Big issues for small feet : developmental, biomechanical and clinical narratives on children's footwear

The effects of footwear on the development of children's feet has been debated for many years and recent work from the developmental and biomechanical literature has challenged long-held views about footwear and the impact on foot development. This narrative review draws upon existing studies from developmental, biomechanical and clinical literature to explore the effects of footwear on the development of the foot. The emerging findings from this support the need for progress in [children's] footwear science and advance understanding of the interaction between the foot and shoe. Ensuring clear and credible messages inform practice requires a progressive evidence base but this remains big issue in children's footwear research

Enantioselective synthesis of pyrrolydinonyl thymine nucleoside analogues

Enantioselective synthesis of a novel kind of optically active nucleoside analogues from natural malic acid is described. In the given nucleoside analogues the tetrahydrofuran ring is replaced by a pyrrolidinonyl ring bearing both a primary and a secondary hydroxy groups which could be useful for the preparation of novel oligonucleotides. Assay of the prepared nucleoside analogues showed non-activity against virus

Asymmetric synthesis of polyhydroxy pyrrolidinonyl nucleoside analogues from tartaric acid

Asymmetric synthesis of novel optically active nucleoside analogues 7 from natural tartaric acid is described. In the given nucleoside analogues an optically active polyhydroxy pyrrolidinonyl ring is in place of the tetrahydrofuran ring

On the security of supersingular isogeny cryptosystems

We study cryptosystems based on supersingular isogenies. This is an active area of research in post-quantum cryptography. Our first contribution is to give a very powerful active attack on the supersingular isogeny encryption scheme. This attack can only be prevented by using a (relatively expensive) countermeasure. Our second contribution is to show that the security of all schemes of this type depends on the difficulty of computing the endomorphism ring of a supersingular elliptic curve. This result gives significant insight into the difficulty of the isogeny problem that underlies the security of these schemes. Our third contribution is to give a reduction that uses partial knowledge of shared keys to determine an entire shared key. This can be used to retrieve the secret key, given information leaked from a side-channel attack on the key exchange protocol. A corollary of this work is the first bit security result for the supersingular isogeny key exchange: Computing any component of the j-invariant is as hard as computing the whole j-invariant. Our paper therefore provides an improved understanding of the security of these cryptosystems. We stress that our work does not imply that these systems are insecure, or that they should not be used. However, it highlights that implementations of these schemes will need to take account of the risks associated with various active and side-channel attacks.SCOPUS: cp.kinfo:eu-repo/semantics/published22nd International Conference on the Theory and Application of Cryptology and Information Security, ASIACRYPT 2016; Hanoi; Viet Nam; 4 December 2016 through 8 December 2016ISBN: 978-366253886-9Volume Editors: Cheon J.H.Takagi T.Publisher: Springer Verla

NAD deficiency, congenital malformations and niacin supplementation

Background Congenital malformations can manifest as combinations of phenotypes that co-occur more often than expected by chance. In many such cases it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral and renal defects, amongst others, in four unrelated patients. Methods Genomic sequencing was used to identify potentially pathogenic gene variants in four families. The variants were functionally tested using in vitro enzyme activity assays, and by quantifying metabolites in patient plasma. We engineered mouse models with similar variants using CRISPR/Cas9. Results Variants were identified in 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU) genes encoding kynurenine pathway enzymes. Three patients carried homozygous variants predicting loss-of-function changes in the HAAO or KYNY proteins (HAAO p.D162*, HAAO p.W186*, or KYNU p.V57Efs*21). Another patient carried heterozygous KYNU variants (p.Y156* and p.F349Kfs*4). The mutant enzymes had greatly reduced activity in vitro. Nicotinamide adenine dinucleotide (NAD) is synthesized de novo from tryptophan via the kynurenine pathway. The patients had reduced circulating NAD levels. Haao or Kynu null mouse embryos developed similar defects to the patients due to NAD deficiency. In null mice, averting NAD deficiency during gestation prevented defects. Conclusions Disruption of NAD synthesis causes a deficiency and congenital malformations in humans and mice. Niacin supplementation during gestation prevented the malformations in mice