Spatial Variations of Fundamental Constants

We show that observational limits on the possible time variation of constants of Nature are significantly affected by allowing for both space and time variation. Bekenstein's generalisation of Maxwell's equations to allow for cosmological variation of $alpha$ is investigated in a universe containing spherically symmetric inhomogeneities. The time variation of $alpha$ is determined by the local matter density and hence limits obtained in high-density geophysical enviroments are far more constraining than those obtained at high redshift. This new feature is expected to be a property of a wide class of theories for the variation of constants.Comment: 4 page

Control techniques for mechatronic assisted surgery

The treatment response for traumatic head injured patients can be improved by using an autonomous robotic system to perform basic, time-critical emergency neurosurgery, reducing costs and saving lives. In this thesis, a concept for a neurosurgical robotic system is proposed to perform three specific emergency neurosurgical procedures; they are the placement of an intracranial pressure monitor, external ventricular drainage, and the evacuation of chronic subdural haematoma. The control methods for this system are investigated following a curiosity led approach. Individual problems are interpreted in the widest sense and solutions posed that are general in nature. Three main contributions result from this approach: 1) a clinical evidence based review of surgical robotics and a methodology to assist in their evaluation, 2) a new controller for soft-grasping of objects, and 3) new propositions and theorems for chatter suppression sliding mode controllers. These contributions directly assist in the design of the control system of the neurosurgical robot and, more broadly, impact other areas outside the narrow con nes of the target application. A methodology for applied research in surgical robotics is proposed. The methodology sets out a hierarchy of criteria consisting of three tiers, with the most important being the bottom tier and the least being the top tier. It is argued that a robotic system must adhere to these criteria in order to achieve acceptability. Recent commercial systems are reviewed against these criteria, and are found to conform up to at least the bottom and intermediate tiers. However, the lack of conformity to the criteria in the top tier, combined with the inability to conclusively prove increased clinical benefit, particularly symptomatic benefit, is shown to be hampering the potential of surgical robotics in gaining wide establishment. A control scheme for soft-grasping objects is presented. Grasping a soft or fragile object requires the use of minimum contact force to prevent damage or deformation. Without precise knowledge of object parameters, real-time feedback control must be used to regulate the contact force and prevent slip. Moreover, the controller must be designed to have good performance characteristics to rapidly modulate the fingertip contact force in response to a slip event. A fuzzy sliding mode controller combined with a disturbance observer is proposed for contact force control and slip prevention. The robustness of the controller is evaluated through both simulation and experiment. The control scheme was found to be effective and robust to parameter uncertainty. When tested on a real system, however, chattering phenomena, well known to sliding mode research, was induced by the unmodelled suboptimal components of the system (filtering, backlash, and time delays). This reduced the controller performance. The problem of chattering and potential solutions are explored. Real systems using sliding mode controllers, such as the control scheme for soft-grasping, have a tendency to chatter at high frequencies. This is caused by the sliding mode controller interacting with un-modelled parasitic dynamics at the actuator-input and sensor-output of the plant. As a result, new chatter-suppression sliding mode controllers have been developed, which introduce new parameters into the system. However, the effect any particular choice of parameters has on system performance is unclear, and this can make tuning the parameters to meet a set of performance criteria di cult. In this thesis, common chatter-suppression sliding mode control strategies are surveyed and simple design and estimation methods are proposed. The estimation methods predict convergence, chattering amplitude, settling time, and maximum output bounds (overshoot) using harmonic linearizations and invariant ellipsoid sets

California Methanol Assessment; Volume II, Technical Report

A joint effort by the Jet Propulsion Laboratory and the California Institute of Technology Division of Chemistry and Chemical Engineering has brought together sponsors from both the public and private sectors for an analysis of the prospects for methanol use as a fuel in California, primarily for the transportation and stationary application sectors. Increasing optimism in 1982 for a slower rise in oil prices and a more realistic understanding of the costs of methanol production have had a negative effect on methanol viability in the near term (before the year 2000). Methanol was determined to have some promise in the transportation sector, but is not forecasted for large-scale use until beyond the year 2000. Similarly, while alternative use of methanol can have a positive effect on air quality (reducing NOx, SOx, and other emissions), a best case estimate is for less than 4% reduction in peak ozone by 2000 at realistic neat methanol vehicle adoption rates. Methanol is not likely to be a viable fuel in the stationary application sector because it cannot compete economically with conventional fuels except in very limited cases. On the production end, it was determined that methanol produced from natural gas will continue to dominate supply options through the year 2000, and the present and planned industry capacity is somewhat in excess of all projected needs. Nonsubsidized coal-based methanol cannot compete with conventional feedstocks using current technology, but coal-based methanol has promise in the long term (after the year 2000), providing that industry is willing to take the technical and market risks and that government agencies will help facilitate the environment for methanol. Given that the prospects for viable major markets (stationary applications and neat fuel in passenger cars) are unlikely in the 1980s and early 1990s, the next steps for methanol are in further experimentation and research of production and utilization technologies, expanded use as an octane enhancer, and selected fleet implementation. In the view of the study, it is not advantageous at this time to establish policies within California that attempt to expand methanol use rapidly as a neat fuel for passenger cars or to induce electric utility use of methanol on a widespread basis

Beneficial modulation of the gut microbiota

peer-reviewedThe human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.C.J.W, C.M.G. and P.D.C are supported by a SFI PI award “Obesibiotics” (11/PI/1137

In silico identification of bacteriocin gene clusters in the gastrointestinal tract, based on the Human Microbiome Project’s reference genome database

peer-reviewedBackground The human gut microbiota comprises approximately 100 trillion microbial cells which significantly impact many aspects of human physiology - including metabolism, nutrient absorption and immune function. Disturbances in this population have been implicated in many conditions and diseases, including obesity, type-2 diabetes and inflammatory bowel disease. This suggests that targeted manipulation or shaping of the gut microbiota, by bacteriocins and other antimicrobials, has potential as a therapeutic tool for the prevention or treatment of these conditions. With this in mind, several studies have used traditional culture-dependent approaches to successfully identify bacteriocin-producers from the mammalian gut. In silico-based approaches to identify novel gene clusters are now also being utilised to take advantage of the vast amount of data currently being generated by next generation sequencing technologies. In this study, we employed an in silico screening approach to mine potential bacteriocin clusters in genome-sequenced isolates from the gastrointestinal tract (GIT). More specifically, the bacteriocin genome-mining tool BAGEL3 was used to identify potential bacteriocin producers in the genomes of the GIT subset of the Human Microbiome Project’s reference genome database. Each of the identified gene clusters were manually annotated and potential bacteriocin-associated genes were evaluated. Results We identified 74 clusters of note from 59 unique members of the Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and Synergistetes. The most commonly identified class of bacteriocin was the >10 kDa class, formerly known as bacteriolysins, followed by lantibiotics and sactipeptides. Conclusions Multiple bacteriocin gene clusters were identified in a dataset representative of the human gut microbiota. Interestingly, many of these were associated with species and genera which are not typically associated with bacteriocin production.CJW, CMG and PDC are supported by a SFI PI award to PDC “Obesibiotics” (11/PI/1137)

Targeting the Microbiota to Address Diet-Induced Obesity: A Time Dependent Challenge

peer-reviewedLinks between the gut microbiota and host metabolism have provided new perspectives on obesity. We previously showed that the link between the microbiota and fat deposition is age- and time-dependent subject to microbial adaptation to diet over time. We also demonstrated reduced weight gain in diet-induced obese (DIO) mice through manipulation of the gut microbiota with vancomycin or with the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac+), with metabolic improvement achieved in DIO mice in receipt of vancomycin. However, two phases of weight gain were observed with effects most marked early in the intervention phase. Here, we compare the gut microbial populations at the early relative to the late stages of intervention using a high throughput sequencing-based analysis to understand the temporal relationship between the gut microbiota and obesity. This reveals several differences in microbiota composition over the intervening period. Vancomycin dramatically altered the gut microbiota composition, relative to controls, at the early stages of intervention after which time some recovery was evident. It was also revealed that Bac+ treatment initially resulted in the presence of significantly higher proportions of Peptococcaceae and significantly lower proportions of Rikenellaceae and Porphyromonadaceae relative to the gut microbiota of L. salivarius UCC118 bacteriocin negative (Bac-) administered controls. These differences were no longer evident at the later time. The results highlight the resilience of the gut microbiota and suggest that interventions may need to be monitored and continually adjusted to ensure sustained modification of the gut microbiota.The authors are supported in part by Teagasc, Science Foundation Ireland (in the form of a research centre grant to the Alimentary Pharmabiotic Centre and PI awards to PWOT and PC) and by Alimentary Health Ltd

Analysis of Health Benefits Conferred by Lactobacillus Species from Kefir

peer-reviewedLactobacilli are among the most common microorganisms found in kefir; a traditional fermented milk beverage produced locally in many locations around the world. Kefir has been associated with a wide range of purported health benefits; such as antimicrobial activity; cholesterol metabolism; immunomodulation; anti-oxidative effects; anti-diabetic effects; anti-allergenic effects; and tumor suppression. This review critically examines and assesses these claimed benefits and mechanisms with regard to particular Lactobacillus species and/or strains that have been derived from kefir; as well as detailing further potential avenues for experimentation.Work in PWOTs laboratory is supported by grants from Science Foundation Ireland to APC Microbiome Ireland, and from the (Govt. Ireland) Department of Agriculture, Food and Marine FIRM scheme. Work in PCs laboratory is supported by grants from Science Foundation Ireland to APC Microbiome Ireland and Vistamilk, from the (Govt. Ireland) Department of Agriculture, Food and Marine FIRM scheme, Enterprise Ireland and by the EU (MASTER; an Innovation Action funded by the European Commission under the Horizon 2020 Programme under grant number 818368)