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Alzheimer’s Disease Aβ-Amyloid Plaque morphology Varies According to APOE Isotype

World Journal of Neuroscience 2023年第3期13卷 118-133页

作者： Ina Caesar K. Peter R. Nilsson per hammarström mikael Lindgren Stefan Prokop James Schmeidler Vahram Haroutunian David m. Holtzman Patrick R. Hof Sam Gandy Department of Neurology Icahn School of Medicine at Mount Sinai New York NY USA Department of Physics Chemistry and Biology Link&#246ping University Link&#246ping Sweden Department of Physics Norwegian University of Science and Technology Trondheim Norway Department of Neuropathology Charité Universit&#228tsmedizin Berlin Berlin Germany Department of Psychiatry Icahn School of Medicine at Mount Sinai New York NY USA Alzheimer’s Disease Research Center Icahn School of Medicine at Mount Sinai New York NY USA James J. Peters VA medical Center Bronx NY USA Nash Family Department of Neuroscience and Friedman Brain Institute Icahn School of Medicine at Mount Sinai New York NY USA Department of Neurology Hope Center for Neurological Disorders Knight Alzheimer’s Disease Research Center Washington University St. Louis MO USA Ronald m. Loeb Center for Alzheimer’s Disease Icahn School of Medicine at Mount Sinai New York NY USA

Background: The apolipoprotein E (APOE, gene;apoE, protein) ε4 allele is the most commonly identified genetic risk factor for typical late-onset sporadic Alzheimer’s disease (AD). Each APOE ε4 allele roughly triples the relative risk for AD compared to that of the reference allele, APOE ε3. methods: We have employed hyperspectral fluorescence imaging with an amyloid-specific, conformation-sensing probe, p-FTAA, to elucidate protein aggregate structure and morphology in fresh frozen prefrontal cortex samples from human postmortem AD brain tissue samples from patients homozygous for either APOE ε3 or APOE ε4. Results: As expected APOE ε4/ε4 tissues had a significantly larger load of CAA than APOE ε3/ε3. APOE isoform-dependent morphological differences in amyloid plaques were also observed. Amyloid plaques in APOE ε3/ε3 tissue had small spherical cores and large coronas while amyloid plaques in APOE ε4/ε4 tissues had large irregular and multi-lobulated plaques with relatively smaller coronas. Despite the different morphologies of their cores, the p-FTAA stained APOE ε3/ε3 amyloid plaque cores had spectral properties identical to those of APOE ε4/ε4 plaque cores. Conclusions: These data support the hypothesis that one mechanism by which the APOE ε4 allele affects AD is by modulating the macrostructure of pathological protein deposits in the brain. APOE ε4 is associated with a higher density of amyloid plaques (as compared to APOE ε3). We speculate that multilobulated APOE ε4-associated plaques arise from multiple initiation foci that coalesce as the plaques grow.

关键词： Alzheimer’s Disease Amyloid Apolipoprotein Luminescent Conjugated Oligothiophenes Hyperspectral Separation

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This year's Nobel Prize to gastroenterology:Robin Warren and Barry marshall awarded for their discovery of Helicobacter pylori as pathogen in the gastrointestinal tract

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World Journal of Gastroenterology 2006年第19期12卷 3126-3127页

作者： per m Hellstr(o|¨)m Department of medicine Unit of Gastroenterology and Hepatology Karolinska University HospitalSolnaStockholmSweden

TO THE EDITORPeptic ulcer disease is a major health care concern in the society today, in view of personal suffering as well as economical health care costs.

关键词： Helicobacter pylori Nobel Prize Gastroenterology Helicobacter Infections History, 21st Century Humans Inflammation Peptic Ulcer Stomach Neoplasms

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BOUNDARY PROCEDURES FOR THE TImE-DEPENDENT BURGERS' EQUATION UNDER UNCERTAINTY

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Acta mathematica Scientia 2010年第2期30卷 539-550页

作者： per Pettersson Jan Nordstrm Gianluca Iaccarino mechanical Engineering and Institute for Computational mathematical Engineering Stanford University Division of Scientific Computing Department of Information TechnologyUppsala University School of mechanical Industrial and Aeronautical EngineeringUniversity of the Witvatersrand Department of Aeronautics and Systems Integration FOIThe Swedish Defense Research Agency

The Burgers＇ equation with uncertain initial and boundary conditions is approximated using a Polynomial Chaos Expansion （PCE） approach where the solution is represented as a series of stochastic, orthogonal polynomials. The resulting truncated PCE system is solved using a novel numerical discretization method based on spatial derivative operators satisfying the summation by parts property and weak boundary conditions to ensure stability. The resulting PCE solution yields an accurate quantitative description of the stochastic evolution of the system, provided that appropriate boundary conditions are available. The specification of the boundary data is shown to influence the solution; we will discuss the problematic implications of the lack of precisely characterized boundary data and possible ways of imposing stable and accurate boundary conditions.

关键词： stochastic Burgers' equation uncertainty quantification polynomial chaos

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Laparoscopic distal pancreatectomy for adenocarcinoma of the pancreas

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World Journal of Gastroenterology 2014年第37期20卷 13402-13411页

作者： Bergthor Bjrnsson per Sandstrm Department of Surgery County Council of stergtland and Department of Clinical and Experimental MedicineFaculty of Health SciencesLinkping University

Since the first report on laparoscopic distal pancreatectomy (LDP) appeared in the 1990s, the procedure has been performed increasingly frequently to treat both benign and malignant lesions of the pancreas. many earlier publications have shown LDP to be a good alternative to open distal pancreatectomy for benign lesions, although this has never been studied in a prospective, randomized manner. The evidence for the use of LDP to treat adenocarcinoma of the pancreas is not as well established. The purpose of this review is to evaluate the current evidence for LDP in cases of pancreatic adenocarcinoma. We conducted a review of English language publications reporting LDP results between 1990 and 2013. All studies reporting results in patients with histologically proven pancreatic adenocarcinoma were included. Thirty-nine publications were found and included in the results for a total of 309 cases of pancreatic adenocarcinoma (potential double publications were not eliminated). most LDP procedures are performed in selected cases and generally involve smaller tumors than open distal pancreatectomy (ODP) procedures. Some of the papers report unselected cases and include procedures on larger tumors. The number of lymph nodes harvested using LDP is comparable to the number obtained with ODP, as is the frequency of R0 resections. Current data suggest that similar short term oncological results can be obtained using LDP as those obtained using ODP.

关键词： Adenocarcinoma of the pancreas Laparoscopy Distal pancreatectomy Surgical margins Pancreatic resection

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A direct solver with O（N） complexity for integral equations on one-dimensional domains

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Frontiers of mathematics in China 2012年第2期7卷 217-247页

作者： Adrianna GILLmAN Patrick m. YOUNG per-Gunnar mARTINSSON Department of Applied mathematics University of Colorado at Boulder BoulderCO 80309-0526 USA

An algorithm for the direct inversion of the linear systems arising from NystrSm discretization of integral equations on one-dimensional domains is described. The method typically has O（N） complexity when applied to boundary integral equations （BIEs） in the plane with non-oscillatory kernels such as those associated with the Laplace and Stokes＇ equations. The scaling coefficient suppressed by the ＂big-O＂ notation depends logarithraically on the requested accuracy. The method can also be applied to BIEs with oscillatory kernels such as those associated with the Helmholtz and time-harmonic maxwell equations; it is efficient at long and intermediate wave-lengths, but will eventually become prohibitively slow as the wave-length decreases. To achieve linear complexity, rank： deficiencies in the off-diagonal blocks of the coefficient matrix are exploited. The technique is conceptually related to the H- and H2-matrix arithmetic of Hackbusch and coworkers, and is closely related to previous work on Hierarchically Semi-Separable matrices.

关键词： Direct solver integral equation fast direct solver boundary value problem boundary integral equation hierarchically semi-separable matrix mSC 65R20,65F05

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A comparative genomic framework for the fish-tetrapod transition

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Science China(Life Sciences) 2021年第4期64卷 664-666页

作者： per Erik Ahlberg Department of Organismal Biology Uppsala University75236 UppsalaSweden

The evolution of tetrapods(land vertebrates)from lobe-finned fishes,nearly 400 million years ago,was a hugely important *** one thing,if these ancient fishes had not found a way to adapt to life out of the water,we humans would not *** investigate this event we can look at the fossil record,but that only tells us about changes in the skeleton.

关键词： skeleton record fish

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Alcohol consumption in patients with primary sclerosing cholangitis

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World Journal of Gastroenterology 2012年第24期18卷 3105-3111页

作者： Hannes Hagstrm per Stl Knut Stokkeland Annika Bergquist Department of Gastroenterology and Hepatology Karolinska University HospitalKarolinska Institutet14186 StockholmSweden Department of medicine Visby HospitalKarolinska Institutet14186 StockholmSweden

AIm:To assess the alcohol drinking patterns in a cohort of primary sclerosing cholangitis(PSC) patients and the possible influence on the development of ***:Ninety-six patients with PSC were evaluated with a validated questionnaire about a patient's lifetime drinking habits:the lifetime drinking history(LDH) *** addition,clinical status,transient elastography and biochemistry values were analysed and *** were defined as having either significant or non-significant *** fibrosis was defined as either an elastography value of ≥ 17.3 kPa or the presence of clinical signs of *** were divided into two groups depending on their alcohol consumption patterns;no/low alcohol consumption(one drink or unit/d) and moderate/high alcohol consumption(≥ 1 drink or unit/d).LDH data were calculated to estimate lifetime alcohol intake(LAI),current alcohol intake,drinks per year before and after diagnosis of *** also calculated the number of episodes of binge-drinking(defined as consuming ≥ 5 drinks per occasion) in total,before and after the diagnosis of ***:The mean LAI was 3882 units of alcohol,giving a mean intake after onset of alcohol consumption of 2.6 units per *** 9% of patients consumed alcohol equal to or more than one unit per *** alcohol intake in patients with significant fibrosis(n = 26) was less than in patients without significant fibrosis(n = 70),as shown by lower values of phosphatidylethanol(B-PEth)(0.1 mol/L vs 0.33 mol/L,respectively,P = 0.002) and carbohydrate-deficient transferrin(CDT)(0.88% vs 1.06%,respectively,P = 0.02).Self-reported LAI was similar between the two *** with significant fibrosis reduced their alcohol intake after diagnosis from 103 to 88 units per year whereas patients without fibrosis increased their alcohol intake after PSC diagnosis from 111 to 151 units/*** were no correlations between elastography values and intake of alcoho

关键词： Alcohol Fibrosis Cirrhosis Lifetime drinkinghistory Primary sclerosing cholangitis

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Comparative analysis of planted and unplanted controls for assessment of rhizosphere priming effect

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Pedosphere 2022年第6期32卷 884-892页

作者： Jian LI per BENGTSON Department of Biology Microbial Ecology GroupLund UniversitySölvegatan 37Lund 22362(Sweden) Key Laboratory of Urban Environment and Health Institute of Urban EnvironmentChinese Academy of Sciences1799 Jimei RoadXiamen 361021(China)

The rhizosphere priming effect(RPE)is increasingly being considered to be an important regulator of soil organic matter(SOm)decomposition and nutrient turnover,with potential importance for the global CO_(2) *** a result,studies on the RPE have rapidly increased in number over the last few *** of these experiments have been performed using unplanted soil as the control,which could potentially lead to incorrect assessment of the ***,we performed a greenhouse experiment to investigate how the choice of control(i.e.,unplanted control and planted control)influenced the quantification of RPE on SOm decomposition and gross nitrogen(N)mineralization,and to link this to differences in microbial and abiotic soil properties between the two *** the planted control,planted seedlings were cut at soil surface 5 d before measurement of the *** RPE on SOm decomposition was positive in pine soil and almost 2-fold higher when calculated from the planted control than from the unplanted *** spruce soil,a negative RPE on SOm decomposition was found when calculated from the planted control,while the RPE was positive when calculated from the unplanted *** RPE on gross N mineralization was found when calculated from the planted control,while a positive RPE of more than 100%was found when calculated from the unplanted *** microbial biomass and growth rate were lower,while the inorganic N content was higher in the unplanted control than in the planted *** microbial community composition and potential enzyme activity in the planted treatment and planted control were similar,but they differed significantly from those in the unplanted *** results showed that the RPE varied widely depending on the choice of control;thus,we suggest that a planted control,in which the aboveground plant parts are removed only a few days before the measurement of RPE,should be used as the control when elucidating the RPE on belowground C and N

关键词： enzyme activity gross nitrogen mineralization microbial community composition nitrogen availability soil organic matter decomposition

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Liver fibrosis in non-alcoholic fatty liver disease-diagnostic challenge with prognostic significance

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World Journal of Gastroenterology 2015年第39期21卷 11077-11087页

作者： per Stal Division of Gastroenterology and Hepatology Karolinska InstitutetDepartment of Digestive DiseasesHuddinge K63Karolinska University Hospital

Non-alcoholic fatty liver disease(NAFLD) is the mostcommon liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis(stage F3) and cirrhosis(stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers(e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques(transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

关键词： Non-alcoholic fatty liver disease Fibrosis mortality Biomarkers Elastography

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Spinal and supraspinal control of motor function during maximal eccentric muscle contraction:Effects of resistance training

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Journal of Sport and Health Science 2018年第3期7卷 282-293页

作者： per Aagaard Department of Sports Science and Clinical Biomechanics University of Southern Denmark

Neuromuscular activity is suppressed during maximal eccentric(ECC)muscle contraction in untrained subjects owing to attenuated levels of central activation and reduced spinal motor neuron(mN)excitability indicated by reduced electromyography signal amplitude,diminished evoked H-reflex responses,increased autogenic mN inhibition,and decreased excitability in descending corticospinal motor *** ECC muscle force recorded during maximal voluntary contraction can be increased by superimposed electrical muscle stimulation only in untrained individuals and not in trained strength athletes,indicating that the suppression in mN activation is modifiable by resistance *** support of this notion,maximum ECC muscle strength can be increased by use of heavy-load resistance training owing to a removed or diminished suppression in neuromuscular ***(weeks to months)of heavy-load resistance training results in increased H-reflex and V-wave responses during maximal ECC muscle actions along with marked gains in maximal ECC muscle strength,indicating increased excitability of spinal mNs,decreased presynaptic and/or postsynaptic mN inhibition,and elevated descending motor ***,the use of supramaximal ECC resistance training can lead to selectively elevated V-wave responses during maximal ECC contraction,demonstrating that adaptive changes in spinal circuitry function and/or gains in descending motor drive can be achieved during maximal ECC contraction in response to heavy-load resistance training.

关键词： Corticospinal excitability Eccentric muscle contraction H-reflex Neuromuscular plasticity Resistance training V-wave

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