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Short-circuit Analysis in Large-scale Distribution Systems With High Penetration of Distributed Generators

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IEEE/CAA Journal of Automatica Sinica 2017年第2期4卷 243-251页

作者： Luka V.Strezoski Marija D.Prica IEEE case school of Engineering Case Western Reserve University

In this paper a short-circuit computation(SCC) procedure for large-scale distribution systems with high penetration of distributed generators based on contemporary technologies is proposed. The procedure is suitable for real-time calculations.Modeling of modern distributed generators differs from the modeling of traditional synchronous and induction generators.Hence, SCC procedures found on the presumption of distribution systems with only traditional generators are not suitable in nowadays systems. In the work presented in this paper, for computation of the state of the system with short-circuit, the improved backward/forward sweep(IBFS) procedure is used.Computation results show that the IBFS procedure is much more robust than previous SCC procedures, as it takes into account all distribution system elements, including modern distributed generators.

关键词： Distributed generation(DG) distribution system distribution management system(DMS) short-circuit computation

Sam68 is a regulator of Toll-like receptor signaling

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Cellular & Molecular Immunology 2017年第1期14卷 107-117页

作者： Jeffrey A Tomalka Tristan J de Jesus Parameswaran Ramakrishnan Department of Pathology School of Medicine Case Western Reserve University and University Hospitals Case Medical Center Cleveland OH 44106 USA

Recognition of pathogens by Toll-like receptors （TLR） activate multiple signaling cascades and expression of genes tailored to mount a primary immune response, inflammation, cell survival and apoptosis. Although TLR-induced activation of pathways, such as nuclear factor kappaB （NF-κB） and mitogen-activated protein kinases （MAPK）, has been well studied, molecular entities controlling quantitative regulation of these pathways during an immune response remain poorly defined. We identified Sam68 as a novel regulator of TLR-induced NF-κB and MAPK activation. We found that TLR2 and TLR3 are totally dependent, whereas TLR4 is only partially dependent on Sam68 to induce the activation of NF-KB c-Rel. Absence of Sam68 greatly decreased TLR2- and TLR3-induced NF-κB p65 activation, whereas TLR4- induced p65 activation in a Sam68-independent manner. In contrast, Sam68 appeared to be a negative regulator of MAPK pathways because absence of Sam68 enhanced TLR2-induced activation of extracellular signal-regulated kinases （ERK） and c-Jun N-terminal kinases （JNK）. Interestingly, TLR2- and TLR3-induced gene expression showed a differential requirement of Sam68. Absence of Sam68 impaired TLR2-induced gene expression, suggesting that Sam68 has a critical role in myeloid differentiation primary response gene 88-dependent TLR2 signaling. TLR3-induced gene expression that utilize Toll/Interleukin-1 receptor-domain-containing adapter-inducing beta interferon pathway, depend only partially on Sam68. Our findings suggest that Sam68 may function as an immune rheostat that balances the activation of NF-κB p65 and c-Rel, as well as MAPK, revealing a potential novel target to manipulate TLR signaling.

关键词： innate immunity MAP kinase NF-kappaB Sam68 TLR

Untangling a complex web: Computational analyses of tumor molecular profiles to decode driver mechanisms

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Journal of Genetics and Genomics 2020年第10期47卷 595-609页

作者： Sirvan Khalighi Salendra Singh Vinay Varadan Division of General Medical Sciences-Oncology Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandOH 44106USA

Genome-scale studies focusing on molecular profiling of cancers across tissue types have revealed a plethora of aberrations across the genomic,transcriptomic,and epigenomic scales.The significant molecular heterogeneity across individual tumors even within the same tissue context complicates decoding the key etiologic mechanisms of this disease.Furthermore,it is increasingly likely that biologic mechanisms underlying the pathobiology of cancer involve multiple molecular entities interacting across functional scales.This has motivated the development of computational approaches that integrate molecular measurements with prior biological knowledge in increasingly intricate ways to enable the discovery of driver genomic aberrations across cancers.Here,we review diverse methodological approaches that have powered significant advances in our understanding of the genomic underpinnings of cancer at the cohort and at the individual tumor scales.We outline the key advances and challenges in the computational discovery of cancer mechanisms while motivating the development of systems biology approaches to comprehensively decode the biologic drivers of this complex disease.

关键词： Mutations Systems biology Mutational significance Functional impact Pan-cancer analysis Multiomics integration

Insights on in-office scar revision and resurfacing procedures

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第3期9卷 249-256页

作者： Amanda Goslawski Eve Tranchito Cyrus C.Rabbani Department of Otolaryngology-Head&Neck Surgery University Hospitals Cleveland Medical CenterClevelandOhioUSA Case Western Reserve University School of Medicine ClevelandOhioUSA

Objective:Many facial plastic surgery procedures can be performed in an office-based setting,ranging from simple chemical peels to reconstructive surgeries to assist with scar revision.The aim of this review is to summarize the current state of facial plastics in-office surgical procedures,including scar revision,dermabrasion,lasers,and chemical peels.Methods:A literature review was conducted with the PubMed search engine with the following keywords:facial plastics,scar revision,dermabrasion,lasers,chemical peels,face,office,and outpatient.The literature was surveyed for relevance,with a focus on realistically which procedures were performed in a facial plastics surgery outpatient clinic.These were then used to compile a review of the current state of this field.Results and Conclusions:There are various scar revision procedures that can be performed in the office setting,including z-plasty,w-plasty,and geometric broken line closure techniques,as well as various nonmedical treatment options to improve the appearance of a scar.Dermabrasion can also be performed to assist with elevated scars.Various lasers are available to enhance cell turnover in the field of facial rejuvenation,scarring,and sun damage.Chemical peels are also available to assist with facial rejuvenation.With the appropriate counseling of the patient and medical staff,these can be safely performed in the office.

关键词： chemical peel dermabrasion laser office scar revision

Diabetic bladder dysfunction

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Chinese Medical Journal 2014年第7期127卷 1357-1364页

作者： Guiming Liu Firouz Daneshgari Urology Institute University Hospitals Case Medical Center and Department of Urology Case Western Reserve University School of Medicine Cleveland Ohio USA

Objective To review studies on diabetic bladder dysfunction （DBD）,a common and bothersome complication of diabetes mellitus.Data sources We performed a search of the English literature through PubMed.The key words used were ＂diabetes＂ and ＂bladder dysfunction＂ or ＂cystopathy＂.Our own data and perspective are included in the discussion.Study selection Studies containing data relevant to DBD were selected.Because of the limited length of this article,we also referenced reviews that contain comprehensive amalgamations of relevant literature.Results The classic symptoms of DBD are decreased bladder sensation,increased bladder capacity,and impaired bladder emptying with resultant elevated post-void residual urine.However,recent clinical and experimental evidence indicate a strong presence of storage problems such as urge incontinence in diabetes.Recent studies of DBD in animal models of type 1 diabetes have revealed temporal effects of diabetes,causing an early phase of compensatory bladder function and a later phase of decompensated bladder function.The pathophysiology of DBD is multifactorial,including disturbances of the detrusor,urothelium,autonomic nerves,and urethra.Polyuria and hyperglycemia play important but distinctive roles in induction of bladder dysfunction in type 1 diabetes.Polyuria causes significant bladder hypertrophy in the early stage of diabetes,whereas oxidative stress in the bladder caused by chronic hyperglycemia may play an important role in the late stage failure of bladder function.Conclusions DBD includes time-dependent and mixed manifestations.The pathological alterations include muscle,nerve,and urothelium.Polyuria and hyperglycemia independently contribute to the pathogenesis of DBD.Treatments for DBD are limited.Future clinical studies on DBD in type 1 and type 2 diabetes should be investigated separately.Animal studies of DBD in type 2 diabetes are needed,from the natural history to mechanisms.Further understanding of the molecular mechanisms of DBD will provide multiple potential targ

关键词： diabetes bladder dysfunction cystopathy complications

Differential regulation of basal expression of inflammatory genes by NF-κB family subunits

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Cellular & Molecular Immunology 2019年第8期16卷 720-723页

作者： Tristan J.de Jesús Joshua T.Centore Parameswaran Ramakrishnan Department of Pathology School of MedicineCase Western Reserve UniversityClevelandOH 44106USA Department of Biochemistry School of MedicineCase Western Reserve UniversityClevelandOH 44106USA The case Comprehensive Cancer Center School of MedicineCase Western Reserve UniversityClevelandOH 44106USA

The nuclear factor kappaB(NF-κB)family of transcription factors regulates immune and inflammatory responses and controls cell survival,proliferation,differentiation,and apoptosis.1 The five subunits of the NF-κB family,(RelA,RelB,c-Rel,p105/p50,and p100/p52),are categorized as activating(RelA,RelB,and c-Rel),or inhibitory(p105/p50 and p100/p52),based on the presence or absence of the transactivation domain and form homo-and heterodimers.Stimulus-dependent activation of NF-κB,either by the classical pathway involving the degradation of the inhibitor of NF-κB(IκB)or by the alternative pathway involving the partial degradation of p100 to p52 and formation of the p52/RelB dimer,has emerged as a central theme in the regulation of NF-κBdependent genes.2–4 However,in Sertoli cells and some neurons,lymphocytes,and malignant cells,NF-κB has been shown to be constitutively active in the nucleus5,6(www.***.edu/nf-kb).Moreover,several recent studies have also identified disease-associated mutations in the NF-κB subunits that affect their expression level and transcriptional activity.2,7 Our understanding of the ways in which the changes in the basal level of NF-κB affect the subsequent basal regulation of the expression of NF-κBdependent genes remain poorly defined.

关键词： inflammatory constitutive subsequent

Perspectives on “the biology of spinal cord regeneration success and failure”

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Neural Regeneration Research 2018年第8期13卷 1358-1359页

作者： Philippa Mary Warren Amanda Phuong Tran Jerry Silver school of Biomedical Sciences University of Leeds Department of Neurosciences Case Western Reserve University

In our recently co-authored Physiological Reviews manuscript entitled ＂The biology of regeneration failure and success after spinal cord injury＂（Tran et al., 2018b）, we sought to provide a comprehensive and up-to-date de- scription of how the glial scar develops following spinal cord injury （SCI） to chronically inhibit axon regeneration.

关键词： the biology of spinal cord regeneration success and failure SCI

The association of inherited variation in the CLOCK gene with breast cancer tumor grade

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Family medicine and Community Health 2017年第2期5卷 103-108页

作者： Neha Gupta Li Li Cheryl L.Thompson Department of Nutrition Case Western Reserve UniversityClevelandOHUSA Department of Family medicine and Community Health Case Western Reserve UniversityClevelandOHUSA case Comprehensive Cancer Center Case Western Reserve UniversityClevelandOHUSA

Background:Sufficient sleep and maintenance of circadian rhythm are important to health.We have shown that short duration of sleep before diagnosis is associated with higher-grade tumors among breast cancer patients.Earlier studies suggest that genetic variation in the CLOCK gene is associated with risk of cancers,including breast cancer.Studies of the association of genetic variation,including in CLOCK,and tumor grade,a standard marker of tumor aggressiveness,are lacking.Methods:We investigated the relationship between single nucleotide polymorphisms(SNPs)in the CLOCK gene and tumor grade and estrogen receptor,progesterone receptor,and human epi-dermal growth factor receptor 2 status in 293 breast cancer patients.Nine SNPs were determined by standard TaqMan assays.Tumor grade,receptor status,and other clinical variables were abstracted from medical records.Results:Two SNPs were excluded because of poor genotyping performance.None of the remaining seven variants had a statistically significant association with breast cancer tumor grade or with receptor status.Conclusion:As with all novel studies,further work is needed to examine the association of CLOCK and other genes in the circadian rhythm pathway with breast cancer tumor grade in other populations.

关键词： Breast cancer SNP tumor grade CLOCK

Survival in men older than 75 years with low- and intermediate-grade prostate cancer managed with watchful waiting with active surveillance

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Family medicine and Community Health 2015年第3期3卷 25-36页

作者： Tzuyung D.Kou Siran M.Koroukian Pingfu Fu Derek Raghavan Gregory S.Cooper Li Li Department of Epidemiology and Biostatistics Case Western Reserve University School of MedicineClevelandOHUSA case Comprehensive Cancer Center Case Western Reserve University School of MedicineClevelandOHUSA Levine Cancer Institute Carolinas Healthcare SystemCharlotteNCUSA Department of Family medicine-Research Division Case Western Reserve University School of MedicineClevelandOHUSA

Objective:Recent studies have reported the underuse of active surveillance or watchful wait-ing for low-risk prostate cancer in the United States.This study examined prostate cancer-specific and all-cause death in elderly patients older than 75 years with low-risk tumors managed with active treatment versus watchful waiting with active surveillance(WWAS).Methods:We performed survival analysis in a cohort of 18,599 men with low-risk tumors(early and localized tumors)who were 75 years or older at the time of prostate cancer diagnosis in the linked Surveillance,Epidemiology,and End Results(SEER)-Medicare database(from 1992 to 1998)and who were followed up through December 2003.WWAS was defined as having an-nual screening for prostate-specific antigen and/or digital rectal examination during the follow-up period.The risks of prostate cancer-specific and all-cause death were compared by Cox regression models.The propensity score matching technique was used to address potential selection bias.Results:In patients with well-differentiated(Gleason score 2-4)and localized disease,those managed with WWAS without delayed treatment had higher risk of all-cause death(hazard ratio 1.20,95%confidence interval 1.13-1.28)but a substantially lower risk of prostate cancer-specific death(hazard ratio 0.62,confidence interval 0.51-0.75)than patients undergoing active treatment.Patients managed with WWAS with delayed treatment had comparable mortality outcomes.Sensi-tivity analyses based on propensity score matching yielded similar results.Conclusion:In men older than 75 years with well-differentiated and localized prostate cancer,WWAS without delayed treatment had a lower risk of prostate cancer-specific death and compa-rable all-cause death as compared with active treatment.Those patients in whom treatment was delayed had comparable mortality outcomes.Our results support WWAS as an initial management option for older men with well-differentiated and localized prostate cancer.

关键词： Epidemiology watchful waiting prostate cancer