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Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

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World j.urnal of Gastrointestinal Oncology 2024年第6期16卷 2487-2503页

作者： Carlos A Castaneda Miluska Castillo Luis A Bernabe j.selyn Sanchez Matteo Fassan Katherine Tello Ignacio Ivan Wistuba Ivan Chavez Passiuri Eloy Ruiz j.venal Sanchez Fernando Barreda daniel Valdivia Yaqueline Bazan Milagros Abad-Licham Claudio Mengoa Hugo Fuentes Paola Montenegro Ebert Poquioma Raul Alatrista Claudio j.Flores Luis Taxa Faculty of Health Sciences Universidad Cientifica del SurLima 15038Peru GECO PERU Grupo de Estudios Clinicos Oncologicos del PeruLima 15038Peru Department of Research Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Faculty of Human Medicine Universidad Ricardo PalmaLima 15039Peru Department of Medicine Surgical Pathology&Cytopathology UnitUniversity of PaduaPadua 35121Italy Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Department of Abdominal Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Medical Specialties Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Regional de Enfermedades Neoplasicas del NorteTrujillo 13001Peru Faculty of Human Medicine Universidad Privada Antenor OrregoTrujillo 13008Peru Department of Surgery Instituto Regional de Enfermedades Neoplasicas del SurArequipa 04002Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Epidemiology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Unidad de Investigación Básica y Traslacional Oncosalud-AUNALima 15038Peru Faculty of Medicine Universidad San Martin de PorresLima 15008Peru

BACKGROUND The influence of Helicobacter-pylori(***)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively *** of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive *** To determine the rates of deficient mismatch-repair(dMMR),HER2-status and *** infection and their association with TIL levels in *** Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)*** density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).*** infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of *** dMMR was found in 34.4%,HER2+in 5%and ***-positive in 55.7%of *** IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)***2-was associated with high IT-CD8(P=0.009).*** was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and *** CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

关键词： Lymphocytes Macrophages Gastric cancer Helicobacter pylori HER2 Mismatch repair

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Design of synthetic materials for intracellular delivery of RNAs： From siRNA-mediated gene silencing to CRISPR/Cas gene editing

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Nano Research 2018年第10期11卷 5310-5337页

作者： j.son B. Miller daniel j. Siegwart Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center Dallas TX 75390 USA Department of Biochemistry University of Texas Southwestern Medical Center Dallas TX 75390 USA

Ribonucleic acids （RNAs） possess great therapeutic potential and can be used to treat a variety of diseases. The unique biophysical properties of RNAs, such as high molecular weight, negative charge, hydrophilicity, low stability, and potential immunogenicity, require chemical modification and development of carriers to enable intracellular delivery of RNAs for clinical use. A variety of nanornaterials have been developed for the effective in vivo delivery of short/ small RNAs, messenger RNAs, and RNAs required for gene editing technologies including clustered regularly interspaced palindromic repeat （CRISPR）/Cas. This review outlines the challenges of delivering RNA therapeutics, explores the chemical synthesis of RNA modifications and carriers, and describes the efforts to design nanomaterials that can be used for a variety of clinical indications.

关键词： nucleic acid therapeutics nanoparticles synthetic nanomaterials RNA interference (RNAi) messenger RNA (mRNA) clustered regularly inter-spaced palindromic repeat(CRISPR)/Cas

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Missing data and the accuracy of Bayesian phylogenetics

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植物分类学报 2008年第3期46卷 307-314页

作者： j.hn j. WIENS daniel S. MOEN Department of Ecology and Evolution Stony Brook University Stony Brook NY 11794-5245 USA

The effect of missing data on phylogenetic methods is a potentially important issue in our attempts to reconstruct the Tree of Life. If missing data are truly problematic, then it may be unwise to include species in an analysis that lack data for some characters (incomplete taxa) or to include characters that lack data for some species. Given the difficulty of obtaining data from all characters for all taxa (e.g., fossils), missing data might seriously impede efforts to reconstruct a comprehensive phylogeny that includes all species. Fortunately, recent simulations and empirical analyses suggest that missing data cells are not themselves problematic, and that in-complete taxa can be accurately placed as long as the overall number of characters in the analysis is large. How-ever, these studies have so far only been conducted on parsimony, likelihood, and neighbor-j.ining methods. Although Bayesian phylogenetic methods have become widely used in recent years, the effects of missing data on Bayesian analysis have not been adequately studied. Here, we conduct simulations to test whether Bayesian analyses can accurately place incomplete taxa despite extensive missing data. In agreement with previous studies of other methods, we find that Bayesian analyses can accurately reconstruct the position of highly incomplete taxa (i.e., 95% missing data), as long as the overall number of characters in the analysis is large. These results suggest that highly incomplete taxa can be safely included in many Bayesian phylogenetic analyses.

关键词：贝叶斯定理系统发生学数据缺失准确度

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Periodic Orbits in Rotating Second Degree and Order Gravity Fields

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Chinese j.urnal of Astronomy and Astrophysics 2008年第1期8卷 108-118页

作者： Wei-Duo Hu daniel j. Scheeres School of Astronautics BeiHang University Beijing 100083 Department of Aerospace Engineering The University of Michigan Ann Arbor MI48109 USA

Periodic orbits in an arbitrary 2nd degree and order uniformly rotating gravity field are studied. We investigate the four equilibrium points in this gravity field. We see that close relation exists between the stability of these equilibria and the existence and stability of their nearby periodic orbits. We check the periodic orbits with non-zero periods. In our searching procedure for these periodic orbits, we remove the two unity eigenvalues from the state transition matrix to find a robust, non-singular linear map to solve for the periodic orbits. The algorithm converges well, especially for stable periodic orbits. Using the searching procedure, which is relatively automatic, we find five basic families of periodic orbits in the rotating second degree and order gravity field for planar motion, and discuss their existence and stability at different central body rotation rates.

关键词： celestial / orbital mechanics - asteroid - periodic orbit - resonance

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RULEMAKING POSSIBILITIES： EFFORTS OF THE UNITED STATES j.DICIAL CONFERENCE ADVISORY COMMITTEE ON EVIDENCE RULES TO ADDRESS THE CHALLENGES TO FORENSIC EXPERT TESTIMONY

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Frontiers of Law in China-Selected Publications from Chinese Universities 2018年第1期13卷 34-42页

作者： daniel j. Capra School of Law University of California Berkeley USA Reed Professor School of Law Fordharn University New York 10023 USA

This piece is an echo to one of the main subj.cts of the Sixth International Conference on Evidence Law and Forensic Science which is to determine what evidentiary reforms are necessary for regulating forensic expert testimony, and how those reforms might be implemented. In United States, the predominant way of evidentiary reform is through rulemaking. As the Reporter of j.dicial Conference Advisory Committee on the Federal Rules of Evidence since 1996, the author, with a pragmatic spirit throughout the article, examines such an effort at the federal level of U.S. in six parts （levels）, starting from the most general, abstract level till fmishing with the most detailed and substantive points. Part I begins with a brief introduction of the hierarchies of evidentiary rulemaking authorities at the federal level of the United States, various interested groups and their interesting interactions in the rulemaking process. The author then shifts to the general topic of writing rules with a specific focus on the level of detail that is to be provided in doing so; Part II further narrows down the scrutiny into writing a rule on forensic expert testimony with an emphasis on the necessity of making such a rule change to the current general standards of FRE; Part III directly addresses the challenges of drafting a rule on forensic evidence in FRE, including a comparation of various alternative drafting models; Part IV and Part V respectively discusses the Reporter＇s comments and the j.stice Department＇s concerns over the drafted rules; and Part VI briefly discusses the feasibility and effectiveness of a Best Practices Manual on forensic evidence in lieu of rulemaking.

关键词： forensics rulemaking reliability expert

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Finite difference methods in financial engineering. A PDE approach

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丛书名： Wiley finance

2006年

作者： daniel j. Duffy

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The N-terminus of COX-1 and its effect on cyclooxygenase-1 catalytic activity

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j.urnal of Genetics and Genomics 2010年第2期37卷 117-123页

作者： Sean Phipps Michael j. Turner daniel L. Simmons Chemistry and Biochemistry Department Brigham Young University

Cyclooxygenases are encoded by COX-1 and COX-2. They share over sixty percent sequence identity in human and are similar to each other in their crystallographic structures. One maj.r difference in the primary structure of these two isozymes is the presence of eight amino acids in the amino-terminal region of COX-1 that are not present in COX-2. The function of this amino acid sequence is unknown. In this study, a human COX-1 mutant （Δ7aa） with this sequence removed was studied in parallel with COX-1. Signal peptide cleavage, N-linked glycosylation, protein expression, distribution and dimerization were not affected by the mutation. The mutant was enzymati-cally active and showed the same sensitivity toward aspirin. The KM for the enzyme remained the same as COX-1. However, the Vmax of the COX-1 mutant decreased by 3.3-fold. We conclude that the COX-1 specific amino-terminal sequence has a subtle but detectable effect on COX-1 catalysis.

关键词： COX-1 COX-2 dimerization glycosylation aspirin KM Vmax

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Mating system and genetic diversity of a rare desert legume Ammopiptanthus nanus (Leguminosae)

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j.urnal of Systematics and Evolution 2009年第1期47卷 57-66页

作者： daniel j.CRAWFORD Department of Ecology and Evolutionary Biology and the Natural History Museum and Biodiversity Research CenterThe University of Kansas

Ammopiptanthus nanus is an endangered evergreen shrub endemic to the deserts of central Asia and plays an important role in delaying further desertification. We examined allozyme variation and AFLP diversity in A. nanus populations and investigated the mating system of this species using progeny arrays assayed for poly-morphic allozyme loci. Mating system analysis in the Keyi’eryongke’er population showed low levels of out-crossing, and strong inbreeding depression. Low levels of genetic variation were detected at both population (allozyme, Pp=14.0%, A=1.14, He=0.031; AFLP, Pp=14.5%, Shannon’s information index I=0.063) and species (allozyme, Pp=21.1%, A=1.21, He=0.040; AFLP, Pp=20.9%, I=0.083) levels; while moderate genetic differentiation existed among populations, as indicated by allozymes (GST=0.081) and AFLP (GST=0.151-0.193). Founder effect, bottlenecks in evolutionary history, the mixed mating system and co-ancestry may have influenced the level of genetic diversity in A. nanus. Markers of both types provide new insights for conservation management, indicating that the Biao’ertuokuoyi and Keyi’eryongke’er populations should be given priority for in situ conservation and regarded as seed sources for ex situ conservation.

关键词： AFLP allozyme Ammopiptanthus conservation endangered plant genetic structure outcrossing rate

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Elucidating regulatory processes of intense physical activity by multi-omics analysis

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Military Medical Research 2024年第4期11卷 479-499页

作者： Ernesto S.Nakayasu Marina A.Gritsenko Young-Mo Kim j.nnifer E.Kyle Kelly G.Stratton Carrie D.Nicora Nathalie Munoz Kathleen M.Navarro daniel Claborne Yuqian Gao Karl K.Weitz Vanessa L.Paurus Kent j.Bloodsworth Kelsey A.Allen Lisa M.Bramer Fernando Montes Kathleen A.Clark Grant Tietj. j.stin Teeguarden Kristin E.Burnum-j.hnson Biological Sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Environmental and Molecular Sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthWestern States DivisionDenverCO 80204USA Computational Analytics Division Pacific Northwest National LaboratoryRichlandWA 99352USA National Security Directorate Pacific Northwest National LaboratoryRichlandWA 99352USA Los Angeles County Fire Department Los AngelesCA 90063USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthRespiratory Health DivisionMorgantownWV 26505USA Environmental and Molecular Toxicology Oregon State UniversityCorvallisOR 97331USA

Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work ***:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise *** profiles ***-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics ***:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of *** blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy *** urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid *** saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory ***:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding j.bs.

关键词： Multi-omics analysis Intense exercise Human performance Biofluids Metabolism Immunity

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Techniques in Wrist and Hand Arthroscopy 1

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2007年

作者： David j. Slutsky daniel j. Nagle

ISBN: (纸本)9780443066979

Enhance your skills in arthroscopic surgery - an increasingly important aspect of the treatment of a variety of traumatic and degenerative ailments of the hand. Leaders in the field describe their preferred approaches in step-by-step detail - emphasizing what outcomes you can expect - and also examine the diagnostic advantages of this precise technique. A bonus DVD features video clips of the procedures described in the book, enabling you to see these performed in real time!

关键词： Hand j.intssurgery

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