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      • KCI등재후보
      • SCISCIESCOPUS

        Ground-State Kinetics of Bistable Redox-Active Donor–Acceptor Mechanically Interlocked Molecules

        Fahrenbach, Albert C.,Bruns, Carson J.,Li, Hao,Trabolsi, Ali,Coskun, Ali,Stoddart, J. Fraser American Chemical Society 2014 Accounts of chemical research Vol.47 No.2

        <P>The ability to design and confer control over the kinetics of theprocesses involved in the mechanisms of artificial molecular machines is at the heart of the challenge to create ones that can carry out useful work on their environment, just as Nature is wont to do. As one of the more promising forerunners of prototypical artificial molecular machines, chemists have developed bistable redox-active donor–acceptor mechanically interlocked molecules (MIMs) over the past couple of decades. These bistable MIMs generally come in the form of [2]rotaxanes, molecular compounds that constitute a ring mechanically interlocked around a dumbbell-shaped component, or [2]catenanes, which are composed of two mechanically interlocked rings. As a result of their interlocked nature, bistable MIMs possess the inherent propensity to express controllable intramolecular, large-amplitude, and reversible motions in response to redox stimuli. In this Account, we rationalize the kinetic behavior in the ground state for a large assortment of these types of bistable MIMs, including both rotaxanes and catenanes. These structures have proven useful in a variety of applications ranging from drug delivery to molecular electronic devices.</P><P>These bistable donor–acceptor MIMs can switch between two different isomeric states. The favored isomer, known as the ground-state co-conformation (GSCC) is in equilibrium with the less favored metastable state co-conformation (MSCC). The forward (<I>k</I><SUB>f</SUB>) and backward (<I>k</I><SUB>b</SUB>) rate constants associated with this ground-state equilibrium are intimately connected to each other through the ground-state distribution constant, <I>K</I><SUB>GS</SUB>. Knowing the rate constants that govern the kinetics and bring about the equilibration between the MSCC and GSCC, allows researchers to understand the operation of these bistable MIMs in a device setting and apply them toward the construction of artificial molecular machines.</P><P>The three biggest influences on the ground-state rate constants arise from (i) ground-state effects, the energy required to breakup the noncovalent bonding interactions that stabilize either the GSCC or MSCC, (ii) spacer effects, where the structures overcome additional barriers, either steric or electrostatic or both, en route from one co-conformation to the other, and (iii) the physical environment of the bistable MIMs. By managing all three of these effects, chemists can vary these rate constants over many orders of magnitude. We also discuss progress toward achieving mechanostereoselective motion, a key principle in the design and realization of artificial molecular machines capable of doing work at the molecular level, by the strategic implementation of free energy barriers to intramolecular motion.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/achre4/2014/achre4.2014.47.issue-2/ar400161z/production/images/medium/ar-2013-00161z_0012.gif'></P>

      • SCOPUSKCI등재

        Can Perioperative Chemotherapy for Advanced Gastric Cancer Be Recommended on the Basis of Current Research? A Critical Analysis

        Bauer, Katrin,Porzsolt, Franz,Henne-Bruns, Doris The Korean Gastric Cancer Association 2014 Journal of gastric cancer Vol.14 No.1

        Purpose: According to current guidelines, perioperative chemotherapy is an integral part of the treatment strategy for advanced gastric cancer. Randomized controlled studies have been conducted in order to determine whether perioperative chemotherapy leads to improved R0 resection rates, fewer recurrences, and prolonged survival. The aim of our project was to critically appraise three major studies to establish whether perioperative chemotherapy for advanced, potentially resectable gastric cancer can be recommended on the basis of their findings. Materials and Methods: We analyzed the validity of the three most important studies (MAGIC, ACCORD, and EORTC) using a standardized questionnaire. Each study was evaluated for the study design, patient selection, randomization, changes in protocol, participating clinics, preoperative staging, chemotherapy, homogeneity of subjects, surgical quality, analysis of the results, and recruitment period. Results: All three studies had serious shortcomings with respect to patient selection, homogeneity of subjects, changes in protocol, surgical quality, and analysis of the results. The protocols of the MAGIC and ACCORD-studies were changed during the study period because of insufficient recruitment, such that carcinomas of the lower esophagus and the stomach were examined collectively. In neither the MAGIC study nor the ACCORD study did patients undergo adequate lymphadenectomy, and only about half of the patients in the chemotherapy group could undergo the treatment specified in the protocol. The EORTC study had insufficient statistical power. Conclusions: We concluded that none of the three studies was sufficiently robust to justify an unrestrained recommendation for perioperative chemotherapy in cases of advanced gastric cancer.

      • SCOPUSKCI등재

        Comparison of International Guidelines on the Accompanying Therapy for Advanced Gastric Cancer: Reasons for the Differences

        Bauer, Katrin,Schroeder, Marcel,Porzsolt, Franz,Henne-Bruns, Doris The Korean Gastric Cancer Association 2015 Journal of gastric cancer Vol.15 No.1

        The purpose of this study was to determine if international guidelines differ in their recommendations concerning additive therapy for advanced, but potentially curable, gastric cancer. A systematic search of the English and German literature was conducted in the databases Medline, Cochrane Database, Embase, and PubMed. The search terms used were 'guidelines gastric cancer,' 'guidelines stomach cancer,' and 'Leitlinien Magenkarzinom.' Six different guidelines published after January 1, 2010, in which the tumors were classified according to the seventh edition of the TNM system (2010), were identified. Although the examined guidelines were based on the same study results, their recommendations concerning accompanying therapy for gastric cancer differ considerably. While perioperative chemotherapy is recommended in Germany, Great Britain, and large parts of Europe, postoperative adjuvant radiochemotherapy or perioperative chemotherapy is recommended in the USA and Canada. In Japan, postoperative adjuvant chemotherapy is recommended. The results of identical studies were interpreted differently in different countries. Since considerable effort is required for each country to separately test relevant studies for their validity and suitability, an international cooperation could simplify the creation of a common basis for guidelines and contribute to improved comparability of international guidelines.

      • KCI등재

        Can Perioperative Chemotherapy for Advanced Gastric Cancer Be Recommended on the Basis of Current Research? A Critical Analysis

        Katrin Bauer,Franz Porzsolt,Doris Henne-Bruns 대한위암학회 2014 Journal of gastric cancer Vol.14 No.1

        Purpose: According to current guidelines, perioperative chemotherapy is an integral part of the treatment strategy for advanced gastric cancer. Randomized controlled studies have been conducted in order to determine whether perioperative chemotherapy leads to improved R0 resection rates, fewer recurrences, and prolonged survival. The aim of our project was to critically appraise three major studies to establish whether perioperative chemotherapy for advanced, potentially resectable gastric cancer can be recommended on the basis of their findings. Materials and Methods: We analyzed the validity of the three most important studies (MAGIC, ACCORD, and EORTC) using a standardized questionnaire. Each study was evaluated for the study design, patient selection, randomization, changes in protocol, participating clinics, preoperative staging, chemotherapy, homogeneity of subjects, surgical quality, analysis of the results, and recruitment period. Results: All three studies had serious shortcomings with respect to patient selection, homogeneity of subjects, changes in protocol, surgical quality, and analysis of the results. The protocols of the MAGIC and ACCORD-studies were changed during the study period because of insufficient recruitment, such that carcinomas of the lower esophagus and the stomach were examined collectively. In neither the MAGIC study nor the ACCORD study did patients undergo adequate lymphadenectomy, and only about half of the patients in the chemotherapy group could undergo the treatment specified in the protocol. The EORTC study had insufficient statistical power. Conclusions: We concluded that none of the three studies was sufficiently robust to justify an unrestrained recommendation for perioperativechemotherapy in cases of advanced gastric cancer.

      • KCI등재

        Comparison of International Guidelines on the Accompanying Therapy for Advanced Gastric Cancer: Reasons for the Differences

        Katrin Bauer,Marcel Schroeder,Franz Porzsolt,Henne-Bruns 대한위암학회 2015 Journal of gastric cancer Vol.15 No.1

        The purpose of this study was to determine if international guidelines differ in their recommendations concerning additive therapy for advanced, but potentially curable, gastric cancer. A systematic search of the English and German literature was conducted in the databases Medline, Cochrane Database, Embase, and PubMed. The search terms used were ‘guidelines gastric cancer,’ ‘guidelines stomach cancer,’ and ‘Leitlinien Magenkarzinom.’ Six different guidelines published after January 1, 2010, in which the tumors were classified according to the seventh edition of the TNM system (2010), were identified. Although the examined guidelines were based on the same study results, their recommendations concerning accompanying therapy for gastric cancer differ considerably. While perioperative chemotherapy is recommended in Germany, Great Britain, and large parts of Europe, postoperative adjuvant radiochemotherapy or perioperative chemotherapy is recommended in the USA and Canada. In Japan, postoperative adjuvant chemotherapy is recommended.The results of identical studies were interpreted differently in different countries. Since considerable effort is required for each country to separately test relevant studies for their validity and suitability, an international cooperation could simplify the creation of a common basis for guidelines and contribute to improved comparability of international guidelines.

      • SCISCIESCOPUS

        A Neutral Naphthalene Diimide [2]Rotaxane

        Jacquot de Rouville, Henri-Pierre,Iehl, Julien,Bruns, Carson J.,McGrier, Psaras L.,Frasconi, Marco,Sarjeant, Amy A.,Stoddart, J. Fraser American Chemical Society 2012 ORGANIC LETTERS Vol.14 No.20

        <P>A neutral donor–acceptor [2]rotaxane, which has been synthesized using click chemistry, has had its solid-state structure and superstructure elucidated by X-ray crystallography. Both dynamic <SUP>1</SUP>H NMR spectroscopy and electrochemical investigations have been employed in an attempt to shed light on both geometrical reorganization and redox-switching processes that are occurring or can be induced within the [2]rotaxane.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/orlef7/2012/orlef7.2012.14.issue-20/ol3022963/production/images/medium/ol-2012-022963_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ol3022963'>ACS Electronic Supporting Info</A></P>

      • KCI등재후보

        실행 요약: 당뇨병의 진단과 관리에서 검사실적 분석에 대한 지침과 권고안

        David B. Sacks,Mark Arnold,George L. Bakris,David E. Bruns,Andrea Rita Horvath,M. Sue Kirkman,Ake Lernmark,Boyd E. Metzger,David M. Nathan 대한진단검사의학회 2011 Laboratory Medicine Online Vol.1 No.4

        Background: Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially. Approach: An expert committee compiled evidencebased recommendations for the use of laboratory analysis in patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. A draft of the guidelines was posted on the Internet, and the document was modified in response to comments. The guidelines were reviewed by the joint Evidence-Based Laboratory Medicine Committee of the AACC and the National Academy of Clinical Biochemistry and were accepted after revisions by the Professional Practice Committee and subsequent approval by the Executive Committee of the American Diabetes Association. Content: In addition to the long-standing criteria based on measurement of venous plasma glucose, diabetes can be diagnosed by demonstrating increased hemoglobin A1c (HbA1c) concentrations in the blood. Monitoring of glycemic control is performed by the patients measuring their own plasma or blood glucose with meters and by laboratory analysis of Hb A1c. The potential roles of noninvasive glucose monitoring, genetic testing,and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. Summary: The guidelines provide specific recommendations based on published data or derived from expert consensus. Several analytes are found to have minimal clinical value at the present time, and measurement of them is not recommended.

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