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Journal of Computational Mathematics 2024年第2期42卷 432-453页

作者： Mahboub Baccouch Department of Mathematics University of Nebraska at OmahaOmaha NE 68182USA

In this paper,we develop and analyze a finite difference method for linear second-order stochastic boundary-value problems(SBVPs)driven by additive white noises.First we regularize the noise by the Wong-Zakai approximation and introduce a sequence of linear second-order SBVPs.We prove that the solution of the SBVP with regularized noise converges to the solution of the original SBVP with convergence order O(h)in the meansquare sense.To obtain a numerical solution,we apply the finite difference method to the stochastic BVP whose noise is piecewise constant approximation of the original noise.The approximate SBVP with regularized noise is shown to have better regularity than the original problem,which facilitates the convergence proof for the proposed scheme.Convergence analysis is presented based on the standard finite difference method for deterministic problems.More specifically,we prove that the finite difference solution converges at O(h)in the mean-square sense,when the second-order accurate three-point formulas to approximate the first and second derivatives are used.Finally,we present several numerical examples to validate the efficiency and accuracy of the proposed scheme.

关键词： Boundary-value problems Finite-difference method Additive white noise Wiener process Mean-square convergence Wong-Zakai approximation

Considerations for the use of porcine organ donation models in preclinical organ donor intervention research

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Animal Models and Experimental Medicine 2024年第3期7卷 283-296页

作者： Frazer I.Heinis Shaheed Merani Nicholas W.Markin Kim F.Duncan Michael J.Moulton Lance Fristoe William E.Thorell Raechel A.Sherrick Tami R.Wells Matthew T.Andrews Marian Urban School of Natural Resources Institute of Agriculture and Natural ResourcesUniversity of Nebraska-LincolnLincolnNebraskaUSA Division of Transplantation and Vascular Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Department of Anesthesiology University of Nebraska Medical CenterOmahaNebraskaUSA Division of Cardiothoracic Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Clinical Perfusion Nebraska Medicine-Nebraska Medical CenterOmahaNebraskaUSA Department of Neurosurgery University of Nebraska Medical CenterOmahaNebraskaUSA Nutrition and Health Sciences College of Education and Human SciencesUniversity of Nebraska-LincolnLincolnNebraskaUSA Department of Comparative Medicine University of Nebraska Medical CenterOmahaNebraskaUSA

Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical transplantation.Animal models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia-reperfusion injury,organ preservation strategies,and future donor-based interventions.Important considerations include cost,public opinion regarding the conduct of animal research,translational value,and relevance of the animal model for clinical practice.We present an overview of two porcine models of organ donation:donation following brain death(DBD)and donation following circulatory death(DCD).The cardiovascular anatomy and physiology of pigs closely resembles those of humans,making this species the most appropriate for pre-clinical research.Pigs are also considered a potential source of organs for human heart and kidney xenotransplantation.It is imperative to minimize animal loss during procedures that are surgically complex.We present our experience with these models and describe in detail the use cases,procedural approach,challenges,alternatives,and limitations of each model.

关键词： animal model brain death circulatory death organ transplantation

An analysis of air pollution associated with the 2023 sand and dust storms over China:Aerosol properties and PM_(10) variability

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Geoscience Frontiers 2024年第2期15卷 155-168页

作者： Mikalai Filonchyk Michael P.Peterson Lifeng Zhang Haowen Yan Faculty of Geomatics Lanzhou Jiaotong UniversityLanzhou 730070China Gansu Provincial Engineering Laboratory for National Geographic State Monitoring Lanzhou 730070China Department of Geography/Geology University of Nebraska OmahaOmahaNE 68182USA

Every spring,a large part of China is confronted with sand and dust storms(SDS)–mainly originating in the Gobi(including Chinese and Mongolian Gobi)and Taklamakan deserts.In March-April 2023,most of northern,northwestern and northeastern China was struck by three sandstorms that affected an area with more than 500 million people.In this study,aerosol optical,microphysical and radiative properties were studied during these SDS events using an integrated approach that combines satellite,terrestrial and re-analysis data.The results showed that dusty conditions were observed in most areas north of the Yangtze River(Chang Jiang)with daily average PM_(10)concentrations exceeding 1000 lg/m^(3) in many cities.VIIRS aerosol optical depth(AOD)at 550 nm during three SDS events exceeded a value of 1 throughout nearly the entire northern part of the country.The AERONET data obtained from the AOE_Baotou site showed a significant increase in total AOD and a corresponding decrease in AE during the SDS.The single scattering albedo(SSA),asymmetry parameter(ASY),real refractive index(RRI)and imaginary refractive index(IRI)values indicate an abundance of scattering coarse-mode particles.Aerosol radiative forcing(ARF)at top of the atmosphere and at the earth’s surface was nearly always negative during the period and ranged from48.5 to+2.7 Wm^(-2)and from180.8 to66.6 Wm^(-2),resulting in high positive ARF values at ATM(from+63.8 to+132.3 Wm^(-2)).Each of these affects the heating of the atmosphere and cooling on the earth’s surface.The atmospheric heating rates ranged from 1.8 to 3.7 K day1.The formation of these SDS mainly resulted from the passage of cold fronts associated with low pressure systems in the Gobi and Taklamakan deserts,creating conditions for dust to rise into the atmosphere and move further downwind.

关键词： Dust storm PM_(10) Aerosol optical depth Radiative forcing VIIRS AERONET

LOD score exclusion analyses for candidate disease susceptibility genes using case-parents design

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Progress in Natural Science:Materials International 2006年第1期16卷 30-38页

作者： DENG Hongwen1,2,3 and GAO Guimin2,4 (1.Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China 2.Osteoporosis Research Center, Creighton University Medical Center, omaha NE 68131, USA 3. Department of Biomedical Sciences, Creighton University, omaha NE 68131, USA 4. Virginia Bioin format ics Institute and Department of Statistics, Virginia Polytechnic Institute and State University, Blacksburg VA 24061-0315, USA) Laboratory of Molecular and Statistical Genetics College of Life Sciences Hunan Normal University Changsha 410081 China Osteoporosis Research Center Creighton University Medical Center Omaha NE 68131 United States Department of Biomedical Sciences Creighton University Omaha NE 68131 United States Virginia Bioinformatics Institute and Department of Statistics Virginia Polytechnic Institute and State University Blacksburg VA 24061-0315 United States

The focus of almost all the association studies of candidate genes is to test for their importance. We recently developed a LOD score approach that can be used to test against the importance of candidate genes for complex diseases and quantitative traits in random samples. As a complementary method to regular association analyses, our LOD score approach is powerful but still affected by the population admixture, though it is more conservative. To control the confounding effect of population heterogeneity, we develop here a LOD score exclusion analysis using case-parents design, the basic design of the transmission disequilibrium test (TDT) approach that is immune to population admixture. In the analysis, specific genetic effects and inheritance models at candidate genes can be analyzed and if a LOD score is ≤ - 2. 0, the locus can be excluded from having an effect larger than that specified. Simulations show that this approach has reasonable power to exclude a candidate gene having small genetic effects if it is not a disease susceptibility locus (DSL) with sample size often employed in TDT studies. Similar to association analyses with the TDT in nuclear families, our exclusion analyses are generally not affected by population admixture. The exclusion analyses may be implemented to rule out candidate genes with no or minor genetic effects as supplemental analyses for the TDT. The utility of the approach is illustrated with an application to test the importance of vitamin D receptor (VDR) gene underlying the differential risk to osteoporosis.

关键词： association studies candidate genes case-parents design disease susceptibility locus exclusion mapping LOD score.

Interaction effects between estrogen receptor α and vitamin D receptor genes on age at menarche in Chinese women

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Acta Pharmacologica Sinica 2005年第7期26卷 860-864页

作者： Hong XU~(1,2) Ji-rong LONG~3 Miao-xin LI~1 Hong-wen DENG~(1,3) 1 Laboratory of Molecular and Statistical Genetics,College of Life Sciences,Hu-nan Normal University,Changsha 410081,China 2 Department of Physiology,Jiangxi Medical College,Nanchang 330006,China 3 Osteoporosis Research Center and Department of Biomedical Sciences,Creighton University Medical Center,601 N 30th St,Suite 6787,omaha,NE 68131,USA Laboratory of Molecular and Statistical Genetics College of Life Sciences Hu-nan Normal University Changsha China Department of Physiology Jiangxi Medical College Nanchang China Osteoporosis Research Center and Department of Biomedical Sciences Creighton University Medical Center Omaha USA

Aim:To evaluate whether estrogen receptor α(ER-α)and vitamin D receptor(VDR)genes are associated with the age at menarche in Chinese women.Methods:A total of 390 pre-menopausal Chinese women were genotyped at the ER-α PvuII,XbaI,and VDR Apal loci using polymerase chain reaction(PCR)-restriction frag-ment length polymorphism(RFLP).Results:Neither the ER-α gene nor the VDRgene individually had significant effects on the age at menarche in our subjects(P>0.10).However,evidence of interaction effects between the two genes wereobserved:with the aa genotype at the VDR ApaI locus,subjects with haplotypePX at the ER-α gene had,on average,6 months later onset of menarche than thenon-carriers(P=0.01).Conclusion:We found that neither the ER-α gene or theVDR gene had a significant association with the age at menarche individually.However,potential interaction effects between the two genes were observed inChinese women.

关键词： menarche association haplotype estrogen receptor a gene vitamin D receptor gene

Caveolin-1 gene silencing promotes the activation of PI3K/AKT dependent on Erα36 and the transformation of MCF10A^(CE)

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Science China(Life Sciences) 2010年第5期53卷 598-605页

作者： FENG Shuang1,WANG Yang1,WANG Xi1,WANG ZhaoYi3,CUI YuYing1,LIU Jing4,ZHAO ChunHui1,JIN Mei1,2 & ZOU Wei1,2 1 College of Life Science,Liaoning Normal University,Dalian 116029,China 2 Liaoning Key Laboratory of Biotechnology and Molecular Drug R&D,Dalian 116029,China 3 Cancer Center,Creighton University,2500 California Plaza,omaha,NE 68178,USA 4 First Clinical Hospital of Dalian Medical University,Dalian 116011,China College of Life Science Liaoning Normal University Dalian China Cancer Center Creighton University Omaha USA First Clinical Hospital of Dalian Medical University Dalian China Liaoning Key Laboratory of Biotechnology and Molecular Drug R&D Dalian China

ERα36,a variant of estrogen receptor-α,acts as a dominant-negative factor in both estrogen-dependent and estrogen-independent transactivation signaling pathways,and is a key factor in the promotion,progression and prognosis of breast cancers.Caveolin-1,a 22-to 24-kD integral membrane protein,may function as a tumor suppressor in inhibiting of many growth-promoting signaling pathways.It was shown that downregulation of Caveolin-1 strengthens the interaction of ERα and Caveolin-1.In conclusion,Caveolin-1 gene silencing activated the PI3K/AKT signaling pathway in an ERα36-dependent way.Our finding may provide a promising therapeutic target of breast cancer.

关键词： Caveolin-1 Estrogen receptor PI3K/AKT

Prestin forms tetramer with each subunit being mechanically independent

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Journal of Otology 2009年第2期4卷 86-97页

作者： WANG Xiang 1, GUO Wei-wei 2, HE David Zhi-Zhou1, YANG Shi-Ming 2 1 Department of Biomedical Sciences, Creighton University School of Medicine, omaha, NE 68178, USA 2 Institute of Otolaryngology, Department of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Beijing 100853 Department of Biomedical Sciences Creighton University School of Medicine Omaha NE 68178 USA Institute of Otolaryngology Department of Otolaryngology Head and Neck Surgery Chinese PLA General Hospital Beijing 100853

Prestin is the motor protein of cochlear outer hair cells （OHCs）. It is able to perform rapid and reciprocal electromechanical conversion that underlies OHC electromotility. Due to the inadequate size of a single prestin molecule to form the2 nm intramembraneous protein particles （IMPs） in the OHC lateral membrane （LM）, the possibility of prestin oligomerization has been proposed. It has been suggested that prestin molecules form highorder oligomers, most likely as the tetramer, in heterologous systems. In OHCs, however, the oligomeric structure of prestin remains unclear. Here we calculated the prestin-related charge density in both gerbil and guinea pig OHCs through measuring their nonlinear capacitance （NLC） and LM surface area, showing that the average charge density （22, 608 μm-2 in gerbils; 19, 460 μm-2 in guinea pigs） is statistically 4 times the average density of IMPs （5,686 μm-2 in gerbils; 5, 000 μm-2 in guinea pigs）. This suggests that each IMP contains four prestin molecules based upon the notion that each prestin transfers a single elementary charge, implying that prestin forms tetramers in OHCs. To determine whether the prestin tetramer functions as a mechanical unit, we subsequently compared the slope factors （α） of electromotility and NLC simultaneously measured from the same OHC, showing that the α values of the two are statistically the same. This suggests that each prestin molecule in the tetramer is mechanically independent and equally contributes to OHC electromotility.

关键词： Prestin oligomer outer hair cells electromotility nonlinear capacitance gerbil

Convergence and Superconvergence of the Local Discontinuous Galerkin Method for Semilinear Second‑Order Elliptic Problems on Cartesian Grids

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Communications on Applied Mathematics and Computation 2022年第2期4卷 437-476页

作者： Mahboub Baccouch Department of Mathematics University of Nebraska at OmahaOmahaNE 68182USA

This paper is concerned with convergence and superconvergence properties of the local discontinuous Galerkin(LDG)method for two-dimensional semilinear second-order elliptic problems of the form−Δu=f(x,y,u)on Cartesian grids.By introducing special GaussRadau projections and using duality arguments,we obtain,under some suitable choice of numerical fuxes,the optimal convergence order in L2-norm of O(h^(p+1))for the LDG solution and its gradient,when tensor product polynomials of degree at most p and grid size h are used.Moreover,we prove that the LDG solutions are superconvergent with an order p+2 toward particular Gauss-Radau projections of the exact solutions.Finally,we show that the error between the gradient of the LDG solution and the gradient of a special Gauss-Radau projection of the exact solution achieves(p+1)-th order superconvergence.Some numerical experiments are performed to illustrate the theoretical results.

关键词： Semilinear second-order elliptic boundary-value problems Local discontinuous Galerkin method A priori error estimation Optimal superconvergence Supercloseness Gauss-Radau projections

GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation

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Bone Research 2022年第1期10卷 150-164页

作者： Jawed Akhtar Siddiqui Parthasarathy Seshacharyulu Sakthivel Muniyan Ramesh Pothuraju Parvez Khan Raghupathy Vengoji Sanjib Chaudhary Shailendra Kumar Maurya Subodh Mukund Lele Maneesh Jain Kaustubh Datta Mohd Wasim Nasser Surinder Kumar Batra Department of Biochemistry and Molecular Biology University of Nebraska Medical CenterOmahaNEUSA Department of Pathology and Microbiology University of Nebraska Medical CenterOmahaNEUSA Fred&Pamela Buffett Cancer Center University of Nebraska Medical CenterOmahaNE 68198-5870USA Eppley Institute for Research in Cancer and Allied Diseases University of Nebraska Medical CenterOmahaNEUSA

Bone metastases occur in patients with advanced-stage prostate cancer(PCa). The cell-cell interaction between PCa and the bone microenvironment forms a vicious cycle that modulates the bone microenvironment, increases bone deformities, and drives tumor growth in the bone. However, the molecular mechanisms of PCa-mediated modulation of the bone microenvironment are complex and remain poorly defined. Here, we evaluated growth differentiation factor-15(GDF15) function using in vivo preclinical PCa-bone metastasis mouse models and an in vitro bone cell coculture system. Our results suggest that PCa-secreted GDF15 promotes bone metastases and induces bone microarchitectural alterations in a preclinical xenograft model. Mechanistic studies revealed that GDF15 increases osteoblast function and facilitates the growth of PCa in bone by activating osteoclastogenesis through osteoblastic production of CCL2 and RANKL and recruitment of osteomacs. Altogether, our findings demonstrate the critical role of GDF15 in the modulation of the bone microenvironment and subsequent development of PCa bone metastasis.

关键词： GDF15 metastasis RANKL

Treatment trends of muscle invasive bladder cancer: Evidence from the Surveillance, Epidemiology, and End Results database, 1988 to 2013

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Asian Journal of Urology 2023年第1期10卷 9-18页

作者： Victor Chalfant Michael L.Blute Jr Peter Silberstein Urology at CHI Health Creighton University Medical Center omaha NEUSA Hematology Oncology at CHI Health Creighton University Medical Center omaha NEUSA

Objective:Guidelines for muscle-invasive bladder cancer(MIBC)recommend that patients receive neoadjuvant chemotherapy with radical cystectomy as treatment over radical cystectomy alone.Though trends and practice patterns of MIBC have been defined using the National Cancer Database,data using the Surveillance,Epidemiology,and End Results(SEER)program have been poorly described.Methods:Using the SEER database,we collected data of MIBC according to the American Joint Commission on Cancer.We considered differences in patient demographics and tumor charac-teristics based on three treatment groups:chemotherapy(both adjuvant and neoadjuvant)with radical cystectomy,radical cystectomy,and chemoradiotherapy.Multinomial logistic regression was performed to compare likelihood ratios.Temporal trends were included for each treatment group.Kaplan-Meier curves were performed to compare cause-specific sur-vival.A Cox proportional-hazards model was utilized to describe predictors of survival.Results:Of 16728 patients,10468 patients received radical cystectomy alone,3236 received chemotherapy with radical cystectomy,and 3024 received chemoradiotherapy.Patients who received chemoradiotherapy over radical cystectomy were older and more likely to be African American;stage III patients tended to be divorced.Patients who received chemotherapy with radical cystectomy tended to be males;stage II patients were less likely to be Asian than Caucasian.Stage III patients were less likely to receive chemoradiotherapy as a treatment op-tion than stage II.Chemotherapy with radical cystectomy and chemoradiotherapy are both un-derutilized treatment options,though increasingly utilized.Kaplan-Meier survival curves showed significant differences between stage II and III tumors at each interval.A Cox proportional-hazards model showed differences in gender,tumor stage,treatment modality,age,andmarital status.Conclusion:Radical cystectomy alone is still the most commonly used treatment for muscle-invasive bladder cancer based on temporal trends.Signific

关键词： Muscle-invasive bladdercancer Bladder-preservation therapy Chemoradiotherapy Transurethral resectionof bladder tumor Surveillance Epidemiology,and EndResultsProgram Patient demographics Practicetrends Kaplan-Meier survival curves