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CMOS Design of Ternary Arithmetic Devices Wu Xunwei *** Electronic Engineering,Hangzhou university,Hangzhou 310028F.P rosser *** Computer Science,indiana university,U.S.A.

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Journal of Computer Science & Technology 1991年第4期6卷 376-382页

作者：吴训威 F.Prosser Dept.of Electronic Engineering Hangzhou UniversityHangzhou 310028 Dept.of Computer Science Indiana UniversityU.S.A.

This paper presents CMOS circuit designs of a ternary adder and a ternary multiplier,formulated using transmission function *** carry signals appearing in these designs allow conventional look-ahead carry techniques to be *** with previous similar designs,the circuits proposed in this paper have advantages such as low dissipation,low output impedance,and simplicity of construction.

关键词： CMOS Design of Ternary Arithmetic Devices Wu Xunwei Dept.of Electronic Engineering,Hangzhou university,Hangzhou 310028F.P rosser Design

维普期刊数据库

Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension

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Chronic Diseases and Translational Medicine 2024年第2期10卷 102-117页

作者： Nicholas R.Powell Tyler Shugg Jacob Leighty Matthew Martin Rolf P.Kreutz Michael T.Eadon Dongbing Lai Tao Lu Todd C.Skaar Division of Clinical Pharmacology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Pharmacology and Toxicology School of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Cardiology School of MedicineKrannert Institute of CardiologyIndiana UniversityIndianapolisIndianaUSA Division of Nephrology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Department of Medical and Molecular Genetics School of MedicineIndiana UniversityIndianapolisIndianaUSA

Background Hypertension(HTN)involves genetic variability in the renin-angiotensin system and influences antihypertensive *** previously reported that angiotensinogen(AGT)messenger RNA(mRNA)is endogenously bound by miR-122-5p and rs699 A>G decreases reporter mRNA in the microRNA functional-assay *** AGT promoter variant rs5051 C>T is in linkage disequilibrium(LD)with rs699 A>G and increases AGT *** independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C>T counterbalances AGT decreased by rs699 A>G,and when these variants occur independently,it translates to HTN-related *** We used in silico,in vitro,in vivo,and retrospective models to test this *** In silico,rs699 A>G is predicted to increase miR-122-5p binding affinity by 3%.Mir-eCLIP results show rs699 is 40–45 nucleotides from the strongest microRNA-binding site in the AGT ***,rs699 A>G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression ***-Tissue Expression(GTEx)and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A>G occurs independently from rs5051 C>***,GTEx and the in vitro experiments suggest rs699 A>G confers cell-type-specific effects on AGT mRNA abundance,and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A>G associations with *** We found that rs5051 C>T and rs699 A>G significantly associate with systolic blood pressure in Black participants in the UK Biobank,demonstrating a fourfold larger effect than in White *** studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C>T or rs699 A>*** like this will help clinicians move beyond the use of race as a surrogate for genotype.

关键词： angiotensinogen genetic and genomic medicine hypertension rs699

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Exploiting sound for emerging applications of extracellular vesicles

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Nano Research 2024年第2期17卷 462-475页

作者： Zhuhao Wu Hongwei Cai Chunhui Tian Zheng Ao Lei Jiang Feng Guo Department of Intelligent Systems Engineering Indiana UniversityBloomingtonIN 47405USA

Extracellular vesicles are nano-to micro-scale,membrane-bound particles released by cells into extracellular space,and act as carriers of biomarkers and therapeutics,holding promising potential in translational ***,the challenges remain in handling and detecting extracellular vesicles for disease diagnosis as well as exploring their therapeutic capability for disease ***,we review the recent engineering and technology advances by leveraging the power of sound waves to address the challenges in diagnostic and therapeutic applications of extracellular vesicles and biomimetic *** first introduce the fundamental principles of sound waves for understanding different acoustic-assisted extracellular vesicle *** discuss the acoustic-assisted diagnostic methods including the purification,manipulation,biosensing,and bioimaging of extracellular ***,we summarize the recent advances in acoustically enhanced therapeutics using extracellular vesicles and biomimetic ***,we provide perspectives into current challenges and future clinical applications of the promising extracellular vesicles and biomimetic nanovesicles powered by sound.

关键词： extracellular vesicles exosomes biomimetic nanovesicles acoustics disease diagnostics therapeutics

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

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World Journal of Gastroenterology 2024年第13期30卷 1815-1835页

作者： Samantha Sharma Naresh Singh Anita Ahmed Turk Isabella Wan Akshay Guttikonda Julia Lily Dong Xinna Zhang Mateusz Opyrchal Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202United States Division of Hematology/Oncology Department of MedicineIndiana University School of MedicineIndianapolisIN 46202United States Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202United States

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical *** considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely *** the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint *** aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor *** therapies thus have shown promising results in many clinical trials alone or in *** efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical *** trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair ***,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC *** this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the *** review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in *** underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

关键词： Colorectal cancer Immune checkpoint inhibitors Clinical trials Immunotherapy Microsatellite instability Microsatellite stability DNA mismatch repair

Franklin Perkins. 2014. Heaven and Earth Are Not Humane： The Problem of Evil in Classieal Chinese Philosophy. Bloomington, IN： indiana university Press, 2014, 295pp., ISBN： 9780253011725.

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Frontiers of Philosophy in China 2015年第1期10卷 153-158页

作者： Michael D. K. Ing lndiana university

Heaven and Earth Are Not Humane is a genuine contribution to the field of Chinese philosophy. By engaging in a kind of ＂rooted global philosophy,＂ Franklin Perkins addresses issues inherent to early Chinese texts in a way that renders them meaningful for contemporary philosophers） Perkins facilitates a cross-cultural dialogue between those in early China and those concerned with the problem of evil in European history. In doing this, Perkins not only demonstrates a grasp of the major primary texts and the relevant secondary literature, but he also demonstrates a breadth of knowledge that extends into contemporary Chinese thought, as well as into recently unearthed Chinese manuscripts and countless figures in the Western philosophical tradition.

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Photo-activated microtubule targeting drugs: Advancing therapies for colorectal cancer

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World Journal of Gastroenterology 2024年第26期30卷 3257-3260页

作者： Naresh Singh Samantha Sharma Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202United States

Over the years immunotherapy has demonstrably improved the field of cancer ***,achieving long-term survival for colorectal cancer(CRC)patients remains a significant unmet *** immunotherapies incor-porating targeted drugs like MEK or multi-kinase inhibitors have offered some palliative ***,substantial gaps remain in the current therapeutic armamentarium for *** recent years,there has been a surge of interest in exploring novel treatment strategies,including the application of light-activated drugs in conjunction with optical *** approach holds promise for achie-ving localized and targeted delivery of cytotoxic agents,such as microtubule-targeting drugs,directly to cancerous cells within the colon.

SARS-CoV2 Nsp3 protein triggers cell death and exacerbates amyloid β42-mediated neurodegeneration

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Neural Regeneration Research 2024年第6期19卷 1385-1392页

作者： Aditi Singh Anuradha Venkatakrishnan Chimata Prajakta Deshpande Soumya Bajpai Anjali Sangeeth Mrigendra Rajput Amit Singh Department of Biology University of Dayton Premedical Program University of Dayton Center for Tissue Regeneration and Engineering at Dayton (TREND) University of Dayton The Integrative Science and Engineering Center University of Dayton Center for Genomic Advocacy (TCGA) Indiana State University

Infection caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV2) virus, responsible for the coronavirus disease 2019(COVID-19) pandemic, induces symptoms including increased inflammatory response, severe acute respiratory syndrome(SARS), cognitive dysfunction like brain fog, and cardiovascular defects. Long-term effects of SARS-CoV2 COVID-19 syndrome referred to as post-COVID-19 syndrome on age-related progressive neurodegenerative disorders such as Alzheimer’s disease remain understudied. Using the targeted misexpression of individual SARS-CoV2 proteins in the retinal neurons of the Drosophila melanogaster eye, we found that misexpression of nonstructural protein 3(Nsp3), a papain-like protease, ablates the eye and generates dark necrotic spots. Targeted misexpression of Nsp3 in the eye triggers reactive oxygen species production and leads to apoptosis as shown by cell death reporters, terminal deoxynucleotidyl transferase(TdT) dUTP Nick-end labeling(TUNEL) assay, and dihydroethidium staining. Furthermore, Nsp3 misexpression activates both apoptosis and autophagy mechanism(s) to regulate tissue homeostasis. Transient expression of SARS-CoV2 Nsp3 in murine neuroblastoma, Neuro-2a cells, significantly reduced the metabolic activity of these cells and triggers cell death. Misexpression of SARS-CoV2 Nsp3 in an Alzheimer’s disease transgenic fly eye model(glass multiple repeats [GMR]>amyloid β42) further enhances the neurodegenerative rough eye phenotype due to increased cell death. These findings suggest that SARS-CoV2 utilizes Nsp3 protein to potentiate cell death response in a neurodegenerative disease background that has high pre-existing levels of neuroinflammation and cell death.

关键词： Alzheimer's disease apoptosis autophagy COVID-19 Drosophila necrosis Neuro-2a cells neurodegeneration post COVID-19 syndrome SARS-CoV2

Remote estimates of suspended particulate matter in global lakes using machine learning models

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International Soil and Water Conservation Research 2024年第1期12卷 200-216页

作者： Zhidan Wen Qiang Wang Yue Ma Pierre Andre Jacinthe Ge Liu Sijia Li Yingxin Shang Hui Tao Chong Fang Lili Lyu Baohua Zhang Kaishan Song Northeast Institute of Geography and Agroecology CASChangchunJilin130102China Department of Geology Indiana University∼Purdue UniversityIndianapolisIN44602USA university of Chinese Academy of Sciences Beijing100100China College of Geography and Urban Planning Liaocheng UniversityLiaochengChina

Suspended particulate matter(SPM)in lakes exerts strong impact on light propagation,aquatic ecosystem productivity,which co-varies with nutrients,heavy metal and micro-pollutant in *** lakes,SPM exerts strong absorption and backscattering,ultimately affects water leaving signals that can be detected by satellite *** regression models based on specific band or hand ratios have been widely used for SPM estimate in the past with moderate *** are still rooms for model accuracy improvements,and machine learning models may solve the non-linear relationships between spectral variable and SPM in *** assembled more than 16,400 in situ measured SPM in lakes from six continents(excluding the Antarctica continent),of which 9640 samples were matched with Landsat overpasses within±7 *** machine learning algorithms and two simple regression methods(linear and partial least squares models)were used to estimate SPM in lakes and the performance were *** overcome the problem of imbalance datasets in regression,a Synthetic Minority Over-Sampling technique for regression with Gaussian Noise(SMOGN)was adopted in this *** comparison,we found that gradient boosting decision tree(GBDT),random forest(RF),and extreme gradient boosting(XGBoost)models demonstrated good spatiotemporal transferability with SMOGN processed dataset,and has potential to map SPM at different year with good quality of Landsat land surface reflectance *** all the tested modeling approaches,the GBDT model has accurate calibration(n=6428,R^(2)=0.95,MAPE=29.8%)from SPM collected in 2235 lakes across the world,and the validation(n=3214,R^(2)=0.84,MAPE=38.8%)also exhibited stable ***,the good performances were also exhibited by RF model with calibration(R^(2)=0.93)and validation(R^(2)=0.86,MAPE=24.2%)*** applied GBDT and RF models to map SPM of typical lakes,and satisfactory result was *** addition,the GBDT model was evaluated b

关键词： Landsat imagery Remote estimation SPM Transferability

On the Trail of Self-Directed Online Learners

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ECNU Review of Education 2024年第2期7卷 406-419页

作者： Curtis J.Bonk 朱美娜 School of Education Indiana University201 N.Rose AvenueBloomingtonIN 4740lUSA Wayne State university

Purpose We describe a series of more than a dozen studies on self-directed online learning spanning over a ***/Approach/Methods We incorporated surveys,interviews,focus groups,and content analyses into these research studies,which initially targeted the goals,motivations,and challenges of learners using open educational resources and OpenCourseWare and then focused on learning from massive open online courses(MOOCs).This research accelerated after creating a database of over 3,000 MOOC instructors,through which we explored cultural sensitivity and personalization practices in MOOCs as well as instructional design considerations and challenges,MOOC instructor professional development and career development,instructor motivation and engagement,and student and instructor perceptions of self-directed *** This study reveals that self-directed online learners(SDOLs)seek learning environments offering freedom,choice,control,and a sense of autonomy and that both learners and instructors have intrinsic motivation for engaging in open online learning ***/Value Based on this research with both MOOC instructors and MOOC learners,we offer instructional design guidelines to address SDOLs’needs and assist in efforts to foster a new generation of SDOLs.

关键词： MOOCs motivation online learning self-directed learning self-management self-monitoring