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Dark,beyond Deep:A Paradigm Shift to Cognitive AI with Humanlike Common Sense

Engineering 2020年第3期6卷 310-345页

作者： Yixin Zhu Tao Gao Lifeng Fan Siyuan Huang mark Edmonds Hangxin Liu Feng Gao Chi Zhang Siyuan Qi Ying Nian Wu Joshua b.Tenenbaum Song-Chun Zhu Center for Vision CognitionLearningand AutonomyUniversity of CaliforniaLos AngelesCA 90095USA Center for brains Mindsand MachinesMassachusetts Institute of TechnologyCambridgeMA 02139USA

Recent progress in deep learning is essentially based on a“big data for small tasks”paradigm,under which massive amounts of data are used to train a classifier for a single narrow *** this paper,we call for a shift that flips this paradigm upside ***,we propose a“small data for big tasks”paradigm,wherein a single artificial intelligence(AI)system is challenged to develop“common sense,”enabling it to solve a wide range of tasks with little training *** illustrate the potential power of this new paradigm by reviewing models of common sense that synthesize recent breakthroughs in both machine and human *** identify functionality,physics,intent,causality,and utility(FPICU)as the five core domains of cognitive AI with humanlike common *** taken as a unified concept,FPICU is concerned with the questions of“why”and“how,”beyond the dominant“what”and“where”framework for understanding *** are invisible in terms of pixels but nevertheless drive the creation,maintenance,and development of visual *** therefore coin them the“dark matter”of *** as our universe cannot be understood by merely studying observable matter,we argue that vision cannot be understood without studying *** demonstrate the power of this perspective to develop cognitive AI systems with humanlike common sense by showing how to observe and apply FPICU with little training data to solve a wide range of challenging tasks,including tool use,planning,utility inference,and social *** summary,we argue that the next generation of AI must embrace“dark”humanlike common sense for solving novel tasks.

关键词： Computer vision Artificial intelligence Causality Intuitive physics Functionality Perceived intent Utility

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Male fertility following childhood cancer: current conceptsand future therapies

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Asian Journal of Andrology 2003年第4期5卷 325-337页

作者： mark F. H. brougham Christopher J. H.Kelnar Richard M.Sharpe W.Hamish b.Wallace Royal Hospital for Sick Children Edinburgh United KingdomRoyal Hospital for Sick Children Edinburgh United KingdomMRC Human Reproductive Sciences Unit Centre for Reproductive Biology University of Edinburgh United KingdomRoyal Hospital for Sick Children Edinburgh United Kingdom

Prepubertal boys treated for cancer may exhibit impaired fertility in later life. A number of chemotherapeu tic agents have been identified as being gonadotoxic, and certain treatment regimens, such as that used for H... 详细信息

bstract>Prepubertal boys treated for cancer may exhibit impaired fertility in later life. A number of chemotherapeu tic agents have been identified as being gonadotoxic, and certain treatment regimens, such as that used for Hodgkin's disease, are particularly associated with subsequent infertility. Radiotherapy may also cause gonadal damage, most notably following direct testicular irradiation or total body irradiation. because of the varied nature of the cytotoxic insult, it can be difficult to predict the likelihood of infertility in later life. Currently it is not possible to detect gonadal damage early due to the lack of a sensitive marker of gonadal function in the prepubertal age *** cryopreservation is currently the only method of preserving fertility in patients receiving gonadotoxic therapy. This is only applicable to postpubertal patients and can be problematic in the adolescent age group. At present there is no provision for the prepubertal boy, although there are a number of experimental methods currently being investigated. by harvesting testicular tissue prior to gonadotoxic therapy, restoration of fertility could be achieved following treatment, either by germ cell transplantation or by in vitro maturation of the germ cells harvested. Alternatively, rendering the testes quiescent during cytotoxic treatment may protect the germ cells from subsequent damage. In addition to the many scientific and technical issues to be overcome prior to clinical application of these techniques, a number of ethical and legal issues must also be addressed to ensure a safe and realistic prospect for future fertility in these patients.

关键词： infertility childhood cancer semen cryopreservation germ cell transplantation In vitro germ cell maturation assisted reproductive techniques

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Regulated upon activation,normal T cell expressed and secreted(RANTES)levels in the peripheral blood of patients with Alzheimer’s disease

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Neural Regeneration Research 2021年第4期16卷 775-779页

作者： Gabriela Vacínová Daniela Vejražkova Robert Rusina Iva Holmerová Hana Vaňková Eva Jarolímová Josef Včelák běla bendlová markéta Vaňková Department of Molecular Endocrinology Institute of EndocrinologyPragueCzech Republic Department of Anthropology and Human Genetics Faculty of ScienceCharles UniversityPragueCzech Republic Department of Neurology Third Faculty of Medicine of Charles University and Thomayer Hospital PragueCzech Republic II.Internal Medicine Clinic Third Faculty of MedicineCharles UniversityPragueCzech Republic Faculty of Humanitites Charles University PragueCzech Republic

Alzheimer’s disease(AD)is the most common type of dementia,but it is very difficult to diagnose with certainty,so many AD studies have attempted to find early and relevant diagnostic *** upon activation,normal T cell expressed and secreted(RANTES,also known as C-C chemokine ligand)is a chemokine involved in the migration of T cells and other lymphoid *** in RANTES levels and its expression in blood or in cerebrospinal fluid have been reported in some neurodegenerative diseases,such as Parkinson’s disease and multiple sclerosis,but also in metabolic diseases in which inflammation plays a *** aim of this observational study was to assess RANTES levels in peripheral blood as clinical indicators of *** levels of RANTES were investigated in 85 AD patients in a relatively early phase of AD(median 8.5 months after diagnosis;39 men and 46 women;average age 75.7 years),and in 78 control subjects(24 men and 54 women;average age 66 years).We found much higher plasma levels of RANTES in AD patients compared to controls.A negative correlation of RANTES levels with age,disease duration,Fazekas scale score,and the medial temporal lobe atrophy(MTA)score(Scheltens’s scale)was found in AD patients,i.e.,the higher levels corresponded to earlier stages of the *** RANTES levels were not correlated with cognitive *** AD patients,RANTES levels were positively correlated with the levels of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α,which is consistent with the wellknown fact that AD is associated with inflammatory *** levels were also positively correlated with insulin levels in AD patients,with insulin resistance(HOMA-R)and pancreatic beta cell function(HOMA-F).This study evaluated several clinical and metabolic factors that may affect plasma levels of RANTES,but these factors could not explain the increases in RANTES levels observed in AD *** levels of RANTES appear to be an interesting

关键词： Alzheimer’s disease biomarker central nervous system cognitive impairment inflammation RANTES

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Focused transcription from the human CR2/CD21 core promoter is regulated by synergistic activity of TATA and Initiator elements in mature b cells

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Cellular & Molecular Immunology 2016年第1期13卷 119-131页

作者： Rhonda L Taylor mark N Cruickshank Mahdad Karimi Han Leng Ng Elizabeth Quail Kenneth M Kaufman John b Harley Lawrence J Abraham betty P Tsao Susan A boackle Daniela Ulgiati School of Pathology and Laboratory Medicine Centre for Genetic Origins of Health and Disease The University of Western Australia Crawley WA Australia biochemistry and Molecular biology School of Chemistry and Biochemistry The University of Western Australia Crawley WA Australia Telethon Kids Institute The University of Western Australia Crawley WA Australia Cincinnati Children's Hospital Medical Center Cincinnati OH USA US Department of Veterans Affairs Medical Center Cincinnati OH USA Division of Rheumatology Department of Medicine University of California at Los Angeles Los Angeles CA USA Division of Rheumatology University of Colorado School of Medicine Aurora CO USA

Complement receptor 2 （CR2/CD21） is predominantly expressed on the surface of mature b cells where it forms part of a coreceptor complex that functions, in part, to modulate b-cell receptor signal strength. CR2/CD21 expression is tightly regulated throughout b-cell development such that CR2/CD21 cannot be detected on pre-b or terminally differentiated plasma cells. CR2/CD21 expression is upregulated at b-cell maturation and can be induced by IL-4 and CD40 signaling pathways. We have previously characterized elements in the proximal promoter and first intron of CR2/CD21 that are involved in regulating basal and tissue-specific expression. We now extend these analyses to the CR2/CD21 core promoter. We show that in mature b cells, CR2/~D21 transcription proceeds from a focused TSS regulated by a non-consensus TATA box, an initiator element and a downstream promoter element. Furthermore, occupancy of the general transcriptional machinery in pre-b versus mature b-cell lines correlate with CR2/CD21 expression level and indicate that promoter accessibility must switch from inactive to active during the transitional b-cell window.

关键词： b cells core promoter CR2/CD21 molecular biology transcription factor

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Recurrent hepatitis C after liver transplant

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World Journal of Gastroenterology 2014年第31期20卷 10668-10681页

作者： Andrew S deLemos Paul A Schmeltzer mark W Russo Department of Medicine Center for Liver Diseases and Transplantation Carolinas Medical Center

End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28 b genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5 b polymerase inhibitors and NS5 A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients.

关键词： Hepatitis C Liver transplant Donor risk factors Immunosuppression Protease inhibitors Fibrosing cholestatic hepatitis C Acute cellular rejection Cytomegalovirus

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Strong near-infrared and ultrafast femtosecond nonlinearities of a covalently-linked triply-fused porphyrin dimer-SWCNT nanohybrid

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Nano Research 2022年第2期15卷 1355-1365页

作者： Lulu Fu Jun Ye Hui Li Zhipeng Huang mark GHumphrey Chi Zhang China-Australia Joint Research Center for Functional Molecular Materials School of Chemical and Material EngineeringJiangnan UniversityWuxi 214122China China-Australia Joint Research Center for Functional Molecular Materials School of Chemical Science and Engineerinz Ton^ii UniversityShanghai 200092China Research School of Chemistry Australian National UniversityCanberraACT 2601Australia

Functional materials displaying large ultrafast third-order optical nonlinearities across a wide spectral region and broad temporal domain are required for all-optical signal *** desirable is nonlinear optical(NLO)activity at near-infrared(NIR)wavelengths with femtosecond *** the first triply-fused porphyrin dimer(TFP)-functionalized single-walled carbon nanotube(SWCNT)nanohybrid was successfully constructed by covalently grafting TFPs onto *** results of Z-scan techniques demonstrate that the newly obtained TFP-SWCNT nanohybrid was found with a strong NLO performance under both nanosecond and femtosecond *** the nanosecond regime,an enhancement in optical limiting(OL)of the TFP-SWCNT nanohybrid is seen at 532 nm when compared with the performance of porphyrin monomer-functionalized SWCNT nanohybrid *** femtosecond irradiation,the TFP-SWCNT nanohybrid exhibits a particularly strong OL effect with a giant two-photon absorption(TPA)cross section value(ca.15,500 GM)at 800 nm pulses that mainly stems from intense TPA of TFP,in sharp contrast to the Por-SWCNT nanohybrid which exhibits only saturable absorption under identical *** results demonstrate that the newly-developed TFP-SWCNT nanohybrid is a very promising OL candidate for practical applications across wide spectral and temporal domains,and that covalently functionalizing carbon-based materials with triply-fused chromophores may be a useful approach to engineering adaptable photonic devices with broad-ranging NLO activity.

关键词： triply-fused porphyrin dimer carbon nanotube near-infrared femtosecond nonlinear optical materials

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Applications of next-generation sequencing to the study of biological invasions

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Current Zoology 2015年第3期61卷 488-504页

作者： Marc RIUS Steve bOURNE Harry Guy HORNSbY mark A. CHAPMAN Ocean and Earth Science National Oceanography Centre Southampton University of Southampton SO 14 3ZH UK Centre for biological Sciences Life Sciences Building 85 University of Southampton Southampton SO 17 1B J UK

Through the widespread implementation of next-generation sequencing （NGS）, analyses of the whole genome （the entire DNA content） and the whole transcriptome （the genes being expressed） are becoming commonplace. NGS enables the analysis of a vast amount of previously unattainable genetic information. Despite this potential, NGS has yet to be widely imple- mented in genetic studies of biological invasions. The study of the genomic causes and consequences of biological invasions al- lows a deeper understanding of the molecular mechanisms underpinning the invasion process. In this review, we present a brief introduction to NGS followed by a synthesis of current research in the genomics and transcriptomics of adaptation and coloniza- tion. We then highlight research opportunities in the field, including：（1） assembling genomes and transcriptomes of non-model organisms, （2） identifying genomic regions and candidate genes underlying evolutionary processes, and （3） studying the adaptive role of gene expression variation. In particular, because introduced species face a broad range of physiological and biotic chal- lenges when colonizing novel and variable environments, transcriptomics will enable the study of gene regulatory pathways that may be responsible for acclimation or adaptation. To conclude, we identify a number of research approaches that will aid our fu- ture understanding of biological invasions

关键词： Exotic species Genomics Genotype-environment interactions Invasive species Invasion genetics Invasion route Non-indigenous species Non-native species

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Network Analysis Reveals A Signaling RegulatoryLoop in PIK3CA-mutated breast Cancer Predicting Survival Outcome

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Genomics, Proteomics & bioinformatics 2017年第2期15卷 121-129页

作者： Shauna R. McGee Chabane Tibiche mark Trifiro Edwin Wang National Research Council Canada Montreal QC H4P 2R2 Canada Department of Experimental Medicine McGill University Montreal QC H3A 2B2 Canada Center for bioinformatics McGill University Montreal QC H3G OB1 Canada Lady Davis Institute for Medical Research of the Jewish General Hospital Montreal QC H3T 1E2 Canada Center for Health Genomics and Informatics Calgary AB T2N 4N1 Canada Department of biochemistry & Molecular biology/Medical Genetics/Oncology University of Calgary Cumming School of Medicine Calgary AB T2N 4N1 Canada Alberta Children's Hospital Research Institute Calgary AB T2N 4N1 Canada Arnie Charbonneau Cancer Research Institute Calgary AB T2N 4N1 Canada O'brien Institute for Public Health Calgary AB T2N 4N1 Canada

Mutated genes are rarely common even in the same pathological type between cancer patients and as such, it has been very challenging to interpret genome sequencing data and difficult to predict clinical outcomes. PIK3 CA is one of a few genes whose mutations are relatively popular in tumors. For example, more than 46.6% of luminal-A breast cancer samples have PIK3 CA mutated, whereas only 35.5% of all breast cancer samples contain PIK3 CA mutations. To understand the function of PIK3 CA mutations in luminal A breast cancer, we applied our recentlyproposed Cancer Hallmark Network Framework to investigate the network motifs in the PIK3CA-mutated luminal A tumors. We found that more than 70% of the PIK3CA-mutated luminal A tumors contain a positive regulatory loop where a master regulator(PDGF-D), a second regulator(FLT1) and an output node(SHC1) work together. Importantly, we found the luminal A breast cancer patients harboring the PIK3 CA mutation and this positive regulatory loop in their tumors have significantly longer survival than those harboring PIK3 CA mutation only in their tumors. These findings suggest that the underlying molecular mechanism of PIK3 CA mutations in luminal A patients can participate in a positive regulatory loop, and furthermore the positive regulatory loop(PDGF-D/FLT1/SHC1) has a predictive power for the survival of the PIK3 CAmutated luminal A patients.

关键词： Network analysis PIK3CA mutation Network motif breast cancer Genome sequencing Survival

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bacteriospermia among smallholder artificial insemination boars in the Philippines and potential associated factors

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Asian pacific Journal of Reproduction 2023年第1期12卷 35-41页

作者： Santiago T.Peña Jr. Ma.Delia A.Pagente bianca Therese P.Ymas mark Edd b.Janier Department of Veterinary basic Sciences College of Veterinary MedicineVisayas State UniversityBaybay CityLeyte 6521Philippines

Objective:To determine the prevalence of bacteriospermia,the bacterial load,and the potential factors associated with bacterial contamination in boar semen collected by local smallholder artificial insemination ***:Fifteen individual raw semen samples were collected from locally available artificial insemination boars owned by different smallholder boar operators within the 5th district of Leyte,Philippines and were subjected to standard bacteriological culture and identification,including a survey of potentially associated *** and bacterial count were determined accordingly,while boar characteristics and collection practices were clustered following agglomerative hierarchical clustering ***:One hundred percent contamination with a bacterial count of(2.01±0.38)×10^(3) CFU/mL was *** least 73.33%of the samples were positive for bacillus spp.,while other identified isolates included Enterobacter spp.,Staphylococcus spp.,***,Pseudomonas spp.,Citrobacter spp.,and Klebsiella ***:Despite the high prevalence of bacteriospermia,the bacterial count is ***,on-farm practices on boar health and management,semen collection,and sanitation as well as the enhancement of basic protocols to control contamination should be conscientiously considered in smallholder artificial insemination operation.

关键词： bacteriospermia Local artificial insemination boars boar sperm Artificial insemination Semen quality Smallholder pigs

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Oxidative stress and antioxidants in hepatic pathogenesis

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World Journal of Gastroenterology 2010年第48期16卷 6035-6043页

作者： Hye-Lin Ha Hye-Jun Shin mark A Feitelson Dae-Yeul Yu Disease Model Research Laboratory Aging Research CenterKorea Research Institute of Bioscience and Biotechnology Department of Functional Genomics University of Science and Technology Department of biology College of Science and TechnologyTemple University

Long term hepatitis b virus (HbV) infection is a major risk factor in pathogenesis of chronic liver diseases,including hepatocellular carcinoma (HCC). The HbV encod-ed proteins,hepatitis b virus X protein and preS,appear to contribute importantly to the pathogenesis of HCC. both are associated with oxidative stress,which can damage cellular molecules like lipids,proteins,and DNA during chronic infection. Chronic alcohol use is another important factor that contributes to oxidative stress in the liver. Previous studies reported that treatment with antioxidants,such as curcumin,silymarin,green tea,and vitamins C and E,can protect DNA from damage and regulate liver pathogenesis-related cascades by reducing reactive oxygen species. This review summarizes some of the relationships between oxidative stress and liver pathogenesis,focusing upon HbV and alcohol,and suggests antioxidant therapeutic approaches.

关键词： Hepatitis b virus Hepatitis b virus X protein Alcohol Chronic liver disease Oxidative stress Antioxidant

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