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

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Four-quadrant operation ZVS DC/DC LUO converters

DC-DC converters are an important aspect in portable electronic devices such as cell phones, laptop computers and electric cars which power are supplied primarily from batteries. These electronic devices may require several voltage level requirements for different parts of the device. DC-DC converter is a method to convert a voltage level to another voltage level to suit the application needs rather than having multiple batteries to suit each and every part of a particular application. Generally, there are two different methods used to convert DC voltages, namely switched-mode fixed frequency pulse width modulation (PWM) DC-DC converter and the variable frequency quasi-resonant converters. Switched-mode fixed frequency pulse width modulation (PWM) DC-DC converter usually has high electronic noise and is usually complex.Master of Science (Power Engineering

Engineering functional nanomaterials for photonic applications

The tremendous progress in nanotechnology has provided diverse nanosized materials with unique and interesting features including but not limited to fluorescence, high sensitivity, high loading capacity, and photothermal properties which are beneficial for a wide range of photonic applications. Photons are employed in photonics to detect, transmit, transport, and process information that can achieve a tremendous enhancement in efficiency, capacity, simplicity, and speed. In view of these advantages, this thesis aims to perform in-depth studies of the synthesis and properties characterization that centered on three types of nanomaterial groups, including polymer, carbon, and perovskite-based nanoparticles. This work also exploits the respective unique features to showcase the potential of these nanoparticles in photonic applications. The work outlined in this thesis will be divided into three major photonic applications: i) cancer therapeutics, ii) single and multiphoton cellular imaging, and iii) sensing of trace level pollutants in food and water samples. Despite the remarkable advances made in understanding cancer biology and the development of new cancer therapies, cancer mortality is one of the rising mortalities causes throughout the world, and research has shown that this trend is expected to persist. In particular, pancreatic cancer is one of the deadliest with pancreatic cancer patients having a median survival rate of fewer than 6 months and the overall 5-year survival rate is less than 5%. Traditional pancreatic cancer treatments including, surgery, radiation, and chemotherapy, come with some adverse side effects such as low specificity, dose-limiting toxicity, poor pharmacokinetics, and insufficient uptake at the targeted site. Addressing these concerns, nanomaterial-based delivery systems stand as the alternative to overcome the limitations of traditional delivery of therapeutic agents. The employment of nanomaterials offers unparalleled options to introduce new functionalities for synergistic therapy, as well as to modulate fundamental properties such as solubility, drug-release behavior, blood circulation half-life, and immunogenicity. The nanoparticle-based delivery system can also provide a more effective administration route, reduce potential toxicity, offer protection towards therapeutic agents, encapsulate drugs with poor aqueous solubility, deliver therapeutic loads to targeted sites, and increase therapeutic efficiency, thus lowers dosage and frequency of administration. On the basis of the aforementioned facts, the first section in this thesis focus on developing biodegradable charged polyester-based vectors (BCPVs) for the co-delivery of K-ras and Notch1 siRNA to overcome drug resistance to gemcitabine (chemotherapeutic drug) in Mia PaCa-2, a pancreatic cancer cell line. K-ras regulates many downstream single molecules such as Raf kinase, Raf guanine, and nucleotide exchange factors that regulate cell growth, differentiation, and survival. Mutated K-ras gene at codon 12 keeps the constitutive GTPase activity and locks the protein to the guanosine triphosphate-bound “on” state, resulting in the cells having tumor phenotype and eventually evolve into cancer. On the other hand, overexpression of Notch1 resulted in the acquisition of epithelia-mesenchymal transition (EMT) phenotype by pancreatic cancer cells. EMT is often linked with resistance to chemotherapeutic drugs, thus lowering the therapeutic efficacy of chemotherapeutic agents. Hence, the silencing of both K-ras and Notch1 is a promising strategy since both genes are significant contributors to pancreatic tumorigenesis. BCPVs which are based on cationic polylactide has shown great potential as a delivery vehicle due to its low toxicity, biodegradability and biocompatible. In this work, BCPVs was used as a delivery vehicle for the co-delivery of K-ras and Notch1 siRNA to silence the multiple gene mutations in pancreatic cancer cells and to reduce drug resistance to gemcitabine. After treatment, the cell migration, proliferation and invasion were clearly inhibited, and the cell apoptosis was evidently increased by the synergistic therapeutic effect of the nanocomplex. The combinational RNAi therapy was also found to be able to improve the sensitivity of the Mia PaCa-2 cells towards gemcitabine. In the following chapter, graphene quantum dots (GQDs) were synthesized, characterized, and employed as a light-triggered fluorescent nanocarrier for co-delivery of K-ras siRNA and Doxorubicin (DOX) for combinational gene and chemotherapy for pancreatic cancer treatment. GQDs was employed as a nanocarrier due to its facile synthesis approach, low toxicity, biocompatible, and unique optical properties. DOX is an anthracycline antibiotic that has been found to be highly effective in killing cancer cells in both solid and liquid tumors by binding to DNA-associated topoisomerase enzymes II. To achieve a nanocomplex capable of performing combinational therapy, a GQD/DOX/BCPV/siRNA nanocomplex consists of DOX and siRNA with the assistance of BCPVs to modify the surface properties of GQDs for the co-loading of DOX and siRNA through electrostatic interaction. The formation of the nanocomplexes was carefully optimized to ensure the optimal loading of the therapeutic agents. The delivery and therapeutic efficiency of the GQD/DOX/BCPV/siRNA were evaluated in MiaPaCa-2 cells. After treatment, the expression of the K-ras gene, cell proliferation, migration and invasion were reduced while the population of apoptotic cells was enhanced. Furthermore, by exploiting the unique absorption at 650 nm, the GQDs can serve as photothermal agents that can serve as a trigger to release the DOX and siRNA from the GQD/DOX/BCPV/siRNA nanocomplex under near-infrared light (NIR) irradiation. The synergistic therapeutic effects of the GQD/DOX/BCPV/siRNA nanocomplex were found to be enhanced under NIR light irradiation. In the second section of the thesis, novel water-soluble CsPbBr3 nanocrystals were developed for targeted single and multiphoton imaging of cancer cells. Optical imaging is a non-invasive technique for visualizing cancer cells and investigating physiological processes in vitro and in vivo. An ideal optical fluorescent agent typically requires high photoluminescence quantum yield, excellent colloidal stability, long-term photostability, and exhibit multiphoton absorption. In the past decade, perovskite has been gaining huge attention for applications such as solar cells, light-emitting diodes, and photodetectors. However, their highly ionic properties have rendered the material to be highly susceptible to degradation when in contact with water and oxygen. To counter this, we present novel water-soluble CsPbBr3 nanocrystals prepared by first coating the CsPbBr3¬¬¬¬ nanocrystals with a silica shell followed by PEGylation in a phospholipid micelle. The resultant nanocrystals exhibited multiphoton absorption property, which is highly desirable for biological imaging due to the higher penetration depth, lower autofluorescence, improved sensitivity, enhanced resolution, and lower phototoxicity. The CsPbBr3/SiO2/mPEG-DSPE demonstrated good aqueous stability and photostability under various test conditions, i.e., long-term aqueous stability, continuous UV irradiation, and continuous ultrasonication. The CsPbBr3/SiO¬2/mPEG-DSPE nanocrystals were also found to be stable after being dispersed in various biological mediums. The cytotoxicity CsPbBr3/SiO¬2/mPEG-DSPE nanocrystals were evaluated using MTT assay in four different cell lines, including PANC-1, Mia PaCa-2, RAW264.7, and CaCo-2 cells. Next, the CsPbBr3/SiO¬2/mPEG-DSPE nanocrystals were employed as a fluorescent label for targeted single and multiphoton imaging of cancer cells. In the last section, the focus of the thesis is directed towards the approach of using nanoparticles for sensing applications. We first investigated the potential use of CsPbBr3/SiO¬2/mPEG-DSPE nanocrystals for the fluorescence detection of color additives in water samples and food products. Color additives, also known as dyes, can be a major contributor of toxic species to the environment. In the textile industry alone, a large amount of wastewater containing residual dyes is being discharged into rivers and streams, affecting the light penetrating the water and subsequently affecting the natural ecosystem and polluting the water source. Moreover, color additive such as Rhodamine 6G (R6G) is used in food that is often targeted at children. R6G is a derivative of xanthene dyes and can potentially affect the reproductive and development growth in human. Henceforth, we fabricated water-stable CsPbBr3/SiO¬2/mPEG-DSPE nanocrystals as a ratiometric fluorescence sensor to detect the presence of R6G. The emission of the CsPbBr3/SiO¬2/mPEG-DSPE at 518 nm decrease linearly while a new peak at 565 nm increase linearly in the presence of a concentration of R6G. The proposed nanosensor has a detection limit of 0.01 ppm and a linear operating range from 0 to 10 ppm. Other common color additives were also added to the CsPbBr3/SiO¬2/mPEG-DSPE solution and no significant changes in fluorescence intensity were observed, indicating the high selectivity of the nanosensor towards R6G. The CsPbBr3/SiO¬2/mPEG-DSPE nanosensor was also employed to detect the presence of R6G in real food and water samples that contain complex backgrounds such as dissolved nutrients and metal ions. The FRET detection mechanism was also investigated by measuring the lifetime of CsPbBr3/SiO¬2/mPEG-DSPE in the absence and presence of R6G. Lastly, this section also explored the use of carbon dots as a fluorescence sensor for the detection of ferric ions in water samples and intracellularly. Excessive intake of iron is detrimental to human health, leading to many serious diseases such as hemochromatosis leading to liver damage, increased inflammatory markers, and weakened cognitive and motor growth in children. While water that is heavily contaminated by iron is easily detectable owing to the unpleasant taste and stain, trace-level iron contamination in water may not be visible to the naked eyes and long-term exposures remain dangerous to the public. In this work, a facile one-step microwave-assisted pyrolysis is adopted to produce fluorescent carbon dots as a highly sensitive fluorometric sensing probe for Fe3+ ions in aqueous solution. The carbon dots were carefully characterized by transmission electron microscopy, UV-Vis spectrometry, Raman spectrometry, Fourier-transform infrared spectroscopy, X-ray photoelectron spectrometry, and fluorometer. The fluorescence of the carbon dots was found to decrease with increasing concentration of Fe3+ ions. The LOD was determined to be 0.16 µM with a linear operating range from 0 – 500 µM. It was also found that by employing a pH tuning technique, the selectivity of the sensing probe towards Fe3+ was significantly improved by reducing the interference effect of Cu2+, Co2+, and Ag+. The carbon dots were also employed as a fluorescent agent for cellular imaging and can be used as a semi-quantitative fluorescent probe for intracellular detection of Fe3+ ions in Mia PaCa-2 cells. In summary, this thesis mainly focused on achieving three different photonic applications including cancer therapeutics, multiphoton cellular imaging, and sensing using polymeric, carbon, and perovskite-based nanoparticles. We envisioned that these works can further unveil the potential for future translation of these nanomaterials into commercial photonics applications.Doctor of Philosoph

Biogreen synthesis of carbon dots for biotechnology and nanomedicine applications

Over the past decade, carbon dots have ignited a burst of interest in many different fields, including nanomedicine, solar energy, optoelectronics, energy storage, and sensing applications, owing to their excellent photoluminescence properties and the easiness to modify their optical properties through doping and functionalization. In this review, the synthesis, structural and optical properties, as well as photoluminescence mechanisms of carbon dots are first reviewed and summarized. Then, we describe a series of designs for carbon dot-based sensors and the different sensing mechanisms associated with them. Thereafter, we elaborate on recent research advances on carbon dot-based sensors for the selective and sensitive detection of a wide range of analytes, including heavy metals, cations, anions, biomolecules, biomarkers, nitroaromatic explosives, pollutants, vitamins, and drugs. Lastly, we provide a concluding perspective on the overall status, challenges, and future directions for the use of carbon dots in real-life sensing.Published versio

A facile synthesis of label-free carbon dots with unique selectivity-tunable characteristics for ferric ion detection and cellular imaging applications

This work reports the synthesis of nitrogen and sulfur co-doped carbon dots (NS-CDs) via a one-step facile microwave-assisted pyrolysis using citric acid and thiourea as the carbon precursor and dopant, respectively. The resultant NS-CDs were found to be uniform in size and can be dispersed in aqueous solution. With an average size of 4.73 ± 0.65 nm, the NS-CDs exhibit excitation-dependent and pH-dependent photoluminescence properties in the visible range. Moreover, the NS-CDs also possessed a relatively high photoluminescence quantum yield of 28.9% and strong photostability in a high ionic strength environment. The NS-CDs were highly selective for Fe³⁺ detection in a water sample, achieving a limit of detection (LOD) of 0.16 μM. On top of this, the NS-CDs also demonstrated high detection sensitivity with a LOD of 0.17 μM and improved selectivity to Fe³⁺ in an acidic environment (pH 2). Specifically, the interference effect from Cu²⁺, Co²⁺, and Ag⁺ was lowered by 15%, 18%, and 64% respectively, highlighting an additional merit for the as-synthesized NS-CDs. This concept of pH tuning can be implemented to exploit the detection capability in both neutral and acidic environments to create specific analytical responses correlating to a specific targeted metal ion. Finally, we also demonstrated the versatility of the NS-CDs by employing them as a low-toxicity fluorescent label and for semi-quantitative Fe³⁺ sensing in cancer cells

Water-stable all-inorganic perovskite nanocrystals with nonlinear optical properties for targeted multiphoton bioimaging

CsPbX3nanocrystals have been employed in various optoelectronic applications, such as light-emitting diodes and solar cells. Nevertheless, widespread application of CsPbX3nanocrystals has been largely restricted by their poor aqueous stability. Despite the tremendous efforts focused on encapsulating the CsPbX3nanocrystals, it is still very challenging to achieve CsPbX3nanocrystals with good aqueous stability. This work describes the preparation and encapsulation methods for CsPbBr3/SiO2/mPEG-DSPE nanocrystals that can be readily dispersed in water and biological buffers. To the best of our knowledge, this is the first work that reports multiphoton emissions from CsPbBr3/SiO2/mPEG-DSPE nanocrystals in water. The protection afforded by the silica shell and phospholipid micelles enables the CsPbBr3/SiO2/mPEG-DSPE nanocrystals in aqueous solution to exhibit enhanced long-term stability and better shielding against ultrasonication treatment and continuous light irradiation than bare CsPbBr3nanocrystals. The toxicity of the CsPbBr3/SiO2/mPEG-DSPE nanocrystals has been evaluated in various cell lines. Subsequently, the encapsulated nanocrystals were used for targeted single and multiphoton imaging of cancer cells. This work not only describes the preparation of water-stable CsPbBr3nanocrystals but also paves the way for their applications in multiphoton bioimaging applications.Ministry of Education (MOE)Nanyang Technological UniversityNational Research Foundation (NRF)Submitted/Accepted versionThis research was supported by Nanyang Technological University under its start-up grant (M4080514); the Ministry of Education under its AcRF Tier 2 grants (MOE2017-T2-2-002 and MOE2019-T2-1-006); and the National Research Foundation (NRF) Singapore under its NRF Investigatorship (NRF-NRFI-2018-04)

Carbon allotrope-based optical fibers for environmental and biological sensing : a review

Recently, carbon allotropes have received tremendous research interest and paved a new avenue for optical fiber sensing technology. Carbon allotropes exhibit unique sensing properties such as large surface to volume ratios, biocompatibility, and they can serve as molecule enrichers. Meanwhile, optical fibers possess a high degree of surface modification versatility that enables the incorporation of carbon allotropes as the functional coating for a wide range of detection tasks. Moreover, the combination of carbon allotropes and optical fibers also yields high sensitivity and specificity to monitor target molecules in the vicinity of the nanocoating surface. In this review, the development of carbon allotropes-based optical fiber sensors is studied. The first section provides an overview of four different types of carbon allotropes, including carbon nanotubes, carbon dots, graphene, and nanodiamonds. The second section discusses the synthesis approaches used to prepare these carbon allotropes, followed by some deposition techniques to functionalize the surface of the optical fiber, and the associated sensing mechanisms. Numerous applications that have benefitted from carbon allotrope-based optical fiber sensors such as temperature, strain, volatile organic compounds and biosensing applications are reviewed and summarized. Finally, a concluding section highlighting the technological deficiencies, challenges, and suggestions to overcome them is presented.Published versio

NIR-responsive nanomaterials and their applications; upconversion nanoparticles and carbon dots: a perspective

Near‐infrared (NIR) light responsive materials have received much attention for diverse applications due to their excellent optical properties. This type of material exhibits upconverted luminescence, a non‐linear optical process in which two or more low energy photons, usually from NIR light irradiation are transformed to high energy photons emission through energy transfer upconversion, excited state absorption, photon avalanche or multiphoton absorption. The NIR range of excitation source is favorable for biological imaging and cancer theranostic applications due to their high penetration depth, low autofluorescence, minimal light scattering, reduced photodamage, and negligible phototoxicity. Having these properties, NIR responsive materials such as upconversion nanoparticles (UCNPs) and carbon dots (CDs) which perform upconversion luminescence are actively exploited in a wide variety of applications such as display and sensory technology. While CDs are well known for their versatility in using different chemicals and green precursors to achieve tunable optical properties, UCNPs also have the advantage that a continuous‐wave NIR laser can be used as the excitation source. This article reviews the properties of these two materials in the aspects of luminescence mechanisms and their recent developments in cancer theranostics, display technology, biosensing and metal ions sensing applications. © 2018 Society of Chemical Industr

Carbon dot-functionalized interferometric optical fiber sensor for detection of ferric ions in biological samples

This work reports an interferometric optical microfiber sensor functionalized with nitrogen- and sulfur-codoped carbon dots (CDs) for the detection of ferric ions (Fe3+). Compared to other CD-based ferric ion sensors, the sensing mechanism of this presented sensor is dependent on the refractive index modulations due to selective Fe3+ adsorption onto the CD binding sites at the tapered region. This is the first study in which CD-based sensing was performed at the solid phase as a chelator, which does not rely on its fluorescence properties. The detection performance of the proposed sensor is not only comparable to a conventional fluorescence-based CD nanoprobe sensor but also capable of delivering quantitative analysis results and ease of translation to a sensor device for on-site detection. The presented sensor exhibits Fe3+ detection sensitivity of 0.0061 nm/(μg/L) in the linear detection range between 0 and 300 μg/L and a detection limit of 0.77 μg/L based on the Langmuir isotherm model. Finally, the potential use of the CD-functionalized optical microfiber sensor in the real environmental and biological Fe3+ monitoring applications has also been validated in this work.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)Accepted versio