a promising new supramolecular stabilization strategy to overcome enthalpy/entropy compensation and produce ultrahigh affinity [2]­pseudorotaxane complexes in water and biological media

Additional file 2 of Infants’ and toddlers’ physical activity and sedentary time as measured by accelerometry: a systematic review and meta-analysis

Additional file 2: Table S2. Quality Assessment for Included Studies (n = 24)

CORE-GATECH-GROUP/serpent-tools: 0.5.2a1 - Pre-release

A collection of python parsing tools and data containers to make interacting with SERPENT outputs easy, intuitive, and flawless. This is a pre-release intended to trigger the Zenodo build</p

Additional file 1 of Infants’ and toddlers’ physical activity and sedentary time as measured by accelerometry: a systematic review and meta-analysis

Additional file 1: Table S1. Sample Search Strategy (EMBASE)