课后习题部分答案(2013版)

逻辑学（第3版）课后练习题答案（部分）人大出版社-图文逻辑学课后练习题答案（部分）王震14年11月8日整理第一章练习题答案二、在下列命题或推理中，哪些具有共同的逻辑形式，用公式表示出来。

1和5：所有S是P2和7：所有P是M，所有S不是M，所以，所有S不是P。

3和8：只有p，才q。

6和9：如果p，那么q；p；所以，q。

三、选择题1.C2.C3.ABCD4.BE第二章练习题答案一、判定下列断定的正误。

1.错误2.错误3.正确4.错误5.错误6.正确7.错误8.错误二、运用本章的相关知识以及相关常识，回答下列问题。

1.错误。

定义过宽。

2.错误。

定义过宽。

3.错误。

“勇敢”和“勇敢的战士”之间不存在属种关系。

4.错误。

“喜马拉雅山”和“珠穆朗玛峰”之间不存在属种关系。

三、在以下各句的括号中填入哪个或哪些选项是适当的？1.C2.ABC3.A4.A5.B6.BC7.B8.B9.BC10.AC四、下列各题中括号内的话，是从内涵方面还是从外延方面来说明标有横线的概念的？1.分别从内涵和外延2.从内涵3.分别从内涵和外延4.分别从内涵和外延5.分别从内涵和外延6.分别从内涵和外延五、从两种概念分类的角度（单独概念与普遍概念、正概念和负概念）说明下列各题中标有横线的概念属于哪一种类。

1.“美术作品”是普遍概念、正概念。

2.“《孔乙己》”是单独概念、正概念；“作品”是普遍概念、正概念。

3.“非司机”是普遍概念、负概念。

4.“中国女子排球队”是单独概念、正概念；“世界冠军”是普遍概念、正概念。

5.“中国工人阶级”是单独概念、正概念。

6.“国家检察机关”是单独概念、正概念。

六、试分析下列各题中标有横线的语词是在集合意义下使用的，还是在非集合意义下使用的？1.集合2.非集合3.非集合4.集合5.1）集合2）非集合3）非集合6.集合7.集合七、下列各组概念是什么关系？1.真包含2.全异（反对）3.交叉4.真包含于5.全异6.全异（矛盾）7.全同8.全异（反对）八、用欧拉图表示下列各题中标有横线的概念之间的关系：十、对下列概念各作一次限制与概括。

Chapter 6 Circulating Methylated DNA as Biomarkers for Cancer DetectionHongchuan Jin, Yanning Ma, Qi Shen andXian WangAdditional information is available at the end of the chapter/10.5772/514191. IntroductionIn addition to genetic alterations including deletion or point mutations, epigenetic changes such as DNA methylation play an important role in silencing tumor suppressor genes dur‐ing cancer development. By adding a methyl group from S-adenosyl-L-methionine to the cy‐tosine pyrimidine or adenine purine ring, DNA methylation is important to maintain genome structure and regulate gene expression. In mammalian adult tissues, DNA methyla‐tion occurs in CpG dinucleotides that often cluster in the genome as CpG islands in the 5’regulatory regions of the genes. Through recruiting transcriptional co-repressors including methyl-CpG-binding domain proteins (MBDs) and chromatin remodeling proteins like his‐tone deacetylases (HDACs) or impeding the binding of transcriptional activators, DNA methylation could suppress the transcription of many tumor suppressor genes critical to cancer initiation and progression [1-3].More and more results confirmed that cancer is a multi-stage process fuelled by many epige‐netic changes in addition to genetic changes in DNA sequence [4]. Chemical molecules like Trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-Aza-CdR) targeting epigenetic regula‐tors such as histone modifications and DNMTs (DNA methyltransferases) have been found to inhibit tumor growth both in vitro and in vivo. By reversing the epigenetic silencing of important tumor suppressor genes, an increasing number of epigenetic drugs such as 5-Aza-CdR, 5-Aza-CR and Vorinostat (SAHA) are currently investigated in the clinical trials for cancer treatment as a single drug or in combination with other epigenetic drugs or other ap‐proaches such as chemotherapy and showed very promising activities by offering signifi‐cant clinical benefits to cancer patients [5-13].© 2013 Jin et al.; licensee InTech. This is an open access article distributed under the terms of the CreativeCommons Attribution License (/licenses/by/3.0), which permits unrestricted use,distribution, and reproduction in any medium, provided the original work is properly cited.As one of the major epigenetic changes to inactivate tumor suppressor genes critical to hu‐man cancer development, DNA methylation was recognized as the biomarker for cancer de‐tection or outcome prediction in addition to the identification of novel tumor suppressor genes. DNA mutations will occur randomly in any nucleotides of one particular gene and the comprehensive determination of DNA mutations is thus very difficult and time-consum‐ing. In contrast, aberrant DNA hypermethylation usually takes place in defined CpG Islands within the regulatory region of the genes and it is much more convenient to detect DNA methylation in a quantitatively manner. In addition, DNA methylation can be amplified and is thus easily detectable using PCR-based approaches even when the DNA concentration af‐ter sample extraction is relatively low. Due to such advantages over DNA mutation- or pro‐tein-based biomarkers, DNA methylation-based biomarkers have been intensively investigated in the recent years. A large body of research reports has proved the value of DNA methylations in the prognosis prediction and detection of various cancers. DNAs used for such methylation analyses are usually extracted from tumor tissues harvested after sur‐gical operation or biopsy, thus limiting its wide application as the biomarkers for the early detection or screening of human cancers. Recently, it has been reported that there are certain amount of circulating DNAs in the peripheral blood of cancer patients, providing an ideal source to identify novel biomarkers for non-invasive detection of cancers. Both genetic and epigenetic changes found in the genomic DNAs extracted from primary tumor cells could be detected in the circulating DNAs, indicating that the detection of methylated DNAs in the circulation represents a new direction to develop novel biomarkers for cancer detection or screening in a non-invasive manner.2. Cell free DNA in the circulationAccording to the origin of circulating tumor-related DNA, it could be grouped into circulat‐ing cell free DNA or DNA from cells in the blood such as circulating tumor cells (CTC) in cancer patients (Figure 1).In 1869, the Australian physician Thomas Ashworth observed CTCs in the blood of a cancer patient. Therefore, it was postulated that CTCs were responsible for the tumor metastases in distal sites and should have important prognostic and therapeutic implications [14-16].However, the number of CTCs is very small compared with blood cells. Usually around 1-10CTCs together with several million blood cells could be found in 1 ml of whole blood, mak‐ing the specific and sensitive detection of CTCs very difficult [17-18]. Until recently, technol‐ogies with the requisite sensitivity and reproducibility for CTC detection have been developed to precisely analyze its biological and clinical relevance. The US Food and Drug Administration (FDA) approved the test for determining CTC levels in patients with meta‐static breast cancer in 2004. Currently, it has been expanded to other cancer types such as advanced colorectal cancer and prostate cancer. Although CTCs-counting based test have proven its value in predicting prognosis and monitoring therapeutic effects, the number of CTCs per ml of blood limited its sensitivity greatly [19]. With the development of high-sen‐sitive PCR-based methods, the detection of gene mutations or epigenetic changes such asMethylation - From DNA, RNA and Histones to Diseases and Treatment138DNA methylation within small amount of CTCs could be the next generation of CTC-based test for cancer detection. However, the cost of such tests will be greatly exacerbated, thuslimiting its wide application in the clinic [20-22].Figure 1. Circulating tumor cells and cell free DNA. Circulating Tumor cells (CTC) escape from primary sites and spread into the vessel to form metastases in the distal organs with. Cell free DNAs (cf-DNAs) are released into the circulation from dead cancer cells or proliferating tumor cells. RBC: red blood cell; WBC: white blood cell.Although its origin and biological relevance remains unknown, circulating cell free DNA (cf-DNA) is supposed to be valuable source to identify cancer markers with ideal sensitivity and specificity for non-invasive detection of cancer [23-24]. Early in 1948, two French scientists Mandel and Metais firstly reported the presence of cf-DNAs in human plasma [25]. Such an important discovery has been unnoticed for a long time until cell-free circulating nucleic acid was found to promote the spread and metastasis of crown gall tumor in plants [26]. Subse‐quently, increased level of cf-DNAs was found in patients with various diseases such as lupus erythematosus and rheumatoid arthritis cancer [27-28]. In 1977, Leon et al. reported that higher level of circulating DNA in the plasma of cancer patients when compared to healthy con‐trols. Moreover, greater amounts of cf-DNA were found in the peripheral blood of cancer patients with tumor metastases and cf-DNA levels decreased dramatically after radiothera‐py while persistently high or increasing DNA concentrations were associated with a lack of response to treatment [29], clearly revealing the potential value of cf-DNA as biomarker for cancer detection. Following studies confirmed that cf-DNAs in the plasma contains genetic and epigenetic changes specific to DNAs within the tumor cells from primary tissues, indicat‐ing that tumor specific cf-DNAs are originated from tumor cells rather than lymphocytes reacting towards the disease [30-31]. For example, K-Ras mutation was found in cf-DNA from 17 out of 21 patients with pancreatic adenocarcinoma and mutations were similar in corre‐sponding plasma and tissues samples. Importantly, such DNA alterations were found inCirculating Methylated DNA as Biomarkers for Cancer Detection/10.5772/51419139patients with pancreatitis who were diagnosed as pancreatic cancer 5-14 months later, indi‐cating that release of tumor-specific DNA into the circulation is an early event in cancer development and cf-DNA could be used as the biomarkers for early cancer detection [32].Treatment resulted in disappearance of K-Ras mutations in plasma DNA in six of nine pa‐tients. Three patients with a persistently positive K-Ras gene mutation in plasma samples from patients before and after treatment showed early recurrence or progression and pancreatic carcinoma patients with the mutant-type K-ras gene in plasma DNA exhibited a shorter survival time than patients with the wild-type gene, indicating the cf-DNA could be of value in monitoring disease progression or evaluating treatment response [31, 33].Through quantitatively analyzing plasma DNAs from patients with organ transplantation,Lo et al found that the majority of plasma DNAs was released from the hematopoietic sys‐tem. However, donor DNA could be detected in the plasma of recipients suffering from the graft rejection because of the large amount of cell death which promotes the release of donor DNAs into the peripheral blood of the recipients [34]. Therefore, it was postulated that cell-free tumor related DNA could originate from the apoptotic tumor cells since high-rate of apoptosis indeed occurs in primary and metastatic tumor tissues. However, cf-DNA quanti‐ties are significantly reduced in cancer patients after radiotherapy when a great number of tumor cells were believed to undergo apoptotic cell death and cf-DNAs in supernatants of cultured cancer cells increases with cell proliferation rather than apoptosis or necrosis, indi‐cating that proliferating tumor cells could actively release cf-DNA into the tumor microen‐vironment and circulation.In contrast to labile RNAs that were included into the actively secreted exosomes, the nature of cf-DNAs remains to be clarified. As negatively charged molecules, cf-DNA was bound by plasma proteins to escape from endonuclease-mediated degradation. Unfortunately, plasma proteins bound to cf-DNAs was not well characterized yet. Meanwhile, secreted exosomes could remodel microenviroments and promote tumor metastasis since RNAs within exo‐somes especially microRNA with high stability may influence gene expression in neighbor cells. The biological relevance of cf-DNAs remains unknown. DNA was believed to be more structural rather than functional. However, it was supposed that cf-DNA could play a role as vaccine in tumor microenvironment.3. Methods for the detection of methylated DNAIt is unclear so far whether serum or plasma is better for cf-DNA extraction. Although the DNA amount is significantly higher in the serum, the majority of the increase was due to the release of nuclear acids from destroyed blood cells during blood clotting [35]. In addition,the time gap between blooding drawing and DNA extraction as well as the methodologies used for DNA isolation contribute greatly to the amount of cf-DNA harvested. On an aver‐age, around 30 ng cf-DNA could be extracted from one ml of blood sample [36]. Therefore,in order to determine the quantity of potential cf-DNA-based biomarkers precisely and pro‐mote its wide application for cancer detection, it is very important to unify the source asMethylation - From DNA, RNA and Histones to Diseases and Treatment140well as the methodologies for cf-DNA extraction and use various internal controls to adjustpossible inter-laboratory variations.Figure 2. Schematic introductions of various methods for methylation analyses. MSP, BGS and COBRA are based on bisulfite-mediated conversion of unmethylated cytosines into uracils. CpG methylation could block DNA digestion by some restriction enzymes, making it possible to determine methylation status independent of bisulfite treatment by analyzing digestion products. Alternatively, DNA fragments containing methylated CpG sites could be enriched by an‐ti-methylcytosine antibody or methylation binding proteins. Advances in next generation genome sequencing tech‐nology led to the development of noel techniques such as SMRT which can specially analyze 5-methylcytosines with genome wide coverage.In general, the detection of DNA methylation could be bisulfite-dependent or -independent (Figure 2).The chemical reaction of sodium bisulfite with DNA could convert unmethylated cytosine of CpG into uracil or UpG but leave methylated cytosine of CpG unchanged. The following analyses such as methylation-and unmethylation specific polymerase chain reaction (M- and U-SP), bisulfite genome sequencing (BGS) or combined bisulfite restriction analysis (CO‐BRA) could determine the conversion of CpG sites of interest, thus reflecting their methyla‐tion status as methylated or unmethylated [37]. With varied resolution levels, different bisulfite-dependent DNA methylation analysis methods detect the conversion after bisulfite treatment of genomic DNA, which could have certain artificial effects such as incomplete conversion of unmethylated CpG into UpG, leading to high rate of false negative conclusion of DNA methylation status.Recently, some new modifications of cytosine in CpG dinucleotides have been discovered such as 5-hydoxymethylcytosine which was called the sixth base since 5-methylcytosine was named as the fifth base [38]. Generated from the oxidation of 5-methylcytosine by the Tet family of enzymes, 5-hydoxymethylcytosine was first found in bacteriophages and recentlyCirculating Methylated DNA as Biomarkers for Cancer Detection/10.5772/51419141shown to be abundant in human and mouse brains as well as in embryonic stem cells [39-40]. Although the exact relevance of 5-hydoxymethylcytosine in the genome is still not fully clarified, it has been found to regulate gene expression or promote DNA demethyla‐tion. The in vitro synthesized artificial oligonucleotides containing 5-hydoxymethylcyto‐sines can be converted into unmodified cytosines when introduced into mammalian cells,indicating that 5-hydoxymethylcytosine might be one of intermediate products during ac‐tive DNA demethylation [41]. Therefore, the increase of 5-hydoxymethylcytosine might re‐flect the demethylation of CpG dinucleotides. Unfortunately, 5-hydoxymethylcytosines,similar to 5-methylcytosines, appear to be resistant to bisulfite-mediated conversion and PCR could amplify DNA fragments containing 5-hydoxymethylcytosines or 5-methylcyto‐sines with similar efficiency [42-43]. Therefore, bisulfite-dependent methylation analyses could produce false positive results by counting 5-hydoxymethylcytosines into 5-methylcy‐tosines. In addition to 5-hydroxymethylcytosines, some forms of DNA modifications such as the seventh base, 5-formylcytosine and the eighth base, 5-carboxylcytosine, have been found in mammalian cells recently [44-47]. As the products of 5-hydoxymethylcytosine oxidation through TET hydroxylases, both 5-formylcytosine and 5-carboxylcytosine will be read as the uracil after bisulfite conversion, thus making it impossible for bisulfite-dependent analyses to distinguish unmodified cytosines from 5-formylcytosines and 5-carboxylcytosines.Bisulfite independent analyses such as MedIP (methylated DNA immunoprecipitation)could more or less detect DNA methylation specifically. In bisulfite independent analyses, 5-methylcytosines are differentiated from unmethylated cytosine by either enzyme digestion or affinity enrichment. DNA methylation analysis using restriction enzyme digestion is based on the property of some methylation-sensitive and -resistant restriction enzymes such as HpaII and MspI that target CCGG for digestion. HpaII fails to cut it once the second cyto‐sine was methylated while MspI-mediated digestion is not affected by DNA methylation,thus making it possible to determine the methylation status of CpG in the context of CCGG tetranucleotides by analyzing the products of DNAs digested by HpaII and MspI respective‐ly. As a primary method to analyze DNA methylation, it can only determine the methyla‐tion of CpG in the context of CCGG tetranucleotides and will overlook the majority of CpG dinucleotides in the genome.The development of monoclonal antibody specific to 5-methylcytosines revolutionized the analyses of DNA methylation [48-49]. Immunoprecipitated DNA by this antibody could be subject to DNA microarray or even deep sequencing to reveal novel sequences or sites con‐taining 5-methylcytosines [50]. This antibody specifically recognizes 5-methylcytosines but not 5-hydoxymethylcytosines. However, 5-methylcytosines could present not only in CpG dinucleotides but also in CHH or CHG trinucleotides, especially in plants, human embryon‐ic stem cells and probably cancer cells as well. CHH methylation indicates a 5-methylcyto‐sine followed by two nucleotides that may not be guanine and CHG methylation refers to a 5-methylcytosine preceding an adenine, thymine or cytosine base followed by guanine. Such non-CpG DNA methylations were enriched at transposons and repetitive regions, although the exact biological relevance remains unknown. However, antibody against 5-methylcyto‐Methylation - From DNA, RNA and Histones to Diseases and Treatment142sine may precipitate methylated CHH and CHG trinucleotide containing DNA fragments in addition to DNA sequences with methylated CpG sites.DNA methylation functions as the signal for DNA-interacting proteins to maintain genome structure or regulate gene expression. The proteins such as MBD1 (methyl-CpG binding do‐main protein 1), MeCP2 (methyl CpG binding protein 2) and MBD4 (methyl-CpG binding domain protein 4) bind methylated CpG specifically to regulate gene expression [51-52].Therefore, methyl-CpG binding domain could specifically enrich differentially methylated regions (DMRs) of physiological relevance [53]. Similar to MeDIP, MBD capture specifically enrich methylated CpG sites rather than hydroxymethlated CpG sites. The detailed analysis to compare MeDIP and MBD capture revealed that both enrichment techniques are sensitive enough to identify DMRs in human cancer cells. However, MeDIP enriched more methylat‐ed regions with low CpG densities while MBD capture favors regions of high CpG densities and identifies the greater proportion of CpG islands [49].Recently, the advance of next generation sequencing led to the development of several novel techniques, making it possible to quantitatively analyze DNA methylation at single nucleo‐tide resolution with genome wide coverage. Both the single molecule real time sequencing technology (SMRT) and the single-molecule nanopore DNA sequencing platform could dis‐criminate 5-methylcytosines from other DNA bases including 5-hydroxymethylcytosines even methyladenine independent of bisulfite conversion [54-55]. With many advantages such as less bias during template preparation, lower cost and better accuracy, such new techniques could offer more methods to detect DNA methylation with high specificity and sensitivity in addition to more potential DNA methylation based biomarkers for cancer de‐tection and screening.4. Potential DNA methylation biomarkers for cancer detectionIt has been questioned whether the methylated DNA in the circulation is sensitive to detect cancers early enough for curative resection. However, the development of sensitive detection methods confirmed the potential value of DNA methylation in cancer detection (Table 1).Most of DNA methylation biomarkers are well-known tumor suppressor genes silenced in primary tumor tissues. However, the biomarks do not have to be functional relevant. For ex‐ample, currently well-used biomarkers such as AFP (Alpha-Fetal Protein), PSA (Prostate-specific antigen) and CEA (Carcinoembryonic antigen) are not tumor suppressor genes with important biological functions. Profiling of methylated DNA in the circulation instead of primary tumor tissues with MeDIP or MBD capture or other methylation specific analyses methods would identify more potential biomarks rather than functional important tumor suppressor genes.Circulating Methylated DNA as Biomarkers for Cancer Detection/10.5772/51419143Cancer Markers Sensitivity Specificity Methods Ref.Bladder cancer CDKN2A (ARF) CDKN2A(INK4A)CDKN2A (INK4A)13/27 (48%)2/27 (7%)19/86 (22%)N/AN/A31/31 (100%)MSPMSPMSP[58][59]Breast cancer CDKN2A (INK4A)CDKN2A (INK4A)5/35 (14%)6/43 (14%)N/AN/AMS-AP-PCRMS-AP-PCR[56][57]Colorectal cancerMLH1CDKN2A (INK4A) CDKN2A(INK4A) CDKN2A (INK4A)ALX4CDH4NGFRRUNX3SEPT9TMEFF23/18 (17%)14/52 (27%)13/94 (11%)21/58 (36%)25/30 (83%)32/46 (70%)68/133 (51%)11/17 (65%)92/133 (69%)87/133 (65%)N/A44/44 (100%)N/AN/A36/52 (70%)17/17 (100%)150/179 (84%)10/10 (100%)154/179 (86%)123/179 (69%)MSPMSPMSPMSPMSPMSPMSPMSPMSPMSP[60][61][62][63][64][65][66][67][66]Esophageal cancer APCAPCCDKN2A (INK4A)13/52 (25%)2/32 (6%)7/38 (18%)54/54 (100%)54/54 (100%)N/AMSPMSPMSP[68][69]Gastric cancer CDH1CDKN2A (INK4A)CDKN2B (INK4B)DAPK1GSTP1Panel of five 31/54 (57%)28/54 (52%)30/54 (56%)26/54 (48%)18/54 (15%)45/54 (83%)30/30 (100%)30/30 (100%)30/30 (100%)30/30 (100%)30/30 (100%)30/30 (100%)MSPMSPMSPMSPMSPMSP[70]Head and neck cancer CDKN2A (INK4A)DAPK1MGMTPanel of threeDAPK18/95 (8%)3/95 (3%)14/95 (15%)21/95 (22%)N/AN/AN/AN/AN/AN/AMSPMSPMSPMSPMSP[71][72]Liver cancer CDKN2A (INK4A) CDKN2B(INK4B)13/22 (45%)4/25 (16%)48/48 (100%)35/35 (100%)MSPMSP[73][74]Lung cancer CDKN2A (INK4A)DAPK1GSTP1MGMTPanel of fourCDKN2A (INK4A)APC 3/22 (14%)4/22 (18%)1/22 (5%)4/22 (18%)11/22 (50%)N/A42/89 (47%)N/AN/AN/AN/AN/AN/A50/50 (100%)MSPMSPMSPMSPMSPMSPMSP[75][76][77]Methylation - From DNA, RNA and Histones to Diseases and Treatment 144Cancer Markers Sensitivity Specificity Methods Ref.CDKN2A (INK4A)CDKN2A (INK4A)77/105 (73%)12/35 (34%)N/A15/15 (100%)MSP MSP [78][79]Prostate cancer GSTP1GSTP123/33 (70%)25/69 (36%)22/22 (100%)31/31 (100%)MSP MSP[80][81]Table 1. Methylated DNA biomarkers in the literature.Most of the methods used for methylation biomarkers analyses are still bisulfite dependent.Few reports used MS-AP-PCR (methylation-sensitive arbitrarily primed PCR) which takes the advantage of methylation sensitive restriction endonucleases to distinguish methylated CpG from unmethylated form, although the sensitivity seems to be lower than MSP [56-57].Interestingly, combination of more than one methylated DNA as a methylation panel could great increase the sensitivity for cancer detection without significant reduction of specificity.Unfortunately, most of studies were performed in a retrospective manner. More prospective studies with large sample sizes will be warranted to compare different approaches especial‐ly bisulfite-independent methods in addition to confirm the value of DNA methylation for cancer detection.5. Conclusion and PerspectivesWith the development of the next generation genome sequencing as well as single molecular PCR, it became possible to analyze trace amount of DNAs including circulating cell-free DNA. Circulating tumor cells have been proven its value in prognosis predication even ear‐ly detection of various cancers. The analyses of methylated DNAs in the circulating will be the next promising epigenetic biomarkers for cancer detection. As one of the intermediate products of DNA demethylation, 5-hydroxymethlcytosines are resistant to bisulfite conver‐sion. Therefore, it should be carefully to interpret the data of methylation analyses based on bisulfite treatment due to potentially high rate of false positive results. Although some me‐thylated DNAs were found to valuable as a single biomarker for cancer detection, more po‐tential DNA methylations will be found after the wide application of SMRT and other sequencing platforms with high speed, depth and accuracy. DNA methylation signatures in‐cluding a panel of methylated DNAs will show the potential in the early diagnosis or screening and prognosis or therapy response prediction of many cancers. In addition, such DNA methylation biomarkers could be more sensitive and specific for cancer detection when combined with well-used biochemical biomarkers. However, unified methods with gold standards will be warranted to promote the development and clinical application of DNA methylation biomarkers.Circulating Methylated DNA as Biomarkers for Cancer Detection/10.5772/51419145AcknowledgementsThis work was supported by the National Natural Science Foundation of China (81071963;81071652), Program for Innovative Research Team in Science and technology of Zhejiang Province (2010R50046) and Program for Qianjiang Scholarship in Zhejiang Province (2011R10061; 2011R10073).Author detailsHongchuan Jin, Yanning Ma, Qi Shen and Xian Wang **Address all correspondence to: wangx118@Department of Medical Oncology, Laboratory of Cancer Epigenetics, Biomedical Research Center, Sir Runrun Shaw Hospital, Zhejiang University, ChinaReferences[1]Jones, P. A., & Baylin, S. B. (2007). The epigenomics of cancer. Cell , 128, 683-692.[2]Jones, P. A., & Baylin, S. B. (2002). The fundamental role of epigenetic events in can‐cer. 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Annu Rev Med, 63, 199-215.[15]Zhe, X., Cher, M. L., & Bonfil, R. D. (2011). Circulating tumor cells: finding the needlein the haystack. Am J Cancer Res, 1, 740-751.[16]Fidler, I. J. (2003). The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothe‐sis revisited. Nat Rev Cancer, 3, 453-458.[17]Ghossein, RA, Bhattacharya, S, & Rosai, J. (1999). Molecular detection of micrometa‐stases and circulating tumor cells in solid tumors. Clin Cancer Res, 5, 1950-1960. [18]Pelkey, TJ, Frierson, H. F., Jr, & Bruns, D. E. (1996). Molecular and immunological de‐tection of circulating tumor cells and micrometastases from solid tumors. Clin Chem, 42, 1369-1381.[19]Mocellin, S., Keilholz, U., Rossi, C. R., & Nitti, D. (2006). Circulating tumor cells: the‘leukemic phase’ of solid cancers. Trends Mol Med, 12, 130-139.[20]Chimonidou, M., Strati, A., Tzitzira, A., Sotiropoulou, G., Malamos, N., Georgoulias,V., & Lianidou, E. S. (2011). DNA methylation of tumor suppressor and metastasis suppressor genes in circulating tumor cells. Clin Chem, 57, 1169-1177.[21]Garcia-Olmo, D. C., Gutierrez-Gonzalez, L., Ruiz-Piqueras, R., Picazo, M. G., & Gar‐cia-Olmo, D. (2005). Detection of circulating tumor cells and of tumor DNA in plas‐ma during tumor progression in rats. Cancer Lett, 217, 115-123.。

《信息检索导论》课后练习答案王斌最后更新日期 2013/9/28第一章布尔检索习题1-1 [*] 画出下列文档集所对应的倒排索引（参考图1-3中的例子）。

文档 1 new home sales top forecasts文档 2 home sales rise in july文档 3 increase in home sales in july文档 4 july new home sales rise习题1-2 [*] 考虑如下几篇文档：文档1 breakthrough drug for schizophrenia文档2 new schizophrenia drug文档3 new approach for treatment of schizophrenia文档4 new hopes for schizophrenia patientsa. 画出文档集对应的词项—文档矩阵；解答：breakthrough 1 0 0 0drug 1 1 0 0for 1 0 1 1hopes 0 0 0 1new 0 1 1 1patients 0 0 0 1schizophrenia 1 1 1 1treatment 0 0 1 0b. 画出该文档集的倒排索引（参考图 1-3中的例子）。

解答：参考a。

习题1-3 [*] 对于习题1-2中的文档集，如果给定如下查询，那么返回的结果是什么？a.schizophrenia AND drug解答：{文档1，文档2}b.for AND NOT (drug OR approach）解答：{文档4}习题1-4 [*] 对于如下查询，能否仍然在O(x+y)次完成？其中x和y分别是Brutus和Caesar所对应的倒排记录表长度。

如果不能的话，那么我们能达到的时间复杂度是多少？a.Brutus AND NOT Caesarb.Brutus OR NOT Caesar解答：a.可以在O(x+y)次完成。

教材练习题参考答案第二章货币资金【参考答案】（1）①出差借支时借：其他应收款一一张某1000贷：银行存款1000②归来报销时借：管理费用850库存现金150贷：其他应收款1000（2）①开立临时采购户吋借：其他货币资金一一外埠存款80 000贷：银行存款80 000②收到购货单位发票时借：原材料60 000应交税费一一应交增值税（进项税额）10 200贷：其他货币资金一一外埠存款70 200③将多余资金转回原来开户行时借：银行存款9 800贷：其他货币资金一一外埠存款9 800（3）①收到开户银行转来的付款凭证吋借:其他货币资金一一信用卡3 000贷：银行存款3 000②收到购物发票账单时借：管理费用2 520贷：其他货币资金一一信用卡25 20（4）拨出备用金时借：备用金1000贷：银行存款10 00（5）总务部门报销时借:管理费用900贷：库存现金9 00（6）①期末盘点发现短缺时借：待处理财产损溢一一待处理流动资产损溢50贷：库存现金50②经批准计入损益吋借：管理费用5 0贷：待处理财产损溢一一待处理流动资产损溢50第三章应收款项【参考答案】1.（1）办妥托收银行收款手续时：借:应收账款11700贷：主营业务收入10 000应交税费一应交增值税（销项税额）17 0 00（2）如在10天内收到货款时借：银行存款11 466财务费用23 4贷：应收账款11700（3）如在30内收到货款时借：银行存款11700贷：应收账款117002.（1）收到票据时借：应收票据93 6 00贷：主营业务收入80 000应交税费一应交增值税（销项税额）13 600（2）年终计提票据利息借:应收票据15 60贷:财务费用1560（3 ）到期收回货款借:银行存款98 280贷：应收票据95 160财务费用3 1203.（1）第一年末借:资产减值损失5 000贷：坏账准备5 000（2）第二年末借:资产减值损失7 500贷：坏账准备7 500（3 ）第三年末借：坏账進备1500贷：资产减值损失1500（3）第四年6月发生坏账时借：坏账准备18 000贷:应收账款18 00010月收回己核销的坏账时借:应收账款5 00 0贷：坏账准备5 000借：银行存款5 000贷：应收账款5000年末计提坏账准备时借：资产减值损失1 2 000贷：坏账准备12 00 0第四章存货【参考答案】1.（1）实际成本核算：该批甲材料的实际总成本=20 000+200=2 0 200 （元）借：原材料•甲材料20 2 00应交税费•应交增值税3 400贷：银行存款23 600（2）计划成本核算①购进借:材料采购■甲材料20 200应交税费•应交增值税3 400贷：银行存款23 600②入库材料成本差异=20 200-990X18 =2380元，超支差异借：原材料--- 甲材料17 820 （=990X18）材料成本差异2380贷：材料采购——甲材料20 20 02.（1）先进先出法6月7日①发出A材料的成本=200X 60+20 0X 66=25 20 0 （元）6月18日②发出A材料的成本=300X 66 +500X 70=54 800 （元）6月29日③发出A材料的成本=100 X70+200X68 =20 600 （元）期末结存A材料成本=300X68=20 400 （元）（2）月末一次加权平均法加权平均单位成本二（12 000+109 0 00） 4- （200+1 600） ^67.22 （元/公斤）期末结存A材料的成本=300 X67.22=201 66 （元）本月发出A 材料的成本二（12 000+109 00 0） -20166=1 00834 （元）（3 ）移动加权平均法6月5日①购进后移动平均单位成本二（12000+33 000）一（200+500） =64.29 （元/公斤）6月7日结存A材料成本=300X64 .29=19287 （元）6 月7 日发出A 材料成本=（12000+330 00） -19287=25713 （元）6月16日②购进后移动平均单位成本二（19287+42 000） 4- （300+600） =68.10 （元/公斤）6月18日结存A材料成本=100X68 .10=6810 （元）6 月18 日发出A 材料成本二（19287+4200 0） -6810=54 477 （元）6月27日③购进后移动平均单位成本二（6810+34000 ）0 （100+500 ）=68.02 （元/公斤）6月29日结存A材料成本=300X68.02 =20406 （元）6月29日发出A材料成本二（68 10+34000）・20406=2040 4 （元）期末结存A材料成本=300X68 .02=20406 （元）3.A产品：有销售合同部分：A产品可变现净值=40X （1105）=4 20（万元），成本=40X10=400 （万元），这部分存货不需计提跌价准备。

习题33.1选择题(1) 有一半径为R 的水平圆转台，可绕通过其中心的竖直固定光滑轴转动，转动惯量为J ，开始时转台以匀角速度ω0转动，此时有一质量为m 的人站在转台中心，随后人沿半径向外跑去，当人到达转台边缘时，转台的角速度为(A)02ωmRJ J+ (B) 02)(ωR m J J + (C)02ωmRJ(D) 0ω [答案： (A)](2) 如题3.1（2）图所示，一光滑的内表面半径为10cm 的半球形碗，以匀角速度ω绕其对称轴OC 旋转，已知放在碗内表面上的一个小球P 相对于碗静止，其位置高于碗底4cm ，则由此可推知碗旋转的角速度约为 (A)13rad/s (B)17rad/s (C)10rad/s (D)18rad/s(a) (b)题3.1（2）图[答案： (A)](3)如3.1(3)图所示，有一小块物体，置于光滑的水平桌面上，有一绳其一端连结此物体，；另一端穿过桌面的小孔，该物体原以角速度ω在距孔为R 的圆周上转动，今将绳从小孔缓慢往下拉，则物体 （A ）动能不变，动量改变。

（B ）动量不变，动能改变。

（C ）角动量不变，动量不变。

（D ）角动量改变，动量改变。

（E ）角动量不变，动能、动量都改变。

[答案： (E)]3.2填空题(1) 半径为30cm 的飞轮，从静止开始以0.5rad·s -2的匀角加速转动，则飞轮边缘上一点在飞轮转过240˚时的切向加速度a τ= ，法向加速度a n=。

[答案：0.15; 1.256](2) 如题3.2（2）图所示，一匀质木球固结在一细棒下端，且可绕水平光滑固定轴O转动，今有一子弹沿着与水平面成一角度的方向击中木球而嵌于其中，则在此击中过程中，木球、子弹、细棒系统的守恒，原因是。

木球被击中后棒和球升高的过程中，对木球、子弹、细棒、地球系统的守恒。

题3.2（2）图[答案：对o轴的角动量守恒，因为在子弹击中木球过程中系统所受外力对o轴的合外力矩为零，机械能守恒](3) 两个质量分布均匀的圆盘A和B的密度分别为ρA和ρB (ρA>ρB)，且两圆盘的总质量和厚度均相同。

【达内培训】2013年计算机二级VFP表单设计与应用课后习题答案第八章表单设计与应用大纲要求使用表单设计器：（1）在表单中加入和修改控件对象。

（2）设定数据环境。

知识要点1.表单表单(Form)就是一个输入或显示某种信息的界面(窗口)，是Visual FoxPro提供的用于建立应用程序界面的工具之一。

被大量应用于人机交互界面的设计当中。

应用表单设计功能，可以设计出具有Windows风格的各种程序界面。

由于表单使用非常频繁，所以在VFP中，专门提供了一个表单设计器来设计表单程序。

表单是一个容器，除含有窗口的标准控件标题栏、控制按钮外，可以向表单中添加各种对象，如按钮、文本框、表格、图片等。

在表单设计器环境下可以进行添加、删除与布局控件的操作。

2. 对象对象（Object）是反映客观事物属性与行为特征的描述。

客观世界里的任何实体都可以被看作是对象。

对象可以是具体的物，也可以指某些概念。

从编程的角度来看，对象是一种将数据和操作过程结合在一起的数据结构，或者是一种具有属性（数据）和方法（过程和函数）的集合体。

事实上程序中的对象就是对客观世界中对象的一种抽象描述。

每个对象都具有描述其特征的属性，与附属于它的行为。

对象把事物的属性和行为封装在一起，是一个动态的概念。

对象是面向对象编程的基本元素，是“类”的具体实例。

（1）对象属性：属性用来表示对象的状态。

（2）对象方法：对象方法是描述对象行为的过程。

对象的属性特征标识了对象的物理性质，对象的行为特征描述了对象可执行的行为动作；对象的每一种属性，都是与其他对象加以区别的特性，都具有一定的含义，并赋予一定的值；对象大多数是可见的，也有一些特殊的对象是不可见的。

3．类v 类是对一类相似对象的性质描述，这些对象具有相同种类的属性以与方法就好比是一个摸板。

对象是类的一个实例。

v 类的类型子类和父类v 类的四大特征来源§继承性——说明了子类延用父类特征的能力；§多态性——指一些关联的类包含同名的方法程序，但方法程序的内容可以不同，具体调用在运行时根据对象的类确定；§封装性——说明包含和隐藏对象信息，如内部数据结构和代码的能力；§抽象性——指提取一个类或对象与众不同的特征，而不对该类的所有信息进行处理；4．子类与继承在面向对象的方法里，继承是指在基于现有的类创建新类时，新类继承了现有类里的方法和属性。

《中国近现代史纲要2013年修订版》 课后思考题参考答案目录上编 (3)综述 (3)1.为什么说鸦片战争是中国近代史的起点？ (3)2,怎么认识近代中国的主要矛盾,社会性质及其基本特征 (3)3,如何理解近代中国的两大历史任务及其相互关系 (4)第一章 (4)1,资本—帝国主义的入侵给中国带来了什么 (4)2,近代中国进行的反侵略战争具有什么意义 (5)3,中国近代历次反侵略战争失败的根本上原因和教训是什么 (5)第二章 (6)1,如何认识太平天国农民战争的意义和失败的原因,教训 (6)2,何认识洋务运动的性质和失败的原因,教训 (7)3,如何认识戊戌维新运动的意义和失败的原因,教训 (7)第三章 (8)1、革命派和改良派论战中是如何论述革命的必要性、正义性、进步性的？ (8)2、为什么说孙中山领导的辛亥革命引起了近代中国的历史性巨大变化？ (8)3、辛亥革命为什么会失败？它的失败说明了什么？ (8)中编 (9)综述 (9)1、中国的新民主主义革命是在什么时代条件下和国际环境中发生发展的？这对中国革命事业带来哪些影响？ (9)2、为什么中国的新民主主义革命必须把帝国主义、封建主义、官僚资本主义作为对象？ (10)3、如何理解近代中国的三种建国方案，两个中国之命运？为什么中国共产党的建国方案最终成为中国人民的共同选择？ (10)第四章 (11)1、中国的先进分子为什么和怎样选择了马克思主义？ (11)2、为什么说中国共产党的成立是“开天辟地”的大事变？ (11)3、中国共产党成立后，中国革命呈现了哪些新面貌？为什么？ (11)第五章 (12)1,以毛泽东为主要代表的共产党人是如何探索和开辟中国革命新道路的 (12)2,20世纪20年代后期,30年代前中期,中国共产党内为什么连续出现"左"倾错误 . 123,中国共产党是如何总结历史经验,加强党的思想理论建设的 (13)第六章 (13)1,为什么说中国的抗日战争是神圣的民族解放战争 (13)2,为什么说中国共产党是中国人民抗日战争的中流砥柱 (14)3.怎样评价国民党政府在抗日战争中执行的路线和正面战场的地位与作用 (14)4,为什么国人民抗日战争是弱国战胜强国的范例其基本经验是什么 (14)第七章 (15)1,抗日战争胜利后,国民党政府为什么会陷人全民的包围中并迅速走向崩溃 (15)2,如何认识民主党派的历史作用中国共产党领导的多党合作,政治协商的格局是怎样形成的 (16)3,什么说"没有共产党就没有新中国" 中国革命取得胜利的基本经验是什么 (16)下编 (17)综述 (17)1.为什么说中华人民共和国的成立开创了中国历史的新纪元 (17)2.新中国成立以来取得了哪些历史性成就这些成就说明了什么 (17)第八章 (18)1、为什么说新民主主义社会是一个过渡性的社会？ (18)2、怎样理解社会主义制度在中国的确立是历史和人民的选择？ (18)3、为什么说完成社会主义改造是中国历史上最伟大和最深刻的社会变革？ (18)第九章 (19)1,中国共产党人在1956年至1957年的早期探索中对社会主义建设有哪些理论建树 (19)2,怎样认识建立独立的,比较完整的工业体系和国民经济体系的重大意义 (20)3,为什么说毛泽东是探索中国社会主义建设道路的开创者怎样认识和评价毛泽东的历史地位 (20)第十章 (21)1,为什么说中共十一届三中全会是新中国成立以来的伟大历史转折 (21)2,试述改革开放和现代化建设的历史进程和基本经验. (22)3,中共十一届三中全会以来中国特色社会主义取得哪些主要成就？取得这些成绩和进步的根本原因是什么？ (23)上编综述1.为什么说鸦片战争是中国近代史的起点？鸦片战争是中国近代史的开端，原因有四：第一，战争后中国的社会性质发生了根本性变化，由一个落后封闭但独立自主的封建国家沦为一个半殖民地半封建社会。

电磁场与电磁波课后习题及答案三章习题解答三章习题解答3.1 真空中半径为a 的⼀个球⾯，球的两极点处分别设置点电荷q 和q -，试计算球⾚道平⾯上电通密度的通量Φ(如题3.1图所⽰)。

解由点电荷q 和q -共同产⽣的电通密度为33[]4q R R π+-+-=-=R R D 22322232()(){}4[()][()]r z r z r z a r z a q r z a r z a π+-++-+-++e e e e 则球⾚道平⾯上电通密度的通量d d zz SSS Φ====??D S D e22322232()[]2d 4()()aq a ar r r a r a ππ--=++? 22121)0.293()aqaq q r a =-=-+ 3.2 1911年卢瑟福在实验中使⽤的是半径为a r 的球体原⼦模型，其球体内均匀分布有总电荷量为Ze -的电⼦云，在球⼼有⼀正电荷Ze （Z 是原⼦序数，e 是质⼦电荷量），通过实验得到球体内的电通量密度表达式为02314ra Ze r r r π??=-D e ，试证明之。

解位于球⼼的正电荷Ze 球体内产⽣的电通量密度为 124rZer π=D e 原⼦内电⼦云的电荷体密度为 333434a a Ze Zer r ρππ=-=- 电⼦云在原⼦内产⽣的电通量密度则为 32234344r ra r Ze rr r ρπππ==-D e e题3.1 图题3. 3图()a故原⼦内总的电通量密度为 122314ra Ze r r r π??=+=-D D D e 3.3 电荷均匀分布于两圆柱⾯间的区域中，体密度为30C m ρ, 两圆柱⾯半径分别为a 和b ，轴线相距为c )(a b c -<，如题3.3图()a 所⽰。

求空间各部分的电场。

解由于两圆柱⾯间的电荷不是轴对称分布，不能直接⽤⾼斯定律求解。

但可把半径为a 的⼩圆柱⾯内看作同时具有体密度分别为0ρ±的两种电荷分布，这样在半径为b 的整个圆柱体内具有体密度为0ρ的均匀电荷分布，⽽在半径为a 的整个圆柱体内则具有体密度为0ρ-的均匀电荷分布，如题3.3图()b 所⽰。

财务管理陈绍宇张家祥课后习题答案1.与激进型营运资本投资策略相比，适中型营运资本投资策略的()。

(2017) [单选题] *A.持有成本和短缺成本均较低B.持有成本和短缺成本均较高C.持有成本较高，短缺成本较低(正确答案)D.持有成本较低，短缺成本较高答案解析：【答案】C【解析】相比于激进型营运资本投资策略，适中型营运资本投资策略流动资产/收入比率较高，所以持有成本较高，而短缺成本较低。

2.企业采用保守型流动资产投资策略时，流动资产的()。

(2013) [单选题] *A.短缺成本较高B.管理成本较低C.机会成本较低D.持有成本较高(正确答案)答案解析：【答案】D【解析】保守型流动资产投资策略，表现为安排较高的流动资产/收入比率，承担较大的持有成本，但短缺成本较小。

3.下列关于流动资产投资策略的说法中，不正确的是()。

[单选题] *A.流动资产最优的投资规模，取决于持有成本和短缺成本总计的最小化B.流动资产投资大于最优投资规模时，流动资产持有成本大于其短缺成本C.在保守型流动资产投资策略下，公司的短缺成本较小D.激进型流动资产投资策略，表现为较低的流动资产与收入比，公司承担的风险较低(正确答案)答案解析：【答案】D【解析】激进型流动资产投资政策，表现为较低的流动资产与收入比。

该政策可以节约流动资产的持有成本，例如节约资金的机会成本。

与此同时，公司要承担较大的风险，例如经营中断和丢失销售收入等短缺成本。

所以选项D的说法不正确。

4.甲公司是一家生产和销售电暖气的企业，夏季是其生产经营淡季，应收账款、存货和应付账款处于正常状态。

根据如下：甲公司资产负债表，该企业的营运资本筹资策略是()。

[单选题] *A.保守型筹资策略(正确答案)B.适中型筹资策略C.激进型筹资策略D.无法判断答案解析：【答案】A【解析】经营淡季，存在净金融性流动资产,说明易变现率大于1,属于保守型筹资策略，选项A正确。

5.下列关于适中型营运资本筹资政策的说法中，正确的是()。