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World Journal of Gastroenterology 2017年第34期23卷 6197-6200页

作者： konstantinos papamichael adam s cheifetz Center for Inflammatory Bowel Diseases Division of GastroenterologyBeth-Israel Deaconess Medical CenterHarvard Medical School

Perianal fistulas can occur to up to one-third of patients with Crohn's disease(CD) leading to significant disabling disease and morbidity. Fistulising perianal CD treatment often necessitates a combined pharmacological and surgical approach. Anti-tumor necrosis factor(anti-TNF) therapy, particularly infliximab, has been shown to be very effective for both perianal and internal fistulising CD. Nevertheless, current data suggest that sustained remission and long-term complete fistula healing can be achieved in only 30% to 50% of patients. Moreover, these percentages refer mostly to clinical rather than deep remission, defined as endoscopic and radiologic remission, which is quickly emerging as the preferred goal of therapy. Unfortunately, the therapeutic options for perianal fistulising CD are still limited. As such, it would be of great value to be able to predict, and more importantly, prevent treatment failure in these patients by early and continued optimization of antiTNF therapy. similar to ulcerative colitis and luminal CD, recent data demonstrate that higher infliximab concentrations are associated with better clinical outcomes in patients with perianal fistulising CD. This suggests that therapeutic drug monitoring and a treatto-trough therapeutic approach may emerge as the new standard of care for optimizing anti-TNF therapy in patients with perianal fistulising CD.

关键词： Inflammatory bowel disease Infliximab Adalimumab Magnetic resonance imaging Drug monitoring Fistula healing

Microbial manipulation as primary therapy for Crohn's disease

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World Journal of Gastroenterology 2013年第10期19卷 1513-1516页

作者： Randy s Longman Arun swaminath Division of Digestive and Liver Disease Department of MedicineColumbia University Medical CenterNew YorkNY 10032United States

While antimicrobials are clinically effective in preventing post-operative recurrence,the role for antibiotics in primary therapy for Crohn's disease(CD) remains *** recent multicenter phase 2 trial by Prantera et al received wide attention because it demonstrated an increase in the week 12 remission rate in patients with moderately active CD treated with rifaximin and renewed interest in microbial manipulation as primary therapy for *** this commentary,we discuss aspects of durability,immune cell polarization,and safety of microbial manipulation as primary therapy for CD.

关键词： Inflammatory bowel disease Rifaximin Microbiome

Brain repair for Parkinson's disease:is the answer in the matrix?

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Neural Regeneration Research 2018年第7期13卷 1187-1188页

作者： Niamh Moriarty Eilís Dowd Pharmacology & Therapeutics and Galway Neuroscience Centre National University of Ireland

Two hundred years after James Parkinson first described the cardinal motor symptoms of the disorder that would later bear his name,there is still an irrefutable need for a therapy that targets the underlying pathophys... 详细信息

关键词： Brain repair for Parkinson’s disease:is the answer in the matrix

Astrophysical s-factor and reaction rate for 15N(p,γ)16O within the modified potential cluster model

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Chinese Physics C 2024年第4期48卷 130-145页

作者： s.B.Dubovichenko A.s.Tkachenko R.Ya.Kezerashvili N.A.Burkova B.M.Yeleusheva Fesenkov Astrophysical Institute 050020 AlmatyKazakhstan New York City College of Technology City University of New YorkBrooklyn11201 New YorkUSA Graduate school and University Center City University of New York10016 New YorkUSA al-Farabi Kazakh National University 050040 AlmatyKazakhstan

We study radiative p^(15)N capture on the ground state of ^(16)O at stellar energies within the framework of a modified potential cluster model(MPCM)with forbidden states,including low-lying *** investigation of the ^(15)N(p,γ0)^(16)O reaction includes the consideration of ^(3)s_(1) resonances due to E1 transitions and the contribution of the ^(3)P_(1) scattering wave in the p+^(15)N channel due to the ^(3)P_(1)→^(3)P_(0)M1 *** calculated the astrophysical low-energy s-factor,and the extrapolated s(0)turned out to be within 34.7−40.4 keV·*** important role of the asymptotic constant(AC)for the ^(15)N(p,γ0)16O process with interfering ^(3)s_(1)(312)and ^(3)s_(1)(962)resonances is elucidated.A comparison of our calculation for the s-factor with existing experimental and theoretical data is addressed,and a reasonable agreement is *** reaction rate is calculated and compared with the existing *** has negligible dependence on the variation of AC but shows a strong impact of the interference of ^(3)s_(1)(312)and ^(3)s_(1)(962)resonances in reference to the CNO Gamow windows,especially at low *** estimate the contribution of cascade transitions to the reaction rate based on the exclusive experimental data from ***.C.85,065810(2012).The reaction rate enhancement due to the cascade transitions is observed from T_(9)>0.3 and reaches the maximum factor~1.3 at T_(9)=*** present the Gamow energy window and a comparison of rates for radiative proton capture reactions ^(12)N(p,γ)^(13)O,^(13)N(p,γ)^(14)O,^(14)N(p,γ)^(15)O,and ^(15)N(p,γ)^(16)O obtained in the framework of the MPCM and provide the temperature windows,prevalence,and significance of each process.

关键词： low and astrophysical energies p^(15)N system thermonuclear reaction rate potential cluster model CNO-cycle

Adenosine A1 receptor ligands bind toα-synuclein:implications forα-synuclein misfolding andα-synucleinopathy in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 809-834页

作者： Elisabet Jakova Mohamed Taha Moutaoufik Jeremy s.Lee Mohan Babu Francisco s.Cayabyab Department of surgery College of MedicineUniversity of SaskatchewanSaskatoonSKCanada Department of Chemistry and Biochemistry Faculty of ScienceUniversity of ReginaReginaSKCanada Department of Biochemistry Microbiology and ImmunologyCollege of MedicineUniversity of SaskatchewanSaskatoonSKCanada.

Background:Accumulatingα-synuclein(α-syn)aggregates in neurons and glial cells are the staples of many synucleinopathy disorders,such as Parkinson’s disease(PD).since brain adenosine becomes greatly elevated in ageing brains and chronic adenosine A1 receptor(A1R)stimulation leads to neurodegeneration,we determined whether adenosine or A1R receptor ligands mimic the action of known compounds that promoteα-syn aggregation(e.g.,the amphetamine analogue 2-aminoindan)or inhibitα-syn aggregation(e.g.,Rasagiline metabolite 1-aminoindan).In the present study,we determined whether adenosine,A1R receptor agonist N^(6)-Cyclopentyladenosine(CPA)and antago-nist 8-cyclopentyl-1,3-dipropylxanthine(DPCPX)could directly interact withα-syn to modulateα-syn aggregation and neurodegeneration of dopaminergic neurons in the substantia nigra(sN).Methods:Nanopore analysis and molecular docking were used to test the binding properties of CPA and DPCPX withα-syn in ***-Dawley rats were administered with 7-day intraperitoneal injections of the A1R ligands and 1-and 2-aminoindan,and levels ofα-syn aggregation and neurodegeneration were examined in the sN pars compacta and hippocampal regions using confocal imaging and Western ***:Using nanopore analysis,we showed that the A1R agonists(CPA and adenosine)interacted with the N-terminus ofα-syn,similar to 2-aminoindan,which is expected to promote a“knot”conformation andα-syn *** contrast,the A1R antagonist DPCPX interacted with the N-and C-termini ofα-syn,similar to 1-aminoindan,which is expected to promote a“loop”conformation that preventsα-syn *** docking studies revealed that adenosine,CPA and 2-aminoindan interacted with the hydrophobic core ofα-syn N-terminus,whereas DPCPX and 1-aminoindan showed direct binding to the N-and C-terminal hydrophobic *** imaging and Western blot analyses revealed that chronic treatments with CPA alone or in combination with 2-aminoindan increasedα-syn

关键词： Alpha-synucleinopathy Adenosine A1 receptor N6-cyclopentyladenosine 8-cyclopentyl-1 3-dipropylxanthine 1-aminoindan 2-aminoindan Neuroprotection Neurodegeneration Protein misfolding

Genetic interactions and modifi er genes in Hirschsprung's disease

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World Journal of Gastroenterology 2011年第45期17卷 4937-4944页

作者： Adam s Wallace Richard B Anderson Department of Anatomy and Cell Biology University of Melbourne

Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung' s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modif ier genes.

关键词： Neural crest Enteric nervous system Hirschsprung’s disease Aganglionosis Modif ier genes

An Analog of Einstein’s General Relativity Emerging from Classical Finite Elasticity Theory:Analytical and Computational Issues

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Communications in Computational Physics 2013年第8期14卷 801-818页

作者： C.Cherubini s.Filippi Nonlinear Physics andMathematicalModeling Lab University Campus Bio-MedicoI-00128Via A.del Portillo 21RomeItaly International Center for Relativistic Astrophysics-I.C.R.A. University of Rome“La Sapienza”I-00185 RomeItaly

The“analogue gravity formalism”,an interdisciplinary theoretical scheme developed in the past for studying several non relativistic classical and quantum systems through effective relativistic curved space-times,is here applied to largely deformable elastic bodies described by the nonlinear theory of solid *** the simplest nonlinear constitutive relation for the elastic material given by a Kirchhoff-st Venant strain-energy density function,it is possible to write for the perturbations an effective space-time metric if the deformation is purely longitudinal and depends on one spatial coordinate *** and numerical studies of the corresponding dynamics are performed in selected cases and physical implications of the results obtained are finally discussed.

关键词： Finite elasticity general relativity analogue gravity finite elements method

Theoretical study of structural and electronic properties of oligo(thiophene-phenylene)s in comparison with oligothiophenes and oligophenylenes

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Chinese Chemical Letters 2008年第1期19卷 123-126页

作者： H.Zgou s.M.Bouzzine s.Bouzakraoui M.Hamidi M.Bouachrine Unité de Recherche sur les Macromolécules et Modélisation Faculté des Sciences et TechniquesB.P.509 Boutalamine5200 ErrachidiaMorocco Unité de Chimie Théorique AppliquéeFaculté des Sciences et TechniquesB.P.509 Boutalamine5200 ErrachidiaMorocco Unité de Chimie Théorique Appliquée Faculté des Sciences et TechniquesB.P.509 Boutalamine5200 ErrachidiaMorocco Unité de Recherche sur les Macromolécules et Modélisation Faculté des Sciences et TechniquesB.P.509 Boutalamine5200 ErrachidiaMorocco

In this work, a quantum-chemical investigation on the structural and opto-electronic properties of oligo（thiophene-phenylene）（4TP） is carried out. The results are discussed in comparison with the properties of corresponding oligothiophene （8T） and oligophenylene （8P）. As the opto-electronic properties of this type of conducting polymers are governed by their electronic band gap, we shall also present a comparison among HOMO, LUMO and band gap energies of these three materials.

关键词： Conjugated polymers Oligothiophene Oligophenylene Oligo(thiophene-phenylene) DFT

s1P: the elixir of life for naive T cells

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Cellular & Molecular Immunology 2018年第7期15卷 657-659页

作者： Michaël Pérès Anne Montfort Nathalie Andrieu-Abadie Céline Colacios Bruno ségui INsERM UMR1037 Centre de Recherches en Cancérologie de ToulouseToulouse 31037France Facultéde pharmacie UniversitéToulouse III Paul-SabatierToulouse 31062France Laboratoire d’hématologie CHU de ToulouseToulouse 31059France Equipe Labellisée Ligue Contre Le Cancer Toulouse 31037France Correspondence:Professor B SéguiPhDINSERMUMR1037 CRCTCentre de Recherches en Cancérologie de Toulouse2 avenue Hubert CurienToulouse 31037France

During their life,T cells are constantly circulating throughout the ***-1-phosphate(s1P),a sphingolipid metabolite,triggers T cell egress from the thymus and secondary lymphoid organs(sLO)into the lymph and the *** phenomenon is dependent on the s1P gradient between lymphoid organs(including thymus and sLO)and the lymphatic and blood vessels,which exhibit low,intermediate and high s1P levels,respectively.T cells follow the s1P gradient via the engagement of the G-protein-coupled receptor s1P receptor 1(s1P1)expressed on T cells.1 s1P production is regulated by various sphingolipid-metabolizing *** sphingosine kinases 1 and 2(sKs),encoded by sphk1 and sphk2,phosphorylate the sphingosine(sph)into ***,s1P can be dephosphorylated to sph by s1P phosphatases 1 and 2,encoded by sgpp1 and ***,s1P can be irreversibly degraded by the s1P Lyase(sPL),encoded by sgpl1,into phosphoethanolamine and hexadecenal.

关键词： organs al. lymphoid

Multiclass recognition of Alzheimer’s and Parkinson’s disease using various machine learning techniques: A study

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International Journal of Modeling, simulation, and scientific Computing 2022年第1期13卷 235-250页

作者： Chetan Balaji D.s.suresh Department of ECE Channabasaveshwara Institute of Technology Tumkur KarnatakaIndia Visvesvaraya Technological University BelagaviKarnatakaIndia

The aging population is primarily affected by Alzheimer’s disease(AD)that is an incur-able neurodegenerative *** is a need for an automated efficient technique to diagnose Alzheimer’s in its early *** techniques are used to diagnose *** and neuroimaging methodologies are widely used to highlight changes in the electrical activity of the brain signals that are helpful for early ***’s disease(PD)is a major neurological disease that results in an average of 50,000 new clinical diagnoses worldwide every *** voice features are majorly used as the main means to diag-nose *** major symptoms of PD are loss of intensity,the monotony of loudness and pitch,reduction in stress,unidentified silences,and *** though various innovative models are proposed by explorers about Alzheimer’s and Parkinson’s classifi-cation diseases,still there is a need for efficient learning methodologies and *** paper provides a review on using machine learning(ML)together with several fea-ture extraction techniques that is helpful in the early detection of AD with Parkinson’*** novelty and objective of this study are that the CAD technique is used to improve the accuracy of early diagnosis of *** proposed technique depends on the nonlinear process for data dimension reduction,feature removal,and classification using kernel-based support vector machine(sVM)*** dimension of the input space is radically diminished with kernel *** the learning set is labeled,it creates sense to utilize this information to make a dependable method of dropping the input space *** different techniques of ML are explained under the major approaches ***,artificial neural network(ANN),deep learning(DL),and ensemble methods.A comprehensive assessment is presented at sVM,ANN,and DL approaches for better detection of Alzheimer’s with PD highlighting future insights.

关键词： Electroencephalograph support vector machine Alzheimer’s disease control normal machine learning