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"Stevenson, Alexander"
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The public sector : managing the unmanageable
\"The Public Sector: Managing the Unmanageable offers practical advice to public sector managers on how to develop techniques to deal with the challenges they face, particularly in the areas of accountability, setting targets, risk management/encouraging innovation, managing people, decision making and working with politicians. Based on original interviews with politicians and senior public sector managers, including the last four cabinet secretaries, it is full of anecdotes, actionable lessons and insights. Each chapter takes a specific aspect of management and starts by explaining why it is different in the public sector, then sets out ways for public sector managers to handle those differences and ends with an executive summary and a checklist to prompt managers to think about how they might change what they currently do\"-- Provided by publisher.
Book
Vehicle Position Detection Based on Machine Learning Algorithms in Dynamic Wireless Charging
Dynamic wireless charging (DWC) has emerged as a viable approach to mitigate range anxiety by ensuring continuous and uninterrupted charging for electric vehicles in motion. DWC systems rely on the length of the transmitter, which can be categorized into long-track transmitters and segmented coil arrays. The segmented coil array, favored for its heightened efficiency and reduced electromagnetic interference, stands out as the preferred option. However, in such DWC systems, the need arises to detect the vehicle’s position, specifically to activate the transmitter coils aligned with the receiver pad and de-energize uncoupled transmitter coils. This paper introduces various machine learning algorithms for precise vehicle position determination, accommodating diverse ground clearances of electric vehicles and various speeds. Through testing eight different machine learning algorithms and comparing the results, the random forest algorithm emerged as superior, displaying the lowest error in predicting the actual position.
Journal Article
Robert Louis Stevenson's Treasure Island
Young Jim Hawkins is aboard a ship on a grand adventure, sailing to an island to search for buried treasure.
Book
Anthropogenic habitat alteration leads to rapid loss of adaptive variation and restoration potential in wild salmon populations
Phenotypic variation is critical for the long-term persistence of species and populations. Anthropogenic activities have caused substantial shifts and reductions in phenotypic variation across diverse taxa, but the underlying mechanism(s) (i.e., phenotypic plasticity and/or genetic evolution) and long-term consequences (e.g., ability to recover phenotypic variation) are unclear. Here we investigate the widespread and dramatic changes in adult migration characteristics of wild Chinook salmon caused by dam construction and other anthropogenic activities. Strikingly, we find an extremely robust association between migration phenotype (i.e., spring-run or fall-run) and a single locus, and that the rapid phenotypic shift observed after a recent dam construction is explained by dramatic allele frequency change at this locus. Furthermore, modeling demonstrates that continued selection against the spring-run phenotype could rapidly lead to complete loss of the spring-run allele, and an empirical analysis of populations that have already lost the spring-run phenotype reveals they are not acting as sustainable reservoirs of the allele. Finally, ancient DNA analysis suggests the spring-run allele was abundant in historical habitat that will soon become accessible through a large-scale restoration (i.e., dam removal) project, but our findings suggest that widespread declines and extirpation of the spring-run phenotype and allele will challenge reestablishment of the spring-run phenotype in this and future restoration projects. These results reveal the mechanisms and consequences of human-induced phenotypic change and highlight the need to conserve and restore critical adaptive variation before the potential for recovery is lost.
Journal Article
Multiscale imaging of basal cell dynamics in the functionally mature mammary gland
The mammary epithelium is indispensable for the continued survival of more than 5,000 mammalian species. For some, the volume of milk ejected in a single day exceeds their entire blood volume. Here, we unveil the spatiotemporal properties of physiological signals that orchestrate the ejection of milk from alveolar units and its passage along the mammary ductal network. Using quantitative, multidimensional imaging of mammary cell ensembles from GCaMP6 transgenic mice, we reveal how stimulus evoked Ca2+ oscillations couple to contractions in basal epithelial cells. Moreover, we show that Ca2+-dependent contractions generate the requisite force to physically deform the innermost layer of luminal cells, compelling them to discharge the fluid that they produced and housed. Through the collective action of thousands of these biological positive-displacement pumps, each linked to a contractile ductal network, milk begins its passage toward the dependent neonate, seconds after the command.
Journal Article
Performance Analysis of Commercial Passive Balancing Battery Management System Operation Using a Hardware-in-the-Loop Testbed
With increased usage, individual batteries within the battery pack will begin to show disparate voltage and State of Charge (SOC) profiles, which will impact the time at which batteries become balanced. Commercial battery management systems (BMSs), used in electric vehicles (EVs) and microgrids, typically send out signals suggesting removal of individual batteries or entire packs to prevent thermal runaway scenarios. To reuse these batteries, this paper presents an analysis of an off-the-shelf Orion BMS with a constrained cycling approach to assess the voltage and SOC balancing and thermal performances of such near-to-second life batteries. A scaled-down pack of series-connected batteries in 6s1p and 6s2p topologies are cycled through a combination of US06 drive and constant charge (CC) profiles using an OPAL-RT real-time Hardware-in-the-loop (HIL) simulator. These results are compared with those obtained from the Matlab/Simulink model to present the error incurred in the simulation environment. Results suggest that the close-to-second life batteries can be reused if operated in a constrained manner and that a scaled-up battery pack topology reduces incurred error.
Journal Article
THUR 001 An unusual (ne)urological presentation
We present the case of a 78-year-old female with a background of diabetes, who presented with acute-onset hemichorea whilst on the surgical ward under the care of the Urology team. She had an extensive past medical history including type two diabetes; additionally, she reported she had experienced similar transient symptoms during an admission ten months previously. CT and MRI brain demonstrated no acute ischaemic changes. A thorough drug history revealed no causative agent, and her blood tests were unremarkable. Her capillary blood glucose charts showed a severe hypoglycaemic episode two days prior to the onset of symptoms with similar hypoglycaemic episodes noted during her last admission. A diagnosis of hypoglycaemia-induced hemichorea was made and the patient was started on tetrabenazine. Our case of an elderly diabetic patient with new-onset hemichorea secondary to hypoglycaemia highlights the importance of identifying and optimising glycaemic control in this vulnerable cohort.
Journal Article
THUR 002 An unusual presentation: two aetiologies for the price of one
70-year-old female receptionist presented with acute onset lower back pain whilst sitting down. She tried to weight bear but felt her left leg ‘gave way’. There were no sensory complaints and no sphincter disturbance. Positive examination findings in her left lower limb include reduced tone, power 2/5 throughout, and left extensor plantar. In addition, she had absent knee and ankle reflexes bilaterally and loss of pinprick and temperature sensation on the right side up to L1 dermatome, with preservation of vibration and proprioception. She had a normal sensory examination of her left lower limb and rectal examination was unremarkable. Clinically, she has an atypical form of Brown-Séquard syndrome with weakness in the left lower limb and sensory loss in the right lower limb with a sensory level. MRI lumbar/sacral spine showed L3 slipped anteriorly with L3/4 disc bulge resulting in cauda equina syndrome. She was re-scanned five days later including thoracic spine and found to have an acute left hemi-cord infarct at T8/9. This case demonstrates the importance of scanning the relevant sections of the cord and to keep a broad differential in mind, as there can be two aetiologies at work which might misguide the clinician at first glance.
Journal Article
Dysregulated G2 phase checkpoint recovery pathway reduces DNA repair efficiency and increases chromosomal instability in a wide range of tumours
Defective DNA repair is being demonstrated to be a useful target in cancer treatment. Currently, defective repair is identified by specific gene mutations, however defective repair is a common feature of cancers without these mutations. DNA damage triggers cell cycle checkpoints that are responsible for co-ordinating cell cycle arrest and DNA repair. Defects in checkpoint signalling components such as ataxia telangiectasia mutated (ATM) occur in a low proportion of cancers and are responsible for reduced DNA repair and increased genomic instability. Here we have investigated the AURKA-PLK1 cell cycle checkpoint recovery pathway that is responsible for exit from the G2 phase cell cycle checkpoint arrest. We demonstrate that dysregulation of PP6 and AURKA maintained elevated PLK1 activation to promote premature exit from only ATM, and not ATR-dependent checkpoint arrest. Surprisingly, depletion of the B55α subunit of PP2A that negatively regulates PLK1 was capable of overcoming ATM and ATR checkpoint arrests. Dysregulation of the checkpoint recovery pathway reduced S/G2 phase DNA repair efficiency and increased genomic instability. We found a strong correlation between dysregulation of the PP6-AURKA-PLK1-B55α checkpoint recovery pathway with signatures of defective homologous recombination and increased chromosomal instability in several cancer types. This work has identified an unrealised source of G2 phase DNA repair defects and chromosomal instability that are likely to be sensitive to treatments targeting defective repair.
Journal Article
The ATM Ser49Cys Variant Effects ATM Function as a Regulator of Oncogene-Induced Senescence
An apical component of the cell cycle checkpoint and DNA damage repair response is the ataxia-telangiectasia mutated (ATM) Ser/Thr protein kinase. A variant of ATM, Ser49Cys (rs1800054; minor allele frequency = 0.011), has been associated with an elevated risk of melanoma development; however, the functional consequence of this variant is not defined. ATM-dependent signalling in response to DNA damage has been assessed in a panel of patient-derived lymphoblastoid lines and primary human melanocytic cell strains heterozygous for the ATM Ser49Cys variant allele. The ATM Ser49Cys allele appears functional for acute p53-dependent signalling in response to DNA damage. Expression of the variant allele did reduce the efficacy of oncogene expression in inducing senescence. These findings demonstrate that the ATM 146C>G Ser49Cys allele has little discernible effect on the acute response to DNA damage but has reduced function observed in the chronic response to oncogene over-expression. Analysis of melanoma, naevus and skin colour genomics and GWAS analyses have demonstrated no association of this variant with any of these outcomes. The modest loss of function detected suggest that the variant may act as a modifier of other variants of ATM/p53-dependent signalling.
Journal Article