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Not all arrestins are created equal: Therapeutic implications of the functional diversity of the β-arrestins in the heart

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World Journal of Cardiology 2019年第2期11卷 47-56页

作者： Anastasios lymperopoulos shelby l wertz Celina M Pollard Victoria l Desimine Jennifer Maning Katie A McCrink laboratory for the Study of Neurohormonal Control of the Circulation Department of Pharmaceutical Sciences (Pharmacology) College of PharmacyNova Southeastern University Jackson Memorial Hospital Massachusetts General Hospital

The two ubiquitous, outside the retina, G protein-coupled receptor(GPCR)adapter proteins, β-arrestin-1 and-2(also known as arrestin-2 and-3,respectively), have three major functions in cells: GPCR desensitization, i.e.,receptor decoupling from G-proteins; GPCR internalization via clathrin-coated pits; and signal transduction independently of or in parallel to G-proteins. Bothβ-arrestins are expressed in the heart and regulate a large number of cardiac GPCRs. The latter constitute the single most commonly targeted receptor class by Food and Drug Administration-approved cardiovascular drugs, with about onethird of all currently used in the clinic medications affecting GPCR *** β-arrestin-1 and-2 play important roles in signaling and function of several GPCRs, in particular of adrenergic receptors and angiotensin II type 1 receptors,in cardiac myocytes, they have been a major focus of cardiac biology research in recent years. Perhaps the most significant realization coming out of their studies is that these two GPCR adapter proteins, initially thought of as functionally interchangeable, actually exert diametrically opposite effects in the mammalian myocardium. Specifically, the most abundant of the two β-arrestin-1 exerts overall detrimental effects on the heart, such as negative inotropy and promotion of adverse remodeling post-myocardial infarction(MI). In contrast, β-arrestin-2 is overall beneficial for the myocardium, as it has anti-apoptotic and antiinflammatory effects that result in attenuation of post-MI adverse remodeling,while promoting cardiac contractile function. Thus, design of novel cardiac GPCRligands that preferentially activate β-arrestin-2 over β-arrestin-1 has the potential of generating novel cardiovascular therapeutics for heart failure and other heart diseases.

关键词： Adverse remodeling β-arrestin Biased signaling Cardiac myocyte Cardiac fibroblast contractility Functional divergence G protein-coupled receptor Heart failure Hormone Myocardial infarction Signal transducer

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Social learning contributions to the etiology and treatment of functional abdominal pain and inflammatory bowel disease in children and adults

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World Journal of Gastroenterology 2007年第17期13卷 2397-2403页

作者： Rona l levy shelby l langer William E Whitehead School of Social Work University of WashingtonUnited States Center for Functional GI and Motility Disorders University-of-North-Carolina-at-Chapel-Hill-United-State

This paper reviews empirical work on cognitive and social learning contributions to the etiology and treatment of illness behavior associated with functional abdominal pain and inflammatory bowel disease. A particular emphasis is placed on randomized controlled trials, the majority of which are multi-modal in orientation, incorporating elements of cognitive behavioral therapy, social learning, and relaxation. Based on this review, we offer methodological and clinical suggestions: (1) Research investigations should include adequate sample sizes, long-term follow-up assessments, and a credible, active control group. (2) Standard gastrointestinal practice should include, when appropriate, learning opportunities for patients and family members, for example, instruction regarding the encouragement of wellness behavior.

关键词： Functional abdominal pain Cognitivebehavioral therapy Social learning Irritable bowelsyndrome Inflammatory bowel disease Illness behavior

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Scalable, Green Chain Transfer Agent for Cationic RAFT Polymerizations

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Chinese Journal of Chemistry 2023年第4期41卷 399-404页

作者： Scott W.Spring Chloe S.Cerione Jesse H.Hsu shelby l.Shankel Brett P.Fors Department of Chemistry and Chemical Biology Cornell UniversityIthacaNew York14853 United States

Cationic polymerizations of vinyl ethers have gained recent attention due to their ability to produce robust,biorenewable *** developments have been largely enabled by the advent of cationic reversible addition−fragmentation chain-transfer(RAFT)polymerization;however,the scalability and sustainability of this method are hindered by current chain-transfer agents(CTAs),which exist as viscous,colored oils requiring complex syntheses and solvent-intensive ***,we produce a solid,colorless CTA through a green synthetic route in 83%yield on a 50-gram *** investigate the utility of this CTA in chemical,electrochemical,photochemical,and acid-initiated methods,revealing that it achieves efficient polymerization with excellent control over molecular weight,low dispersity values,high chain end fidelity,and temporal control in cationic RAFT polymerizations.

关键词： Vinyl ethers CTA Cationic polymerization Green RAFT

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Agency and Relationship Dissatisfaction Associated with Orthorexia Symptomatology

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Open Journal of Psychiatry 2018年第3期8卷 345-354页

作者： Crystal D. Oberle shelby l. lipschuetz Department of Psychology Texas State University San Marcos TX USA

This study explored whether orthorexia symptomatology is linked to gender-related personality traits and to levels of satisfaction in one’s romantic relationships. Undergraduate students (418 women, 98 men) completed an online survey with measures to assess orthorexia symptomatology, agency, unmitigated agency, communion, unmitigated communion, and relationship satisfaction. Orthorexia symptomatology was positively correlated with levels of agency (r = 0.18;p p = 0.51), communion (p = 0.76), unmitigated communion (p = 0.17), and relationship status (p = 0.99). Among the participants who were in a committed relationship, symptomatology was negatively correlated with relationship satisfaction (p = 0.01), and this correlation was most pronounced for those with higher levels of unmitigated agency (p = 0.01). Orthorexia is associated with the agency personality trait, indicative of one’s need to be independent and to achieve personal accomplishments. However, particularly for those individuals whose agency becomes unmitigated, characterized by selfishness and avoidance of others, orthorexia symptomatology predicts significant dissatisfaction in romantic relationships.

关键词： Orthorexia Relationship Satisfaction Agency Communion

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Healthcare Resource Utilization and Associated Costs in Patients with Advanced Melanoma Receiving First-line Ipilimumab

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Journal of Cancer Therapy 2015年第10期6卷 833-840页

作者： Ahmad Tarhini shelby l. Corman Sumati Rao Kim Margolin Xiang Ji Sonam Mehta Marc F. Botteman University of Pittsburgh Cancer Institute Pittsburgh USA Pharmerit International Bethesda USA Bristol-Myers Squibb Plainsboro USA Stanford University Stanford USA

Background: To describe healthcare costs, excluding ipilimumab drug costs, in patients with advanced melanoma receiving ipilimumab in the US community practice setting. Methods: This was a retrospective chart review of unresectable stage III/IV melanoma patients who received first-line ipilimumab monotherapy between 04/2011 and 09/2012. Healthcare resource utilization included inpatient, emergency, specialist and hospice visits, laboratory tests, radiation, surgeries, and nursing home stays. Publicly available US unit costs were applied to each resource type to estimate costs, which were analyzed by time periods: during ipilimumab treatment, post-ipilimumab treatment (post-regimen), and within 90 days prior to death (pre-death). Generalized linear mixed models were used to explore cost predictors during the treatment period, on a per-dose-interval basis, defined as the time between ipilimumab doses. Results: Data were abstracted from 273 patient charts at 34 sites. Excluding ipilimumab drug costs, total monthly costs during the treatment regimen, post-regimen, and pre-death periods were $690, $2151, and $5123, respectively. Total healthcare costs were 27 times higher during dose intervals with a grade 3/4 adverse event compared with intervals without a grade 3/4 adverse event. Eastern Cooperative Oncology Group performance status ≥ 2 (vs 0) was also associated with significantly higher cost per dose interval. Conclusions: In this population, monthly costs exclusive of drug were significantly lower during the treatment period than in subsequent periods. Unfavorable ECOG PS was associated with significant increases in cost per dose interval. Grade 3/4 adverse events were associated with a marked increase in healthcare costs, but occurred in a small proportion of dose intervals.

关键词： Healthcare Resource Utilization Ipilimumab Melanoma

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Review of the optimal timing and technique for extensor tendon reconstruction in composite dorsal hand wounds

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Plastic and Aesthetic Research 2019年第8期6卷 1-9页

作者： shelby lies Asher Horowitz Gordon lee Andrew Y.Zhang Department Plastic Surgery University Texas SouthwesternDallasTX 75390USA Department Plastic Surgery Stanford UniversityPalo AltoCA 94304USA

Aim: The management of complex dorsal hand wounds with extensor tendon loss is controversial. Treatment has focused on soft tissue coverage, but there is limited evidence comparing immediate vs. staged tendon reconstruction. This review evaluates existing literature to determine the optimal management of composite hand defects. Methods: A MEDlINE database review was performed including objective measurements such as number of operations, total active motion, grip strength, days to maximum range of motion (ROM), and return to work. Data extraction included demographics, surgical techniques, complications, and relative outcome. We compared primary and secondary staged reconstruction to correlate any significant differences in outcome and determine optimal timing and technique for extensor tendon reconstruction. We extracted information on flap types including regional and free tissue transfer with tendinous components vs. staged tendon grafts. Results: Comparison of outcomes showed that patients with immediate reconstruction had fewer operations, faster return to maximum ROM, and greater chance of returning to work. The most successful single stage flaps include the radial forearm, suitable for reconstructing one to three tendons and the dorsalis pedis for three or four tendons;however, there were significantly more complications in immediate reconstruction particularly regarding donor site morbidity. Pedicled flaps had better total active motion. The two-stage approach resulted in acceptable functional outcomes without significant complications. ;Conclusion: Immediate cutaneous tendinous flaps have clear advantages over staged approaches for reconstruction ofcomposite dorsal hand wounds. Benefits include less operations, faster time to maximum ROM, and higher percent of patients returning to work;however, significantly more flap related complications were seen. Immediate pedicled radial forearm provided the best total active motion with least complications. When pati

关键词： Composite dorsal hand wound flap extensor tendon reconstruction

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Probing Molecular Magnetism by Neutron Scattering

Probing Molecular Magnetism by Neutron Scattering

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第七届全国物理无机化学学术会议

作者： shelby E.Stavretis Andrey A.Podlesnyak Yongqiang Chen luke l.Daemen Seth C.Hunter lei Chen You Song Xuetai Chen Ziling Xue Department of Chemistry University of Tennessee Quantum Condensed Matter Division Oak Ridge National Laboratory State Key laboratory of Coordination Chemistry Nanjing National Laboratory of MicrostructuresSchool of Chemistry and Chemical Engineering Nanjing University

＜正＞Zero-field splitting（ZFS）is an intrinsic magnetic property of transition-metal complexes with at least two unpaired electrons and no first-order contribution to the angular *** single-molecule magnets（SMMs）with large axial ZFS parameters D have been actively studied due to their slow magnetic relaxation,quantum tunneling,and potential applications in,e.g.,information storage and quantum computation.

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高浓度焦化废水硝化/反硝化系统的操作经验

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燃料与化工 2005年第1期36卷 58-61页

作者： Sam E.shelby Jr. 孙可美国

1998年,美国钢铁公司为格里焦化厂设计建设了一套新的焦化废水处理装置.该装置由除油、均化、蒸氨脱酸、活性污泥硝化与反硝化等工序组成.总氮含量2～3g/l的蒸氨废水进入生化处理装置中处理.两个曝气槽均由综合澄清区、厌氧区和好氧区组... 详细信息

1998年,美国钢铁公司为格里焦化厂设计建设了一套新的焦化废水处理装置.该装置由除油、均化、蒸氨脱酸、活性污泥硝化与反硝化等工序组成.总氮含量2～3g/l的蒸氨废水进入生化处理装置中处理.两个曝气槽均由综合澄清区、厌氧区和好氧区组成,在每个曝气槽内可完成硝化、反硝化和二次澄清.该装置是焦化工业中第一套高氮废水的厌氧/好氧处理装置,也是世界上首次应用厌氧/好氧/综合澄清的废水处理装置.

关键词：硝化/反硝化焦化废水处理曝气蒸氨废水好氧生化处理活性污泥装置均化焦化厂

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