Publications by authors named "Michael B Smith"

78 Publications

A novel phosphoglycerol serine-glycine lipodipeptide of is a TLR2 ligand.

J Lipid Res 2020 12 10;61(12):1645-1657. Epub 2020 Sep 10.

Department of Oral Health and Diagnostic Sciences, University of Connecticut School of Dental Medicine, Farmington, CT, USA.

is a Gram-negative anaerobic periodontal microorganism strongly associated with tissue-destructive processes in human periodontitis. Following oral infection with the periodontal bone loss in mice is reported to require the engagement of Toll-like receptor 2 (TLR2). Serine-glycine lipodipeptide or glycine aminolipid classes of engage human and mouse TLR2, but a novel lipid class reported here is considerably more potent in engaging TLR2 and the heterodimer receptor TLR2/TLR6. The novel lipid class, termed Lipid 1256, consists of a diacylated phosphoglycerol moiety linked to a serine-glycine lipodipeptide previously termed Lipid 654. Lipid 1256 is approximately 50-fold more potent in engaging TLR2 than the previously reported serine-glycine lipid classes. Lipid 1256 also stimulates cytokine secretory responses from peripheral blood monocytes and is recovered in selected oral and intestinal Bacteroidetes organisms. Therefore, these findings suggest that Lipid 1256 may be a microbial TLR2 ligand relevant to chronic periodontitis in humans.
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http://dx.doi.org/10.1194/jlr.RA120000951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707167PMC
December 2020

Glycine Lipids of Porphyromonas gingivalis Are Agonists for Toll-Like Receptor 2.

Infect Immun 2020 03 23;88(4). Epub 2020 Mar 23.

Department of Chemistry, University of Connecticut, Storrs, Connecticut, USA.

The serine-glycine dipeptide lipid classes, including lipid 430 and lipid 654, are produced by the periodontal pathogen and can be detected in lipid extracts of diseased periodontal tissues and teeth of humans. Both serine-glycine lipid classes were previously shown to engage human and mouse Toll-like receptor 2 (TLR2) and to inhibit mouse osteoblast differentiation and function through engagement of TLR2. It is not clear if other lipids related to serine-glycine lipids are also produced by The goal of this investigation was to determine whether produces additional lipid classes similar to the serine-glycine lipids that possess biological properties. (ATCC 33277) was grown in broth culture, and lipids were extracted and fractionated by high-performance liquid chromatography (HPLC). Lipids were separated using semipreparative HPLC, and specific lipid classes were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-multiple reaction monitoring (LC-MRM) mass spectrometric approaches. Two glycine lipid classes were identified, termed lipid 567 and lipid 342, and these lipid classes are structurally related to the serine-glycine dipeptide lipids. Both glycine lipid classes were shown to promote TLR2-dependent tumor necrosis factor alpha (TNF-α) release from bone marrow macrophages, and both were shown to activate human embryonic kidney (HEK) cells through TLR2 and TLR6 but not TLR1. These results demonstrate that synthesizes glycine lipids and that these lipids engage TLR2 similarly to the previously reported serine-glycine dipeptide lipids.
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http://dx.doi.org/10.1128/IAI.00877-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093120PMC
March 2020

Treasure hunt for peptides with undefined chemical modifications: Proteomics identification of differential albumin adducts of 2-nitroimidazole-indocyanine green in hypoxic tumor.

J Mass Spectrom 2020 Feb 22;55(2):e4376. Epub 2019 Jul 22.

Department of Chemistry, University of Connecticut, Storrs, CT, 06269.

2-Nitroimidazole is a well-known chemical probe targeting hypoxic environments of solid tumors, and its derivatives are widely used as imaging agents to investigate tissue and tumor hypoxia. However, the underlying chemistry for the hypoxia-detection capability of 2-nitroimidazole is still unclear. In this study, we deployed a biotin conjugate of 2-nitroimidazole-indocyanine green (2-nitro-ICG) for the investigation of in vivo hypoxia-probing mechanism of 2-nitro-ICG compounds. By implementing mass spectrometry-based proteomics and exhaustive data mining, we report that 2-nitro-ICG and its fragments modify mouse serum albumin as the primary protein target but at two structurally distinct sites and possibly via two different mechanisms. The identification of probe-modified peptides not only contributes to the understanding of the in vivo metabolism of 2-nitroimidazole compounds but also demonstrates a competent analytical workflow that enables the search for peptides with undefined modifications in complex proteome digests.
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http://dx.doi.org/10.1002/jms.4376DOI Listing
February 2020

Phagosomal Copper-Promoted Oxidative Attack on Intracellular Mycobacterium tuberculosis.

ACS Infect Dis 2018 11 6;4(11):1623-1634. Epub 2018 Sep 6.

Department of Chemistry , University of Connecticut , 55 N. Eagleville Road , Storrs , Connecticut 06269 , United States.

Copper (Cu) ions are critical in controlling bacterial infections, and successful pathogens like Mycobacterium tuberculosis (Mtb) possess multiple Cu resistance mechanisms. We report, as proof of concept, that a novel Cu hypersensitivity phenotype can be generated in mycobacteria, including Mtb, through a peptide, DAB-10, that is able to form reactive oxygen species (ROS) following Cu-binding. DAB-10 induces intramycobacterial oxidative stress in a Cu-dependent manner in vitro and during infection. DAB-10 penetrates murine macrophages and encounters intracellular mycobacteria. Significant intracellular Cu-dependent protection was observed when Mtb-infected macrophages were treated with DAB-10 alongside a cell-permeable Cu chelator. Treatment with the Cu chelator reversed the intramycobacterial oxidative shift induced by DAB-10. We conclude that DAB-10 utilizes the pool of phagosomal Cu ions in the host-Mtb interface to augment the mycobactericidal activity of macrophages while simultaneously exploiting the susceptibility of Mtb to ROS. DAB-10 serves as a model with which to develop next-generation, multifunctional antimicrobials.
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http://dx.doi.org/10.1021/acsinfecdis.8b00171DOI Listing
November 2018

Oral Manifestations of Menopause: An Interprofessional Intervention for Dental Hygiene and Physician Assistant Students.

J Dent Hyg 2017 Dec;91(6):21-32

Interprofessional education (IPE) is a means of fostering integration and collaboration between health care professions. The purpose of this study was to evaluate the effect of an IPE educational module on dental hygiene (DH) and physician assistants (PA) students' knowledge of the oral manifestations of menopause and overall confidence in treating these conditions. A convenience sample of DH and PA students was used for this mixed-method study. Quantitative data was collected with pre- and post-tests using a modified Readiness for Interprofessional Learning Survey (RIPLS) and a principle investigator (PI)-designed knowledge of menopause test, to determine the students' attitudes and learning levels. Students participated in a one-time workshop that included an educational presentation on the oral manifestations of menopause and a case study exercise using a pseudo-standardized patient. Students from both disciplines, worked in preselected groups to create a patient care plan addressing the oral manifestations of menopause. Qualitative data was collected from student comments. Study results indicate an increase in participants' knowledge of the oral manifestations of menopause (p<0.05). Results also suggest improved attitudes toward interprofessional teamwork and collaboration (p<0.05), positive professional identity (p<0.05), roles and responsibilities (p<0.05) for IPEC core competencies RR1, RR2, RR3, RR4, interprofessional communication (p<0.05) for IPEC core competencies CC3, CC4, CC 6. Qualitative data from interprofessional care plan formulation and debriefing demonstrated facilitation of gained confidence in applying new skills related to the oral manifestations of menopause. Patients experiencing menopause are susceptible to oral manifestations. Implementation of an IPE intervention demonstrated correlation between an IPE experience and participants' knowledge, attitudes and confidence. Preparing students to meet the needs of menopausal women may ultimately decrease oral discomfort and improve overall quality of life.
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December 2017

Simulation of the GCR spectrum in the Mars curiosity rover's RAD detector using MCNP6.

Life Sci Space Res (Amst) 2017 Aug 6;14:43-50. Epub 2017 Jul 6.

University of Tennessee, Department of Nuclear Engineering, Pasqua Nuclear Engineering Building, 1004 Estabrook Road, U.S.A. Knoxville, TN 37996.

The paper presents results from MCNP6 simulations of galactic cosmic ray (GCR) propagation down through the Martian atmosphere to the surface and comparison with RAD measurements made there. This effort is part of a collaborative modeling workshop for space radiation hosted by Southwest Research Institute (SwRI). All modeling teams were tasked with simulating the galactic cosmic ray (GCR) spectrum through the Martian atmosphere and the Radiation Assessment Detector (RAD) on-board the Curiosity rover. The detector had two separate particle acceptance angles, 4π and 30 ° off zenith. All ions with Z = 1 through Z = 28 were tracked in both scenarios while some additional secondary particles were only tracked in the 4π cases. The MCNP6 4π absorbed dose rate was 307.3 ± 1.3 µGy/day while RAD measured 233 µGy/day. Using the ICRP-60 dose equivalent conversion factors built into MCNP6, the simulated 4π dose equivalent rate was found to be 473.1 ± 2.4 µSv/day while RAD reported 710 µSv/day.
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http://dx.doi.org/10.1016/j.lssr.2017.07.003DOI Listing
August 2017

Deposition and hydrolysis of serine dipeptide lipids of Bacteroidetes bacteria in human arteries: relationship to atherosclerosis.

J Lipid Res 2017 10 16;58(10):1999-2007. Epub 2017 Aug 16.

Department of Oral Health and Diagnostic Sciences, University of Connecticut School of Dental Medicine, Farmington, CT 06030

Multiple reaction monitoring-MS analysis of lipid extracts from human carotid endarterectomy and carotid artery samples from young individuals consistently demonstrated the presence of bacterial serine dipeptide lipid classes, including Lipid 654, an agonist for human and mouse Toll-like receptor (TLR)2, and Lipid 430, the deacylated product of Lipid 654. The relative levels of Lipid 654 and Lipid 430 were also determined in common oral and intestinal bacteria from the phylum Bacteroidetes and human serum and brain samples from healthy adults. The median Lipid 430/Lipid 654 ratio observed in carotid endarterectomy samples was significantly higher than the median ratio in lipid extracts of common oral and intestinal Bacteroidetes bacteria, and serum and brain samples from healthy subjects. More importantly, the median Lipid 430/Lipid 654 ratio was significantly elevated in carotid endarterectomies when compared with control artery samples. Our results indicate that deacylation of Lipid 654 to Lipid 430 likely occurs in diseased artery walls due to phospholipase A2 enzyme activity. These results suggest that commensal Bacteriodetes bacteria of the gut and the oral cavity may contribute to the pathogenesis of TLR2-dependent atherosclerosis through serine dipeptide lipid deposition and metabolism in artery walls.
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http://dx.doi.org/10.1194/jlr.M077792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625123PMC
October 2017

Convergent synthesis of a deuterium-labeled serine dipeptide lipid for analysis of biological samples.

J Labelled Comp Radiopharm 2017 05 16;60(6):274-285. Epub 2017 Apr 16.

Department of Chemistry, The University of Connecticut, Storrs, CT, USA.

Bacterial serine dipeptide lipids are known to promote inflammatory processes and are detected in human tissues associated with periodontal disease or atherosclerosis. Accurate quantification of bacterial serine lipid, specifically lipid 654 [((S)-15-methyl-3-((13-methyltetradecanoyl)oxy)hexadecanoyl)glycyl-l-serine, (3S)-l-serine] isolated from Porphyromonas gingivalis, in biological samples requires the preparation of a stable isotope internal standard for sample supplementation and subsequent mass spectrometric analysis. This report describes the convergent synthesis of a deuterium-substituted serine dipeptide lipid, which is an isotopically labeled homologue that represents a dominant form of serine dipeptide lipid recovered in bacteria.
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http://dx.doi.org/10.1002/jlcr.3498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500292PMC
May 2017

Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants.

Pediatrics 2016 05 25;137(5). Epub 2016 Apr 25.

This is the first clinical practice guideline from the American Academy of Pediatrics that specifically applies to patients who have experienced an apparent life-threatening event (ALTE). This clinical practice guideline has 3 objectives. First, it recommends the replacement of the term ALTE with a new term, brief resolved unexplained event (BRUE). Second, it provides an approach to patient evaluation that is based on the risk that the infant will have a repeat event or has a serious underlying disorder. Finally, it provides management recommendations, or key action statements, for lower-risk infants. The term BRUE is defined as an event occurring in an infant younger than 1 year when the observer reports a sudden, brief, and now resolved episode of ≥1 of the following: (1) cyanosis or pallor; (2) absent, decreased, or irregular breathing; (3) marked change in tone (hyper- or hypotonia); and (4) altered level of responsiveness. A BRUE is diagnosed only when there is no explanation for a qualifying event after conducting an appropriate history and physical examination. By using this definition and framework, infants younger than 1 year who present with a BRUE are categorized either as (1) a lower-risk patient on the basis of history and physical examination for whom evidence-based recommendations for evaluation and management are offered or (2) a higher-risk patient whose history and physical examination suggest the need for further investigation and treatment but for whom recommendations are not offered. This clinical practice guideline is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient outcomes, support implementation, and provide direction for future research. Each key action statement indicates a level of evidence, the benefit-harm relationship, and the strength of recommendation.
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http://dx.doi.org/10.1542/peds.2016-0590DOI Listing
May 2016

Targeting tumor hypoxia: a third generation 2-nitroimidazole-indocyanine dye-conjugate with improved fluorescent yield.

Org Biomol Chem 2015 Dec;13(46):11220-7

Department of Biomedical Engineering and Electrical Engineering, University of Connecticut, Storrs, CT, USA.

Tumor hypoxia is associated with the rapid proliferation and growth of malignant tumors, and the ability to detect tumor hypoxia is important for predicting tumor response to anti-cancer treatments. We have developed a class of dye-conjugates that are related to indocyanine green (ICG, ) to target tumor hypoxia, based on in vivo infrared fluorescence imaging using nitroimidazole moieties linked to indocyanine fluorescent dyes. We previously reported that linking 2-nitroimidazole to an indocyanine dicarboxylic acid dye derivative () using an ethanolamine linker (ethanolamine-2-nitroimidazole-ICG, ), led to a dye-conjugate that gave promising results for targeting cancer hypoxia in vivo. Structural modification of the dye conjugate replaced the ethanolamine unit with a piperazineacetyl unit and led a second generation dye conjugate, piperzine-2-nitroimidazole-ICG (). This second generation dye-conjugate showed improved targeting of tumor hypoxia when compared with . Based on the hypothesis that molecules with more planar and rigid structures have a higher fluorescence yield, as they could release less absorbed energy through molecular vibration or collision, we have developed a new 2-nitroimidazole ICG conjugate, , with two carbon atoms less in the polyene linker. Dye-conjugate was prepared from our new dye (), and coupled to 2-nitroimidazole using a piperazine linker to produce this third-generation dye-conjugate. Spectral measurements showed that the absorption/emission wavelengths of 657/670 were shifted ∼100 nm from the second-generation hypoxia dye of 755/780 nm. Its fluorescence quantum yield was measured to be 0.467, which is about 5 times higher than that of (0.083). In vivo experiments were conducted with balb/c mice and showed more than twice the average in vivo fluorescence intensity in the tumor beyond two hours post retro-orbital injection as compared with . These initial results suggest that may significantly improve in vivo tumor hypoxia targeting.
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http://dx.doi.org/10.1039/c5ob01460cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651866PMC
December 2015

Pros and cons ….

Evid Based Child Health 2014 Dec;9(4):749-50

Department of Paediatrics, Craigavon Hospital, Craigavon, Northern Ireland.

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http://dx.doi.org/10.1002/ebch.1986DOI Listing
December 2014

Photoacoustic imaging enhanced by indocyanine green-conjugated single-wall carbon nanotubes.

J Biomed Opt 2013 Sep;18(9):096006

University of Connecticut, Departments of Biomedical Engineering and Electrical and Computer Engineering, Storrs, Connecticut 06269.

A photoacoustic contrast agent that is based on bis-carboxylic acid derivative of indocyanine green (ICG) covalently conjugated to single-wall carbon nanotubes (ICG/SWCNT) is presented. Covalently attaching ICG to the functionalized SWCNT provides a more robust system that delivers much more ICG to the tumor site. The detection sensitivity of the new contrast agent in a mouse tumor model is demonstrated in vivo by our custom-built photoacoustic imaging system. The summation of the photoacoustic tomography (PAT) beam envelope, referred to as the "PAT summation," is used to demonstrate the postinjection light absorption of tumor areas in ICG- and ICG/SWCNT-injected mice. It is shown that ICG is able to provide 33% enhancement at approximately 20 min peak response time with reference to the preinjection PAT level, while ICG/SWCNT provides 128% enhancement at 80 min and even higher enhancement of 196% at the end point of experiments (120 min on average). Additionally, the ICG/SWCNT enhancement was mainly observed at the tumor periphery, which was confirmed by fluorescence images of the tumor samples. This feature is highly valuable in guiding surgeons to assess tumor boundaries and dimensions in vivo and to achieve clean tumor margins to improve surgical resection of tumors.
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http://dx.doi.org/10.1117/1.JBO.18.9.096006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759855PMC
September 2013

A milestone.

Evid Based Child Health 2013 Jan;8(1):1-2

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http://dx.doi.org/10.1002/ebch.1901DOI Listing
January 2013

An ounce of prevention….

Evid Based Child Health 2013 May;8(3):753

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http://dx.doi.org/10.1002/ebch.1919DOI Listing
May 2013

An Introduction to Survival, Evasion, Resistance, and Escape (SERE) Medicine.

Authors:
Michael B Smith

J Spec Oper Med 2013 ;13(2):25-32

When an individual finds himself/herself in a survival, evasion, resistance, or escape (SERE) scenario, the ability to treat injuries/illnesses can be the difference between life and death. SERE schools are responsible for preparing military members for these situations, but the concept of SERE medicine is not particularly well defined. To provide a comprehensive working description of SERE medicine, operational and training components were examined. Evidence suggests that SERE medicine is diverse, injury/illness patterns are situationally dependent, and treatment options often differ from conventional clinical medicine. Ideally, medical lessons taught in SERE training are based on actual documented events. Unfortunately, the existing body of literature is dated and does not appear to be expanding. In this article, four distinct facets of SERE medicine are presented to establish a basis for future discussion and research. Recommendations to improve SERE medical curricula and data-gathering processes are also provided.
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April 2016

Targeting tumor hypoxia with 2-nitroimidazole-indocyanine green dye conjugates.

J Biomed Opt 2013 Jun;18(6):66009

University of Connecticut, Electrical and Computer Engineering Department, Storrs, Connecticut 06269, USA.

Tumor hypoxia is a major indicator of treatment resistance to chemotherapeutic drugs, and fluorescence optical tomography has tremendous potential to provide clinically useful, functional information by identifying tumor hypoxia. The synthesis of a 2-nitroimidazole-indocyanine green conjugate using a piperazine linker (piperazine-2-nitroimidazole-ICG) capable of robust fluorescent imaging of tumor hypoxia is described. In vivo mouse tumor imaging studies were completed and demonstrate an improved imaging capability of the new dye relative to an earlier version of the dye that was synthesized with an ethanolamine linker (ethanolamine-2-nitroimidazole-ICG). Mouse tumors located at imaging depths of 1.5 and 2.0 cm in a turbid medium were imaged at various time points after intravenous injection of the dyes. On average, the reconstructed maximum fluorescence concentration of the tumors injected with piperazine-2-nitroimidazole-ICG was twofold higher than that injected with ethanolamine-2-nitroimidazole-ICG within 3 h postinjection period and 1.6 to 1.7 times higher beyond 3 h postinjection. The untargeted bis-carboxylic acid ICG completely washed out after 3 h postinjection. Thus, the optimal window to assess tumor hypoxia is beyond 3 h postinjection. These findings were supported with fluorescence images of histological sections of tumor samples and an immunohistochemistry technique for identifying tumor hypoxia.
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http://dx.doi.org/10.1117/1.JBO.18.6.066009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680745PMC
June 2013

Management of apparent life-threatening events in infants: a systematic review.

J Pediatr 2013 Jul 14;163(1):94-9.e1-6. Epub 2013 Feb 14.

Department of Pediatrics, Division of Hospital Medicine, Seattle Children's Hospital and the University of Washington, Seattle, WA 98105, USA.

Objective: To determine in patients who are well-appearing and without a clear etiology after an apparent life-threatening event (ALTE): (1) What historical and physical examination features suggest that a child is at risk for a future adverse event and/or serious underlying diagnosis and would, therefore, benefit from testing or hospitalization? and (2) What testing is indicated on presentation and during hospitalization?

Study Design: Systematic review of clinical studies, excluding case reports, published from 1970 through 2011 identified using key words for ALTE.

Results: The final analysis was based on 37 studies; 18 prospective observational, 19 retrospective observational. None of the studies provided sufficient evidence to fully address the clinical questions. Risk factors identified from historical and physical examination features included a history of prematurity, multiple ALTEs, and suspected child maltreatment. Routine screening tests for gastroesophageal reflux, meningitis, bacteremia, and seizures are low yield in infants without historical risk factors or suggestive physical examination findings.

Conclusion: Some historical and physical examination features can be used to identify risk in infants who are well-appearing and without a clear etiology at presentation, and testing tailored to these risks may be of value. The true risk of a subsequent event or underlying disorder cannot be ascertained. A more precise definition of an ALTE is needed and further research is warranted.
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http://dx.doi.org/10.1016/j.jpeds.2012.12.086DOI Listing
July 2013

On consideration of radiated power in RF field simulations for MRI.

Magn Reson Med 2013 Jan 3;69(1):290-4. Epub 2012 Apr 3.

Medtronic, Inc., Minneapolis, Minnesota, USA.

In numerical analyses of radiofrequency (RF) fields for MRI, RF power is often permitted to radiate out of the problem region. In reality, RF power will be confined by the magnet bore and RF screen enclosing the magnet room. We present numerical calculations at different frequencies for various surface and volume coils, with samples from simple spheres to the human body in environments from free space to a shielded RF room. Results for calculations within a limited problem region show radiated power increases with frequency. When the magnet room RF screen is included, nearly all the power is dissipated in the human subject. For limited problem regions, inclusion of a term for radiation loss results in an underestimation of transmit efficiency compared to results including the complete bore and RF screen. If the term for radiated power is not included, calculated coil efficiencies are slightly overestimated compared to the complete case.
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http://dx.doi.org/10.1002/mrm.24244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3393780PMC
January 2013

Imaging tumor hypoxia by near-infrared fluorescence tomography.

J Biomed Opt 2011 Jun;16(6):066009

University of Connecticut, Department of Electrical and Computer Engineering, Storrs, Connecticut 06269, USA.

We have developed a novel nitroimidazole indocyanine dye conjugate for tumor-targeted hypoxia fluorescence tomography. The hypoxia probe has been evaluated in vitro using tumor cell lines and in vivo with tumor targeting in mice. The in vitro cell studies were performed to assess fluorescence labeling differences between hypoxia and normoxia conditions. When treated with the hypoxia probe, a fluorescence emission ratio of 2.5-fold was found between the cells incubated under hypoxia compared to the cells in normoxia condition. Hypoxia specificity was also confirmed by comparing the cells treated with indocyanine dye alone. In vivo tumor targeting in mice showed that the fluorescence signals measured at the tumor site were twice those at the normal site after 150 min post-injection of the hypoxia probe. On the other hand, the fluorescence signals measured after injection of indocyanine dye were the same at tumor and normal sites. In vivo fluorescence tomography images of mice injected with the hypoxia probe showed that the probe remained for more than 5 to 7 h in the tumors, however, the images of mice injected with indocyanine only dye confirmed that the unbound dye washed out in less than 3 h. These findings are supported with fluorescence images of histological sections of tumor samples using a Li-COR scanner and immunohistochemistry technique for tumor hypoxia.
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http://dx.doi.org/10.1117/1.3589348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133800PMC
June 2011

Polymer-mediated cyclodehydration of alditols and ketohexoses.

Carbohydr Res 2011 Sep 24;346(13):1662-70. Epub 2011 Apr 24.

University of Connecticut, Department of Chemistry, Storrs, CT 06269-3060, USA.

The polymer PEDOT(+) (1 or 2) mediates a cyclodehydration reaction with alditols 3, 5, 7, 9, in hydrocarbon solvents, to give cyclic ethers 4, 6, 8, or 10, respectively, in high yield with a trivial isolation protocol. Polymers 1 or 2 also mediate the cyclodehydration of ketohexoses such as d-fructose, but not aldohexoses, to the important industrial intermediate 5-hydroxymethylfurfural (17), under milder conditions when compared to reactions mediated by mineral acids. A cascade reaction with ketohexoses is observed in toluene via cyclodehydration followed by Friedel-Crafts alkylation of the initially formed benzylic alcohol to give 16.
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http://dx.doi.org/10.1016/j.carres.2011.04.017DOI Listing
September 2011

Synthesis of 3-guaninyl- and 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone nucleosides.

J Org Chem 2011 Jul 16;76(14):5574-83. Epub 2011 Jun 16.

Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, United States.

L- and D-glutamic acids, as well as trans-4-hydroxy-L-proline, are converted to the corresponding 3-guaninyl-5-hydroxymethyl-2-pyrrolidinone (4) or 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone (5) nucleoside analog. The protecting group used to block the lactam nitrogen in key intermediates has a significant effect on the diastereoselectivity of the coupling reaction with adenine or guanine.
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http://dx.doi.org/10.1021/jo2004617DOI Listing
July 2011

Reducing SAR and enhancing cerebral signal-to-noise ratio with high permittivity padding at 3 T.

Magn Reson Med 2011 Feb 30;65(2):358-62. Epub 2010 Nov 30.

Departments of Radiology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania, USA.

Previous works have shown that placement of a high-dielectric pad can improve image intensity in a region adjacent to the pad, or that placement of dielectric pads around a large surface of the head can improve image homogeneity on an entire plane through the head in high-field MRI. Here, experimental results show that use of high-dielectric pads around the human head can reduce the required input radiofrequency power by 50% while enhancing image signal-to-noise ratio by 20-40% throughout the cerebrum at 3 T. Thus, dielectric pads may be used to provide a relatively simple and low-cost method for improving quality and safety of MRI in a variety of applications at 3 T.
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http://dx.doi.org/10.1002/mrm.22695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073646PMC
February 2011

Olfactory deficit detected by fMRI in early Alzheimer's disease.

Brain Res 2010 Oct 13;1357:184-94. Epub 2010 Aug 13.

Department of Radiology, The Pennsylvania State University College of Medicine, Center for NMR Research, PA, USA.

Alzheimer's disease (AD) is accompanied by smell dysfunction, as measured by psychophysical tests. Currently, it is unknown whether AD-related alterations in central olfactory system neural activity, as measured by functional magnetic resonance imaging (fMRI), are detectable beyond those observed in healthy elderly. Moreover, it is not known whether such changes are correlated with indices of odor perception and dementia. To investigate these issues, 12 early stage AD patients and 13 nondemented controls underwent fMRI while being exposed to each of three concentrations of lavender oil odorant. All participants were administered the University of Pennsylvania Smell Identification Test (UPSIT), the Mini-Mental State Examination (MMSE), the Mattis Dementia Rating Scale-2 (DRS-2), and the Clinical Dementia Rating Scale (CDR). The blood oxygen level-dependent (BOLD) signal at primary olfactory cortex (POC) was weaker in AD than in HC subjects. At the lowest odorant concentration, the BOLD signals within POC, hippocampus, and insula were significantly correlated with UPSIT, MMSE, DRS-2, and CDR scores. The BOLD signal intensity and activation volume within the POC increased significantly as a function of odorant concentration in the AD group, but not in the control group. These findings demonstrate that olfactory fMRI is sensitive to the AD-related olfactory and cognitive functional decline.
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http://dx.doi.org/10.1016/j.brainres.2010.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515873PMC
October 2010

MRM: The twenty-fifth anniversary.

Authors:
Michael B Smith

Magn Reson Med 2009 Dec;62(6):1361

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http://dx.doi.org/10.1002/mrm.22308DOI Listing
December 2009

An unexpectedly facile cyclization of polyhydric alcohols.

Org Lett 2009 Aug;11(16):3722-5

Department of Chemistry, University of Connecticut, 55 N. Eagleville Road, Storrs, Connecticut 06269-3060, USA.

Contrary to previous reports in the literature, the reaction of polyhydric alcohols such as sorbitol or mannitol gives good yields of the tetrahydroxyoxepane derivative in the presence of an acid catalyst, in refluxing toluene, with complete retention of stereochemistry.
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http://dx.doi.org/10.1021/ol9013427DOI Listing
August 2009

A perspective on errors, bias, and interpretation in the forensic sciences and direction for continuing advancement.

J Forensic Sci 2009 Jul 26;54(4):798-809. Epub 2009 May 26.

FBI Laboratory, 2501 Investigation Parkway, Quantico, VA 22135, USA.

The forensic sciences are under review more so than ever before. Such review is necessary and healthy and should be a continuous process. It identifies areas for improvement in quality practices and services. The issues surrounding error, i.e., measurement error, human error, contextual bias, and confirmatory bias, and interpretation are discussed. Infrastructure is already in place to support reliability. However, more definition and clarity of terms and interpretation would facilitate communication and understanding. Material improvement across the disciplines should be sought through national programs in education and training, focused on science, the scientific method, statistics, and ethics. To provide direction for advancing the forensic sciences a list of recommendations ranging from further documentation to new research and validation to education and to accreditation is provided for consideration. The list is a starting point for discussion that could foster further thought and input in developing an overarching strategic plan for enhancing the forensic sciences.
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http://dx.doi.org/10.1111/j.1556-4029.2009.01081.xDOI Listing
July 2009

MRI and histological analysis of beta-amyloid plaques in both human Alzheimer's disease and APP/PS1 transgenic mice.

J Magn Reson Imaging 2009 May;29(5):997-1007

Department of Radiology (Center for NMR Research), Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.

Purpose: To investigate the relationship between MR image contrast associated with beta-amyloid (Abeta) plaques and their histology and compare the histopathological basis of image contrast and the relaxation mechanism associated with Abeta plaques in human Alzheimer's disease (AD) and transgenic APP/PS1 mouse tissues.

Materials And Methods: With the aid of the previously developed histological coil, T(2) (*)-weighted images and R(2) (*) parametric maps were directly compared with histology stains acquired from the same set of Alzheimer's and APP/PS1 tissue slices.

Results: The electron microscopy and histology images revealed significant differences in plaque morphology and associated iron concentration between AD and transgenic APP/PS1 mice tissue samples. For AD tissues, T(2) (*) contrast of Abeta-plaques was directly associated with the gradation of iron concentration. Plaques with significantly less iron load in the APP/PS1 animal tissues are equally conspicuous as the human plaques in the MR images.

Conclusion: These data suggest a duality in the relaxation mechanism where both high focal iron concentration and highly compact fibrillar beta-amyloid masses cause rapid proton transverse magnetization decay. For human tissues, the former mechanism is likely the dominant source of R(2) (*) relaxation; for APP/PS1 animals, the latter is likely the major cause of increased transverse proton relaxation rate in Abeta plaques. The data presented are essential for understanding the histopathological underpinning of MRI measurement associated with Abeta plaques in humans and animals.
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http://dx.doi.org/10.1002/jmri.21731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723054PMC
May 2009

Clinical questions in the ED.

Am J Emerg Med 2008 Oct;26(8):962-3

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http://dx.doi.org/10.1016/j.ajem.2008.04.001DOI Listing
October 2008

Preferential protonation and methylation site of thiopyrimidine derivatives in solution: NMR data.

J Phys Chem B 2008 Mar 20;112(10):3259-67. Epub 2008 Feb 20.

Institute of Organic and Physical Chemistry, Arbuzov Str. 8, Kazan, Russian Federation.

Protonation (alkylation) sites of several thiopyrimidine derivatives were directly determined by 1H-15N (1H-13C) heteronuclear single quantum coherence/heteronuclear multiple bond correlation methods, and it was found that in all compounds, protonation (methylation) occurred at the N1 nitrogen. GIAO DFT chemical shifts were in full agreement with the determined tautomeric structures. According to ab initio calculations, the stability of the different protonated forms and methylated derivatives was favored due to thermodynamic control and not kinetic control.
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http://dx.doi.org/10.1021/jp710952rDOI Listing
March 2008