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SARS-CoV-2 Epitopes following Infection and Vaccination Overlap Known Neutralizing Antibody Sites

Research 2022年第2期2022卷 71-84页

作者： Li Yang Te Liang Lane M.Pierson Hongye Wang jesse K.Fletcher Shu Wang Duran Bao Lii Zhang Zhen Huang Wenshu Zheng Xiaomei Zhang Heewon Park Yuwen Li james E.Robinson amy K.Fechan Christopher j.Lyon jing Cao Lisa A.Morici Chenzhong Li Chad j.Roy Xiaobo Yu Tony Hu Center for Cllular and Molecular Diagnostics Tulane University Schoo of Medicine1430 Tulane AveNew OrleansLA 70112USA Department of Biochemisty and Molecular Biology Tulane University School of Medicine1430 Tulane AveNew OrleansLA 70112USA Beijing Key Laboratory for Forest Pest Control Bejjing Foresiry UniersilyBeijing 10083.China State Key Laboratory of Proteommics Beijing Protcome Resarch CenterNattional Center for Protein Sciences-Beiing(PHOENIX Center)Beijing Institute of LijfeomicsBeijing 102206China Hayward Genetis Cener Department of PediatricsTulane Universily School of Medicine1430 Tulane AveNew OrleansLA 70112USA Department of Pediatrics Tulane Uhriversity School of Medicine1430 Ttulane AveNew OrleansLA 70112USA Infectious Disease Depariment Ochsner Clinic FoundationNew OrleansLA 70121USA Universty of Texas Souhwestern Medical Cener 5323 Harry Himes BlvdDallasTX 75390USA Department of Microbiology Imruolog Tulane Untiversity School of Medicine 1430 Tulane AveNew OrleansLA 70112USA Division of Microbiology Tulane National Primate Research Center18703 Three Rivers RoadCovingtonLA 70433USA

Identification of epitopes targeted following virus infection or vaccination can guide vaccine design and development of therapeutic interventions targeting functional sites,but can be ***,we employed peptide microarrays to map linear peptide epitopes(LPEs)recognized following SARS-CoV-2 infetion and *** detected by nonhuman primate(NHP)and patient IgMs after SARS-CoV-2 infection extensively overlapped,localized to functionally important virus regions,and aligned with reported neutralizing antibody binding *** LPE overlap occurred atfter infection and vaccination,with LPE clusters specifc to each stimulus,where strong and conserved LPEs mapping to sites known or likely to inhibit spike protein ***-specifc LPEs tended to map to sites known or likely to be afected by structural changes induced by the proline substitutions in the mRNA vaccine's S *** LPEs to regions of known functional importance in this manner may acelerate vaccine evaluation and discovery of targets for sile secific therapeutic interventions.

关键词： vaccine Antibody likely

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Risk Factors for Failure of OPAT （Outpatient Parenteral Antimicrobial Therapy） in Veterans with Staphylococcus aureus Bacteremia

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journal of Pharmacy and Pharmacology 2016年第6期4卷 241-247页

作者： john j. Veillette Leslie Bittner Marion j. Skalweit Usha Stiefel Christopher j. Burant amy A.Hirsch Sharanie Sims Pharmacy Service Louis Stokes Cleveland Department of Veterans Affairs Medical Center (LSCDVAMC) Cleveland OH USA Medicine Service LSCDV.4MC Cleveland OH USA Case Western Reserve University School of Medicine Cleveland OH USA Cleveland Geriatric Research Education and Clinical Center (GRECC) LSCDVAMC Cleveland OH USA Case Western Reserve University Frances Payne Bolton School of Nursing Cleveland OH USA

To identify risk factors for failure of OPAT （outpatient parenteral antimicrobial therapy） among veterans with SAB （Staphylococcus aureus bacteremia）, a retrospective review was conducted of all patients receiving OPAT for SAB between 01/2011-09/2013 at a large, tertiary-care VA （Veterans＇ Affairs） medical center. Treatment failure was defined as incomplete therapy, therapy extension, infection relapse, or hospital admission or surgical intervention within 60 days of therapy completion. Of 118 SAB patients treated with OPAT, 101 met inclusion criteria. Treatment failure occurred in 36 （35.6%） patients. In multivariate analysis, heart failure （OR 3.67; CI 1.13-12.0）, previous OPAT （OR 14.1; CI 2.02-97.8）, immunosuppression （OR 10.5; CI 1.74-63.3）, and treatment with daptomycin （OR 9.56; CI 1.89-48.4） were independently associated with failure. A trend toward lower failure rates was seen in the community living center, a VA long-term care facility possessing its own infectious diseases consultation service. In veterans with SAB, specific health factors were associated with higher rates of OPAT failure. Given the morbidity and cost of SAB treatment failures, similar analyses may benefit other large OPAT programs to optimize the selection of patients and settings in which successful treatment will most likely occur.

关键词： Risk factors failure OPAT Staphylococcus aureus bacteremia.

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A Retrospective Comparison of Interscalene Continuous Catheter Verse Single-Injection with Liposomal Bupivacaine in Total Shoulder Arthroplasty

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Open journal of Anesthesiology 2021年第9期11卷 269-278页

作者： Benjamin j. Kenny Emily S. Schmidt amy W. Wozniak Scott W. Byram Department of Anesthesiology and Perioperative Medicine Loyola University Chicago IL USA

Background: One common method of pain control for total shoulder arthroplasty is long-duration delivery of local anesthetic via interscalene brachial plexus block (ISB) with a continuous catheter. Alternatively, liposomal bupivacaine has also been administered as an ISB as a means to prolong the analgesic effect. This study was completed to measure the non-inferiority of single-injection ISB with liposomal bupivacaine compared with ISB continuous catheter for total shoulder arthroplasty. Methods: We performed a retrospective chart review of patients who underwent total shoulder arthroplasty using either an ISB continuous catheter or a single injection ISB with liposomal bupivacaine for post operative analgesia. The primary goal of this study was to determine if single-injection with liposomal bupivacaine conferred non-inferior pain scores compared to the continuous catheter. Secondary outcomes evaluated oxygen saturation as a measure of hemidiaphragmatic paresis, post operative opioid requirements, and difference in cost. Results: We identified 333 patients for the study: 126 received continuous catheter and 207 received single-injection with liposomal bupivacaine. The median length of stay was 1 day. Pain scores for those treated with single-injection with liposomal bupivacaine were non-inferior to pain scores of those treated with the continuous catheter on post-op days 0, 1 and 2. Pain scores were lower for single-injection with liposomal bupivacaine patients on days 3 and 4, however they did not reach statistical significance. There was no significant difference in oxygen saturation between the two groups. Both groups had similar daily morphine milligram equivalent requirements. Liposomal bupivacaine ISB was also found to be less expensive. Conclusion: Single-injection ISB with liposomal bupivacaine provides non-inferior analgesia at a reduced cost compared with continuous catheter ISB for total shoulder arthroplasty.

关键词： Regional Anesthesia Interscalene Nerve Block Total Shoulder Arthroplasty Liposomal Bupivacaine Continuous Catheter Peri-Operative Analgesia

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Left Atrial Appendage Occlusion Device: Evaluation of Surgical Implant Success and <i>in Vivo</i>Corrosion Performance

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Surgical Science 2012年第1期3卷 28-33页

作者： jonathan Snyder amy M. Engel Kevin C. White Noah Budiansky j. Michael Smith Department of Surgery Good Samaritan Hospital Cincinnati USA E. Kenneth Hatton MD Institute for Research and Education Cincinnati USA Exponent Inc. Natick Massachusetts USA

Objective: The purpose of this study was to compare the in vivo corrosion resistance of the implanted titanium, nitinol annular occlusion device to a control device, i.e. an implantable device containing nitinol, approved by the FDA and currently on the market. Methods: The annular occlusion device is a self-closing, implantable clip. Three canines underwent placement of devices on the left and right atrial appendages. Two Vnus U-clips were secured to either atrium. On post-operative day 95, animals underwent en-bloc cardiac resection via the previous left thoracotomy incision. The annular occlusion device and U-clips were dissected free from the atria. The polyester fabric and tissue ingrowth were removed from the devices and were sent for corrosion analysis. Results: Gross examination of resected hearts of two canines revealed no abnormalities. The compressed endocardial surfaces were completely fused and the appendages fully necrosed. All devices were located and harvested. The annular occlusion device clips and Medtronic Vnus U-clips were evaluated using scanning electron microscopy. Both low and high magnification examination of the nitinol springs and the site of insertion of the nitinol springs into the titanium tubes in the annular occlusion device showed no evidence of localized corrosion. In no case was any evidence of general or localized corrosion found in the form of metallic oxidation. Conclusion: The annular occlusion device provides safe and reliable exclusion of the left atrial ap-pendage without evidence of general or localized corrosion over the 95-day exposure period in canines and may therefore provide a reasonable therapeutic option for stroke risk reduction in patients with atrial fibrillation.

关键词： Atrial Appendage Occlusion Device Atrial Fibrillation Exclusion of Left Atrial Appendage

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Analysis of daily activity data from implanted cardiac defibrillators: The minimum clinically important difference and relationship to mortality/life expectancy

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World journal of Cardiovascular Diseases 2012年第3期2卷 129-135页

作者： Michael j. Shoemaker amy B. Curtis Eric Vangsnes Michael G. Dickinson Rajib Paul Department of Statistics Western Michigan University Kalamazoo USA Interdisciplinary Health Sciences PhD Program Western Michigan University Kalamazoo USA Physician Assistant Program Western Michigan University Kalamazoo USA Spectrum Health Frederik Meijer Heart and Vascular Institute Grand Rapids USA

Background: Daily activity is a potentially important measure for assessing prognosis in individuals with chronic heart failure (CHF), and few studies have investigated the prognostic value of daily activity measurement. The present study sought to determine whether there is an association between daily activity and mortality/mean life expectancy as predicted by the Seattle Heart Failure Model (SHFM), and to provide an estimate of the anchor-based minimum clinically important difference (MCID) for daily activity measured by single-axis accelerometers in implanted cardiac defibrillators. Methods: This study utilized a retrospective chart review of 102 medical records of patients with CHF and Medtronic? implanted cardiac defibrillators (ICDs). Mean daily activity was calculated for a two week period prior to both a baseline and follow-up routine clinical visit. Clinical characteristics from the baseline clinic visit were used for calculating SHFM estimates of mean life expectancy, 1-year mortality, and 5-year mortality. A five-point global rating scale was scored based on documented clinician impression, patient self-report, and laboratory and cardiographic tests for determining the MCID. Results: There was a moderate correlation between baseline daily activity and each of the SHFM prognostic indicators: 1-year mortality (r = 0.36, p < 0.001, 5-year mortality (r = 0.40, p < 0.001), and life expectancy (r = 0.43, p < 0.001). The MCID for a decline in daily activity was approximately 0.5 hours and was approximately 1.0 hours for improvement in daily activity. Conclusions: Although previous re- search has established the short-term predictive value of ICD-measured daily activity for CHF-related clinical events, no prior study has examined the longer-term prognostic value of ICD-based daily activity. The results of the present study suggest that low daily activity, as recorded by ICDs in patients with CHF, should prompt a more formal evaluation of prognosis using the SHFM

关键词： Heart Failure Daily Activity Prognosis Cardiac Defibrillator

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Probing the Impact of Solvent on the Strength of Lewis Acids via Fluorescent Lewis Adducts

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Precision Chemistry 2023年第1期1卷 49-56页

作者： amy E.Laturski joshua R.Gaffen Paul Demay-Drouhard Christopher B.Caputo Thomas Baumgartner Department of Chemistry York UniversityTorontoON M3J 1P3Canada

Various methods have been developed to measure the strength of a Lewis acid.A major challenge for these measurements lies in the complexity that arises from variable solvent interactions and perturbations of Lewis acids as their reaction environment ***,we investigate the impact of solvent effects on Lewis acids for the first time as measured by the fluorescent Lewis adduct(FLA)*** binding of a Lewis acid in various solvents reveals a measurable dichotomy between both polarity and donor ability of the *** not strictly separable,we observe that the influence of solvent polarity on Lewis acid unit(LAU)values is distinctly opposite to the influence of donor *** dichotomy was confirmed by titration data,illustrating that solvation effects can be appropriately and precisely gauged by the FLA method.

关键词： Fluorescence Fluorescent Lewis adducts Lewis acids Effective Lewis acidity Solvent polarity Solvent donor strength

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宇宙的中年不辉煌

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科学（中文版） 2005年第3期292卷 30-37页

作者： amy j.Barger 田锦美国麦迪逊威斯康星大学

直到不久前,大多数天文学家还认为宇宙已经进入了一个令人异常烦恼的中年期.按照这一说法,宇宙的早期历史--从宇宙诞生起到大爆炸后60亿年这段时期的历史--可以说是一个壮观的烟火大表演时代:星系互相碰撞然后合并,庞大的黑洞吞食着巨... 详细信息

直到不久前,大多数天文学家还认为宇宙已经进入了一个令人异常烦恼的中年期.按照这一说法,宇宙的早期历史--从宇宙诞生起到大爆炸后60亿年这段时期的历史--可以说是一个壮观的烟火大表演时代:星系互相碰撞然后合并,庞大的黑洞吞食着巨量的旋涡气体,无数恒星如雨后春笋般在宇宙的每一角落里冒出来.反观随后的80亿年,星系的合并逐渐变得十分罕见,巨无霸般的黑洞慢慢趋于沉寂,而恒星的形成也每况愈下,最终变成只是偶尔闪现一下的星火.许多天文学家一度相信他们正在目击宇宙历史的终结;未来的唯一前景就是一个了无生气且老态龙钟的宇宙在永无休止地膨胀.

关键词：宇宙恒星黑洞形成步伐中年

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The spike protein of SARS-CoV-2 variant A.30 is heavily mutated and evades vaccine-induced antibodies with high efficiency

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Cellular & Molecular Immunology 2021年第12期18卷 2673-2675页

作者： Prerna Arora Cheila Rocha amy Kempf Inga Nehlmeier Luise Graichen Martin S.Winkler Martin Lier Sebastian Schulz Hans-Martin jäck Anne Cossmann Metodi V.Stankov Georg M.N.Behrens Stefan Pöhlmann Markus Hoffmann Infection Biology Unit German Primate CenterKellnerweg 437077GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073GöttingenGermany Department of Anesthesiology University of Göttingen Medical CenterGeorg-August University of GöttingenRobert-Koch-Straße 4037075GöttingenGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054ErlangenGermany Department for Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625HannoverGermany

The COVID-19 pandemic,caused by SARS-CoV-2,continues to rage in many countries,straining health systems and *** protect against severe disease and death and are considered central to ending the ***-19 vaccines(and SARS-CoV-2 infection)elicit antibodies that are directed against the viral spike(S)protein and neutralize the ***,the emergence of SARS-CoV-2 variants with S protein mutations that confer resistance to neutralization might compromise vaccine efficacy[1].

关键词： antibodies vaccine death

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CaMKH binding to GluN2B is critical for memory consolidation

CaMKH binding to GluN2B is critical for memory consolidation

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： amy R.Halt R.F.Dallapiazza j.W.Hell Alcino j.Silva Departments of Pharmacology and Psychiatry and Neurosurgery Roy J.and Lucille A.Carver College of MedicineUniversity of IowaIowa CityIA 52242USA Department of Neurobiology Semel InstituteDepartment of PsychologyBrain Research InstituteUniversity of CaliforniaLos AngelesCalifornia90095USA

Memory is essential for our normal daily lives and our sense of ***,our knowledge of molecular and cellular mechanisms of memory formation and retention is *** influx through the NMDA-type glutamate receptor(NMDAR) and the ensuing activation of the Ca and calmodulin-dependent protein kinase(CaMKII) are required for memory formation and its physiological correlate,long-term potentiation(LTP).The Ca influx induces CaMKII binding to the NMDAR to strategically recruit CaMKII to synapses that are undergoing potentiation. We show that mice with two point mutations that impair CaMKII binding to the NMDAR GluN2B subunit initially learn the Morris water maze and acquire contextual fear conditioning under standard conditions to the same degree as wild type mice but show deficiency during the period of early memory consolidation in these ***, the activity-driven interaction of CaMKII with the NMDAR is important for imprinting memory traces.

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Pharmacodynamics of CNTO 530 and Darbepoetin-α in Human TNF-α Transgenic Mice, a Murine Model of Anemia of Chronic Disease

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Pharmacology & Pharmacy 2011年第1期2卷 17-30页

作者： Ram Achuthanandam Dorie Makropoulos Laura johns amy Volk Kerry Brosnan jin Lu Wojciech Krzyzanski Peter j. Bugelski 不详

CNTO 530 and darbepoetin-a are long lived erythropoietin receptor agonists (ERAs). Clinically, anemia of chronic disease (ACD) is associated with increased expression of tumor necrosis factor-a (TNF-a) and mice transgenic for human TNF-a develop ACD. The purpose of this investigation was to compare the effects of these agents in a murine model of ACD. Human TNF-a expressing (Tg 197) mice were administered a single subcutaneous dose of CNTO 530 or darbepoetin-a and the pharmacodynamic response in bone marrow spleen and peripheral blood evaluated. RBC life span and reticulocyte age distribution were also evaluated. CNTO 530 induced a dose responsive increase in reticulocytes, RBCs and Hgb in both wild type and Tg197 mice. Although the reticulocyte response was similar to wild types, the RBC and Hgb response to CNTO 530 in Tg197 mice was blunted. There was no statistically significant difference in RBC life span with either compound. Darbepoetin-α caused a greater peak in % dead Pro/basophilic erythroblasts, greater peak EMH in the spleen and a greater increase in reticulocyte maturation time. In contrast, despite a similar peak increase, CNTO 530 caused a more sustained response of reticulocyte, EMH, RBC and Hgb, consistent with increased exposure. In conclusion, CNTO 530 and darbepoetin-a increased RBC and hemoglobin in a murine model of ACD. Compared to darbepoetin-a, CNTO 530 had a more sustained effect, consistent with increased exposure.

关键词： Fusion Protein Recombinant Flow Cytometry Erythropoiesis

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