Tuning the selectivity of the CO2 hydrogenation reaction using boron-doped cobalt-based catalysts.

Direct CO2 hydrogenation to value-added chemicals is a promising path toward realizing the "carbon-neutral" goal. However, controlling the selectivity of CO2 hydrogenation toward desired products (e.g., CO and CH4) using non-precious metal-based catalysts is important but challenging. It is imperative to explore catalysts with high activity and stability. Herein, boron-doped cobalt nanoparticles supported on H-ZSM-5 were devised for CO2 hydrogenation to produce CO in a gas-solid flow system. Our results demonstrate that boron doping not only increases the CO2 adsorption capability of the catalyst but also optimizes the electronic state of Co for CO desorption during hydrogenation process. As a result, the boron-doped cobalt catalysts displayed an enhanced CO selectivity of 94.5% and a CO2 conversion rate of 45.6%, which is much higher than that of Co-ZSM-5 without boron doping. This study shows that the strategic design of metal borides is important for controlling the selectivity of desired products in the CO2 hydrogenation reaction.

Integrated Cobaloxime and Mesoporous Silica-Supported Ruthenium/Diamine Co-Catalysis for One-Pot Hydration/Reduction Enantioselective Sequential Reaction of Alkynes.

This study developed a cost-efficient hydration/asymmetric transfer hydrogenation (ATH) process for the one-pot synthesis of valuable chiral alcohols from alkynes. During this process, the initial homogeneous cobaloxime-catalyzed hydration of alkynes was followed by heterogeneous Ru/diamine-catalyzed ATH transformation of the in-situ generated ketones, which provided varieties of chiral alcohols in good yields with up to 99% ee values. The immobilized Ru/diamine catalyst could be recycled at least three times before its deactivation in the sequential reaction system. This work shows a general method for developing one-pot asymmetric sequential catalysis towards sustainable organic synthesis.

Thermoresponsive Pickering Emulsions Stabilized by Silica Nanoparticles in Combination with Alkyl Polyoxyethylene Ether Nonionic Surfactant.

We put forward a simple protocol to prepare thermoresponsive Pickering emulsions. Using hydrophilic silica nanoparticles in combination with a low concentration of alkyl polyoxyethylene monododecyl ether (C12En) nonionic surfactant as emulsifier, oil-in-water (o/w) emulsions can be obtained, which are stable at room temperature but demulsified at elevated temperature. The stabilization can be restored once the separated mixture is cooled and rehomogenized, and this stabilization-destabilization behavior can be cycled many times. It is found that the adsorption of nonionic surfactant at the silica nanoparticle-water interface via hydrogen bonding between the oxygen atoms in the polyoxyethylene headgroup and the SiOH groups on particle surfaces at low temperature is responsible for the in situ hydrophobization of the particles rendering them surface-active. Dehydrophobization can be achieved at elevated temperature due to weakening or loss of this hydrogen bonding. The time required for demulsification decreases with increasing temperature, and the temperature interval between stabilization and destabilization of the emulsions is affected by the surfactant headgroup length. Experimental evidence including microscopy, adsorption isotherms, and three-phase contact angles is provided to support the mechanism.

pH-Responsive Pickering Emulsions Stabilized by Silica Nanoparticles in Combination with a Conventional Zwitterionic Surfactant.

pH-responsive oil-in-water Pickering emulsions were prepared simply by using negatively charged silica nanoparticles in combination with a trace amount of a zwitterionic carboxyl betaine surfactant as stabilizer. Emulsions are stable to coalescence at pH ≤ 5 but phase separate completely at pH > 8.5. In acidic solution, the carboxyl betaine molecules become cationic, allowing them to adsorb on silica nanoparticles via electrostatic interactions, thus hydrophobizing and flocculating them and enhancing their surface activity. Upon increasing the pH, surfactant molecules are converted to zwitterionic form and significantly desorb from particles' surfaces, triggering dehydrophobization and coalescence of oil droplets within the emulsion. The pH-responsive emulsion can be cycled between stable and unstable many times upon alternating the pH of the aqueous phase. The average droplet size in restabilized emulsions at low pH, however, increases gradually after four cycles due to the accumulation of NaCl. Experimental evidence including adsorption isotherms, zeta potentials, microscopy, and three-phase contact angles is given to support the postulated mechanisms.

Switchable Pickering emulsions stabilized by silica nanoparticles hydrophobized in situ with a conventional cationic surfactant.

A stable oil-in-water Pickering emulsion stabilized by negatively charged silica nanoparticles hydrophobized in situ with a trace amount of a conventional cationic surfactant can be rendered unstable on addition of an equimolar amount of an anionic surfactant. The emulsion can be subsequently restabilized by adding a similar trace amount of cationic surfactant along with rehomogenization. This destabilization-stabilization behavior can be cycled many times, demonstrating that the Pickering emulsion is switchable. The trigger is the stronger electrostatic interaction between the oppositely charged ionic surfactants compared with that between the cationic surfactant and the (initially) negatively charged particle surfaces. The cationic surfactant prefers to form ion pairs with the added anionic surfactant and thus desorbs from particle surfaces rendering them surface-inactive. This access to switchable Pickering emulsions is easier than those employing switchable surfactants, polymers, or surface-active particles, avoiding both the complicated synthesis and the stringent switching conditions.

An ontology-based method for secondary use of electronic dental record data.

A key question for healthcare is how to operationalize the vision of the Learning Healthcare System, in which electronic health record data become a continuous information source for quality assurance and research. This project presents an initial, ontology-based, method for secondary use of electronic dental record (EDR) data. We defined a set of dental clinical research questions; constructed the Oral Health and Disease Ontology (OHD); analyzed data from a commercial EDR database; and created a knowledge base, with the OHD used to represent clinical data about 4,500 patients from a single dental practice. Currently, the OHD includes 213 classes and reuses 1,658 classes from other ontologies. We have developed an initial set of SPARQL queries to allow extraction of data about patients, teeth, surfaces, restorations and findings. Further work will establish a complete, open and reproducible workflow for extracting and aggregating data from a variety of EDRs for research and quality assurance.

Reusing electronic patient data for dental clinical research: a review of current status.

OBJECTIVES: The reuse of electronic patient data collected during clinical care has received increased attention as a way to increase our evidence base. The purpose of this paper was to review studies reusing electronic patient data for dental research. DATA SOURCES: 1527 citations obtained by searching MEDLINE and Embase databases, hand-searching seven dental and informatics journals, and snowball sampling. STUDY SELECTION: We included studies reusing electronic patient data for research on dental and craniofacial topics, alone or in combination with medical conditions, medications and outcomes. Studies using administrative or research databases and systematic reviews were excluded. Three reviewers extracted data independently and performed analysis jointly RESULTS: The 60 studies reviewed covered epidemiological (32 studies), outcomes (16), health services research (10) and other (2) topics; were primarily retrospective (58 studies); varied significantly in sample size (9-153,619 patients) and follow-up period (1-12 years); often drew on other data sources in addition to electronic ones (25); but rarely tapped electronic dental record (EDR) data in private practices (3). Type of research was not associated with data sources used, but research topics/questions were. The most commonly reported advantages of reusing electronic data were being able to study large samples and saving time, while data quality and the inability to capture study-specific data were identified as major limitations. CONCLUSIONS: Dental research reusing electronic patient data is nascent but accelerating. Future EDR design should focus on enhancing data quality, begin to integrate research data collection and implement interoperability with electronic medical records to facilitate oral-systemic investigations. CLINICAL SIGNIFICANCE: Measuring and improving the quality of dental care requires that we begin to reuse electronic patient data collected in practice for clinical research. Practice data can potentially serve as a useful complement to data collected in traditional research studies.

Natural Language Processing methods and systems for biomedical ontology learning.

While the biomedical informatics community widely acknowledges the utility of domain ontologies, there remain many barriers to their effective use. One important requirement of domain ontologies is that they must achieve a high degree of coverage of the domain concepts and concept relationships. However, the development of these ontologies is typically a manual, time-consuming, and often error-prone process. Limited resources result in missing concepts and relationships as well as difficulty in updating the ontology as knowledge changes. Methodologies developed in the fields of Natural Language Processing, information extraction, information retrieval and machine learning provide techniques for automating the enrichment of an ontology from free-text documents. In this article, we review existing methodologies and developed systems, and discuss how existing methods can benefit the development of biomedical ontologies.

Heuristic sample selection to minimize reference standard training set for a part-of-speech tagger.

Part-of-speech tagging represents an important first step for most medical natural language processing (NLP) systems. The majority of current statistically-based POS taggers are trained using a general English corpus. Consequently, these systems perform poorly on medical text. Annotated medical corpora are difficult to develop because of the time and labor required. We investigated a heuristic-based sample selection method to minimize annotated corpus size for retraining a Maximum Entropy (ME) POS tagger. We developed a manually annotated domain specific corpus (DSC) of surgical pathology reports and a domain specific lexicon (DL). We sampled the DSC using two heuristics to produce smaller training sets and compared the retrained performance against (1) the original ME modeled tagger trained on general English, (2) the ME tagger retrained on the DL, and (3) the MedPost tagger trained on MEDLINE abstracts. RESULTS showed that the ME tagger retrained with a DSC was superior to the tagger retrained with the DL, and also superior to MedPost. Heuristic methods for sample selection produced performance equivalent to use of the entire training set, but with many fewer sentences. Learning curve analysis showed that sample selection would enable an 84% decrease in the size of the training set without a decrement in performance. We conclude that heuristic sample selection can be used to markedly reduce human annotation requirements for training of medical NLP systems.

Automating tissue bank annotation from pathology reports - comparison to a gold standard expert annotation set.

Surgical pathology specimens are an important resource for medical research, particularly for cancer research. Although research studies would benefit from information derived from the surgical pathology reports, access to this information is limited by use of unstructured free-text in the reports. We have previously described a pipeline-based system for automated annotation of surgical pathology reports with UMLS concepts, which has been used to code over 450,000 surgical pathology reports at our institution. In addition to coding UMLS terms, it annotates values of several key variables, such as TNM stage and cancer grade. The object of this study was to evaluate the potential and limitations of automated extraction of these variables, by measuring the performance of the system against a true gold standard - manually encoded data entered by expert tissue annotators. We categorized and analyzed errors to determine the potential and limitations of information extraction from pathology reports for the purpose of automated biospecimen annotation.

Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53.

Nitric oxide (NO) is a potent tumor radiosensitizer; however, its clinical use is limited by systemic side effects. We have demonstrated previously that gene transfer of the human inducible NO synthase (iNOS) gene into tumor cells and tumors induces high-output NO production that significantly enhances tumor radioresponsiveness, with no observed side effects. Notably, iNOS gene transfer enhances tumor radioresponsiveness via apoptotic cell death. Because NO and ionizing radiation are both known to promote p53-dependent apoptosis, we hypothesized that p53 activation might be a primary mechanism for the synergy of these two genotoxic stresses. We report that NO and ionizing radiation synergistically activate p53 in colorectal cancers grown in athymic mice by augmenting phosphorylation of p53 at serine 15. The effect of NO and ionizing radiation on tumor cell apoptosis and tumor radioresponsiveness is significantly reduced in p53 knockout isogenic cancer cell lines. Furthermore, the transfer of both p53 and iNOS genes into tumor cells lacking functional p53 enhanced their radioresponsiveness more than transfer of either gene alone.

Adenoviral gene transfer of the human inducible nitric oxide synthase gene enhances the radiation response of human colorectal cancer associated with alterations in tumor vascularity.

Nitric oxide is a potent radiosensitizer of tumors, but its use clinically is limited by serious side effects when administered systemically. We have demonstrated previously that gene transfer of the inducible nitric oxide synthase gene (iNOS) into colorectal cancer cells enhances radiation-induced apoptosis in vitro. The objectives of this study were to further characterize the effects of iNOS gene transfer on the radiosensitivity of human colorectal cancer cells in vitro and tumors grown in athymic nude mice. Adenoviral gene transfer of iNOS (AdiNOS) into human colorectal cancer cell lines (HCT-116 and SNU-1040 cells) significantly enhanced the effects of radiation with sensitizing enhancement ratios (0.1) of 1.65 and 1.6, respectively. The radiation enhancement induced by iNOS was associated with increased iNOS expression and nitric oxide production and prevented by L-NIO, an enzymatic inhibitor of iNOS. AdiNOS treatment of HCT-116 tumors combined with radiation (2 Gy x three fractions) led to a 3.4-fold greater (P < 0.005) tumor growth delay compared with radiation (RT) alone. AdiNOS plus RT also caused significant (P < 0.01) tumor regression with 63% of tumors regressing compared with only 6% of tumors treated with RT. AdiNOS plus RT significantly (P < or = 0.001) increased the percentage of apoptotic cells (22 +/- 4%) compared with either tumors treated with control vector plus RT (9 +/- 1%), AdiNOS alone (9 +/- 3%), or no treatment (2 +/- 1%). These radiosensitizing effects of AdiNOS occurred at low infection efficiency (4% of tumor infected), indicating a significant bystander effect.

Overexpression of the human inducible nitric oxide synthase gene enhances radiation-induced apoptosis in colorectal cancer cells via a caspase-dependent mechanism.

Nitric oxide (NO) has been reported to sensitize cancer cells to radiation. Since delivery of NO to tumors is limited in vivo by systemic toxicity of NO, we examined the potential of gene delivery of the human inducible nitric oxide synthase (iNOS) gene as a means of achieving high output NO production. We successfully transduced two colorectal cancer cell lines as evidenced by increased iNOS protein accumulation and nitrite production. We found that overexpression of iNOS enhanced the effects of radiation on apoptosis in both cell lines in a caspase-dependent fashion. Gene transfer of iNOS holds much promise as a potential radiosensitizer of cancer cells since it increases apoptosis in an additive manner with radiation.

Gene transfer of human manganese superoxide dismutase protects small intestinal villi from radiation injury.

Small bowel toxicity represents a major dose-limiting side effect of radiation treatment for many malignancies. We examined the effects of overexpressing human manganese superoxide dismutase (MnSOD) in the small intestine in mice to prevent radiation enteritis. Mice were treated with the human MnSOD gene delivered enterally using a nontoxic, replication-defective herpes simplex virus (HSV)-1-based vector. HSV vectors containing the human MnSOD transgene and green fluorescent protein (GFP) transgene, or GFP transgene alone, were constructed and injected intraluminally into a 2cm length of small intestine of C3H/HeNsd mice. Total body irradiation of 15 Gy was delivered to mice inoculated 24 hours earlier with either HSV-MnSOD (10(3) to 10(8) plaque-forming units), control HSV-GFP, or no vector. At 24 or 72 hours after irradiation, mice were killed and villi areas were measured from appropriate segments of the small intestine. Control irradiated mice showed a decreased villi area of 82% by day 3 after irradiation, whereas treatment of mice with HSV-MnSOD 10(8) plaque-forming units led to only a 16% decrease in villi area (P < 0.001) before radiation. Similar findings were seen on day 3 and were associated with a significant (P < 0.001) preservation of enteric protein content in HSV-MnSOD-treated mice. A dose-dependent effect of MnSOD in preventing radiation-induced small bowel injury was evident. These data demonstrate that overexpression of human MnSOD via a replication-defective herpes viral vector is an efficacious method of protecting the small intestine from ionizing radiation damage.