23 research outputs found
Supercritical fluid injection of nonvolatiles with resonant two photon ionization detection in supersonic beam mass spectrometry
Supercritical fluids of N2O and CO2 are used to solubilize nonvolatile compounds for supersonic jet expansions. R2PI is then used to ionize these compounds in a time of flight mass spectrometer. By tuning the dye laser wavelength a cold wavelength ionization spectrum can be obtained that is characteristic of that species.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87289/2/612_1.pd
Supercritical fluid jet expansions of polar aromatic carboxylic acids using simple derivatization with detection by resonant two-photon ionization
In this work simple derivatization is used as a means of enhancing the solubility of polar aromatic carboxylic acids in supercritical CO2 and N2O. The supercritical fluid is then expanded from 200 atm and 40[deg]C through a pulsed injection orifice into vacuum as a supersonic jet for analysis by laser resonant two-photon ionization spectroscopy in a time-of-flight mass spectrometer. The use of derivatization reduces the polarity of these carboxylic acids and thus greatly enhances their solubility in these fluids. The result is that strong ionization signals from the jet are detected in the mass spectrometer at relatively low temperatures where these molecules, many of which are thermally labile, will not decompose. The laser ionization method allows soft ionization of these compounds where the molecular ion is generally the base peak and a characteristic fragment due to simple C[alpha]-C[beta] cleavage is often observed. By monitoring the molecular ion as a function of wavelength a cold laser ionization spectrum with sharp spectral features can be obtained in these supersonic expansions from high pressure supercritical fluids thus demonstrating that optical selectivity is still retained even after derivatization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27585/1/0000629.pd
A reference-grade wild soybean genome
Wild relatives of crop plants are invaluable germplasm for genetic improvement. Here, Xie et al. report a reference-grade wild soybean genome and show that it can be used to identify structural variation and refine quantitative trait loci
A reference-grade wild soybean genome
Efficient crop improvement depends on the application of accurate genetic information contained in diverse germplasm resources. Here we report a reference-grade genome of wild soybean accession W05, with a final assembled genome size of 1013.2 Mb and a contig N50 of 3.3 Mb. The analytical power of the W05 genome is demonstrated by several examples. First, we identify an inversion at the locus determining seed coat color during domestication. Second, a translocation event between chromosomes 11 and 13 of some genotypes is shown to interfere with the assignment of QTLs. Third, we find a region containing copy number variations of the Kunitz trypsin inhibitor (KTI) genes. Such findings illustrate the power of this assembly in the analysis of large structural variations in soybean germplasm collections. The wild soybean genome assembly has wide applications in comparative genomic and evolutionary studies, as well as in crop breeding and improvement programs
Bioreactor technologies to support liver function in vitro
Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drives efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models.National Institutes of Health (U.S.) (R01 EB010246)National Institutes of Health (U.S.) (P50-GM068762-08)National Institutes of Health (U.S.) (R01-ES015241)National Institutes of Health (U.S.) (P30-ES002109)5UH2TR000496-02National Science Foundation (U.S.). Emergent Behaviors of Integrated Cellular Systems (CBET-0939511)United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039
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
Resonant Two-photon Ionization And High Pressure Fluid Injection In Supersonic Beam Mass Spectrometry.
Supersonic molecular beam spectroscopy has great potential for selectivity in chemical analysis. In this work, we used resonant two-photon ionization (R2PI) spectroscopy in supersonic beams in order to obtain ultraviolet ionization spectra with sharp features for unique identification of different species. This wavelength selective ionization was utilized for detection in a time-of-flight mass spectrometer (TOF). The spectroscopy of several disubstituted benzenes have been studied near their origin transitions. These molecules have low quantum yields in fluorescence but can be detected easily with R2PI. Since they absorb at different wavelengths, discrimination of one such compound in a mixture is possible. In aromatic molecules substituted with chlorine and bromine isotopes, relatively large vibrational isotope shifts have been observed 2.5 cm\sp{-1}). Isotopic selection was thus observed in the TOF and enhancement factor in the case of chlorine isotopes may be on the order of 60 or more. Substituent effects were studied in the R2PI of mono- and disubstituted halogenated benzenes and halogenated toluene, phenol and aniline derivatives. The ionization phenomena were explained in terms of steric and coulombic interactions, and Frank-Condon transition probability. In the case of azabenzenes, a three-photon process was proposed for the efficient ionization observed. In this process, the first photon excites a molecule to a resonant state, a second photon then excites the molecule to a upper high lying Rydberg state, and a third photon ionizes the molecule. The wavelength spectra reflect the absorption of the n -\ \pi\sp{\*} transition. In order to extend this technique to the analysis of nonvolatile and thermally labile compounds, supercritical fluids were used as the carriers. A pulsed valve has been designed to operate at pressures of up to 380 atm and nearly 200\sp\circC. The reduction in duty cycle has allowed the use of a 200 m orifice which significantly increases the on-axis density in the jet. Several nonvolatile polynuclear aromatic hydrocarbons have been introduced into the vapor phase and detected using R2PI in the TOF at moderate temperatures. A simple derivatization procedure has been used to increase the solubilities of polar aromatic carboxylic acids for supercritical CO\sb2 and N\sb2O injection into a mass spectrometer. In addition, high pressure liquids such as methanol and water were used to introduce polar aromatic amines into the supersonic beams.Ph.D.Analytical chemistryPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/128128/2/8801420.pd
The study of current trend on drug abuse behaviour in Hong Kong
This research aims to address three notable aspects of the current trend of Drug abuse behaviour in Hong Kong. Glancing at the latest figures from the Central Registry for Drug Abuse(CRDA)released on March 27, 2014, our group noticed the following: First, there was a decreasing trend on the reported drug abuse population, meaning that less people were taking drugs. Second, the median time for abusers to be discovered by the CRDA reporting agencies has been increasing, meaning that it is taking longer for law enforcement agencies to detect the drug abuser. Regarding the pattern of use, the figures revealed that the majority of drug abusers took drugs at home or at a friend’s home, makingit more difficult to be detected. Last but not least, in view of the increasingly hidden nature of drug abuse, the CRDA has proposed the introduction of the RESCUE Drug Testing(RDT)Scheme. Its purpose is not for prosecution, but to identify drug abusers as early as possible and refer them to counseling and treatment in a timely manner. In view of such, our group target pursued answers to the following research questions:
1. What factors caused drug abusers to quit their drug habit?
2. What factors caused the increased median time for drug abusers to be discovered?
3. Does the introduction of the RESCUE Drug Testing (RDT) Scheme result in a change in the hidden nature of drug use in Hong Kong?
This research highlights the reasons that drug abusers quit. It could be useful to circulate these successful cases to other persons who are still thinking about quitting. In addition, the research findings on the causes of the hidden nature of the problem and the former drug abusers’ views on the RDT Scheme could be helpful for other relevant organizations in formulating new policies.published_or_final_versionCriminologyMasterMaster of Social Science
Polymer-Stabilized Micelles Reduce the Drug Rapid Clearance In Vivo
Micelles are self-assembled nanoscaled aggregates from amphiphilic unimers and can be used to encapsulate hydrophobic drugs. However, the dynamic exchanging of unimers between micelles and bulk solution often leads to micelle destabilization and subsequent leaking of the encapsulated substances. Thus, we incorporated a hydrophobic polymer into the micellar core for interlacing the unimers and stabilizing the micelle structure. The polymer-stabilized and non-polymer-stabilized micelles have similar physicochemical properties including small sizes (~35 nm), negative surface charges (~−35 mV), and high drug contents (~15%). Drugs encapsulated in polymer-stabilized micelles are released in a slower rate than are non-polymer-stabilized micelles. From in vivo pharmacokinetic studies, drugs loaded in polymer-stabilized micelles have lower clearance and higher plasma concentration and lower volume distribution than non-polymer-stabilized micelles have. In conclusion, polymer-stabilized micelles can reduce rapid drug clearance via strengthening of the micellar structure and increase in the available drug amount in plasma, thus broadening pharmaceutical applications of micelles