Increasing the civil service retirement age in Hong Kong : a study of policy processes and dynamics

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Structural insights into the electron/proton transfer pathways in the quinol : fumarate reductase from Desulfovibrio gigas

Guan, H., Hsieh, Y., Lin, P. et al. Structural insights into the electron/proton transfer pathways in the quinol : fumarate reductase from Desulfovibrio gigas. Sci Rep 8, 14935 (2018) doi:10.1038/s41598-018-33193-

Structural insights into the electron/proton transfer pathways in the quinol : fumarate reductase from Desulfovibrio gigas

The membrane-embedded quinol: fumarate reductase (QFR) in anaerobic bacteria catalyzes the reduction of fumarate to succinate by quinol in the anaerobic respiratory chain. The electron/protontransfer pathways in QFRs remain controversial. Here we report the crystal structure of QFR from the anaerobic sulphate-reducing bacterium Desulfovibrio gigas (D. gigas) at 3.6 Å resolution. The structure of the D. gigas QFR is a homo-dimer, each protomer comprising two hydrophilic subunits, A and B, and one transmembrane subunit C, together with six redox cofactors including two b-hemes. One menaquinone molecule is bound near heme bL in the hydrophobic subunit C. This location of the menaquinone-binding site differs from the menaquinol-binding cavity proposed previously for QFR from Wolinella succinogenes. The observed bound menaquinone might serve as an additional redox cofactor to mediate the proton-coupled electron transport across the membrane. Armed with these structuralinsights, we propose electron/proton-transfer pathways in the quinol reduction of fumarate to succinate in the D. gigas QFR.Guan, H., Hsieh, Y., Lin, P. et al. Structural insights into the electron/proton transfer pathways in the quinol : fumarate reductase from Desulfovibrio gigas. Sci Rep 8, 14935 (2018) doi:10.1038/s41598-018-33193-

Biomimetic lubricant-infused titania nanoparticle surfaces via layer-by-layer deposition to control biofouling

Lubricant-infused surfaces have attracted a lot of attention in antifouling applications. Previously, lubricant-infused surfaces fabricated by a layer-by-layer process involved two or more polyelectrolytes and needed post-treatments to generate pores. Here, the paper proposes a layer-by-layer sol-gel process to prepare a lubricant-infused surface. This process only involves a single material and without any post-treatment. The nanostructured titania layers were layer-by-layer assembled onto 316L stainless steel substrates by immersing the substrates into a titanium (IV) butoxide ethanol solution. The titania layers were subsequently surface-functionalized by fluorinated silanes and infiltrated with fluorinated lubricant to form lubricant-infused nanoparticle surfaces. The physicochemical properties of the lubricant-infused nanoparticle surfaces dominated the antifouling performance. These results give some insight into the construction of lubricant-infused nanoparticle surfaces with desirable liquid repellency and antifouling properties via a layer-by-layer sol-gel process

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Selective Transport and Targeted Assembly in the 1,2-Propanediol Bacterial Microcompartment

This dissertation is the culmination of my graduate studies in the laboratory of Todd O. Yeates at UCLA. The research presented here is a study of 1,2-propanediol utilization (Pdu), a scavenger pathway used by common gut bacteria to thrive in the human gut environment. Encapsulating the Pdu pathway is a novel non-membrane, proteinaceous shell (approximately 100-200 nm in diameter) also known as a bacterial microcompartment (BMC) and the focus of investigation in the present work. BMCs are a conserved mechanism for housing metabolic processes that involve volatile or toxic intermediates. They are found in approximately 20% of sequenced bacterial genomes. However, little is known about BMC properties for small molecule transport and assembly. My dissertation work revealed important aspects of selective transport and shell protein organization for the Pdu BMC and other BMC shell proteins through hypothesis-driven research. As an introduction to this dissertation, chapter 1 summarizes the history of research on Pdu BMCs and recent applications in biotechnology. Chapter 2 is a comprehensive review, reprinted with permission from Microbiology and Molecular Biology Reviews (see Acknowledgments), of diverse bacterial microcompartments of known function and their possible applications in bioengineering of fuel and drug biosynthesis. Chapter 3 is an exposition on biochemical and structural characterization on selective transport of small molecules in the shell protein PduA, testing my first hypothesis about substrate entry and toxic intermediate encapsulation. This article is reprinted with permission from Proceedings of the National Academy of Sciences (see Acknowledgments). To follow up on the results of Chowdhury, Chun, et al. (2015), Chapter 4 presents a molecular dynamics approach to study free energy barriers to small molecules through the shell protein PduA, which supported our previous conclusions. This manuscript is in submission for journal peer review. Another type of BMC shell protein, called EutL, is a promising candidate for pore-conducting small molecule transport. In Chapter 5, I describe molecular dynamics studies on EutL, previously reported by several groups in open and closed pore conformations by X-ray crystallography, in order to observe the large structural rearrangements required for conformational transition. Chapter 6 reports on the study of homologous shell protein, PduB, that I hypothesized can also have an open pore structure. Here, I used Tryptophan emission spectroscopy and X-ray crystallography to test this hypothesis. I outline future work for the continuation of this project.Lastly, the latter part of my dissertation focuses on questions of BMC shell assembly, a difficult topic of study due to non-uniform distributions of size and shape among BMCs of a particular system and highly redundant motifs in the BMC shell. Chapter 7 details the structural and in vivo studies of the shell protein PduJ that has 80% amino acid sequence identity to PduA. However, PduJ is found to not be functionally synonymous with PduA and its genic location in the Pdu operon may affect its post-translational assembly. This research was published electronically ahead of print in Molecular Microbiology (June 2016) and is reprinted here with permission (see Acknowledgments). Finally, Chapter 8 chronicles the study of Pdu enzyme N-terminal peptides binding Pdu BMC shell proteins for two reasons. First, the literature on this subject contributed by many research groups is sometimes inconsistent, which may be attributed to the difficulty of studying amphipathic peptides in a biochemical setting. A thorough study of the Pdu enzyme N-terminal peptides using biophysical chemistry has not been carried out prior to this work and would benefit the research community. Second, a more quantitative analysis could be used to mathematically model Pdu BMC assembly and, in combination with data on pore permeability (described in chapter 4) and enzyme kinetics, accurately simulate production efficiency of the Pdu BMC. This information is highly valuable for the industrial scale use of Pdu BMCs, the bioengineering and synthetic biology of which is already an active area of research. I outline the future work for the continuation of this project, with notes in the Appendix, and offer advice for using different techniques.In conclusion, this dissertation work contributes significant findings to the expanding knowledge of the Pdu BMC and details further studies of interest for posterity in the BMC research community

Implementation of web product search engine (Part I)

Online shopping is gaining popularity as the preferred mode of shopping as opposed to being physically at a shop. This mode is also preferred because it reduces the amount of time needed to purchase products by allowing the users to quickly perform a search on their items of choice without having to window shop through an entire shopping mall. The rivalry between these online shops also encourages more innovations in term of ease of finding products and purchasing them. Traditionally, search engines only accept text as a form of query and users will have to describe the physical products they are looking for, which often leads to inaccurate results. For e-Commerce websites, this is increasingly becoming an issue, as users will have difficulty accurately explaining how a certain product looks like in order to find it. By allowing the users to send queries in the form of image, users can then allow search engines to figure out the products more accurately and therefore get more relevant results. The purpose of this project is to develop such an e-Commerce website with the ability to search based on text and images either saved locally on their disks, or hosted on external websites. The users can further refine the results by selecting on several filters or by cropping a selection of the original search image. To allow users to perform these searches and going through the results easily, a User Interface is needed. This interface must be fast to load and easy to use. Through the use of modern web technologies such as hypertext markup, cascading style sheets and JavaScript, the author demonstrates how integration between the user interface and the search engines can deliver a good experience for the users. The ability to easily maintain and extend the website’s current functionality is also considered as a priority in order to allow future modules to be integrated easily.Bachelor of Engineering (Computer Science