text:
Internship|
Fellowship|
De-Coding Indian Intellectual Property Law
Data Exclusivity
Drug Regulation
Comparative Advertising
The Chancellor, Masters & Scholars of the University of Oxford & Ors. v. Rameshwari Photocopy Services & Ors. [DU Photocopying Case]
In a landmark judgment, the Division Bench of the Delhi High Court on December 9, 2016 ruled that the preparation of 'course packs' i.e. compilation of photocopies of the relevant portions of different books prescribed in the syllabus, and their distribution to the students by educational institutions does not constitute infringement of copyright in those books under the Copyright Act, 1957, as long as the inclusion of the works photocopied (irrespective of the quantity) was justified by the purpose of educational instruction. It held that such photocopying qualifies as reproduction of the work by a teacher in the course of instruction and thus does not amount to copyright infringement by virtue of Section 52(1)(i) of the Act. In effect, it held that the educational institutions do not require a license or permission from the publishers for making and distributing course packs to students if the copyrighted materials included in them are necessary for the purpose of instructional use by the teacher to the class.
The suit was instituted before the Delhi High Court in August 2012 by three of the foremost publishers of scholarly, general and reference books in all disciplines of academia, namely, the Oxford University Press, the Cambridge University Press and the Taylor & Francis Group ("Plaintiff-Publishers") for permanent injunction against infringement of copyright in their publications by the University of Delhi ("Delhi University" or "Defendant No. 2") and a photocopy shop named Rameshwari Photocopy Service ("Defendant No. 1") operating in the University under a license from it. The Plaintiff-Publishers alleged that the Defendants had been photocopying substantial excerpts from their publications that were part of the prescribed syllabus and issuing/selling unauthorized compilations of them in the form of course packs or anthologies, thereby infringing their copyright in those publications under Section 51 r/w Section 14 of the Copyright Act. They argued that Delhi University seek a license from the Indian Reprographic Rights Organization ("IRRO"), a copyright society registered under the Act, that permits only up to 15% of a copyrighted work to be reproduced (in a course pack or otherwise).
The suit came up for the first hearing before the court on August 14, 2012. The court appointed a Local Commissioner to visit the premises of Defendant No. 1 without prior notice and seize all allegedly infringing copies of the Plaintiff-Publishers' works made by it after making an inventory of the same.
Thereafter, the Defendants contested the suit by arguing, inter alia, that their actions constituted fair use of the Plaintiff-Publishers' works under sections 52(1)(i), 52(1)(a) and 52(1)(h) of the Act and therefore did not amount to copyright infringement.
For copies of the plaint filed by the Plaintiff-Publishers, the order appointing a Local Commissioner, written statements filed by the Defendants and the notes of arguments submitted, please see the Resources section below.
Also, for the text of the relevant provisions of the Copyright Act, 1957 and a copy of the entire Act, please see below.
Interim Injunction
On October 17, 2012, the Plaintiff-Publishers succeeded in obtaining an interim injunction restraining the Defendant No. 1 from making/selling these course packs. In pertinent part, the Single Judge imposed the following strictures:
"Defendant no.1 is the photocopier running its shop under licence from the defendant no. 2. The defendant no.1 has no right to compile such course packs and books/articles published by the plaintiffs and more so, when defendant no.2/University has taken a stand that that they have no intention to breach any law by making such reproductions as complained of by the plaintiff in the present suit.
The defendant no.1 is accordingly restrained from making or selling course packs and also reproducing the plaintiff?s publication or substantial portion thereof by compiling the same either in a book form or in the form of a course pack, till the final disposal of the said application."
The Delhi University preferred an appeal before the Division Bench of the court against this restraining order which, although not directed at it, recorded it to have made an alleged admission/undertaking that it would not be committing any acts that were claimed to be infringing by the Plaintiff-Publishers. However, the court dismissed the appeal on November 27, 2012, directing the University to file an application before the Single Judge to clarify the scope of the stand taken by it.
For copies of the Single Judge's order granting interim injunction and Division Bench's order dismissing the appeal, please see the Resources section below.
Impleadment of ASEAK and SPEAK as Defendants
In 2013, ASEAK (Association of Students for Equitable Access to Knowledge), an association of students of the Delhi University, approached the High Court to be impleaded as a 'necessary party' to represent the large numbers of students directly affected by the interim injunction and having a direct interest in the outcome of the suit. It stated that the course packs are the only effective means to ensure access to knowledge and is excepted from copyright infringement under Sections 52(1)(a) and 52(1)(i) of the Copyright Act. ASEAK's application was allowed and it was impleaded as Defendant No. 3 on March 1, 2013.
Similarly, SPEAK (Society for Promotion of Equitable Access to Knowledge), a society of scholars and academics from amongst varied disciplines in law and social sciences approached the High Court seeking to be made a 'necessary party'. SPEAK argued that the educational exception contained in Section 52(1)(i) of the Copyright Act ought not to be viewed as a mere exception, but a potent right in favour of students and universities. Pertinently, SPEAK pointed to some of the critical institutional issues and resource constraints around higher education in India. It referred to an empirical study where the authors had demonstrated that a number of legal and social science texts were prohibitively expensive. The latest editions of these texts were not often available in India. Rather the publishers were content with dumping old outdated editions (at lower prices) in India. As for the latest editions, they had to be imported at considerable costs, often exceeding those charged in the western markets, home to many of these profiteering publishers. SPEAK's application was also allowed and it was impleaded as Defendant No. 4 on April 12, 2013.
For copies of the impleadment applications filed by Defendants No. 3 & 4, the orders allowing their impleadment and the written statements and notes of arguments submitted by them, please see the Resources section below.
The Campaign against the Suit
A number of students, academics and civil society members came out strongly in protest against this suit, expressing their concern regarding the implications on access to knowledge and education in India. In an online petition started on Change.ORG, over 1,250 academics and authors wrote as below:
"… As authors and educators, we would like to place on record our distress at this act of the publishers, as we recognize the fact that in a country like India marked by sharp economic inequalities, it is often not possible for every student to obtain a personal copy of a book. In that situation the next best thing would have been for multiple copies of the book to be available in the library so that students are able to access these books without any difficulty. But given the constraints that libraries in India work with, they may only have a single copy of a book and in many instances, none at all. The reason we make course packs is to ensure that students have access to the most relevant portions of the book without which we would be seriously compromising their education."
More than 309 eminent writers and academicians from all over the world, in March 2013, also wrote a letter to the publishers asking them to withdraw the suit. Interestingly, 33 out of these 309 signatories had a direct association with the Plaintiff-Publishers and were authors of works, the copyright in which was allegedly infringed by Delhi University and its photocopier. The signatories included eminent scholars such as Thomas Blom Hansen, Partha Chatterjee, Ayesha Jalal, Christophe Jaffrelot, Veena Das, Pratap Bhanu Mehta, Marc Galanter and Professors Richard Falk, Arjun Appadurai, Jonathan Parry, Ramachandra Guha, Farid Esack, TN Madan, Ian Copland, Tanika Sarkar and Uma Chakravarty.
These prominent authors stated that they were more than happy for students to copy their works. And that the publishers by filing the law suit were not speaking in their name. They also noted that academic publishing was heavily subsidized through their salaries (many of them at publicly funded institutions), government funding to libraries to purchase books and the free labour of academics in peer reviews etc.
Single Bench's Judgment
On September 16, 2016, Justice Rajiv Sahai Endlaw dismissed the entire suit of the plaintiffs. He concluded that the impugned actions of the Defendants do not amount to copyright infringement, relying pertinently upon Section 52(1)(i) of the Act, which provides that any reproduction of a copyrighted work by a teacher or pupil in the course of instruction does not constitute copyright infringement.
Some of the key highlights of the decision are as below:
1. Copyright is not a natural or divine right, but only a statutory right.
"Copyright, specially in literary works, is thus not an inevitable, divine, or natural right that confers on authors the absolute ownership of their creations. It is designed rather to stimulate activity and progress in the arts for the intellectual enrichment of the public. Copyright is intended to increase and not to impede the harvest of knowledge."
2. Section 52 is to be interpreted as a narrow exception but a full-fledged defence in favour of educational institutions and students.
"[T]he rights of persons mentioned in Section 52 are to be interpreted following the same rules as the rights of a copyright owner and are not to be read narrowly or strictly or so as not to reduce the ambit of Section 51, as is the rule of interpretation of statutes in relation to provisos or exceptions. Thus, Sections 14 and 51 on the one hand and Section 52 on the other hand are to be read as any two provisions of a statute."
3. The term 'teacher' in Section 52(1)(i) is not restricted to an individual teacher but extends to educational institutions as a whole.
"There is no reason to interpret Section 52(1)(i) as providing for an individual teacher and an individual pupil and which, neither at the time of inclusion thereof in the statute nor now exists in the society….[M]erely because imparting of education by teachers today is as part of an institution as the defendant no.2 University and it is the defendant no.2 University which on behalf of its teachers is reproducing any copyrighted work by making photocopies thereof, would not mean that Section 52(1)(i) would not be applicable."
4. The word " instruction" in section 52 (1) (i) is not limited to a lecture in the classroom and thus the scope of this provision is not limited to reproduction of a work by a teacher in the course of a lecture but also includes reproduction for the purpose of making and issuing course packs.
"Had the intention of the legislature while incorporating Section 52(1)(i) been to constitute reproduction of any work by a teacher or a pupil in the course of lecture, the legislature would have in Section 52(1)(i) used the word lecture which has been defined in the Act. The word instruction thus has to necessarily mean something other than lecture.….[I]n the context of the teacher, it refers to something which a teacher tells the student to do in the course of teaching or detailed information which a teacher gives to a student or pupil to acquire knowledge of what the students or pupil has approached the teacher to learn."
5. The imparting of instruction does not begin and end in the classroom or tutorials only but extends beyond that and thus Section 52(1)(i) covers reproduction by an educational institution during the entire academic session.
"The words in the course of instruction within the meaning of Section 52(1)(i) supra would include reproduction of any work while the process of imparting instruction by the teacher and receiving instruction by the pupil continues i.e. during the entire academic session for which the pupil is under the tutelage of the teacher and that imparting and receiving of instruction is not limited to personal interface between teacher and pupil but is a process of commencing from the teacher readying herself/himself for imparting instruction, setting syllabus, prescribing text books, reading and ensuring, whether by interface in classroom/tutorials or otherwise by holding tests from time to time or clarifying doubts of students, the pupil stands instructed in what he/she has approached the teacher to learn".
6. Since the reproduction of pages from the books by each of the students, whether by way of photocopying, copying by hand or clicking photographs, for his/her private use does not amount to copyright infringement by virtue of Section 52(1)(a), the photocopying of the same by the university for the benefit of the students due to certain resource constraints cannot be said to be infringement when the result/effect of both is the same.
"I have wondered that if the action of each of the students of having the book issued from the library of defendant No.2 University and copying pages thereof, whether by hand or by photocopy, is not infringement, whether the action of the defendant no.2 University impugned in this suit, guided by the reason of limited number of each book available in its library, the limited number of days of the academic session, large number of students requiring the said book, the fear of the costly precious books being damaged on being subjected to repeated photocopying, can be said to be infringement; particularly when the result/effect of both actions is the same… The answer, according to me, has to be in the negative."
7. Once it is found that the making of course packs by a university does not constitute infringement, it is of no consequence whether the university is doing so by use of a machine installed inside its library or outside, whether it owns that machine or not, whether it allows photocopies to be made by the students themselves or with the assistance of another person and whether such person is its employee or an independent contractor. Thus, the Delhi University's engagement of Defendant No. 1 for making of course packs does not convert its action, which is otherwise held to be not infringement, to infringement.
"In my view, there is no difference in the two situations i.e. whether the photocopying machine is installed within the library or is installed outside the library. In my view it also does not make any difference whether the respondent no.2 University itself purchases the photocopy machine and / or allows the students to photocopy themselves or employs a person for doing photocopy. Once such a action is held to be not offending any provisions of the Copyright Act, merely because the photocopying is done not by the person desirous thereof himself but with the assistance of another human being, would not make the act offending. It matters not whether such person is an employee of the defendant no.2 University or the defendant no.2 University avails the services of a contractor. The position of the defendant no.1 in the present case is found to be that of a contractor to whom the defendant no.2 University has outsourced its work of providing photocopying service for its students. For this reason, it matters not whether the photocopying machine is allowed by the defendant no.2 University to be kept within the library or at some other place outside the library… I thus conclude that the engagement as aforesaid by the defendant No.2 University of defendant No.1 does not convert the action of defendant No.2 University as held hereinabove to be not amounting to infringement of copyright in books, to infringement."
8. IRRO doesn't even come into play since the impugned acts of the defendants were covered under Section 52(1)(i) of the Act, and thus there is no need to pay any licensing fees to IRRO.
"[T]he question of issuing any such direction would arise only upon finding that what the defendant No.2 University is doing is not covered by Section 52 of the Act and which would make it an infringement of the copyright and to avoid which it can go before IRRO."
For a copy of the judgment, please see the Resources section below.
Appeal to the Division Bench
On October 5, 2016, the Plaintiff-Publishers filed an appeal against this decision before the Division Bench of the Delhi High Court. The court admitted the appeal on October 6 but refused to grant an interim injunction against Defendant No. 1 that the Plaintiff-Publishers prayed for. However, it directed the Defendants to maintain a record of photocopied course packs sold. The appeal is now scheduled for hearing on November 29, 2016.
For copies of the appeal and the order admitting the appeal, please see the Resources section below.
Intervention by IRRO and Publishers' Associations API and FIP
On November 5, 2016, intervention applications were filed by the Indian Reprographic Rights Organisation (IRRO) and two publishers' associations, namely, the Association of Publishers in India (API) and the Federation of Indian Publishers (FIP). The applications were allowed by Justice Pradeep Nandrajog and Justice Yogesh Khanna of the Delhi High Court on November 8, 2016.
For copies of the intervention applications and the order allowing them, please see the Resources section below.
Division Bench's Judgment
On December 9, 2016, the Division Bench, comprising Justices Pradeep Nandrajog and Yogesh Khanna, decided the appeal refusing to grant an interim injunction to the plaintiff-publishers and emphatically ruling that making and distribution of course packs to students does not amount to copyright infringement as long as the inclusion of the works photocopied (irrespective of the quantity) was justified by the purpose of educational instruction. Accordingly, it remanded the suit to the single bench for a fact specific determination on whether the copyrighted materials included in the course packs in this case were necessary for the purpose of instructional use by the teacher to the class. Until then, the course packs could continue to be made and supplied to the students.
The key highlights of the judgment, penned by Justice Nandrajog, are as follows:
A. Section 52(1)(i) and Fairness
The court began by noting that since Section 52(1)(i) does not have an express fair use limitation, only the general principle of fair use can be read into it. It rejected the application of the four factors used for determination of fair use in other jurisdictions, especially the US, to this clause. It laudably noted that fairness of the use under this clause is to be determined only by the purpose of the use i.e. education and not by its quantitative or quantitative extent. It also held that the fair dealing standard has been prescribed only in clause (a) of Section 52(1) and thus cannot be imported into its other clauses including clause (i). The relevant paragraphs of the judgment read as follows:
"In the context of teaching and use of copyrighted material, the fairness in the use can be determined on the touchstone of 'extent justified by the purpose'. In other words, the utilization of the copyrighted work would be a fair use to the extent justified for purpose of education. It would have no concern with the extent of the material used, both qualitative or quantitative. The reason being, 'to utilize' means to make or render useful. To put it differently, so much of the copyrighted work can be fairly used which is necessary to effectuate the purpose of the use i.e. make the learner understand what is intended to be understood…Thus, we reject the arguments by learned counsel for the appellants that the four factors on which fair use is determined in jurisdictions abroad RFA(OS) No.81/2016 Page 36 of 58 would guide fair use of copyrighted material during course of instruction. The qualitative and quantitative test which is one of the four tests would not apply to clause (i)… Further, while the Court in B.D. Bhandari's case (supra) did hold that a fair dealing standard was to be read into all clauses of Section 52 of the Copyright Act, 1957, as held hereinabove, a fair dealing standard has only been provided in clause (a) of sub-Section (1) and not in the other clauses of sub-Section (1) of Section 52, and therefore, cannot be read into the other clauses." [paragraphs 33, 35 & 72]
Thus, the Division Bench's judgment clearly held that in order to determine whether the use of a copyrighted work is permitted under Section 52(1)(i), it is only to be seen whether the work used was necessary for achieving the purpose of educational instruction, irrespective of whether only a certain percentage of the work or the entire work is used.
B. Impact of Course Packs on Market of Publishers' Works
The court rejected the argument of the publishers that unauthorized making and distribution of course packs has caused or is likely to cause an adverse impact on the market of their books. It observed that a student is not a potential customer of the multiple books used in the course packs and in the absence of course packs he/she would refer to these books in the library. Interestingly, it further noted that instead, the improved education could very well lead to an expansion of the market for these books.
C. Meaning of 'Reproduction', 'Teacher' and "Pupil'
The court then proceeded to the interpretation of Section 52(1)(i), which formed the core issue in the case. Relying upon Section 13(2) of the General Clauses Act, 1897, it held that the word 'reproduction', meaning 'making a copy of', includes its plural as well i.e. making more than one copy of the original or photocopying. Similarly, it held that the words 'teacher' and 'student' also include 'teachers' and 'students' and thus concluded that making of multiple copies of a work by teachers or students is contemplated under this provision.
D. Meaning of 'In the Course of Instruction'
Next, the court dealt with the question of interpretation of the phrase 'in the course of instruction' that was highly contested between the parties. It accepted the argument of the respondents that irrespective of whether the word 'course' is read as a verb or a noun, the phrase 'in the course of instruction' would mean the entire process or programme of education in a semester and not the process of teaching in the classroom alone. The court acknowledged that teaching does not involve simple lecturing by the teacher and taking of notes by the students in the classroom but an interactive discussion based on the pre-reads etc. by the students that is regulated by the teacher. It further placed reliance on the judgment of the High Court of New Zealand in Longman Group Ltd. v. Carrington Technical Institute Board of Governors[(1991) 2 NZLR 574], wherein the words 'in the course of instruction' in Section 21(4) of the New Zealand Copyright Act, 1962 were interpreted to include "anything in the process of instruction with the process commencing at a time earlier than the time of instruction, at least for a teacher, and ending at a time later, at least for a student. So long as the copying forms part of and arises out of the course of instruction it would normally be in the course of instruction". The court found this to be the only logical interpretation of this phrase and termed the judgment as an authority on this point due to the similarity in the language of Section 52(1)(i) of the Indian Copyright Act and Section 21(4) of the New Zealand Copyright Act. It thus concluded that the phrase 'in the course of instruction' included within its ambit preparation and distribution of course packs to students.
E. Distribution of Course Packs: Publication?
The Division Bench disagreed with the view taken by the Single Bench that distribution of course packs to 'students' does not amount to publication by opining that "[p]ublication need not be for the benefit of or available to or meant for reading by all the members of the community" and that "[a] targeted audience would also be a public". However, it rejected the argument that the issue of course packs in this case amounted to publication on the basis that publication requires an element of profit which was absent in this case.
F. Use of an Intermediary/Agency for Making of Course Packs
The court further dealt with the argument of the publishers that reproduction of works under Section 52(1)(i) can be made only by a teacher or a pupil and not by an intermediary i.e. the photocopier. It rejected this argument by rightly observing that "common sense tells us that neither the teacher nor the pupils are expected to purchase photocopiers and photocopy the literary work to be used during course of instruction in the class room". It further noted that the photocopier in this case was not making any profit apart from the usual profit it would be making by simply photocopying material. Accordingly, it found the argument against use of an agency to be irrelevant.
G. Making of Course Packs by Educational Institutions
The court also rejected the argument of the publishers that Section 52(1)(i) was not applicable to educational institutions but only to an individual teacher. Unlike the Single Judge who clearly held that the benefit of this provision was also available to educational institutions as well and thus to DU, the Division Bench did not even deal with this interpretive question. It simply refused to find any institutional sanction for photocopying in this case for DU's role is limited to laying down the course curriculum and it is the individual teacher/teachers only who select the copyrighted works to be included as reading materials in the course packs. In short, it found that the course packs in this case were made and distributed by the teachers and not DU and thus clearly fell within the ambit of Section 52(1)(i).
H. Int'l Obligations and Foreign Decisions
The argument of the publishers based upon Article 13 of the TRIPS Agreement and Article 9 of the Berne Convention was dismissed by the court noting that "the contents thereof are merely directory and have enough leeway for the signatory countries to enact the copyright law in their municipal jurisdiction concerning use of copyrighted works for purposes of dissemination of knowledge". The court also found the decisions of the US, Canada and UK courts, relied upon by the parties, to be of no relevance in the Indian context because the concept of fair use and fair dealing is different in those countries.
I. IRRO Licensing
The court did not even deal with the fallacious argument made by the publishers that the only way to balance the interests of the students and academic publishers is to direct the universities to obtain licenses from IRRO for reproducing the relevant extracts from their books.
J. Directions
The Division Bench therefore dismissed the appeal concluding that Section 52(1)(i) permits unauthorised preparation and distribution of course packs to students, if the works included therein are necessary for effectuating the purpose of the course packs i.e. educational instruction. It thus remanded the suit to the trial court for factual determination of whether the works included in the course packs in this case were necessary for achieving the purpose of education instruction or not. It also allowed the publishers to amend their plaint and plead the fact of cover to cover photocopying of eight books that found mention in the Local Commissioner's report and directed the trial court to make a factual determination on permissibility of these copies as well. The court refused to grant an interim injunction in favour of the publishers and only directed the photocopier to maintain a record of the course packs photocopied and supplied to students and file the same in the suit every six months.
Open Letter by Oxford University Students and Others Urging OUP to not Appeal to the Supreme Court
On January 23, 2017, a group of 122 students, alumni and academics from Oxford University (OU) sent an open letter to the Delegates of the Oxford University Press (OUP), urging them to refrain from filing an appeal to the Supreme Court against the Division Bench's judgment.
Refusal of Impleadment/Intervention of IRRO & Publishers' Associations API & FIP in Remanded Proceedings
In January 2017, IRRO and publishers' associations, FIP and API, who had intervened in the appeal before the Division Bench, filed applications for intervention and impleadment (respectively) in the remanded proceedings before the Single Bench as well. However, Justice Endlaw (Single Judge), in an order dated January 20, 2017, refused to grant these applications. He noted that the Division Bench had remanded the suit only for a factual determination as to the purpose of inclusion of the copyrighted works in the course packs and no party except the Plaintiff-publishers had a say in it. The applicants stated that they will seek clarification from the Division Bench on the remanded issues within a period of four weeks and requested the Bench to hold over the applications till then. Justice Endlaw accordingly listed the matter on February 28, 2017 and also granted a last opportunity to the Plaintiff-publishers to amend their plaint (as allowed by the Division Bench) within four weeks, so as to the plead the fact of full text copying of books.
Withdrawal of the Suit by Plaintiff-Publishers
On March 9, 2017, the plaintiff-publishers surprisingly withdrew the suit. The public statement released by them on withdrawal read as follows:
"We have taken a considered decision not to pursue the Delhi University Photocopy shop case further in the courts and will today be filing an application with the Delhi High Court to withdraw as plaintiffs. In addition, we will not be submitting an appeal to the Supreme Court of India, following the Delhi High Court Division Bench appeal decision of 09 December, 2016.
We continue to stand by our principles stated throughout this case. We support and seek to enable equitable access to knowledge for students and we understand and endorse the important role that course packs play in the education of students. We support our authors in helping them produce materials of the highest standard and we maintain that copyright law plays an important part in balancing the interests of those creating, curating, and disseminating learning materials with those requiring access to them.
We look forward to working even more closely with academic institutions, teachers and students to understand and address their needs, while also ensuring that all those who contribute to and improve India's education system—including authors and publishers—continue to do so for the long term."
Appeal to the Supreme Court
In April 2017, IRRO filed a Special Leave Petition before the Supreme Court challenging the judgment passed by the Division Bench on December 9, 2016. However, the bench comprising Justices Ranjan Gogoi and Navin Sinha refused to admit the appeal, noting that the special leave petition (SLP) to appeal by IRRO was not even maintainable as the original suit filed before the Delhi High Court had been withdrawn by the plaintiff-publishers and the IRRO was merely an intervenor in the proceedings before the High Court.
Relevant Provisions of the Copyright Act, 1957
Section 52 – Certain acts not to be infringement of copyright
(1) The following acts shall not constitute an infringement of copyright, namely:
(a) a fair dealing with any work, not being a computer programme, for the purposes of-—
(i) private or personal use, including research;
(ii) criticism or review, whether of that work or of any other work;
(iii) the reporting of current events and current affairs, including the reporting of a lecture
delivered in public.
Explanation.—The storing of any work in any electronic medium for the purposes mentioned in this clause, including the incidental storage of any computer programme which is not itself an infringing copy for the said purposes, shall not constitute infringement of copyright.
(b)…(g)
(h) the publication in a collection, mainly composed of non-copyright matter, bona fide intended for instructional use, and so described in the title and in any advertisement issued by or on behalf of the publisher, of short passages from published literary or dramatic works, not themselves published for such use in which copyright subsists:
Provided that not more than two such passages from works by the same author are published by the same publisher during any period of five years.
Explanation.—In the case of a work of joint authorship, references in this clause to passages from works shall include references to passages from works by any one or more of the authors of those passages or by any one or more of those authors in collaboration with any other person.
(i) the reproduction of any work—
(i) by a teacher or a pupil in the course of instruction; or
(ii) as part of the questions to be answered in an examination; or
(iii) in answers to such questions.
(j)…(zc)
A. CS (OS) 2439 of 2012
Plaint filed on behalf of the Plaintiff-Publishers
Written Statement filed on behalf of Rameshwari Photocopy Service (Defendant No 1)
Written Statement filed on behalf of Delhi University (Defendant No. 2)
Written Statement filed on behalf of ASEAK (Defendant No. 3)
Written Statement filed on behalf of SPEAK (Defendant No. 4)
Impleadment Applications
Application on behalf of ASEAK seeking impleadment as Defendant No. 3
Application on behalf of SPEAK seeking impleadment as Defendant No. 4
Note on Arguments
Submissions on behalf of the Plaintiff-Publishers
Submissions on behalf of ASEAK (Defendant No. 3)
Submissions on behalf of SPEAK (Defendant No. 4)
Judgments and Orders
Order dated August 14, 2012 appointing a Local Commissioner
Order dated October 17, 2012 granting interim injunction
Order dated November 27, 2012 dismissing the appeal filed by Delhi University (Defendant No. 2)
Order dated March 1, 2013 allowing impleadment of ASEAK (Defendant No. 3)
Order dated April 12, 2013 allowing impleadment of SPEAK (Defendant No. 4)
Judgment dated September 16, 2016
Order dated January 20, 2017 refusing intervention of IRRO, API and FIP in remanded suit proceedings
B. RFA (OS) 81 of 2016
Appeal filed by the Plaintiff-Publishers
Note on Rejoinder filed by the Plaintiff-Publishers: Part I, Part II, Part III, Part IV
Intervention Applications
Intervention application by Indian Reprographic Rights Organisation (IRRO)
Intervention application by Association of Publishers in India (API)
Intervention application by Federation of Indian Publishers (FIP)
Order dated October 6, 2016 admitting the appeal
Order dated November 8, 2016 allowing intervention applications of IRRO, API and FIP
Judgment dated December 9, 2016
C. Other Resources
a. Legislations
Copyright Act, 1957
b. Articles/Blog Posts
i. SpicyIP
In favour of DU
Cropping Copyright: Education is not an Exception!
A Tantalising Copyright Offer: Lessons from Canada and New Zealand
Breaking News: IRRO Registration Refused!
Legality of Digital Course Packs: The USA Experience
The S(war)tz Legacy and "Open" Lessons for India
President of Costa Rica Passes Executive Order Allowing Photocopying of Academic Materials. India, it's time to wake up
5 Reasons Why Course Packs are Legal in India
Dispelling the Myth that the DU Photocopy Judgment Permits Photocopying of Entire Books
Counterview
Counterview: The outcome of the DU photocopy case isn't necessarily good news for higher academia in India
Counterview – The DU Photocopy case – How wide should educational use exceptions be in the age of photocopier machines?
Does the DU Photocopy Judgment Place Any Limits on Photocopying?
ii. Other
DU Photocopy Case: What Happened and Why It's Important
Simply Put: What a Photocopy Shop's HC Victory over Publishers Means for Copyright
The Information Revolution Will Be Photocopied
Profit and loss: Is photocopying chapters of educational books legal?
Copyright as Exception
Copy-wrongs and the Invisible Subsidy
Copy This
A Blow for the Right to Knowledge
Delhi High Court Strikes a Fine Balance between the Right to Copy and Copyright
The Radical Significance of the DU Photocopy case for Global Copyright
Why Students Need the Right to Copy
Shamnad Basheer Responds
Of Gandhi and a Godfatherly Copyright Offer
Of Gandhi and a Godfatherly Copyright Offer- Part 2
Exceptions and Limitations in the Indian Copyright Law for Education: An Assessment
Exhausting Copyrights and Promoting Access to Education: An Empirical Take
Photocopying Courts India Campus Controversy
Publishers vs Students
Shortcut to Scholarship
The Right to Copy
Reading it Wrong
Media May Have Misjudged Copyright Verdict
c. Foreign Judgments
Alberta (Education) v. Canadian Copyright Licensing Agency (Access Copyright), [2012] 2 SCR 345
CCH Canadian Ltd. v. Law Society of Upper Canada, [2004] 1 SCR 339
Longman Group Ltd. v. Carrington Technical Institute Board of Governors, (1991) 2 NZLR 574
Princeton University Press v. Michigan Document Services Inc., 99 F.3d 1381 (6th Cir. 1996)
Cambridge University Press et al. v. Carl V. Patton et al. (Becker), 769 F.3d 1232 (11th Cir. Ga. 2014)
Cambridge University Press et al. v. Mark P. Becker et al., 863 F. Supp. 2d 1190 (N.D. Ga. 2012)
The Williams & Wilkins Company v. The United States, 487 F.2d 1345 (Ct. Cl. 1973)
D. Fun Stuff
Copyright jingle – Pay Up!
Corporate Counsel/Sr. Corporate Counsel, India-GSP
Legal Analyst in TRIPS and IP Group of WTO's IP, Government Procurement & Competition Division
Intellectual Property, Government Procurement and Competition Division, WTO
ARCIALA, SMU (School of Law)
View All Jobs Post a job
SpicyIP Events: CUSAT's Workshop on Research Methods in IPRs [Kochi, Feb 28 & 29]
Conference Hall, IUCIPRS, CUSAT, Kochi Feb 28, '20 - Feb 29, '20
SpicyIP Events: Workshop on Access to Medicines, TRIPS and Patents in the Developing World [Dec 17-21; Mumbai]
Tata Institute of Social Sciences (TISS), Deonar, Mumbai Dec 17, '19 - Dec 21, '19
SpicyIP Events: CUSAT's 7th Annual 'Rethinking Intellectual Property Rights' Workshop 2020 [Kochi, April 3 – 5, 2020]
Conference Hall, IUCIPRS, CUSAT, Kochi Apr 3, '20 - Apr 5, '20
Should viva voce be a part of the patent agent exam?
Yes, with current 20% weightage
Yes, but only with 10% weightage
Leading IP Academics Fired
This protest petition against unfair dismissals of Prof. N. S. Gopalakrishnan, Ministry of Human Resource Development (MHRD) Chair Professor at Cochin University of Science and Technology (CUSAT) and Prof. Yogesh Pai, MHRD Chair Professor at National Law University at Jodhpur, is now closed.
It was posted on SpicyIP blog on August 28, 2013 by Prof. Shamnad Basheer. Link to petition here: http://spicyipindia.blogspot.in/2013/08/leading-ip-academics-fired-protest.html
Whose Dream Was It Anyway? Plagiarism and Martin… by Balaji Subramanian
'Chhapaak' Credits Conundrum: Does Every… by Pankhuri Agarwal
Article 300A of the Constitution: A constitutional… by Prashant Reddy
Dealing with the cost of cancer treatment in India:… by Prashant Reddy
Looking at the Ferid Allani Order on Software Patents by Swaraj Paul Barooah
God, Sex and Truth – RGV Film in Copyright Row by Divij Joshi
LawStreetIndia IP Headlines
(About this segment)
HC: Denies restraint on copyright in Ayurvedic hair oil's artistic label; Cites CLB order
HC: Additional evidence can't be filed once final hearing date fixed by Controller
HC: Computer related inventions demonstrating 'technical effect' or 'technical contribution' patentable
HC: Non-functional features of shape of goods capable of protection under trade mark law
HC: Dismisses plea for interim injunction against former franchise; Cites different trade dress
HC: Calls upon TM Registry to resolve procedural glitches in trademark prosecution
HC: Quashes order granting stay against use of trade name / trade mark 'TOASHA'
HC: Vacates interim injunction restraining infringement and passing off w.r.t. TM 'Yum Yum'
HC: Denies restraint on infringement of trademark; Cites failure to prove prior use
HC: Sets aside FIR; Copyright infringement a 'non-cognizable offence', relies on SC rulings
said Well said
'Whose Dream Was It Anyway? Plagiarism and...'
Advocate Suman kumar said I have certain doubts on which I want your indulgence. 1.Here market is not a...
'Why Such Small Pittance For Our Music...'
Melanie said One benefit of compulsory licensing that you're missing is the requirement for recording artists to...
said Thank you for doing this exercise. Really appreciate the effort.
'A Look Back at India's Top IP...'
Prabhakar said The Granted Patent No. was US5401504A
'SpicyIP Fellowship 2017-18: The Turmeric Battle'
SpicyIP in the Media
Bloggers Drive Indian IPR Agenda | rediff.com | December 31, 2007
Who Owns Our Laws? | thedailystar.net | January 14, 2020
IP News & Blogs
EP Law Patent Blog
Intellepedia
IP Watch
IP Watchdog
IPRMENTLAW
Worldwide Updates on IP Events
Written Description
Site maintained by Anant Shrivastava


text:
Oba of Benin is NOT Dead - Benin Traditional Council
Posted in: news , nigeria , traditional values
Earlier today, viral reports claimed that his Royal Majesty, Omo n'Oba n'Edo Uku Akpolokpolo Erediauwa, the Oba of Benin, 92, had passed on after been on the throne for 36 years. The Benin Traditional Council has now spoken out about the speculation, which they say has been on for over six months and lacked truth.
The Secretary to the council, Mr. Frank Irabor, explained that it was the responsibility of the council to issue a formal statement, if such a development did occur.
"They have been peddling that rumour for more than a year now, because the Oba has not been coming out.
"If there is anything like that, there is usually a statement from the palace or from the Benin Traditional Council."
"The fact that he has not been coming out, even when the President came last week, does not mean that there is anything like that."
"I don't bother about rumours. I believe in getting information from the authentic source. For more than six months, they have been carrying the rumour."
Although the spokesperson did not specify whether or not the Oba was hale and hearty, he said that inability of the President Jonathan to see the monarch, when he visited the palace, did not give credence to his rumoured death.
Kate Upton Channels Marilyn Monroe In Topless Sexy...
Unemployed Mom Says She's Powerball Jackpot Winner
Kate Brown Becomes Oregon Gov as John Kitzhaber Re...
Is This Don Jazzy's Girlfriend? Says, 'I Swear Dey...
Woman Admits Suffocating Her Newborns, Then Storin...
Bigamist Jailed After First Wife Finds Photos of S...
Nick Gordon Breaks Silence on Bobbi Kristina - Cal...
Happy Valentine's Day - Jimmy Fallon Reads #WhyIm...
Amanda Knox Engaged to Middle School Friend - With...
NYT Writer David Carr Dies at 58 - Tributes and Qu...
Beckyonce - 'Single Loser : Put A Beck On It' Mash...
Drake Drops New Album - If You're Reading This It'...
North West Cries So Much, Kim Kardashian Has To Ta...
Controversy as Facebook Deletes Photo of Mothers B...
If Your Friend's Partner is Cheating - To Tell Or ...
Valentine's Day 101 - How To Have The Perfect Vale...
Be My Val: 5 Craziest Valentine's Day Gift Ideas T...
Rapist Assaults Woman at Knife-Point Forcing Boyfr...
Couple Love - Vincent Enyema Shares Throwback Pict...
See the 9 Most Expensive Escorts Around The World
What I Know About Love and Valentine's Day

redpajama_set_name: RedPajamaCommonCrawl


Search Results - Found 13 results for grammar.
Grammar for the rest of us.
English words with examples how to properly use them, useful ESL practice for those who are willing to learn English.
Learn English through examples and real life dialogue.
Let's Just Be Clear is a blog about the English language—modern written American English, more specifically.
Visit it frequently to learn how to fix common errors, follow modern grammar rules, capture the attention of online readers, and improve your business communication.
Blog of a self-confessed nerd, pointing out random observations in pop culture and society.
Useful information to help your writing come alive, make your words leap off the page and dance around with glee.


Early in 1994, I read an interesting magazine article that touched a chord in me. In response, I decided to seek private therapy to specifically work on how the violent childhood sexual abuse I'd experienced might still be affecting my every day life in ways I wasn't recognizing.
The article was written by a woman who had read an article written by a woman who... it's complicated. I'll start at the beginning.
A woman learned that an unusual quirk of hers was actually quite common and shared by many sexually abused children: she had to keep her feet - at least her toes - out from under the covers at night, no matter how cold it was.
She wondered, if the CSA was affecting her in that sub-conscious way, what other behaviors and feelings was she experiencing, which she thought were difficult but normal or just part of her personality, but were actually from issues she could (perhaps should) work on in therapy?
Counseling helped her greatly, as she dealt with long buried traumas that were still affecting her negatively without her even realizing it. She wrote and published a story about how the simple realization of how she had to keep her toes out led to a much more peaceful and happy life.
Another woman read her story, and realized she ALSO had to keep her feet out from under the covers, no matter how cold it got. She had also been sexually abused, and so began to wonder in the same way; she also went to counseling and unexpectedly found help and healing.
This woman wrote a magazine article about how she had read a story about having to keep toes out from under the covers, her own powerful realization and the positive changes in her life.
A third woman read the magazine article about the story, and guess what? She also had that quirk of "gotta keep my toes out, no matter what!" The story resounded for her as well, and she wrote a magazine article about how reading a magazine article about a story had also led her to seek counseling... see where I'm going with this?!!!
The article I read was written by another woman, who had read an article about an article about an article about a story about having a quirk, which I ALSO shared.
I felt I was in an emotionally stable place in my life, and if ever I was going to explore these highly emotional issues in depth, it should be then. I was ready and willing to truly face and work on my past (and present), and the counseling brought me life-long and life-changing differences.
When my marriage ended in 1995 and my ex abandoned us, I was dealing with the still-new effects of a brain and spinal injury as well. I survived it all (at least in part) because of this eye-opening therapy.
One immediate change was I started NOT having nightmares. I thought it was normal to be terrified every single night by dreams about being killed, about my children being kidnapped and/or killed, about screaming and screaming and crying out for help and no one being able to hear me.
I thought they were normal! You know, the same way that when my children were at someone else's house, even though I knew they were perfectly safe, I'd be sick to my stomach with worry, and sleepless and shaking with anxiety… normal for any parent, right?!
So here is MY story about the article about the article about the article about a story about a quirk that made such an impact on me, and led me to a better life.
I still sleep with a leg or my feet – at the very least, my toes – out from under the covers (no reason not to). However, many aspects of my behavior, both the destructive and damaging as well as just plain weird, have changed for the better. I'm still a work in progress, but I'm on my way!
Wow! This is shocking. I am a sexual abuse survivor. I spent most of my life with my feet outside the covers, but never ever thought about the fact that somewhere along the line I switched to having my feet under the covers. I bet the switch went along with all the therapy I had, and the healing of those issues. I never, ever connected the two issues. Another thing - that I was aware of - is that all my life I could never sleep on my back, but the last several years I love to sleep on my back. There are lots of other things too that changed as healing took place.
I am moved by your story and your bravery. I am also compelled to tell you how eloquently you wrote the story so I understood. Not having been through the type of trauma you faced, all I can do is empathize. I do know that at our age, those childhood things come out in very weird ways... so glad that you are facing the demons head on. Your weight loss journey will be strengthened in the knowledge that some of what you have been swallowing is not food but pain.
I think all of life can be a lifelong healing journey. Congragulations on keeping on working on those issues, even later in life. It's what really makes life living- all these lessons we learn. Sounds like you do lot's of living, lot's of learning. Here's to the lessons we'll find on spark.


text:
Metamorphoses: states of bodily transformation
Elizabeth Hallam (University of Oxford)
Tamara Kohn (University of Melbourne)
Napier 209
Metamorphoses: states of bodily transformation. Panel P16 at conference Shifting States.
This panel explores metamorphoses, asking how human bodies are undergoing transformations in relation to other animals, plants, microorganisms and machines within a range of environments. It asks too how such transformations are caught up in state systems and devices.
Taking inspiration from Kafka, in whose 1915 short story 'Metamorphosis' the central character transforms from human to gigantic insect, and whose writing elsewhere critically examines effects of the state, especially of bureaucracies, this panel explores states of bodily transformation in contemporary life. In what ways are human bodies undergoing transformations in relation to other animals, plants, microorganisms and machines within a range of environments? Furthermore, how are such transformations enabled or impeded by state systems and devices? Disrupting distinctions between human and non-human, bodily metamorphoses happen across the life course, before birth and after death. They are diverse and involve, for instance, developments in biomedical technologies, the design of smart materials, food production, recycling and robotics. How are such transformations currently experienced and communicated through, for example, words and visual images? 2000 years after the death of Ovid - whose epic poem 'Metamorphoses' probes the intensities of love and violence while charting the creation of the world - we ask how metamorphoses are now brought into being, and variously desired, produced, endured or inflicted. How are power relations revealed and critiqued through these transformations, and what are their subjective, social and economic implications? The panel seeks to explore these dynamic processes, and asks how anthropologists can most effectively analyze and represent them. We invite papers from any field of anthropology to explore bodily transformations as broadly as possible, and encourage presentations that may incorporate text, film, drawing, sound and photography.
Metamorphoses: texts, materials, images
'Snapping up' and speaking out on prison metamorphosis
How the da Vinci robot transforms bodies
Transforming and misrepresenting the driver's body
Implantable medical devices and indigenous Australian bodies
Molecular metamorphoses: the half-healths produced by gene therapy
The god within: zoomorphic healing and experiences on the east coast of Sri Lanka


text:
For Giving Tuesday, help lift indigenous artisans out of poverty.
Gavin Cepelak
Chief of Staff, Executive Vice President
Gavin Cepelak is the chief of staff and executive vice president at Pyxera Global. Gavin has experience in team leadership, client management, and implementing corporate leadership, CSR, and business development programs in Asia and Sub-Saharan and North Africa. He has worked at Pyxera Global since 2009 on program design, management, business development, and played a lead role in managing and building the Global Pro Bono practice.
Prior to working at Pyxera Global, he was a United States Peace Corps volunteer assisting small businesses in Morocco and a business development manager and World Bank liaison at the Australian Trade Commission, where he assisted Australian firms to win development contracts and establish partnerships with US-based prime contractors. Gavin has worked or lived extensively in several countries including Australia, the Philippines, Thailand, Singapore, Morocco, South Africa, Kenya, Sri Lanka, China, and India.
Solving the world's most pressing challenges, one community at a time.
Linkedin Facebook Instagram Twitter
Sign up to be the first to receive the latest news and updates from Pyxera Global.
Copyright © 2023 Pyxera Global. All Rights Reserved. | Terms & Conditions | Privacy Policy
Pyxera Global is a federally registered trademark of Pyxera Global, Inc. The Pyxera Global logo is the subject of a US trademark application owned by Pyxera Global, Inc.
We use cookies on our website to enable functionality and provide you the most relevant experience. By clicking "Accept All", you consent to the use of all cookies. You may visit "Cookie Settings" to provide a controlled consent.
_ga_PEZSF9ST5J 2 years This cookie is installed by Google Analytics.


text:
bims-camemi Biomed News
on Mitochondrial metabolism in cancer
twenty papers selected by
Christian Frezza
University of Cambridge, MRC Cancer Unit
In Vivo Evidence for Serine Biosynthesis-Defined Sensitivity of Lung Metastasis, but Not of Primary Breast Tumors, to mTORC1 Inhibition.
Regulatory Roles of PINK1-Parkin and AMPK in Ubiquitin-Dependent Skeletal Muscle Mitophagy.
Revisiting the warburg effect: historical dogma versus current understanding.
Mitochondrial Threonyl-tRNA Synthetase TARS2 Is Required for Threonine-Sensitive mTORC1 Activation.
Alterations in Inter-organelle Crosstalk and Ca2+ Signaling through Mitochondria during Proteotoxic Stresses.
Intercellular Transmission of Hepatic ER Stress in Obesity Disrupts Systemic Metabolism.
Direct genome editing of patient-derived xenografts using CRISPR-Cas9 enables rapid in vivo functional genomics.
Miro1-mediated mitochondrial positioning supports subcellular redox status.
PDA Got SERious Nerves.
Cathepsin B is an executioner of ferroptosis.
Organelle-specific mechanisms of drug-induced autophagy-dependent cell death.
Cancer-secreted miRNAs regulate amino-acid-induced mTORC1 signaling and fibroblast protein synthesis.
Metabolic Reprogramming-A New Era How to Prevent and Treat Graft Versus Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation Has Begun.
Structure and allosteric regulation of human NAD-dependent isocitrate dehydrogenase.
The Metabolic Importance of the Overlooked Asparaginase II Pathway.
The pivotal role of MicroRNAs in glucose metabolism in cancer.
Lactate as a new second messenger shaping intracellular Mg2+ dynamics and bioenergetics.
A stress-induced tyrosine-tRNA depletion response mediates codon-based translational repression and growth suppression.
Aldolase is a sensor for both low and high glucose, linking to AMPK and mTORC1.
Exosome-derived microRNAs improve cardiac function.
Mol Cell. 2020 Dec 15. pii: S1097-2765(20)30827-3. [Epub ahead of print]
Rinaldi G, Pranzini E, Van Elsen J, Broekaert D, Funk CM, Planque M, Doglioni G, Altea-Manzano P, Rossi M, Geldhof V, Teoh ST, Ross C, Hunter KW, Lunt SY, Grünewald TGP, Fendt SM.
In tumors, nutrient availability and metabolism are known to be important modulators of growth signaling. However, it remains elusive whether cancer cells that are growing out in the metastatic niche rely on the same nutrients and metabolic pathways to activate growth signaling as cancer cells within the primary tumor. We discovered that breast-cancer-derived lung metastases, but not the corresponding primary breast tumors, use the serine biosynthesis pathway to support mTORC1 growth signaling. Mechanistically, pyruvate uptake through Mct2 supported mTORC1 signaling by fueling serine biosynthesis-derived α-ketoglutarate production in breast-cancer-derived lung metastases. Consequently, expression of the serine biosynthesis enzyme PHGDH was required for sensitivity to the mTORC1 inhibitor rapamycin in breast-cancer-derived lung tumors, but not in primary breast tumors. In summary, we provide in vivo evidence that the metabolic and nutrient requirements to activate growth signaling differ between the lung metastatic niche and the primary breast cancer site.
Keywords: MCT2; PHGDH; breast cancer; lung environment; mTORC1; metastasis formation; pyruvate; serine biosynthesis; α-ketoglutarate
DOI: https://doi.org/10.1016/j.molcel.2020.11.027
Front Physiol. 2020 ;11 608474
Seabright AP, Lai YC.
The selective removal of damaged mitochondria, also known as mitophagy, is an important mechanism that regulates mitochondrial quality control. Evidence suggests that mitophagy is adversely affected in aged skeletal muscle, and this is thought to contribute toward the age-related decline of muscle health. While our knowledge of the molecular mechanisms that regulate mitophagy are derived mostly from work in non-muscle cells, whether these mechanisms are conferred in muscle under physiological conditions has not been thoroughly investigated. Recent findings from our laboratory and those of others have made several novel contributions to this field. Herein, we consolidate current literature, including our recent work, while evaluating how ubiquitin-dependent mitophagy is regulated both in muscle and non-muscle cells through the steps of mitochondrial fission, ubiquitylation, and autophagosomal engulfment. During ubiquitin-dependent mitophagy in non-muscle cells, mitochondrial depolarization activates PINK1-Parkin signaling to elicit mitochondrial ubiquitylation. TANK-binding kinase 1 (TBK1) then activates autophagy receptors, which in turn, tether ubiquitylated mitochondria to autophagosomes prior to lysosomal degradation. In skeletal muscle, evidence supporting the involvement of PINK1-Parkin signaling in mitophagy is lacking. Instead, 5'-AMP-activated protein kinase (AMPK) is emerging as a critical regulator. Mechanistically, AMPK activation promotes mitochondrial fission before enhancing autophagosomal engulfment of damaged mitochondria possibly via TBK1. While TBK1 may be a point of convergence between PINK1-Parkin and AMPK signaling in muscle, the critical question that remains is: whether mitochondrial ubiquitylation is required for mitophagy. In future, improving understanding of molecular processes that regulate mitophagy in muscle will help to develop novel strategies to promote healthy aging.
Keywords: AMPK; PINK1; Parkin; TBK1; ULK1; mitochondrial fission; mitophagy; skeletal muscle
DOI: https://doi.org/10.3389/fphys.2020.608474
J Physiol. 2020 Dec 21.
Vaupel P, Multhoff G.
Contrary to Warburg's original thesis, accelerated aerobic glycolysis is not a primary, permanent and universal consequence of dysfunctional/impaired mitochondria compensating for poor ATP-yield per mole of glucose. Instead, in most tumours the Warburg effect is an essential part of a "selfish" metabolic reprogramming, which results from the interplay between (normoxic/hypoxic) HIF-1-overexpression, oncogene activation (cMyc, Ras), loss of function of tumour suppressors (mutant-p53, mutant-PTEN, microRNAs and sirtuins with suppressor functions), activated (PI3K/Akt/mTORC1, Ras/Raf/Mek/Erk/cMyc, Jak/Stat3) or deactivated (LKB1/AMPK) signalling pathways, components of the tumour microenvironment, and HIF-1-cooperations with epigenetic mechanisms. Molecular and functional processes of the Warburg effect include: (a) considerably accelerated glycolytic fluxes, (b) adequate ATP generation per unit time to maintain energy homeostasis and electrochemical gradients, (c) backup and diversion of glycolytic intermediates facilitating the biosynthesis of nucleotides, non-essential amino acids, lipids and hexosamines, (d) inhibition of pyruvate entry into mitochondria, (e) excessive formation and accumulation of lactate which stimulates tumour growth and suppression of anti-tumour immunity; in addition, lactate can serve as an energy source for normoxic cancer cells and drives malignant progression and resistances to conventional therapies, (f) cytosolic lactate is mainly exported through upregulated lactate-proton symporters (MCT4), working together with other H+ -transporters, and carbonic anhydrases (CAII, CAIX) which hydrate CO2 from oxidative metabolism to form H+ and bicarbonate, (g) in concert with poor vascular drainage these proton export mechanisms are responsible for extracellular acidification, driving malignant progression and resistances to conventional therapies, (h) maintenance of the cellular redox homeostasis and low ROS formation, and (i) HIF-1 overexpression, mutant-p53 and mutant-PTEN which inhibit mitochondrial biogenesis and functions, negatively impacting cellular respiration rate. The glycolytic switch is an early event in oncogenesis and primarily supports cell survival. All in all, the Warburg effect, i.e., aerobic glycolysis in the presence of oxygen and -in principle- functioning mitochondria, constitutes a major driver of the cancer progression machinery, resistance to conventional therapies, and poor patient outcome. However, as evidenced during the last two decades, in a minority of tumours primary mitochondrial defects can play a key role promoting the Warburg effect and tumour progression due to mutations in some Krebs cycle enzymes and mitochondrial ROS overproduction. Abstract figure legend Driving processes causing the Warburg effect during carcinogenesis (upper part), and mechanisms/consequences of metabolic reprogramming in Warburg phenotypes (lower part) leading to survival advantages, malignant progression and, ultimately, poor patient outcome. This article is protected by copyright. All rights reserved.
Keywords: Warburg effect; aerobic glycolysis; glycolytic phenotype; lactate accumulation; metabolic reprogramming; tumour acidosis; tumour glucose metabolism; tumour mitochondria
DOI: https://doi.org/10.1113/JP278810
Kim SH, Choi JH, Wang P, Go CD, Hesketh GG, Gingras AC, Jafarnejad SM, Sonenberg N.
Mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and proliferation by sensing fluctuations in environmental cues such as nutrients, growth factors, and energy levels. The Rag GTPases (Rags) serve as a critical module that signals amino acid (AA) availability to modulate mTORC1 localization and activity. Recent studies have demonstrated how AAs regulate mTORC1 activity through Rags. Here, we uncover an unconventional pathway that activates mTORC1 in response to variations in threonine (Thr) levels via mitochondrial threonyl-tRNA synthetase TARS2. TARS2 interacts with inactive Rags, particularly GTP-RagC, leading to increased GTP loading of RagA. mTORC1 activity in cells lacking TARS2 is resistant to Thr repletion, showing that TARS2 is necessary for Thr-dependent mTORC1 activation. The requirement of TARS2, but not cytoplasmic threonyl-tRNA synthetase TARS, for this effect demonstrates an additional layer of complexity in the regulation of mTORC1 activity.
Keywords: Rag GTPases; TARS2; amino acid; aminoacyl-tRNA synthetase; mTORC1; threonine
Mitochondrion. 2020 Dec 16. pii: S1567-7249(20)30226-9. [Epub ahead of print]
Ali M, Boosi Narayana Rao K, Majumder P, Sarkar R, Mapa K.
BACKGROUND: Biogenesis and function of mitochondria is profoundly dependent on cytosolic translation of mitochondrial pre-proteins and its subsequent translocation and folding inside the organelle. Continuous exposure of non-native precursor proteins, exposure to damaging by-products of oxidative phosphorylation, load of mis-targeted or misfolded proteins from neighbouring compartments and unremitting demand of communication between mitochondrial and nuclear genomes, continuously pose proteotoxic threats to the organelle. Our knowledge of cellular mechanisms to cope up with such impending threat of proteotoxicity to mitochondria, is currently evolving. In recent years, several unique response and survival pathways have been discovered shedding light on cellular strategies to cope with stressed and dysfunctional mitochondria. As mitochondria compulsorily communicate with nucleus, cytosol and endoplasmic reticulum (ER) for its own biogenesis and function and in turn maintain critical cellular processes for survival, any impairment in communication by stressed or dysfunctional mitochondria may end up with fatal consequences.DISCUSSION: and Implication: In this review, we have discussed about possible sources of mitochondrial proteotoxicity and the recent developments regarding cellular strategies to counter such stress to overcome dysfunctions of the organelle. Mitochondrial communication with neighbouring subcellular compartments like ER and cytosol during proteotoxic stress have been explored. In the context of mitochondrial proteotoxicity, alterations of crucial inter-organelle connections like ER-mitochondria contact sites and its implication on mitochondrial signaling activity like Ca2+ signaling have been dissected. Furthermore, an overview of pathological conditions, mainly neurodegenerative disorders that are known to be associated with mitochondrial proteotoxicity and Ca2+ dysregulation has been presented.
Keywords: Apoptosis; Ca(2+) signaling; Mitochondria; Mitochondria associated ER-membranes (MAMs); Proteotoxic Stress; Unfolded Protein Response (UPR)
DOI: https://doi.org/10.1016/j.mito.2020.12.003
Cell Metab. 2020 Dec 09. pii: S1550-4131(20)30604-5. [Epub ahead of print]
Tirosh A, Tuncman G, Calay ES, Rathaus M, Ron I, Tirosh A, Yalcin A, Lee YG, Livne R, Ron S, Minsky N, Arruda AP, Hotamisligil GS.
Endoplasmic reticulum stress (ERS) has a pathophysiological role in obesity-associated insulin resistance. Yet, the coordinated tissue response to ERS remains unclear. Increased connexin 43 (Cx43)-mediated intercellular communication has been implicated in tissue-adaptive and -maladaptive response to various chronic stresses. Here, we demonstrate that in hepatocytes, ERS results in increased Cx43 expression and cell-cell coupling. Co-culture of ER-stressed "donor" cells resulted in intercellular transmission of ERS and dysfunction to ERS-naive "recipient" cells ("bystander response"), which could be prevented by genetic or pharmacologic suppression of Cx43. Hepatocytes from obese mice were able to transmit ERS to hepatocytes from lean mice, and mice lacking liver Cx43 were protected from diet-induced ERS, insulin resistance, and hepatosteatosis. Taken together, our results indicate that in obesity, the increased Cx43-mediated cell-cell coupling allows intercellular propagation of ERS. This novel maladaptive response to over-nutrition exacerbates the tissue ERS burden, promoting hepatosteatosis and impairing whole-body glucose metabolism.
Keywords: connexin 43; diabetes; endoplasmic reticulum stress; gap junctions; insulin resistance; intercellular communication; unfolded protein response
DOI: https://doi.org/10.1016/j.cmet.2020.11.009
Nat Cancer. 2020 Mar;1(3): 359-369
Hulton CH, Costa EA, Shah NS, Quintanal-Villalonga A, Heller G, de Stanchina E, Rudin CM, Poirier JT.
Patient-derived xenografts are high fidelity in vivo tumor models that accurately reflect many key aspects of human cancer. In contrast to either cancer cell lines or genetically engineered mouse models, the utility of PDXs has been limited by the inability to perform targeted genome editing of these tumors. To address this limitation, we have developed methods for CRISPR-Cas9 editing of PDXs using a tightly regulated, inducible Cas9 vector that does not require in vitro culture for selection of transduced cells. We demonstrate the utility of this platform in PDXs (1) to analyze genetic dependencies by targeted gene disruption and (2) to analyze mechanisms of acquired drug resistance by site-specific gene editing using templated homology-directed repair. This flexible system has broad application to other explant models and substantially augments the utility of PDXs as genetically programmable models of human cancer.
Redox Biol. 2020 Nov 29. pii: S2213-2317(20)31023-5. [Epub ahead of print]38 101818
Alshaabi H, Shannon N, Gravelle R, Milczarek S, Messier T, Cunniff B.
Mitochondria are strategically trafficked throughout the cell by the action of microtubule motors, the actin cytoskeleton and adapter proteins. The intracellular positioning of mitochondria supports subcellular levels of ATP, Ca2+ and reactive oxygen species (ROS, i.e. hydrogen peroxide, H2O2). Previous work from our group showed that deletion of the mitochondrial adapter protein Miro1 leads to perinuclear clustering of mitochondria, leaving the cell periphery devoid of mitochondria which compromises peripheral energy status. Herein, we report that deletion of Miro1 significantly restricts subcellular H2O2 levels to the perinuclear space which directly affects intracellular responses to elevated mitochondrial ROS. Using the genetically encoded H2O2-responsive fluorescent biosensor HyPer7, we show that the highest levels of subcellular H2O2 map to sites of increased mitochondrial density. Deletion of Miro1 or disruption of microtubule dynamics with Taxol significantly reduces peripheral H2O2 levels. Following inhibition of mitochondrial complex 1 with rotenone we observe elevated spikes of H2O2 in the cell periphery and complementary oxidation of mitochondrial peroxiredoxin 3 (PRX3) and cytosolic peroxiredoxin 2 (PRX2). Conversely, in cells lacking Miro1, rotenone did not increase peripheral H2O2 or PRX2 oxidation but rather lead to increased nuclear H2O2 and an elevated DNA-damage response. Lastly, local levels of HyPer7 oxidation correlate with the size and abundance of focal adhesions (FAs) in MEFs and cells lacking Miro1 have significantly smaller focal adhesions and reduced phosphorylation levels of vinculin and p130Cas compared to Miro1+/+ MEFs. Together, we present evidence that the intracellular distribution of mitochondria influences subcellular H2O2 levels and local cellular responses dependent on mitochondrial ROS.
Keywords: Cell migration; Hydrogen peroxide; Miro1; Mitochondrial trafficking; Reactive oxygen species
DOI: https://doi.org/10.1016/j.redox.2020.101818
Trends Cancer. 2020 Dec 16. pii: S2405-8033(20)30329-0. [Epub ahead of print]
Yang X, Chio IIC.
Pancreatic innervation is an important factor in pancreatic cancer etiology and progression. Recent work by Banh et al. has revealed that serine released from the axons of sensory and sympathetic neurons supports pancreatic cancer metabolism during nutrient-deprived conditions. These findings rationalize a therapeutic strategy to combine dietary manipulation and pharmacological denervation to target pancreatic cancer.
Keywords: metabolism; neural input; pancreatic cancer; translation
DOI: https://doi.org/10.1016/j.trecan.2020.12.004
Biochim Biophys Acta Mol Cell Res. 2020 Dec 16. pii: S0167-4889(20)30286-X. [Epub ahead of print] 118928
Nagakannan P, Islam MI, Conrad M, Eftekharpour E.
Ferroptosis is a necrotic form of cell death caused by inactivation of the glutathione system and uncontrolled iron-mediated lipid peroxidation. Increasing evidence implicates ferroptosis in a wide range of diseases from neurotrauma to cancer, highlighting the importance of identifying an executioner system that can be exploited for clinical applications. In this study, using pharmacological and genetic models of ferroptosis, we observed that lysosomal membrane permeabilization and cytoplasmic leakage of cathepsin B unleashes structural and functional changes in mitochondria and promotes a not previously reported cleavage of histone H3. Inhibition of cathepsin-B robustly rescued cellular membrane integrity and chromatin degradation. We show that these protective effects are independent of glutathione peroxidase-4 and are mediated by preventing lysosomal membrane damage. This was further confirmed when cathepsin B knockout primary fibroblasts remained unaffected in response to various ferroptosis inducers. Our work identifies new and yet-unrecognized aspects of ferroptosis and identifies cathepsin B as a mediator of ferroptotic cell death.
Keywords: GPX4; Histone H3; autophagy; glutathione; lipid peroxidation; lysosomes
DOI: https://doi.org/10.1016/j.bbamcr.2020.118928
Matrix Biol. 2020 Dec 13. pii: S0945-053X(20)30118-9. [Epub ahead of print]
Zein L, Fulda S, Kögel D, van Wijk SJL.
The conserved catabolic process of autophagy is an important control mechanism that degrades cellular organelles, debris and pathogens in autolysosomes. Although autophagy primarily protects against cellular insults, nutrient starvation or oxidative stress, hyper-activation of autophagy is also believed to cause autophagy-dependent cell death (ADCD). ADCD is a caspase-independent form of programmed cell death (PCD), characterized by an over-activation of autophagy, leading to prominent self-digestion of cellular material in autolysosomes beyond the point of cell survival. ADCD plays important roles in the development of lower organisms, but also in the response of cancer cells upon exposure of specific drugs or natural compounds. Importantly, the induction of ADCD as an alternative cell death pathway is of special interest in apoptosis-resistant cancer types and serves as an attractive and potential therapeutic option. Although the mechanisms of ADCD are diverse and not yet fully understood, both non-selective (bulk) autophagy and organelle-specific types of autophagy are believed to be involved in this type of cell death. Accordingly, several ADCD-inducing drugs are known to trigger severe mitochondrial damage and endoplasmic reticulum (ER) stress, whereas the contribution of other cell organelles, like ribosomes or peroxisomes, to the control of ADCD is not well understood. In this review, we highlight the general mechanisms of ADCD and discuss the current evidence for mitochondria- and ER-specific killing mechanisms of ADCD-inducing drugs.
Keywords: Autophagy-dependent cell death; ER, ER stress; Mitochondria; Mitophagy
DOI: https://doi.org/10.1016/j.matbio.2020.12.003
EMBO Rep. 2020 Dec 20. e51239
Fong MY, Yan W, Ghassemian M, Wu X, Zhou X, Cao M, Jiang L, Wang J, Liu X, Zhang J, Wang SE.
Metabolic reprogramming of non-cancer cells residing in a tumor microenvironment, as a result of the adaptations to cancer-derived metabolic and non-metabolic factors, is an emerging aspect of cancer-host interaction. We show that in normal and cancer-associated fibroblasts, breast cancer-secreted extracellular vesicles suppress mTOR signaling upon amino acid stimulation to globally reduce mRNA translation. This is through delivery of cancer-derived miR-105 and miR-204, which target RAGC, a component of Rag GTPases that regulate mTORC1 signaling. Following amino acid starvation and subsequent re-feeding, 13 C-arginine labeling of de novo synthesized proteins shows selective translation of proteins that cluster to specific cellular functional pathways. The repertoire of these newly synthesized proteins is altered in fibroblasts treated with cancer-derived extracellular vesicles, in addition to the overall suppressed protein synthesis. In human breast tumors, RAGC protein levels are inversely correlated with miR-105 in the stroma. Our results suggest that through educating fibroblasts to reduce and re-prioritize mRNA translation, cancer cells rewire the metabolic fluxes of amino acid pool and dynamically regulate stroma-produced proteins during periodic nutrient fluctuations.
Keywords: breast cancer; extracellular vesicles; mRNA translation; mTORC1; microRNA
DOI: https://doi.org/10.15252/embr.202051239
Front Pharmacol. 2020 ;11 588449
Kumari R, Palaniyandi S, Hildebrandt GC.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the solitary therapeutic therapy for many types of hematological cancers. The benefits of this procedure are challenged by graft vs. host disease (GVHD), causing significant morbidity and mortality. Recent advances in the metabolomics field have revolutionized our understanding of complex human diseases, clinical diagnostics and allow to trace the de novo biosynthesis of metabolites. There is growing evidence for metabolomics playing a role in different aspects of GVHD, and therefore metabolomic reprogramming presents a novel tool for this disease. Pre-transplant cytokine profiles and metabolic status of allogeneic transplant recipients is shown to be linked with a threat of acute GVHD. Immune reactions underlying the pathophysiology of GVHD involve higher proliferation and migration of immune cells to the target site, requiring shifts in energy supply and demand. Metabolic changes and reduced availability of oxygen result in tissue and cellular hypoxia which is extensive enough to trigger transcriptional and translational changes. T cells, major players in acute GVHD pathophysiology, show increased glucose uptake and glycolytic activity. Effector T (Teff) cells activated during nutrient limiting conditions in vitro or multiplying during GVHD in vivo, depend more on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO). Dyslipidemia, such as the increase of medium and long chain fatty and polyunsaturated acids in plasma of GVHD patients, has been observed. Sphingolipids associate with inflammatory conditions and cancer. Chronic GVHD (cGVHD) patients show reduced branched-chain amino acids (BCAAs) and increased sulfur-containing metabolites post HSCT. Microbiota-derived metabolites such as aryl hydrocarbon receptor (AhR) ligands, bile acids, plasmalogens and short chain fatty acids vary significantly and affect allogeneic immune responses during acute GVHD. Considering the multitude of possibilities, how altered metabolomics are involved in GVHD biology, multi-timepoints related and multivariable biomarker panels for prognosticating and understanding GVHD are needed. In this review, we will discuss the recent work addressing metabolomics reprogramming to control GVHD in detail.
Keywords: allogeneic hematopoietic cell transplantation; glycolysis; graft versus host disease; krebs cycle; t cells
DOI: https://doi.org/10.3389/fphar.2020.588449
Cell Discov. 2020 Dec 22. 6(1): 94
Sun P, Liu Y, Ma T, Ding J.
Human NAD-dependent isocitrate dehydrogenase or HsIDH3 catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the TCA cycle. HsIDH3 exists and functions as a heterooctamer composed of the αβ and αγ heterodimers, and is regulated allosterically and/or competitively by numerous metabolites including CIT, ADP, ATP, and NADH. In this work, we report the crystal structure of HsIDH3 containing a β mutant in apo form. In the HsIDH3 structure, the αβ and αγ heterodimers form the α2βγ heterotetramer via their clasp domains, and two α2βγ heterotetramers form the (α2βγ)2 heterooctamer through insertion of the N-terminus of the γ subunit of one heterotetramer into the back cleft of the β subunit of the other heterotetramer. The functional roles of the key residues at the allosteric site, the pseudo allosteric site, the heterodimer and heterodimer-heterodimer interfaces, and the N-terminal of the γ subunit are validated by mutagenesis and kinetic studies. Our structural and biochemical data together demonstrate that the allosteric site plays an important role but the pseudo allosteric site plays no role in the allosteric activation of the enzyme; the activation signal from the allosteric site is transmitted to the active sites of both αβ and αγ heterodimers via the clasp domains; and the N-terminal of the γ subunit plays a critical role in the formation of the heterooctamer to ensure the optimal activity of the enzyme. These findings reveal the molecular mechanism of the assembly and allosteric regulation of HsIDH3.
Anal Biochem. 2020 Dec 18. pii: S0003-2697(20)30616-3. [Epub ahead of print] 114084
Cooper AJL, Dorai T, Pinto JT, Denton TT.
The asparaginase II pathway consists of an asparagine transaminase [L-asparagine + α-keto acid ⇆ α-ketosuccinamate + L-amino acid] coupled to ω-amidase [α-ketosuccinamate + H2O → oxaloacetate + NH4+]. The net reaction is: L-asparagine + α-keto acid + H2O → oxaloacetate + L-amino acid + NH4+. Thus, in the presence of a suitable α-keto acid substrate, the asparaginase II pathway generates anaplerotic oxaloacetate at the expense of readily dispensable asparagine. Several studies have shown that the asparaginase II pathway is important in photorespiration in plants. However, since its discovery in rat tissues in the 1950s, this pathway has been almost completely ignored as a conduit for asparagine metabolism in mammals. Several mammalian transaminases can catalyze transamination of asparagine, one of which - alanine-glyoxylate aminotransferase type 1 (AGT1) - is important in glyoxylate metabolism. Glyoxylate is a precursor of oxalate which, in the form of its calcium salt, is a major contributor to the formation of kidney stones. Thus, transamination of glyoxylate with asparagine may be physiologically important for the removal of potentially toxic glyoxylate. Asparaginase has been the mainstay treatment for certain childhood leukemias. We suggest that an inhibitor of ω-amidase may potentiate the therapeutic benefits of asparaginase treatment.
Keywords: asparaginase; asparaginase II pathway; transaminases; w-amidase
DOI: https://doi.org/10.1016/j.ab.2020.114084
Pathol Res Pract. 2020 Dec 04. pii: S0344-0338(20)32169-5. [Epub ahead of print]217 153314
Taefehshokr S, Taefehshokr N, Hemmat N, Hajazimian S, Isazadeh A, Dadebighlu P, Baradaran B.
Cancer cells are able to undergo aerobic glycolysis and metabolize glucose to lactate instead of oxidative phosphorylation, which is known as Warburg effect. Accumulating evidence has revealed that microRNAs regulate cancer cell metabolism, which manifest a higher rate of glucose metabolism. Various signaling pathways along with glycolytic enzymes are responsible for the emergence of glycolytic dependence. MicroRNAs are a class of non-coding RNAs that are not translated into proteins but regulate target gene expression or in other words function pre-translationally and post-transcriptionally. MicroRNAs have been shown to be involved in various biological processes, including glucose metabolism via targeting major transcription factors, enzymes, oncogenes or tumor suppressors alongside the oncogenic signaling pathways. In this review, we describe the regulatory role of microRNAs of cancer cell glucose metabolism, including in the glucose uptake, glycolysis, tricarboxylic acid cycle and several signaling pathways and further suggest that microRNA-based therapeutics can be used to inhibit the process of glucose metabolism reprogramming in cancer cells and thus suppressing cancer progression.
Keywords: Cancer; Glucose; Metabolism; MicroRNA
DOI: https://doi.org/10.1016/j.prp.2020.153314
Cell Calcium. 2020 Dec 08. pii: S0143-4160(20)30171-8. [Epub ahead of print]93 102329
Chubanov V, Gudermann T.
Mg2+ is an essential cation controlling many biochemical reactions. Recently, Daw et al. [1] have shown that l-lactate acts as a second messenger triggering a dynamic exchange of Mg2+ between the endoplasmic reticulum and mitochondria to shape energy metabolism. This discovery changes our view on the cellular role of Mg2+.
Keywords: Bioenergetics; Lactate; Mg(2+); Mitochondria; Mrs2
DOI: https://doi.org/10.1016/j.ceca.2020.102329
EMBO J. 2020 Dec 21. e106696
Huh D, Passarelli MC, Gao J, Dusmatova SN, Goin C, Fish L, Pinzaru AM, Molina H, Ren Z, McMillan EA, Asgharian H, Goodarzi H, Tavazoie SF.
Eukaryotic transfer RNAs can become selectively fragmented upon various stresses, generating tRNA-derived small RNA fragments. Such fragmentation has been reported to impact a small fraction of the tRNA pool and thus presumed to not directly impact translation. We report that oxidative stress can rapidly generate tyrosine-tRNAGUA fragments in human cells-causing significant depletion of the precursor tRNA. Tyrosine-tRNAGUA depletion impaired translation of growth and metabolic genes enriched in cognate tyrosine codons. Depletion of tyrosine tRNAGUA or its translationally regulated targets USP3 and SCD repressed proliferation-revealing a dedicated tRNA-regulated growth-suppressive pathway for oxidative stress response. Tyrosine fragments are generated in a DIS3L2 exoribonuclease-dependent manner and inhibit hnRNPA1-mediated transcript destabilization. Moreover, tyrosine fragmentation is conserved in C. elegans. Thus, tRNA fragmentation can coordinately generate trans-acting small RNAs and functionally deplete a tRNA. Our findings reveal the existence of an underlying adaptive codon-based regulatory response inherent to the genetic code.
Keywords: hnRNPA1; oxidative stress; tRNA; tRNA fragments; translation
DOI: https://doi.org/10.15252/embj.2020106696
Cell Res. 2020 Dec 21.
Li M, Zhang CS, Feng JW, Wei X, Zhang C, Xie C, Wu Y, Hawley SA, Atrih A, Lamont DJ, Wang Z, Piao HL, Hardie DG, Lin SC.
Nat Rev Cardiol. 2020 Dec 21.
Robson A.


text:
The benefits of digital solutions for nuclear
Nuclear build projects have some key differences from traditional construction projects. You could try and perfect the design of a nuclear power plant before you start construction but given how long these construction projects take, some aspects of a design can change before you get to the stage where operations can begin. Construction of a new nuclear plant has to begin before every single detail of the design is finalised. A pump that was originally specified three years ago might no longer be in production or standards for welding protocols may change. Since a nuclear power station can be in operation for 60 years it doesn't make sense to build it, file some paperwork and move on. Regular maintenance and replacement of parts requires some sort of system for digging out specifications for a component. The one thing you can be sure of in a nuclear project is that things will change.
Each new nuclear build is unique. Specifications are different depending on local geology, supply chains and site history. When you dig down into the details every pump, flange and bolt must meet some specifications and each component must work with the others in an intricate dance of heat, pressure and flow rates. Designing something this intricate requires input from many different specialisms and generates a vast amount of paperwork. Navigating of all of this information requires a significant amount of effort. You could use Building Information Modelling during the construction phase to make this easier but perhaps something more is needed to keep track of changes during these complex projects with such a long timeframe that relies on multiple specialisms.
Changing the design leads to an update of the drawings but testing and operation is for someone outside of the design team to do. Those tests might reveal that changing one component has a knock on effect for operations elsewhere in the plant. For example, imagine that you realise you will need more flow; this means that you need a bigger pump. It also means that you need a bigger pipe. You might also discover once you've started testing that you need a bigger feed tank to draw from, or more head pressure, or more substantial flanges at critical connection points. As you start to figure out the knock-on effect of this change, you also discover that one part of the plant that you need to access might be behind a wall that has already been substantiated for seismic events. You'll need to demolish the wall, make the change, and then test the wall again. Suddenly, a design change that was simple on paper becomes complex and the cost starts to spiral. And what if, once you're rebuilt that wall, you realise there's another change to be made to a different component? Work on the wall needs to be repeated yet again; the costs continue to spiral and the timeline starts to slip.
The sort of scenario detailed above happens with surprising frequency. A lot of experts are involved in the design and they each have their specialism to focus on. The mechanical engineers responsible for that pump may not know that it's behind a wall and they're unlikely to know about seismic testing. The project manager will certainly have an overview of all of these aspects but their specialism is in management, it's not in mechanical, seismic testing or fluid dynamics. Imagine all of the strands of information connecting all of the different design aspect of each component to each other; that's one hideously messy ball of string. Sometimes, getting these details right involves more than just passing the information along, it takes great insight and an almost supernatural level of foresight.
It makes sense to think of a power plant as a product which requires certain management principles. A Product Lifecycle Management (PLM) system is a bit like an octopus with many tentacles, or fingers, in many pies. It can navigate those multiple, interconnected strands of information and tell you where to look for the knock-on effects of changing one aspect of the design. In nuclear, instead of using PLM to refine a final product prior to manufacture, those same management principles can be applied to change management across design, construction and commissioning.
Taking the above example, the first step for the shift team working on replacing that pump will be to dig out several documents including drawings for electrical circuits, pipework, specifications of the pump, manuals, and the necessary paperwork for a Safe System of Work. It's not easy to find all of this information and make sense of it at 2 am. That shift team needs to figure out where to apply isolations, how to drain down that section of pipework and understand what the risks may be. On nightshift, it's not uncommon to make the wrong decision when you don't have all of the information to hand or to miss a safety critical detail during shift handover. The fitters, mechanics and other doers ask questions of the engineering department as they're working on a new build or on a refit during routine maintenance. This leads to a hold-up as they wait for the engineers to respond. The accumulation of these hold-ups can easily lead to programme overruns and frustrations between departments, and don't forget that we're talking about just one step in a chain of events to replace a pump that should be behind a wall that should be substantiated for seismic events.
Instead of relying on paperwork, imagine using a system that can help to really understand the impact of one single change and allows departments to work together. The shift team can make better decisions and can clearly communicate to everyone affected by that change. You can set-up the PLM system to record the details of a job, and what was done at handover. Setting up this system may not be as easy as filing some paperwork but then finding that paperwork again and collating the right paperwork for a job is a huge challenge that takes time and effort to sort out where the interfaces between departments can slow things down. Each department might only need to spend a little bit extra to get a job done, but these small amounts quickly add up. Instead, a PLM system could harmonise these parts of the business and provide an integrated view of departmental budgets.
Digital solutions are powerful tools for decision making. They can provide information about what a component is connected to and the room it's in. It can also link to tests and issues logs. And those components that your item of interest is connected to? It can tell you about them too. It can also tell you about stock levels in stores. If you have the right tool in your digital toolkit, you can even do what-if analysis to decide in advance what effect a change will have, and whether a change is really needed at all. Going back to our example of a pump behind a concrete wall, if that wall has to come down to provide access, it can also tell you what else should be done in that room while you're there. Manging that change from the update to the design, the planning and building stages, testing and commissioning suddenly becomes a whole lot easier. The project manager can now focus on what to do rather than working out the impact of any change. A digital solution can show when the critical path will be affected allowing the project manager to use their expert judgement to decide what do. It also allows engineers to focus on their specialism rather than on passing information back and forth.
In an environment where the engineers have a key role in providing information to others, it makes sense to have a system in place that allows them to do so easily. At first glance, a PLM system appears to create more work for engineering but if the digital solution is tailored in the right way then it will reduce the burden on that department. Using the right digital solution, even with a seemingly high upfront cost, can help keep a project on budget and on time. When you only have one shot to get your product right, doesn't it make sense to invest in a tool that will allow you to manage design changes effectively, make the right decisions, and save money in the process? And after decades of operations when all of the personal will have changed, wouldn't you want a way of managing records and knowledge, and of retaining expertise that can stand the test of time better than some paper in a filing cabinet can?
Utilising PLM comes with many benefits and there are some hurdles to get over in order to realise them. Commissioning a complex build like a nuclear power plant while the design is being finalised is a challenge, as is navigating the regulatory environment, building the safety case, and applying operating experience from a construction project that doesn't happen very often. It takes in-depth knowledge accumulated over decades to understand these challenges, and to apply processes and operating experience from both nuclear and other industries to truly realise the benefits of digital technology.
To find out more about working with Nuclear Consulting to deliver a digital transformation for a nuclear project please Contact Us.


Scientists are continually discovering new things about the human brain, yet it remains a subject shrouded in mystery. These fifteen facts are just the tip of the iceberg when it comes to studying the brain, but they shed light on some important aspects of the brain.
It's crazy to think that something that is mostly water controls all seven billion people in the world, and that there are 100 billion neurons working constantly to keep us all functioning. Plus, your brain generates enough energy to power a lightbulb, which gives a whole new meaning to the symbol of a lightbulb appearing above someone's head when they get an idea!
If nothing else, after reading this you'll finally understand why yawning is contagious.
What do you think is the most interest fact about the human brain?