يعرض 1 - 10 نتائج من 266 نتيجة بحث عن '"Fernandez, Anthony P"', وقت الاستعلام: 0.91s تنقيح النتائج
  1. 1
    رسالة جامعية

    المساهمون: University/Department: Universitat Autònoma de Barcelona. Departament d'Enginyeria Química

    مرشدي الرسالة: Álvaro Campos, Gregorio, López Díaz, Carmen

    المصدر: TDX (Tesis Doctorals en Xarxa)

    الوصف: El objetivo del presente trabajo de tesis es establecer métodos biocatalíticos para la síntesis de los aminoácidos L-fenilalanina, L-aspartato, β−aminobutirato y de las aminas aromáticas 1-feniletilamina y 3-amino-1-fenilbutano, usando biocatalizadores con actividad transaminasa y amonio liasa inmovilizados por técnicas de formación de enlaces covalentes (en el caso de enzimas) y por atrapamiento (tanto para enzimas como para células). Se establecieron dos métodos enzimáticos para la síntesis del aminoácido aromático esencial L-fenilalanina (Phe). El primer método de síntesis se realizó usando como biocatalizador L-aspartato transaminasa (AAT) de corazón porcino inmovilizado. Se optimizaron los métodos de inmovilización de AAT en los soportes Eupergit® C, MANA-agarosa y LentiKats®. Los biocatalizadores inmovilizados resultantes se emplearon en la síntesis de Phe. La inmovilización en Eupergit® C y LentiKats® permitió mejorar la estabilidad del enzima AAT, así como alcanzar rendimientos de reacción de síntesis de Phe superiores al 70%. Además se estableció un método de síntesis multienzimática “one-pot”, para lo que se acoplaron las reacciones catalizadas por los enzimas aspartasa (AspB) y transaminasa (AT). Se determinó la compatibilidad de los enzimas en las condiciones de reacción (pH 7,5 y 37°C) y se establecieron las concentraciones óptimas de los sustratos (0,15 M de fumarato, 0,3 M de NH4Cl y 0,1 M de fenilpiruvato) y de los enzimas (0,3 U de AspB/mL y 2 U de AT/mL). En estas condiciones, se alcanzó un rendimiento global de reacción de 80%. Para la síntesis de L-aspartato (Asp) se utilizó el enzima L-aspartato amonio liasa o aspartasa (AspB) de Bacillus sp. YM55-1 parcialmente purificado. El enzima se inmovilizó en los soportes Eupergit® C, MANA-agarosa y LentiKats®. Los biocatalizadores inmovilizados se emplearon en la síntesis de altas concentraciones de Asp (≥ 60 g/L). Además, el enzima inmovilizado se reutilizó eficientemente en la síntesis del aminoácido, manteniendo alrededor del 90% de su actividad inicial al cabo de 5 ciclos de reacción en todos los casos. La síntesis de las aminas aromáticas 1-feniletilamina (FEA) y 3-amino-1-fenilbutano (AFB) se llevó a cabo utilizando biocatalizadores (células y/o enzima parcialmente purificado) con actividad ω−transaminasa (ω−TA). Se estableció un método de permeabilización de las membranas de células ω−TA utilizando bromuro de cetrimonio (CTAB). Las células ω−TA se inmovilizaron en el soporte LentiKats® con un 100% de retención de su actividad catalítica. El enzima ω−TA se inmovilizó en varios soportes, obteniéndose los mejores resultados en Eupergit® CM y LentiKats®. La inmovilización en LentiKats®, tanto de células (no permeabilizadas y permeabilizadas) como del enzima, permitió la reutilización de los catalizadores hasta en 5 y 10 ciclos de síntesis de AFB, manteniendo alrededor del 80 y 70% de la actividad inicial, respectivamente. Por último, se comprobó que el enzima aspartasa mutado (AspB-C6) a partir de AspB, cataliza la reacción de aminación regioselectiva del ácido crotónico para producir β−aminobutirato. Este enzima se inmovilizó en los soportes Eupergit® C y MANA-agarosa según los métodos de inmovilización establecidos para el enzima AspB en los mismos soportes. Se obtuvieron rendimientos de inmovilización similares pero las actividades retenidas fueron significativamente inferiores para AspB-C6 que para AspB.

    الوصف (مترجم): The objective of this thesis is to establish biocatalytic methods for the synthesis of the amino acids L-aspartate, L-phenylalanine and β−aminobutyrate, as well as the aromatic amines 1-phenylethylamine and 3-amine-1-phenylbutane, by using biocatalysts with transaminase and ammonia-lyase activity immobilized by covalent attachment techniques (for enzymes) and entrapment (for enzymes and cells). Two methods for the synthesis of the essential aromatic amino acid L-phenylalanine (Phe) were established. The first method was carried out by using L-aspartate transaminase (AAT) from porcine heart as biocatalyst. The immobilization of the enzyme AAT on Eupergit® C, MANA-agarose and LentiKats® supports was optimized, and the three immobilized enzymatic derivatives were used for the synthesis of Phe. AAT immobilized on Eupergit® C and LentiKats® allowed improving the stability of the enzyme as well as reaching reaction yields of Phe over 70%. Moreover, a multi-enzymatic one-pot method for the synthesis of Phe was established by coupling of two consecutive enzymatic reactions catalyzed by aspartase (AspB) and transaminase (AT). The compatibility of both enzymes under the reaction conditions (pH 7,5 and 37°C) was shown; and, the optimum concentration of substrates (0,15 M fumarate, 0,3 M NH4Cl and 0,1 M phenylpyruvate) and enzymes (0,3 U of AspB/mL and 2 U of AT/mL) were established. In these conditions, the global reaction yield was 80%. L-aspartate was synthesized by using the enzyme L-aspartate ammonia-lyase or aspartase (AspB) from Bacillus sp. YM55-1. The enzyme was immobilized on Eupergit® C, MANA-agarose and LentiKats® supports. The immobilized biocatalysts were used for the synthesis of highly concentrated Asp (≥ 60 g/L). Furthermore, the immobilized biocatalysts were efficiently reused in 5 cycles of Asp synthesis, maintaining over 90% of activity and reaching over 90% of conversion in all the cases. The synthesis of the aromatic amine 3-amine-phenylbutane (APB) was carried out by means of cells with ω−transaminase (ω−TA) activity as well as the partially purified enzyme ω−TA. A permeabilization method of the cell membranes with cetrimonium bromide (CTAB) was performed. Cells were immobilized in LentiKats® with 100% retention of the catalytic activity. The enzyme ω−TA was immobilized on several supports, and the best results were obtained with Eupergit® CM and LentiKats® supports. The cells (non-permeabilized and permeabilized) and the enzyme immobilized in LentiKats®, allowed reusing the biocatalysts up to 5 and 10 cycles of synthesis of APB, maintaining around 80 and 70% of the initial activity respectively. Finally, it was shown that the mutated aspartase (AspB-C6) from AspB, catalyzes the regioselective amination of crotonic acid to yield β−aminobutyrate. This enzyme was immobilized on Eupergit® C and MANA-agarose supports, according to the immobilization methods established for AspB on the same supports. The immobilization yields were similar; however the retained activities were lower than those obtained for AspB.

    وصف الملف: application/pdf

  2. 2
    دورية أكاديمية

    المصدر: Naye , F , Toupin-April , K , de Wit , M , LeBlanc , A , Dubois , O , Boonen , A , Barton , J L , Fraenkel , L , Li , L C , Stacey , D , March , L , Barber , C E H , Hazlewood , G S , Guillemin , F , Bartlett , S J , Berthelsen , D B , Mather , K , Arnaud , L , Akpabio , A , Adebajo , A , Schultz , G , Sloan , V S , Gill , ....

    الوصف: OBJECTIVES: Shared decision making (SDM) is a central tenet in rheumatic and musculoskeletal care. The lack of standardization regarding SDM instruments and outcomes in clinical trials threatens the comparative effectiveness of interventions. The Outcome Measures in Rheumatology (OMERACT) SDM Working Group is developing a Core Outcome Set for trials of SDM interventions in rheumatology and musculoskeletal health. The working group reached consensus on a Core Outcome Domain Set in 2020. The next step is to develop a Core Outcome Measurement Set through the OMERACT Filter 2.2. METHODS: We conducted a scoping review (PRISMA-ScR) to identify candidate instruments for the OMERACT Filter 2.2 We systematically reviewed five databases (Ovid MEDLINE®, Embase, Cochrane Library, CINAHL and Web of Science). An information specialist designed search strategies to identify all measurement instruments used in SDM studies in adults or children living with rheumatic or musculoskeletal diseases or their important others. Paired reviewers independently screened titles, abstracts, and full text articles. We extracted characteristics of all candidate instruments (e.g., measured construct, measurement properties). We classified candidate instruments and summarized evidence gaps with an adapted version of the Summary of Measurement Properties (SOMP) table. RESULTS: We found 14,464 citations, read 239 full text articles, and included 99 eligible studies. We identified 220 potential candidate instruments. The five most used measurement instruments were the Decisional Conflict Scale (traditional and low literacy versions) (n=38), the Hip/Knee-Decision Quality Instrument (n=20), the Decision Regret Scale (n=9), the Preparation for Decision Making Scale (n=8), and the CollaboRATE (n=8). Only 44 candidate instruments (20%) had any measurement properties reported by the included studies. Of these instruments, only 57% matched with at least one of the 7-criteria adapted SOMP table. CONCLUSION: We identified 220 candidate instruments used in ...

    وصف الملف: application/pdf

  3. 3
    دورية أكاديمية
  4. 4
    دورية أكاديمية

    المؤلفون: Baldock, Brandi L. (ORCID 0000-0002-8027-2078), Blanchard, Joanna D., Fernandez, Anthony L. (ORCID 0000-0002-2553-2949)

    المصدر: Journal of Chemical Education. Dec 2021 98(12):4046-4053.

    تمت مراجعته من قبل الزملاء: Y

    Page Count: 8

    مستخلص: General chemistry students need to understand the concept of intermolecular forces and use them to predict the properties of materials. To do this, they must create symbolic representations of molecules, relate these to physical observations, and explain them using submicroscopic theoretical constructs. When these concepts are taught separately, students lack the context to fully understand and retain them. In this inquiry-based laboratory experiment, students explored the interrelated concepts of molecular structure and solubility in an applied context and then explained their individual results and the class results using the concept of intermolecular forces. Specifically, they drew the molecular structures of an analogous series of alcohol molecules and evaluated the relative solubility of the alcohols in polar versus nonpolar solvents. Designing the procedure to avoid student exposure to hazardous reagents facilitated their exploration of the underlying concepts. Using Sharpie pigment in each alcohol as an indicator dye helped the students visually assess their relative solubility in different solvents. Students typically observed that the relative solubility of the alcohols in the solvents could be predicted based on key factors that affect molecular polarity and hydrophobicity, in particular hydrocarbon chain length and surface-to-volume ratios. The students explained the pooled class solubility results based on the types and strengths of intermolecular forces present in each substance. Significance testing performed on our pre- and postlaboratory quiz data indicate that completing this experiment significantly improved students' conceptual understanding of structure-property relationships. Item difficulty and discrimination index scores were used to validate these quiz questions.

    Abstractor: As Provided

  5. 5
    دورية أكاديمية

    المؤلفون: Baldock, Brandi L. (ORCID 0000-0002-8027-2078), Fernandez, Anthony L. (ORCID 0000-0002-2553-2949), Franco, Jimmy (ORCID 0000-0002-9085-1356), Provencher, Brian A. (ORCID 0000-0003-2607-9530), McCoy, Mark R. (ORCID 0000-0001-9247-5174)

    المصدر: Journal of Chemical Education. Mar 2021 98(3):833-842.

    تمت مراجعته من قبل الزملاء: Y

    Page Count: 10

    مصطلحات جغرافية: Massachusetts

    مستخلص: During the Spring 2020 semester, many institutions abruptly transitioned their courses from face-to-face instruction to remote learning in response to the COVID-19 pandemic. To address the unique challenges posed by the remote teaching and learning modality, our department used mobile technology to adapt empirically validated instructional strategies for use in our remote courses. At Merrimack College, all faculty and students have iPads and Apple Pencils, and the members of the Department of Chemistry and Biochemistry have incorporated this mobile technology into all of our course offerings. Our continued use of this technology eased the transition for both faculty and students by promoting course continuity and decreasing the cognitive load imposed by the transition. Survey responses suggest that students appreciated the structure provided by scaffolded course materials and synchronous class meetings, which helped keep them engaged in their chemistry courses. Coupling active learning instruction with the Zoom video conferencing platform allowed students to connect with the instructor and other students; this was highly valued by our students. Overall, we can conclude that universal access to technology, creating community using videoconferencing software, and intentional pedagogical choices to incorporate active learning created a positive learning environment for students.

    Abstractor: As Provided

  6. 6
    دورية أكاديمية

    المساهمون: Clinical and Translational Science Collaborative of Cleveland, School of Medicine, Case Western Reserve University, U.S. Department of Defense, Crohn's and Colitis Foundation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health

    المصدر: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224

    مصطلحات موضوعية: Immunology, Immunology and Allergy

    الوصف: Hospitalized patients have an increased risk of developing hospital-acquired sacral pressure injury (HASPI). However, it is unknown whether SARS-CoV-2 infection affects HASPI development. To explore the role of SARS-CoV-2 infection in HASPI development, we conducted a single institution, multi-hospital, retrospective study of all patients hospitalized for ≥5 days from March 1, 2020 to December 31, 2020. Patient demographics, hospitalization information, ulcer characteristics, and 30-day-related morbidity were collected for all patients with HASPIs, and intact skin was collected from HASPI borders in a patient subset. We determined the incidence, disease course, and short-term morbidity of HASPIs in COVID-19(+) patients, and characterized the skin histopathology and tissue gene signatures associated with HASPIs in COVID-19 disease. COVID-19(+) patients had a 63% increased HASPI incidence rate, HASPIs of more severe ulcer stage (OR 2.0, p<0.001), and HASPIs more likely to require debridement (OR 3.1, p=0.04) compared to COVID-19(-) patients. Furthermore, COVID-19(+) patients with HASPIs had 2.2x increased odds of a more severe hospitalization course compared to COVID-19(+) patients without HASPIs. HASPI skin histology from COVID-19(+) patients predominantly showed thrombotic vasculopathy, with the number of thrombosed vessels being significantly greater than HASPIs from COVID-19(-) patients. Transcriptional signatures of a COVID-19(+) sample subset were enriched for innate immune responses, thrombosis, and neutrophil activation genes. Overall, our results suggest that immunologic dysregulation secondary to SARS-CoV-2 infection, including neutrophil dysfunction and abnormal thrombosis, may play a pathogenic role in development of HASPIs in patients with severe COVID-19.

  7. 7
    دورية أكاديمية

    المؤلفون: Provencher, Brian A. (ORCID 0000-0003-2607-9530), Franco, Jimmy (ORCID 0000-0002-9085-1356), Fernandez, Anthony L. (ORCID 0000-0002-2553-2949), Theberge, Stephen, Zwickau, Brenda

    المصدر: Journal of Chemical Education. May 2020 97(5):1303-1309.

    تمت مراجعته من قبل الزملاء: Y

    Page Count: 7

    مستخلص: Educators are constantly looking to improve their pedagogical strategies. This can range from teaching strategies for a specific topic to holistic curriculum changes. Recently, the approach that chemistry departments have chosen to deliver their introductory courses has garnished increasing attention from educators. Our department recently converted our introductory sequence from the traditional two semesters of general chemistry followed by two semesters of organic chemistry to what is often referred to as the 1-2-1 sequence. The 1-2-1 sequence is an introductory sequence in which students take General Chemistry I followed by Organic Chemistry I and II and last General Chemistry II as the fourth introductory course in the introductory sequence. The conversion was motivated by the need to implement a curriculum that more effectively addressed our students' needs and deficiencies and to more effectively utilize department resources to service chemistry majors and the college. The work here highlights the motivation for the conversion, insight into its implementation, and a preliminary investigation on how this change has impacted the Organic Chemistry I class.

    Abstractor: As Provided

  8. 8
    دورية أكاديمية

    المصدر: Décary , S , de Wit , M , Naye , F , Barton , J L , Fraenkel , L , Li , L C , Brooks , P , Stacey , D , Maxwell , L J , Campbell , W , Hofstetter , C , Voshaar , M , Meara , A , Christensen , R , Boonen , A , Suarez-Almazor , M E , Meade , T , March , L , Jull , J E , Alten , R , Morgan , E M , Stewart Hazlewood , G , Barber , C ....

    الوصف: Objective: To gain consensus on the definitions and descriptions of the domains of the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials evaluating shared decision making (SDM) interventions. Methods: Following the OMERACT Handbook methods, our Working Group (WG), comprised of 90 members, including 17 patient research partners (PRPs) and 73 clinicians and researchers, had six virtual meetings in addition to email exchanges to develop draft definitions and descriptions. The WG then conducted an international survey of its members to gain consensus on the definitions and descriptions. Finally, the WG members had virtual meetings and e-mail exchanges to review survey results and finalize names, definitions and descriptions of the domains. Results: WG members contributed to developing the definitions. Fifty-two members representing four continents and 13 countries completed the survey, including 15 PRPs, 33 clinicians and 37 researchers. PRPs and clinicians/researchers agreed with all definitions and descriptions with agreements ranging from 87% to 100%. Respondents suggested wording changes to the names, definitions and descriptions to better reflect the domains. Discussions led to further simplification and clarification to address common questions/concerns about the domains. Conclusion: Our WG reached consensus on the definitions and descriptions of the domains of the core domain set for rheumatology trials of SDM interventions. This step is crucial to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set. Clinical significance: The current study provides consensus-based definitions and descriptions for the domains of the OMERACT core domain set for shared decision making interventions from patients/caregivers, clinicians and researchers. This is a crucial step to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core ...

  9. 9
    دورية أكاديمية

    المصدر: Dermatology (10188665); 2024, Vol. 240 Issue 2, p352-356, 5p

    مستخلص: Introduction: Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with an increased risk of mortality compared to the general population. The causes of this increased risk are not well understood. Misdiagnosis is common in PG, and many studies are limited by the inclusion of misdiagnosed cases. The goal of this study was to review autopsy findings, identify causes of death, and identify factors that may worsen outcomes among deceased patients confirmed to have PG. Methods: Data was retrospectively reviewed from the electronic medical records at five academic hospitals. A search was conducted for deceased patients with a diagnosis of PG who had an autopsy performed between 2010 and 2020. We report a descriptive analysis of 11 patients and their clinical characteristics, causes of death, and autopsy findings. Results: The average age of death was 62.9 years. Seven patients had at least one underlying condition known to be associated with PG including inflammatory bowel disease, inflammatory arthritis, or a hematologic disorder. The most common cause of death was infection (n = 6, 54.5%), followed by pulmonary embolism (n = 3, 27.3%), and myelodysplastic syndrome (n = 2, 18.2%). Six patients (54.5%) were taking systemic steroids at the time of death. Conclusion: The development of PG may shorten life expectancy among those with underlying conditions associated with PG, and common treatments for PG may contribute to the risk of fatal complications. Awareness of the risk of infection, thrombosis, and malignancy among those with PG is necessary for proper management. Further research is needed to explore the relationship between PG and thromboembolism. [ABSTRACT FROM AUTHOR]

    : Copyright of Dermatology (10188665) is the property of Karger AG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

  10. 10
    دورية أكاديمية

    المصدر: Arthritis & Rheumatology ; volume 74, issue 12, page 1906-1915 ; ISSN 2326-5191 2326-5205

    الوصف: Objective Patients with immune‐mediated inflammatory diseases (IMIDs) receiving B cell–depleting therapy (BCDT) are among the most vulnerable to severe COVID‐19, as well as the most likely to suboptimally respond to SARS–CoV‐2 vaccines. However, little is known about the frequency or severity of breakthrough infection in this population. We retrospectively analyzed a large group of vaccinated IMID patients undergoing BCDT in order to identify breakthrough COVID‐19 infections and assess their outcomes. Methods In this retrospective cohort study, the pharmacy records and COVID‐19 registry at the Cleveland Clinic were searched using specific International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes to identify IMIDs patients who 1) received treatment with BCDT, 2) were vaccinated against SARS–CoV‐2, and 3) experienced breakthrough infections. Each electronic medical record was reviewed to extract clinical data and outcomes. Univariate and multivariable logistic/proportional odds regression models were used to examine the risk factors for severe outcomes. Results Of 1,696 IMID patients receiving BCDT, 74 developed breakthrough COVID‐19 prior to December 16, 2021. Outcomes were severe, with 29 patients hospitalized (39.2%), 11 patients requiring critical care (14.9%), and 6 deaths (8.1%). Outpatient anti–SARS–CoV‐2 monoclonal antibodies were used to treat 21 patients, with 1 hospitalization and no deaths. A comparator analysis examining 1,437 unvaccinated IMID patients receiving BCDT over the same time period identified 57 COVID‐19 cases (4.0%), with 28 requiring hospitalization (49.1%), including 7 deaths (12.3%). Conclusion IMID patients receiving BCDT regardless of vaccine status appear to be vulnerable to infection with SARS–CoV‐2, and use of BCDT is frequently associated with severe outcomes. Outpatient use of anti–SARS–CoV‐2 monoclonal antibody therapy appears to be associated with enhanced clinical outcomes.