The role of law and ethics in developing business management as a profession

Currently, business management is far from being recognised as a profession. This paper suggests that a professional spirit should be developed which could function as a filter of commercial reasoning. Broadly, management will not be organised within the framework of a well-established profession unless formal knowledge, licensing, professional autonomy and professional codes of conduct are developed sufficiently. In developing business management as a profession, law may play a key role. Where the idea is that business management should be more professsionalised, managers must show that they are willing to adopt ethical values, while arriving at business decisions. The paper argues that ethics cannot survive without legal regulation, which, in turn, will not be supported by law unless lawyers can find alternative solutions to the large mechanisms of the official society, secured by the monopolised coercion of the nation state. From a micro perspective of law and business ethics, communities can be developed with their own conventions, rules and standards that are generated and sanctioned within the boundaries of the communities themselves

Downregulation of genes with a function in axon outgrowth and synapse formation in motor neurones of the VEGF(delta/delta) mouse model of amyotrophic lateral sclerosis

Background: Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that stimulates vasculogenesis. It has also been shown to act as a neurotrophic factor in vitro and in vivo. Deletion of the hypoxia response element of the promoter region of the gene encoding VEGF in mice causes a reduction in neural VEGF expression, and results in adult-onset motor neurone degeneration that resembles amyotrophic lateral sclerosis (ALS). Investigating the molecular pathways to neurodegeneration in the VEGF(delta/delta) mouse model of ALS may improve understanding of the mechanisms of motor neurone death in the human disease. Results: Microarray analysis was used to determine the transcriptional profile of laser captured spinal motor neurones of transgenic and wild-type littermates at 3 time points of disease. 324 genes were significantly differentially expressed in motor neurones of presymptomatic VEGF(delta/delta) mice, 382 at disease onset, and 689 at late stage disease. Massive transcriptional downregulation occurred with disease progression, associated with downregulation of genes involved in RNA processing at late stage disease. VEGF(delta/delta) mice showed reduction in expression, from symptom onset, of the cholesterol synthesis pathway, and genes involved in nervous system development, including axonogenesis, synapse formation, growth factor signalling pathways, cell adhesion and microtubule-based processes. These changes may reflect a reduced capacity of VEGF(delta/delta) mice for maintenance and remodelling of neuronal processes in the face of demands of neural plasticity. The findings are supported by the demonstration that in primary motor neurone cultures from VEGF(delta/delta) mice, axon outgrowth is significantly reduced compared to wild-type littermates. Conclusions: Downregulation of these genes involved in axon outgrowth and synapse formation in adult mice suggests a hitherto unrecognized role of VEGF in the maintenance of neuronal circuitry. Dysregulation of VEGF may lead to neurodegeneration through synaptic regression and dying-back axonopathy

A Quantum-Proof Non-Malleable Extractor, With Application to Privacy Amplification against Active Quantum Adversaries

In privacy amplification, two mutually trusted parties aim to amplify the secrecy of an initial shared secret $X$ in order to establish a shared private key $K$ by exchanging messages over an insecure communication channel. If the channel is authenticated the task can be solved in a single round of communication using a strong randomness extractor; choosing a quantum-proof extractor allows one to establish security against quantum adversaries. In the case that the channel is not authenticated, Dodis and Wichs (STOC'09) showed that the problem can be solved in two rounds of communication using a non-malleable extractor, a stronger pseudo-random construction than a strong extractor. We give the first construction of a non-malleable extractor that is secure against quantum adversaries. The extractor is based on a construction by Li (FOCS'12), and is able to extract from source of min-entropy rates larger than $1/2$. Combining this construction with a quantum-proof variant of the reduction of Dodis and Wichs, shown by Cohen and Vidick (unpublished), we obtain the first privacy amplification protocol secure against active quantum adversaries

Using zebrafish larval models to study brain injury, locomotor and neuroinflammatory outcomes following intracerebral haemorrhage.

Intracerebral haemorrhage (ICH) is a devastating condition with limited treatment options, and current understanding of pathophysiology is incomplete. Spontaneous cerebral bleeding is a characteristic of the human condition that has proven difficult to recapitulate in existing pre-clinical rodent models. Zebrafish larvae are frequently used as vertebrate disease models and are associated with several advantages, including high fecundity, optical translucency and non-protected status prior to 5 days post-fertilisation. Furthermore, other groups have shown that zebrafish larvae can exhibit spontaneous ICH. The aim of this study was to investigate whether such models can be utilised to study the pathological consequences of bleeding in the brain, in the context of pre-clinical ICH research. Here, we compared existing genetic (bubblehead) and chemically inducible (atorvastatin) zebrafish larval models of spontaneous ICH and studied the subsequent disease processes. Through live, non-invasive imaging of transgenic fluorescent reporter lines and behavioural assessment we quantified brain injury, locomotor function and neuroinflammation following ICH. We show that ICH in both zebrafish larval models is comparable in timing, frequency and location. ICH results in increased brain cell death and a persistent locomotor deficit. Additionally, in haemorrhaged larvae we observed a significant increase in macrophage recruitment to the site of injury. Live in vivo imaging allowed us to track active macrophage-based phagocytosis of dying brain cells 24 hours after haemorrhage. Morphological analyses and quantification indicated that an increase in overall macrophage activation occurs in the haemorrhaged brain. Our study shows that in zebrafish larvae, bleeding in the brain induces quantifiable phenotypic outcomes that mimic key features of human ICH. We hope that this methodology will enable the pre-clinical ICH community to adopt the zebrafish larval model as an alternative to rodents, supporting future high throughput drug screening and as a complementary approach to elucidating crucial mechanisms associated with ICH pathophysiology

CLP1 Founder Mutation Links tRNA Splicing and Maturation to Cerebellar Development and Neurodegeneration

SummaryNeurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans