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Disrupted Maturation of Prefrontal Layer 5 Neuronal Circuits in an Alzheimer’s Mouse Model of Amyloid Deposition

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Neuroscience Bulletin 2023年第6期39卷 881-892页

作者： Chang Chen Jing Wei Xiaokuang Ma Baomei Xia Neha Shakir Jessica K.Zhang Le Zhang Yuehua Cui deveroux ferguson Shenfeng Qiu Feng Bai Department of Neurology Affiliated Drum Tower HospitalMedical School of Nanjing UniversityNanjing210008China Basic Medical Sciences University of Arizona College of Medicine-PhoenixPhoenixAZ85004USA

Mutations in genes encoding amyloid precursor protein(APP)and presenilins(PSs)cause familial forms of Alzheimer’s disease(AD),a neurodegenerative disorder strongly associated with *** is currently unknown whether and how AD risks affect early brain development,and to what extent subtle synaptic pathology may occur prior to overt hallmark AD *** mutant APP/PS1 over-expression mouse lines are key tools for studying the molecular mechanisms of AD *** these lines,the 5XFAD mice rapidly develop key features of AD pathology and have proven utility in studying amyloid plaque formation and amyloidβ(Aβ)-induced *** reasoned that transgenic mutant APP/PS1 over-expression in 5XFAD mice may lead to neurodevelopmental defects in early cortical neurons,and performed detailed synaptic physiological characterization of layer 5(L5)neurons from the prefrontal cortex(PFC)of 5XFAD and wild-type littermate controls.L5 PFC neurons from 5XFAD mice show early APP/Aβ***-cell patch-clamp recording at an early post-weaning age(P22–30)revealed functional impairments;although 5XFAD PFC-L5 neurons exhibited similar membrane properties,they were intrinsically less *** addition,these neurons received smaller amplitude and frequency of miniature excitatory synaptic *** functional disturbances were further corroborated by decreased dendritic spine density and spine head volumes that indicated impaired synapse *** biotinylation followed by Western blot analysis of PFC-L5 tissue revealed that 5XFAD mice showed reduced synaptic AMPA receptor subunit GluA1 and decreased synaptic NMDA receptor subunit *** with this,patch-clamp recording of the evoked L23>L5 synaptic responses revealed a reduced AMPA/NMDA receptor current ratio,and an increased level of AMPAR-lacking silent *** results suggest that transgenic mutant forms of APP/PS1 overexpression in 5XFAD mice leads to early deve

关键词： Alzheimer’s disease Mouse model Synaptic plasticity Long-term potentiation Cortical circuit Electrophysiology Learning and memory

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James ferguson Nicole Swiadek Xavier Monforte Johannes C.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

A simulation-based evaluation of the absolute and comparative approaches in a code compliance process from the energy use perspective: Cold-climate case study

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Building Simulation 2022年第8期15卷 1401-1418页

作者： Sara Gilani Alex ferguson Meli Stylianou CanmetENERGY-Ottawa Natural Resources Canada1 Haanel DrOttawaON K1A 1M1Canada

Like many countries,Canada's building code includes a performance compliance path that compares the energy use of a proposed design to that of a reference ***,provinces across Canada are contemplating an alternative absolute energy use intensity ***,the effect of adopting the absolute approach on house design is not well *** study first developed a proof-of-concept methodology for a technical simulation-based comparison of the two ***,it performed a comparative analysis between the design outcomes of the two approaches using the developed *** this end,statistically representative archetypes were configured to comply with the prescriptive requirements of the building *** characteristics of each archetype were then varied through parametric study,and the resulting energy performance under the absolute and comparative approaches were *** results of this study indicated that the two approaches had different effects on the design and energy use of houses in heating-dominated climate *** performing better under the absolute approach consumed less energy and exhibited more compact architectural *** houses were also less sensitive to improvements in airtightness and envelope than houses performing better under the comparative *** results suggest that adopting the absolute approach based on the energy use intensity metric in building codes would encourage design and construction of houses with higher energy efficiency.

关键词： performance path energy efficiency absolute target percent better than code reference building archetype

An Empirical Study on the Impact of Automation on the Requirements Analysis Process

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Journal of Computer Science & Technology 2007年第3期22卷 338-347页

作者： Giuseppe Lami Robert W.ferguson Istituto di Scienza e Tecnologie dell'Informazione"Alessandro Faedo" 1-56124 Pisa Italy Software Engineering Institute Carnegie Mellon University 15213 PittsburghPAU.S.A.

Requirements analysis is an important phase in a software project. The analysis is often performed in an informal way by specialists who review documents looking for ambiguities, technical inconsistencies and incomplete parts. Automation is still far from being applied in requirements analyses, above all since natural languages are informal and thus difficult to treat automatically. There are only a few tools that can analyse texts. One of them, called QuARS, was developed by the Istituto di Scienza e Tecnologie dell＇Informazione and can analyse texts in terms of ambiguity. This paper describes how QuARS was used in a formal empirical experiment to assess the impact in terms of effectiveness and efficacy of the automation in the requirements review process of a software company.

关键词： requirements/specifications analysis requirements/specifications tools process metrics

Fish oils in parenteral nutrition: Why could these be important for gastrointestinal oncology?

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World Journal of Gastrointestinal Oncology 2015年第9期7卷 128-131页

作者： Lynnette R ferguson ACSRC/Discipline of Nutrition and Dietetics School of Medical Sciences Faculty of Medical and Health Sciences the University of Auckland

By the time a gastroenterology patient is moved to parenteral nutrition, he or she is usually in poor health. All parenteral nutrition formulae contain essen-tial nutrients, avoiding components that could cause an adverse reaction. The lipid component is often provided by a soy extract, containing all the fatty acids considered to be essential in the diet. Several trials have considered parenteral nutrition formulas with added fish oils, high in the long chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid(EPA) and docosahexaenoic acid(DHA). Given the range of biological functions associated with such compounds, especially in reducing inflammatory symptoms, this move would appear rational. However, while data from such trials are often positive, there has been variability among results. Some of this variability could be caused by environmental contaminants in the fish, and/or oxidation of the lipids because of poor storage. The situation is complicated by a recent report that fish oils may counter the effects of platinum chemotherapy. However, this effect associated with a minor component, hexadeca-4,7,10,13-tetraenoic acid. It is suggested that pure DHA and EPA would be beneficial additions to parenteral nutrition, reducing the probability of carcinogenesis and enhancing rational disease management. However, the jury is still out on fish oils more generally.

关键词： Inflammatory bowel diseases Colorectal cancer Fish

Two-Way Interactions Between Equatorially-Trapped Waves and the Barotropic Flow

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Chinese Annals of Mathematics,Series B 2009年第5期30卷 539-568页

作者： James ferguson Boualem KHOUIDER Maryam NAMAZI Department of Mathematics and Statistics University of Victoria Department of Mathematics and Statistics University of VictoriaPO BOX 3045 STN CSC Victoria

Lateral energy exchange between the tropics and the midlatitudes is a topic of great importance for understanding Earth＇s climate system. In this paper, the authors address this issue in an idealized set up through simple shallow water models for the interactions between equatorially trapped waves and the barotropic mode, which supports Rossby waves that propagate poleward and can excite midlatitude teleconnection patterns. It is found here that the interactions between a Kelvin wave and a fixed meridionai shear （mimicking the jet stream） generates a non-trivial meridional velocity and meridional convergence in phase with the upward motion that can attain a maximum of about 50%, which oscillates on frequencies ranging from one day to 10 days. When, on the other hand, the barotropic flow is forced by slowly propagating Kelvin waves a complex flow pattern emerges; it consists of a phase-locked barotropic response that is equatoriaily trapped and that propagates eastward with the forcing Kelvin wave and a certain number of planetary Rossby waves that propagate westward and toward the poles as seen in nature. It is suggested here that the poleward propagating waves are to some sort of multi-way resonant interaction with the phase locked response. Moreover, it is shown here that a numerical scheme with dispersion properties that depend on the direction perpendicular to the direction of propagation, namely the 2D central scheme of Nessyahu and Tadmor, can artificially alter significantly the topology of the wave fields and thus should be avoided in climate models.

关键词： Equatorially trapped waves Wave interactions Jet stream Rossby waves Phase locked Dispersion relation Central scheme Climate modeling

Esophageal resection for high-grade dysplasia and intramucosal carcinoma: When and how?

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World Journal of Gastroenterology 2010年第30期16卷 3786-3792页

作者： Vani JA Konda Mark K ferguson Department of Medicine The University of Chicago Pritzker School of MedicineChicagoIL 60637United States Department of Surgery The University of Chicago Pritzker School of MedicineChicagoIL 60637United States

High-grade dysplasia (HGD) and intramucosal carcinoma (IMC) in the setting of Barrett’s esophagus have traditionally been treated with esophagectomy. However, with the advent of endoscopic mucosal resection and endoscopic ablative therapies, endoscopic therapy at centers with expertise is now an established treatment of Barrett’s-esophagus-related neoplasia, including HGD and IMC. Esophagectomy is today reserved for more selected cases with submucosal invasion, evidence for lymph node metastasis, or unsuccessful endoscopic therapy.

关键词： Barrett’s esophagus High-grade dysplasia Intramucosal carcinoma Endoscopic mucosal resection Esophagectomy

Micro RNA biomarkers predicting risk,initiation and progression of colorectal cancer

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World Journal of Gastroenterology 2016年第33期22卷 7389-7401页

作者： Kyungjin Lee Lynnette R ferguson Medical Programme and Discipline of Nutrition and Dietetics and Auckland Cancer Society Research Centre Faculty of Medical and Health ScienceThe University of Auckland Discipline of Nutrition and Dietetics and Auckland Cancer Society Research Centre Faculty of Medical and Health ScienceThe University of Auckland

Colorectal cancer is a major global cause of morbidity and mortality. Current strategies employed to increase detection of early,curable stages of this disease are contributing to a reduction of the negative health impact from it. While there is a genetic component to the risk of disease,diet and environment are known to have major effects on the risk of an individual for developing the disease. However,there is the potential to reduce the impact of this disease further b y preventing disease develop ment. Biomarkers which can either predict the risk for or early stages of colorectal cancer could allow intervention at a time when prospects could be modified by environmental factors,including lifestyle and diet choices. Thus,such biomarkers could be used to identify high risk individuals who would benefit from lifestyle and dietary interventions to prevent this disease. This review will give an overview on one type of biomarker in the form of micro RNAs,which have the potential to predict an individual's risk for colorectal cancer,as well as providing a highly sensitive and non-invasive warning of disease presence and/or progression. Micro RNA biomarkers which have been studied and whose levels look promising for this purpose include Mi R-18 a,Mi R-21,Mi R-92 a,Mi R-135 b,Mi R-760,Mi R-601. Not only have several individual micro RNAs appeared promising as biomarkers,but panels of these may be even more useful. Furthermore,understanding dietary sources and ways of dietary modulation of these micro RNAs might be fruitful in reducing the incidence and slowing the progression of colorectal cancer.

关键词： Biomarkers Epigenetics Risk Colorectal cancer Predisposition MicroRNA

Recent advances in understanding of interactions between genes and diet in the etiology of colorectal cancer

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World Journal of Gastrointestinal Oncology 2010年第3期2卷 125-129页

作者： Lynnette R ferguson Discipline of Nutrition University of Auckland

At an international level, colorectal cancer (CRC) is a major cause of morbidity and mortality. Diet plays a major etiologic role, and a range of putative dietary carcinogens have been identified. The probability with which these lead to mutations, and thereby cause cancer, is strongly impacted by variants in genes coding for xenobiotic metabolizing or DNA repair enzymes. Nutrient def iciencies also play a role, which will be exacerbated by variants in metabolic genes. However, many of the causal genes in sporadic CRC have hitherto proved elusive. The power of large international collabor ations, coupled with genome-wide association studies, has implicated a major functional role of the tumour growth factor-β pathway in CRC susceptibility. Nutrient regulation of gene expression may be especially important here. Future large collaborative studies must consider gene-gene and gene-diet interactions, coupled with high throughput genomic technologies, in order to uncover the relative roles of genetic variants, mutagenic xenobiotics, nutrient imbalance and gene expression in the etiology of CRC.

关键词： Transforming growth factor β Colorectal cancer Single nucleotide polymorphisms Genome wide association studies Gene expression