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Protein folding, protein homeostasis,and cancer

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Chinese Journal of Cancer 2011年第2期30卷 124-137页

作者： john h. Van Drie Van Drie Research

Proteins fold into their functional 3-dimensional structures from a linear amino acid sequence. In vitro this process is spontaneous; while in vivo it is orchestrated by a specialized set of proteins, called chaperones. Protein folding is an ongoing cellular process, as cellular proteins constantly undergo synthesis and degradation. here emerging links between this process and cancer are reviewed. This perspective both yields insights into the current struggle to develop novel cancer chemotherapeutics and has implications for future chemotherapy discovery.

关键词：蛋白质折叠蛋白质平衡癌症化疗药物氨基酸序列三维结构蛋白合成细胞

Special Values for the Riemann Zeta Function

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Journal of Applied Mathematics and Physics 2021年第5期9卷 1108-1120页

作者： john h. heinbockel Old Dominion University Norfolk Virginia USA

The purpose for this research was to investigate the Riemann zeta function at odd integer values, because there was no simple representation for these results. The research resulted in the closed form expression for representing the zeta function at the odd integer values 2n+1 for n a positive integer. The above representation shows the zeta function at odd positive integers can be represented in terms of the Euler numbers E2n and the polygamma functions ψ(2n)(3/4). This is a new result for this study area. For completeness, this paper presents a review of selected properties of the Riemann zeta function together with how these properties are derived. This paper will summarize how to evaluate zeta (n) for all integers n different from 1. Also as a result of this research, one can obtain a closed form expression for the Dirichlet beta series evaluated at positive even integers. The results presented enable one to construct closed form expressions for the Dirichlet eta, lambda and beta series evaluated at odd and even integers. Closed form expressions for Apéry’s constant zeta (3) and Catalan’s constant beta (2) are also presented.

关键词： Riemann Zeta Function Zeta (2n) Zeta (2n + 1) Apéry’s Constant Catalan Constant

hubble Expansion as an Einstein Curvature

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Journal of Modern Physics 2022年第6期13卷 969-991页

作者： john h. Marr Unit of Computational Science Building 250 Babraham Research Campus Cambridge UK

Extending the spacetime manifold of general relativity (GR) to incorporate the hubble expansion of space as a specific curvature, generates a modified solution with three additional non-zero Christoffel symbols and a reformulated Ricci tensor and curvature. The observational consequences of this reformulation are compared with the ΛCDM model for luminosity distance using the extensive type 1a supernovae (SNe 1a) data with redshift corrected to the CMB, and for angular diameter distance using the recent baryonic acoustic oscillation (BAO) data. For the SNe 1a data, the modified GR and ΛCDM models differ by mag. over zcmb = 0.01 - 1.3, with overall weighted RMS errors of ±0.136μB mag for modified GR and ±0.151μB mag for ΛCDM respectively. The BAO measures span a range z = 0.106 - 2.36, with weighted RMS errors of ±0.034 Mpc with h0 = 67.6 ± 0.25 for the modified GR model, and ±0.085 Mpc with h0 = 70.0 ± 0.25 for the ΛCDM model. The derived GR metric for this new solution describes both the SNe 1a and the BAO observations with comparable accuracy to the w’ΛCDM model. By incorporating the hubble expansion of space within general relativity as a specific curvature term, these observations may be described without requiring additional parameters for either dark matter or accelerating dark energy.

关键词： hubble Expansion General Relativity Luminosity Distance Angular Diameter Distance Dark Mass Dark Energy

Integration of expression profiles and endo-phenotypes in genetic association studies: A Bayesian approach to determine the path from gene to disease

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Open Journal of Genetics 2013年第3期3卷 216-223页

作者： Sharon M. Lutz Sunita Sharma john E. hokanson Scott Weiss Benjamin Raby Christoph.lange Department of Biostatistics Harvard School of Public Health Boston USA Department of Epidemiology University of Colorado at Denver Aurora USA Institute for Genomic Mathematics University of Bonn Bonn Germany The Channing Division of Network Medicine Department of Medicine Bringham and Women’s Hospital Boston USA

In genetic association studies of complex diseases, endo-phenotypes such as expression profiles, epigenetic data, or clinical intermediate-phenotypes provide insight to understand the underlying biological path of the disease. In such situations, in order to establish the path from the gene to the disease, we have to decide whether the gene acts on the disease phenotype primarily through a specific endo-phenotype or whether the gene influences the disease through an unidentified path which is characterized by different intermediate phenotypes. here, we address the question that a genetic locus, given its effect on an endo-phenotype, influences the trait of interest primarily through the path of the endo-phenotype. We propose a Bayesian approach that can evaluate the genetic association between the genetic locus and the phenotype of interest in the presence of the genetic effect on the endo-phenotype. Using simulation studies, we verify that our approach has the desired properties and compare this approach with a mediation approach. The proposed Bayesian approach is illustrated by an application to genome-wide association study for childhood asthma (CAMP) that contains expression profiles.

关键词： Expression Profiles Endo-Phenotypes Genetic Association Studies Bayesian hierarchal Model Pathway Mediation

Laser additive manufacturing for infrastructure repair:A case study of a deteriorated steel bridge beam

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Journal of Materials Science & Technology 2023年第23期154卷 149-158页

作者： Shengbiao Zhang Peijun hou Jiyun Kang Tianyi Li Shahryar Mooraj Yang Ren Catherine h.Chen A.john hart Simos Gerasimidis Wen Chen Department of Mechanical and Industrial Engineering University of Massachusetts Amherst MA 01003 USA Department of Civil and Environmental Engineering University of Massachusetts Amherst MA 01003 SA Department of Materials Science and Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA X-ray Science Division Argonne National Laboratory Lemont IL 60439 USA Massachusetts Department of Transportation Boston MA 02116 USA Department of Mechanical Engineering Massachusetts Institute of Technology Cambridge MA 02139 USA Department of Physics City University of Hong Kong Kowloon Hong Kong China

As our transportation infrastructure ages,its deterioration is becoming a growing *** and effective methods for repair can reduce the need for time-and cost-intensive replacement of structures such as roadway *** this work,laser-based additive manufacturing(AM)was developed for the repair of damaged beams in steel bridges.A corroded structural beam of low-carbon A36 steel was selected for this case study and 316L stainless steel was used for repair due to its excellent mechanical properties and corrosion *** repair experiments were performed on specimens extracted from the beam,and prepared with various groove shapes(Rectangular,Trapezoidal,and U-shaped).More in-depth parametric and microstructural studies were carried out with a series of U-shaped specimens repaired with the linear laser input energy varied from 19.5 to 30.0 J mm–*** tensile properties of the repaired specimens and interface structures were also investigated in *** was found that the repaired specimens had a slightly higher tensile strength despite a reduction in tensile elongation compared to the A36 steel base *** influence of interfacial microstructure and heterogeneity on the mechanical properties of the repaired specimens was *** work suggests the promising potential to employ AM for structural repair and provides fundamental insights into processing-structure-property relationships in laser AM-repaired materials.

关键词： Additive manufacturing Structural repair Mechanical properties Transportation infrastructure Dissimilar joint

Real-world emission factors for Caterpillar 797B heavy haulers during mining operations

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Particuology 2016年第5期14卷 22-30页

作者： Xiaoliang Wang Judith C. Chow Steven D. Kohl Kevin E. Percy Allan h. Legge john G. Watson Desert Research Institute 2215 Raggio Parkway Reno NV 895J2 USA Graduate Faculty University of Nevada Reno NV89503 USA The State Key Laboratory of Loess and Quaternary Geology Institute of Earth Environment Chinese Academy of Sciences Xi'an 710075 China Wood Buffalo Environmental Association 330 Thickwood Boulevard Fort McMurray AB Canada 7DK 1 Y1 Biosphere Solutions 1610 1 lth Avenue N.W. Calgary AB Canada T2N IG9

Real-world fuel-based emission factors （EFs） from Caterpillar 797B diesel heavy haulers when used for oil sands mining operations were measured using an on-hoard portable emissions monitoring system. Average EFs （in g/kg fuel） for 16 separate tests on four trucks were 3150 ± 4 for CO2, 2.51 ± 1.30 for Ch4, 10.28 ± 3.21 for CO, 0.61 ± 0.32 for non-methane hydrocarbons, 55.49 ± 9,75 for NOx （reported as NO2）, 0.70 ± 0.17 for PM2.s （mass of particles with aerodynamic diameter 〈2.5 μm）, and 0.34 ± 0.05 for black carbon （BC）. Ultrafine particle numbers averaged （4.7 ± 4.1 ） × 10^15 particleslkg fuel. Fuel-based EFs of NO, NO2, and particle numbers were higher during idling, whereas PM2.5 and BC EFs were higher during traveling without a load. A comparison of emissions with those reported by oil sands facilities showed large variations, both among the facilities and between the reported emissions and the real-world measurements.

关键词： heavy hauler Emission Nonroad Portable emissions measurement system Mining Oil sands

Identification of the metabolites of biologically active xanthones isolated from halenia elliptica *** by high performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry

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Chinese Chemical Letters 2011年第7期22卷 839-842页

作者： Ru Feng Jian Gong Shi Xiao Wei Liu Chun Tao Che john h.K. Yeung Yan Wang Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 China Department of Ophthalmology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100730 China School of Chinese Medicine The Chinese University of Hong Kong Shatin NT Hong Kong SAR China Department of Pharmacology Faculty of Medicine The Chinese University of Hong Kong Shatin NZ Hong Kong SAR China

Metabolism study has been carried out on 1-hydroxy-2,3,5-trimethoxyxanthone （hM-1） and 1-hydroxy-2,3,4,7- tetramethoxyxanthone （hM-2）, which are two biologically active ingredients isolated from the Tibetan herb, halenia elliptica D. Don., in rat liver microsomes in vitro. A method of high performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry （LCMSn-ESI-IT-TOF） was applied to analyze metabolites of hM-1 and hM-2 on line, and five metabolites were identified containing 1,5-dihydroxy-2,3-dimethoxyxanthone （hM-5）, 1,7-dihydroxy-2,3,4-trimethoxyxanthone （hM-9）, 1,4, 7- trihydroxy-2,3-dimethoxyxanthone （hM-10）, 1,4-dihydroxy-2,3,7-trimethoxyxanthone （hM-11） and 1,2-dilaydroxy-3,4,7- trimethoxyxanthone （hM-12）. Among these metabolites, hM-9, hM-11, and hM-12 were isomers mutually. The results indicated that hM-1 and hM-2 occurred Phase I metabolic reaction of demethylation in rat microsomes in vitro.

关键词： halenia elliptica Xanthone Biotransformation LCMSn-ESI-IT-TOF Metabolite identification

Resistance to venetoclax and hypomethylating agents in acute myeloid leukemia

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Cancer Drug Resistance 2021年第1期4卷 125-142页

作者： Antoine N.Saliba August J.john Scott h.Kaufmann Division of hematology Department of MedicineMayo ClinicRochesterMN 55905USA Department of Molecular Pharmacology and Experimental Therapeutics Mayo ClinicRochesterMN 55905USA Division of Oncology Research Department of OncologyMayo ClinicRochesterMN 55905USA

Despite the success of the combination of venetoclax with the hypomethylating agents(hMA)decitabine or azacitidine in inducing remission in older,previously untreated patients with acute myeloid leukemia(AML),resistance-primary or secondary-still constitutes a significant roadblock in the quest to prolong the duration of *** we review the proposed and proven mechanisms of resistance to venetoclax monotherapy,hMA monotherapy,and the doublet of venetoclax and hMA for the treatment of *** approach the mechanisms of resistance to hMAs and venetoclax in the light of the agents’mechanisms of *** briefly describe potential therapeutic strategies to circumvent resistance to this promising combination,including alternative scheduling or the addition of other agents to the hMA and venetoclax *** the mechanisms of action and evolving resistance in AML remains a priority in order to maximize the benefit from novel drugs and combinations,identify new therapeutic targets,define potential prognostic markers,and avoid treatment failure.

关键词： Venetoclax hypomethylating agents resistance acute myeloid leukemia azacitidine decitabine

Redox therapeutics in hepatic ischemia reperfusion injury

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World Journal of hepatology 2014年第1期6卷 1-8页

作者： Rakesh P Patel john D Lang Alvin B Smith Jack h Crawford Department of Pathology Center for Free Radical Biology University of Alabama at Birmingham Department of Anesthesiology and Pain Medicine University of Washington School of Medicine Department of Anesthesiology University of Alabama Birmingham Division of Cardiothoracic Anesthesia Department of Anesthesiology University of Alabama Birmingham

Ischemia-reperfusion plays a major role in the injury experienced by the liver during transplantation. Much work has been done recently investigating the role of redox species in hepatic ischemia-reperfusion. As animal models are better characterized and developed, and more insights are gained into the pathophysiology of hepatic ischemia reperfusion injury in humans the questions into exactly how oxidants participate in this injury are becoming more refined. These questions include effects of cellular location, timing of injury, and ability of therapeutics to access this site are increasing our appreciation of the complexity of ischemia reperfusion and improving attempts to ameliorate its effects. In this review, we aim to discuss the various methods to alter redox chemistry during ischemia reperfusion injury and future prospects for preventing organ injury during hepatic ischemia reperfusion.

关键词： Ischemia Reperfusion Pre-conditioning Nitrite