Professional English —— for students in college of mathematics and statistics

1. Professional English —— for students in college of mathematics and statistics Lecture 2: Professional Writing on Introduction Section

2. Table of Content Before & when you write Title and Abstract Introduction Surf on examples 2

3. Before You Start to Write • Does your research result meet the standard of a publishable article? • Choose a suitable magazine to publish your result: • A professional or a comprehensive journal? • The type of submission: Article, Review, Report, Letter …… • How to evaluate the journal: • Impact factor; How many papers published per one year; At what percentage papers written by local Chinese are accepted. • => To evaluate the acceptance possibility of your paper 3

4. Before You Start to Write Have you ever downloaded the latest “Instructions for authors”? Are you clear about each entry described in this section? Whether the journal chosen accepts on line submission, which makes communication to the editor convenient? Whether the journal are going to charge the publication fee, and whether you or your boss can afford or not? How many relevant papers do you have? The more the better to (1) logics; (2) grammar; (3) disscussion 4

5. When You Write • Do not try think in Chinese, please think in English. • Incorporate the well studied writing ideas of the foreign people. • Introduction: (1) Introduction to the background information; (2) The importance and your understanding of the scientific problem; (3) How to lead to the research question. • Discussion: The first sentence in each paragraph is the key. • Follow strictly to the requirement of the journal • The same as “Instructions for authors” or recently published papers in the journal • Avoid the usage of “for the first time, this first ever study on XXX”, and so on. (please just state the facts) 5

6. When You Write Is there any requirement on the first page? Have you indicate the Corresponding author? Have you illustrated the Running title, and whether the number of characters in the title is suitable for publishing (< 50)? Whether the no. of characters should be listed on title page? Key words? For editor to choose reviewers in your fields. Is there specific requirement for the Abstract Format: Aim, Method, Result, Conclusion The limitation to the no. of characters (< 400 for example) 6

7. When You Write Follow the required reference format of the journal The limitation of the no. of references. Whether you have cited “In press paper” or “Unpublished data” Choose the “right” references Cite papers published on the most reputable journals (IF > 10, or high rank journal within your field) An unspoken rule: To publish on “good” journal, avoid citing papers from “no-good” journal Self-citation: To publish on Chinese journal, cite papers from the itself (editor may wish you to cite more from his journal) 7

8. When You Write Find someone fluent in English writing (born in China) to proof-read your first draft Can revise “obvious mistakes” in writing and expression Can fully understand what you want to say Find someone fluent in English writing (born in Western country) to proof-read your second draft Can revise “minor mistakes” in the habit of expression Show your appreciation to these who help you Thank you very much for the excellent and professional revision of our manuscript. I would be very happy to acknowledge your great help in the footnote when the paper is ready for publishing. We thank Prof. XXX for his critical reading of the manuscript 8

9. When You Write Avoid punctuation in Chinese input method (will be regarding as “disordered code” or “illegal program”) The correct usage of punctuations and spaces The format of “Abbreviation”, “time”, “Greek alphabet (希腊字母)” and so on. Pay attention of the “Italics” Figure Limitation to the number, size and resolution of figures Try to use figures in grayscale (avoid color figure, information lost and expensive for publication) Where to put the figures, at the end or in the middle of paper? Format of figures: EPS, TIFF for mathematics; JPG, PNG for biology and pharmacy. RGB mode. 9

10. Figure preparationPhotoshop (PS) + Windows Paint Let’s have one lecture on the usage of Photoshop 10

11. When You Write Limitation to number of words (< 2000), characters (< 8000) and printable pages (< 8, including figure and table) Font size (12 point); Line space: double Acknowledgement This work is funded by the National Natural Science Foundation of China (XXXXXXX), by the Chongqing Natural Science Foundation (XXXXXXX). We appreciate Prof. XXX for his critical reading of the manuscript, Prof. XXX for developing XXX technology on XXX aspect of research, Prof. XXX for providing experimental materials on XXXX. 11

12. Title • Abstract • Keywords • Table of contents • Nomenclature • Introduction • Method • Results • Discussion • Conclusion • Acknowledgement • Notes • References • Appendix (supplementary material) Structure of Professional Paper Writing Main Body 12

13. Title & Abstract • Title • Reflect the content, Noun, Eye catching, Upper case • Abstract (100~200 words) • The most important components and a condensed statement of a professional paper, a summary of work & contributions • Structure: research topic (what is the problem), methods used (what is your solution), main conclusion (what is the results) • Written English (Formal) • Useful, Representative, Readable, Clarity, Consistency, Objectivity • Keywords (3~8: research field, question, method, key concept) 13

14. Abstract • Try to be concise but include the following • Describe the problem / issue addressed in the paper (What is it? Is it really important? Challenging?) • State the motivations (filling a gap? overcoming inadequateness and weakness of existing solutions?) • Highlight the ideas and features of your work (in comparison with existing ones – advantages? improvement?) • Highlight the main results of evaluation (analytical or experimental) 14

15. Abstract • Objectives and purposes • Research background, scope, content, problems need to solve, importance and meaning for problem solving • Methods and materials • Materials used, tools and means, processes • Results and discussions • Data collection or acquisition, data analysis • Conclusions • Main conclusion, value and meaning of this research 15

16. Abstract An Abstract must answer questions as: What to study on? How to conduct the study? What is results? What kind of conclusion can be reached? Requirements: Right format Language: standard, fluent, accurate, appropriate, objective No rare expression, abbreviation without indication What kind of conclusion can be reached? 16

17. Limitation on no. of words in AbstractHow to shorten the Abstract Delete unnecessary words, sentences or modifiers “It is reported …”; “Extensive investigations show that …”; “The author discusses …”; “This paper concerned with …”; “In this paper …”; “in detail”; “briefly”; “here”; “mainly”. Delete or reduce background information Just include NEW situation, NEW content Delete useless words This work is a huge improvement to the old technology It is the first even research on … Based on literature review, no research on XX has been found No future works Avoid duplication, especially duplication to the title 17

18. The style of Abstract Complete, Clearance, Clarity Use short sentences, but increase the diversity of chosen words To describe the work (past tense), the conclusion (present tense) Attribute (定语): Adjective (形容词) > Noun (名词)> Gerund (动名词) USE: measurement accuracy; DO NOT USE: measuring accuracy USE: the experimental result; DO NOT USE: the experiment result Noun and Noun phrase (名词短语)> “of” sentence USE: measurement accuracy; DO NOT USE: accuracy of measurement USE: camera curtain shutter; DO NOT USE: curtain shutter of camera USE: equipment structure; DO NOT USE: structure of equipment Verb > the Noun form of verb USE: Thickness of plastic sheets was measured DO NOT USE Measurement of thickness of plastic sheet was made 18

19. The style of Abstract Active voice > Passive voice NOT USE: B is exceeded by A. USE: A exceeds B. Use Article (冠词) correctly: NOT USE: The pressure is a function of the temperature. USE: Pressure is a function of the temperature. Make verb closer to the subject (主语): NOT USE: The decolorization in solutions of the pigment in dioxance, which were exposed to 10 hr of UV irradiation, was no longer irreversible. USE: When the pigment was dissolved in dioxane, decolorization was irreversible after 10 hr of UV irradiation. Simple expression > Complicated expression: USE: increased; NOT USE: has been found to increase USE: results show; NOT USE: from the results, it can be concluded that Difference between English and Chinese expression: Do not use “Because” in Abstract as “因为”, too strong Do not use “not only … but also …” in Abstract, just use “and” 19

20. The style of Abstract Avoid using special characters α => alpha; β = beta; γ = gamma; δ = delta …… Abbreviations and acronyms (缩略语) Radar; Laser; FDA; NCBI; CAD ……, which can be used directly. Words within a specific field, its full expression should appear at least once. When describe method or process, use narrow not broad term NOT USE: run, get, take (too many meaning, misleading). USE: perform, achieve. Common sentence Research goal (in the beginning of Abstract): In order to ……; This paper describes ……; The purpose of this study is …… Study objects and methods: The [curative effect/sensitivity/function] of certain [drug/kit/organ] was [observed/detected/studied] …… Research results: [The result showed/It proved/The authors found] that …… Conclusion, view or suggestion: The authors [suggest/conclude/consider] that …… 20

21. Example A of Abstract Low target discovery rate has been linked to inadequate consideration of multiple factors that collectively contribute to druggability. These factors include sequence, structural, physicochemical, and systems profiles. Methods individually exploring each of these profiles for target identification have been developed, but they have not been collectively used. We evaluated the collective capability of these methods in identifying promising targets from 1019 research targets based on the multiple profiles of up to 348 successful targets. The collective method combining at least three profiles identified 50, 25, 10, and 4% of the 30, 84, 41, and 864 phase III, II, I, and nonclinical trial targets as promising, including eight to nine targets of positive phase III results. This method dropped 89% of the 19 discontinued clinical trial targets and 97% of the 65 targets failed in high-throughput screening or knockout studies. Collective consideration of multiple profiles demonstrated promising potential in identifying innovative targets. Background Problem Methods Results Conclusion 21

22. Example B of Abstract Many drugs are nature derived. Low drug productivity has renewed interest in natural products as drug-discovery sources. Nature-derived drugs are composed of dozens of molecular scaffolds generated by specific secondary-metabolite gene clusters in selected species. It can be hypothesized that drug-like structures probably are distributed in selective groups of species. We compared the species origins of 939 approved and 369 clinical-trial drugs with those of 119 preclinical drugs and 19,721 bioactive natural products. In contrast to the scattered distribution of bioactive natural products, these drugs are clustered into 144 of the 6,763 known species families in nature, with 80% of the approved drugs and 67% of the clinical-trial drugs concentrated in 17 and 30 drug-prolific families, respectively. Four lines of evidence from historical drug data, 13,548 marine natural products, 767 medicinal plants, and 19,721 bioactive natural products suggest that drugs are derived mostly from preexisting drug-productive families. Drug-productive clusters expand slowly by conventional technologies. The lack of drugs outside drug-productive families is not necessarily the result of under-exploration or late exploration by conventional technologies. New technologies that explore cryptic gene clusters, pathways, interspecies crosstalk, and high-throughput fermentation enable the discovery of novel natural products. The potential impact of these technologies on drug productivity and on the distribution patterns of drug-productive families is yet to be revealed. Background Problem Methods Results View or Suggestion 22

23. Example C of Abstract Understanding the molecular mechanisms underlying synergistic, potentiative and antagonistic effects of drug combinations could facilitate the discovery of novel efficacious combinations and multi-targeted agents. In this article, we describe an extensive investigation of the published literature on drug combinations for which the combination effect has been evaluated by rigorous analysis methods and for which relevant molecular interaction profiles of the drugs involved are available. Analysis of the 117 drug combinations identified reveals general and specific modes of action, and highlights the potential value of molecular interaction profiles in the discovery of novel multicomponent therapies Background + Problem Methods Results + Conclusion 23

24. Introduction • One of the most important parts of your paper • People usually read carefully on Abstract and Introduction to find out what is in your paper so as to decide whether it worth further reading, so don’t make them disappointed • You can write Introduction by expanding the abstract • Most important is to show how your work is motivated (background), focus of the paper, main ideas, and significance of results. • Sell your work • use strong tones! • Add outline of paper 24

25. A discussion on the related works • Tell people the background and existing works • Relate these works to your research • It can also be placed at the end of the paper (before conclusion), depending on whether your work heavily depends on these works or not • Purpose: draw the differences 25

26. A discussion on the related works • Be lucid – summarize and classify existing works by describing the main approaches used and results of important works. • Don’t simply give a paper-by-paper description without logical development. • Be critical but skillful in pointing out the weakness of existing works • Don’t overly criticize. • Whenever possible, compare them with your proposed solution • You can borrow ideas / techniques from them but must have some new stuff (improvement or extension, or apply them to new environment. 26

27. Example A of Introduction The majority of clinical drugs achieve their therapeutic effects by binding and modulating the activity of protein targets (Ohlstein et al., 2000; Zambrowicz and Sands, 2003). Intensive efforts in target search (Chiesi et al., 2001; Matter, 2001; Walke et al., 2001; Ilag et al., 2002; Zheng et al., 2006b) have led to the discovery of >1000 research targets (targeted by investigational agents only) (Zheng et al., 2006b). These targets have been derived from analysis of disease relevance, functional roles, expression profiles, and loss-of-function genetics between normal and disease states (Ryan and Patterson, 2002; Nicolette and Miller, 2003; Kramer and Cohen, 2004; Austen and Dohrmann, 2005; Jackson and Harrington, 2005; Lindsay, 2005; Sams-Dodd, 2005). Many of them have been targeted by target-selective leads (Simmons, 2006; Zheng et al., 2006b). Despite heavy spending and exploration of new technologies (Booth and Zemmel, 2004), fewer innovative targets have emerged (Lindsay, 2005), and it typically takes ∼8 to 20 years to derive a marketed drug against these innovative targets (Zheng et al., 2006a). Innovative targets refer to the targets with no other subtype of the same protein successfully explored before. 27

28. Example A of Introduction Low productivity of innovative targets (Lindsay, 2005) has been attributed to problems in target selection and validation (Smith, 2003; Lindsay, 2005; Sams-Dodd, 2005). A particular problem is inadequate physiological and clinical investigations (Rosenberg, 1999; Lindsay, 2005; Sams-Dodd, 2005). Drug effects are due to interactions with various sites of human physiological systems and pathways as well as its intended target, which collectively determine the success of target exploration (Zheng et al., 2006a,b). Current efforts have been focused on target-selective agents minimally interacting with other human members of the target family (Drews, 1997; Ohlstein et al., 2000). However, their possible interactions with other human proteins, pathways, and tissues have not been fully considered, leading to frequent failures in subsequent developmental stages. Therefore, a target cannot be fully validated by considering disease relevance and target selectivity alone (Lindsay, 2005; Sams-Dodd, 2005). 28

29. Example A of Introduction Integrated target and physiology-based approaches have been proposed for target identification and validation (Lindsay, 2005). Different in silico approaches have been explored for target prediction based on sequence similarity (Hopkins and Groom, 2002), structural similarity and binding-site geometric and energetic features (Hajduk et al., 2005), target physicochemicaland other characteristics detected by machine learning (Zheng et al., 2006b), and systems profiles (similarity to human proteins, pathway and tissue distribution) (Yao and Rzhetsky, 2008). We evaluated whether target prediction can be improved by combinations of these approaches, which were tested against 155 clinical trial targets (data are collected from CenterWatch Drugs in Clinical Trials Database 2008), 864 nonclinical trial research targets (Chen et al., 2002), 19 difficult targets currently discontinued in clinical trials (with clinical trial drug discontinued and no new drug entered clinical trial at the moment) (data collected from CenterWatch Drugs in Clinical Trials Database), and 65 nonpromising targets failed in large-scale HTS campaigns (Payne et al., 2007) or found nonviable in knockout studies (Mdluli and Spigelman, 2006). 29

30. Example B of Introduction Many approved and clinical-trial drugs are derived from natural products (1, 2). During the past 2 decades, the focus of drug-discovery efforts has shifted from natural products to synthetic compounds, but this shift has not led to the anticipated increase in drug productivity (3). Despite the shifted focus, nature-derived drugs still constitute a substantial percentage of recently approved drugs. For instance, 12 (26%) of the 46 molecular entities approved by the Food and Drug Administration (FDA) in 2009–2010 are nature derived (SI Appendix, Table S1). There is a renewed interest in natural products as drug-discovery sources (4). The scope of biodiversity and extinction rates (5) demands bioprospecting efforts be prioritized toward the groups of species that are likely to yield new drugs. 30

31. Example B of Introduction Clues to drug-productive species can be obtained from the species-distribution profiles of nature-derived approved and clinical-trial drugs. Although particular species yield potent bioactive compounds at higher rates than others, additional drug-like properties are important for developing these compounds into marketable drugs (6). The nature-derived approved and clinical-trial drugs are composed primarily of several dozen molecular scaffolds (7–9) rather than the numerous bioactive natural-product scaffolds (10, 11). Like other bioactive natural-product scaffolds, the nature-derived privileged drug-like scaffolds are generated by enzymes partly encoded in specific secondary-metabolite gene clusters in selected groups of species (12–14). Questions arise as to whether the privileged drug-like structures are distributed in selective species-groups rather than being scattered in the phylogenetic tree (15) and whether the distribution shows certain traceable patterns that can be explored in future bioprospecting efforts. 31

32. Example B of Introduction A large number of bioactive natural products have been identified (16, 17). Many more are likely to be discovered (17) because of their interaction with specific targets (18). A small percentage of bioactive natural products has been carried forward to derive approved (1) and clinical-trial (2, 19) drugs via direct exploration, semisynthetic modification, structural mimicking, or pharmacophore mapping. The potential for drug development of a natural product depends not only on its bioactivity but also on the drug-likeness of its structure [optimized for enhanced drug-like (6) and reduced unwanted (20–22) properties] and the susceptibility of its target (“druggability”) to drugs [324 targets are confirmed druggable in yielding approved drugs (23), and 292 targets have yielded drugs in clinical trials (24)]. The odds for finding novel drug-like natural products may be improved if one can identify new drug-productive species, particularly endangered ones, before their extinction. 32

33. Example B of Introduction Structurally diverse bioactive natural products are composed of many molecular scaffolds (16, 17). Each scaffold is generated by specific enzyme assemblies (25) encoded in the secondary-metabolite gene clusters of specific species groups (12–14, 26). Partly as a survival strategy (12), structurally diverse natural products are generated by genetic variations and repositioning (27), posttranslational modifications (28), and assembly-line regulation (28). Nonetheless, bioactive secondary metabolites of an individual scaffold typically are produced by species from a specific family (e.g., anthraquinones in Polygonaceae) (14, 29) or from a few families of a specific order (e.g., sordarins of Xylariales) (14, 30). Specifically, 14 of the 26 drug-productive scaffolds from Actinomycetales are from a unique family, six are from a few families within the order, and four are from a few families in this and a few other orders (SI Appendix, Table S2). 33

34. Example B of Introduction Natural products active against individual targets or classes of targets may be composed of multiple scaffolds, many of which are from only a few families. For instance, 53 nicotinic acetylcholine receptor ligands are reported from diverse species (16). Our analysis (SI Appendix, Table S3) showed that these ligands are clustered into 29 scaffolds; 23 of these scaffolds are from a unique family, three are from a few families within a specific order, and three are from a few orders of a specific class. Each of the five approved drugs in the group is from a specific family. Similarly, the 12 nature-derived FDA-approved kinase inhibitor drugs (1, 2) are grouped into three scaffold groups, with each scaffold derived from a few families distributed among only a few orders (SI Appendix, Table S4). 34

35. Example B of Introduction Some families such as Streptomycetaceae, Pseudonocardiaceae, and Trichocomaceae and some genera such as Acremonium and Emericellopsis are highly drug-prolific (14, 15). Compounds synthesized by a specific metabolic pathway typically are active against only a few targets (13). It thus can be hypothesized that privileged drug-like structures targeting selective druggable targets are likely to be concentrated in specific families. This hypothesis can be evaluated, and the distribution patterns of drug-productive species can be revealed by comparing the species origins of the approved and clinical-trial drugs (1, 2) with those of preclinical drugs and bioactive natural products. 35

36. Example B of Introduction We analyzed the species origins of 939 approved drugs (Table S5) (1), 369 clinical-trial drugs (Table S6) (2, 19), 119 preclinical drugs (Table S7) (31, 32), and 19,721 bioactive natural products (Table S8) with particular focus on their distribution patterns in the phylogenetic trees of the Bacteria, Viridiplantae, Fungi, and Metazoa kingdoms or superkingdoms. Nature-derived approved and clinical-trial drugs and their species origins were obtained from published reviews (1, 2, 19) and our own literature search (Table S8). Preclinical drugs are drug candidates that have entered preclinical studies such as safety, pharmacokinetics/absorption, distribution, metabolism, and excretion, active pharmaceutical ingredient preparation, and formulation (33). Following the seminal works on nature-derived drugs (1, 2), we included in our analysis biologics, natural products and their semisynthetic derivatives, mimics, and peptidomimetics. Biologics include peptides (34), and monoclonal antibodies (36). The inclusion or exclusion of biologics and RNA-based drugs had limited effect on our analysis because they primarily are of human or viral origin. For semisynthetic derivatives, mimics, and peptidomimetics, the host species of the parent natural-product leads were analyzed (1, 2). 36

37. Example B of Introduction We also evaluated four lines of evidence from (i) historical drug data, (ii) 13,548 natural products of marine species and their nonmarine counterparts, (iii) 767 medicinal plants, and (iv) 19,721 bioactive natural products to determine whether the distribution patterns of drug-productive families are different from those of bioactive natural products and if the lack of drugs outside drug-productive families is the result of under-exploration or late exploration. 37

38. Example B of Introduction The natural-product leads of drugs and bioactive natural products in this analysis were discovered mostly by conventional technologies rather than by the new technologies that are expected to identify many previously unrecognized bioactive natural products. These technologies are based on the exploration of cryptic metabolic gene clusters (via genomic mining, epigenetic modification, and proteomics) (38–40), metabolic pathway engineering (41, 42), interspecies crosstalk (40, 43, 44), and high-throughput fermentation and screening (45). Their potential contribution to discovery of new drugs is highly anticipated (40, 42, 45). The distribution patterns of the drugs discovered by these technologies may not follow those of the existing drugs derived from conventional technologies. 38

39. Any questions? Thank you!