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TIFR Biology Ph.D Admission Test TIFR-GS 2017

Tata Institute of Fundamental Research (TIFR) is premier institution for advanced research in fundamental sciences. The Institute runs a graduate programs leading to the award of Ph.D., Integrated M.Sc Ph.D. as well as M.Sc. degree in certain subjects. With its distinguished faculty, world class facilities and stimulating research environment, it is an ideal place for aspiring scientists to initiate their career.
The Graduate Programme at TIFR is classified into the following Subjects - Mathematics, Physics, Chemistry, Biology, Computer & Systems Sciences (including Communications and Applied Probability) and Science Education. It is conducted at the Mumbai campus and various National Centres of TIFR.
Graduate School Admissions (GS-2017)
Imported Dates:

  • Nationwide Entrance Examination: December 11, 2016 (Sunday)
  • Last date for application:  October 10, 2016
  • Online payment link will be active upto October 17, 2016
  • DDs sent by post/courier will be accepted upto October 17, 2016
  • Hall Ticket download link will be active from : November 10, 2016
  • Results of the Nationwide Entrance Examination (shortlist for interviews) :January 31, 2017.

Application Procedure:
Students can apply online.  Please follow appropriate link on this website for filling up the application form.  Read the instructions carefully before you start filling up the online application form.  PLEASE DO NOT MAKE MULTIPLE REGISTRATIONS FOR THE SAME SUBJECT.
Manual Applications: Students from remote areas who do not have access to internet may apply manually.   They may send a request for application form (without DD) along with a self-addressed stamped (Rs 20/-) envelope (size 25cm x 17cm) superscribed "GS-2017 (Subject)" to :

For Biology:

Admissions Section
National Centre for Biological Sciences
UAS-GKVK Campus, Bellary Road,
Bangalore 560065.

The filled-in application form should be sent along with DD and two passport size photographs (one pasted on the application and one stapled to it).
Students may appear for the written test in multiple subjects if the timings do not clash.  Please send separate application (including Demand Draft) for each subject. In case of online applicants, students will have to re-register with a different email id.
Students who wish to apply online and make payment by Demand Draft may send the Demand Draft with their name, reference code and telephone number written behind it.  Alternately, students can make online payment through internet banking or by Debit/Credit Card. 

Application Fee (Non-Refundable): 
  • Male Candidates : Rs 600/- for online applications and Rs 650/- for manual applications.   
  • Female Candidates : Rs 100/- for online and manual applications. 

Application fee can be paid online through internet banking or by Debit/Credit Card or by sending Demand Draft. 

Online Payment: After the online payment transaction is successful, please login to your account on our website by using your reference code as your user id and check the payment status of your application.    Normally, online payments are received within 2 working days and a auto email is sent by the system acknowledging the payment.  If your transaction has been successful and your account has been debited and you do not receive the acknowledgement email within 7 days, neither your payment status is updated in your account, you may write to the email ids as given in "Contact Info" section.
Demand Draft: 
Biology: DD should be drawn on State Bank of India in favour of "National Centre for Biological Science" payable at Bangalore.  
For mailing address and contact information, please refer to theContact Info page.
DDs may be sent by speed post/courier with name, reference code and telephone number written behind it.
Online payment link will be active upto October 17, 2016.

DDs sent by post/courier will also be accepted upto October 17, 2016.

 Eligibility: Biology
  • For Ph.D.: Masters in Basic Science or Bachelors in Applied Science.  These include, M.Sc.(Ag.), B.Tech., B.E., B.V.Sc., B.Pharma. (4 years course), MBBS, BDS, M.Pharma. Candidates will be short-listed for interview based on written test marks, CV and Scientific Writeup. 
  • For I-Ph.D./M.Sc.: Bachelors in any Basic Science.
  • For Ph.D. Program in TCIS: M.Sc. in Physics, Chemistry or Biology. 
Previous Question Paper GS 2016
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5 Quick Facts on CRISPR-Cas9 technology- A simple RNA Guided Gene Editing Tool (Summary)

Fact 1: What is CRISPR-Cas9 technology?
  • Currently, CRISPR-Cas9 technology, an RNA guided genome editing system is the simplest, cheapest and the most versatile tool for efficient and precise genome editing. This remarkable technology is derived from microbial defense mechanism.
  • Using this technology we can precisely target desired genes at specific locations in a genome by cutting out the unwanted sequence and replace it with our desired gene or DNA segment.
Fact 2: Why this name, CRISPR-Cas9 technology?
CRISPR Cas9 natural mechanism in bacteria

  • CRISPR  (pronounced crisper) refers to Clustered Regularly Interspaced Short Palindromic Repeats or prokaryotic DNA segments with short repetition of base sequences and between these short repeats there is a spacer DNA derived from previous exposure to bacteriophage or plasmid
  • CRISPR-Cas9 is involved in prokaryotic defense mechanism preventing insertion of foreign DNA segments of bacteriophage and plasmids. Spacer DNA is derived from prior exposure, therefore provides a form of acquired immunity in bacteria. CRISPR-Cas9 plays a crucial role in microbial antiphage defense mechanism
Fact 3: The story of CRISPR-Cas9 technology
CRISPR-Cas9 technology timeline

  • The CRISPR story began in 1987. While studying the iap enzyme involved in isozyme conversion of alkaline phosphatase in E. coli, Nakata and colleagues reported a curious set of 29 nt repeats downstream of the iap gene which is quite different from other repetitive elements in prokaryotes.
Fact 4: How CRISPR-Cas9 works?
CRISPR-Cas9 technology mechanism

  • Two key molecules are involved in gene manipulation by CRISPR-Cas9.
  • Cas9, an endonuclease enzyme and a short segment of RNA called guide RNA or gRNA (sg RNA: single guide RNA or mgRNA: multiple guide RNA)
  • Cas9 is an RNA guided DNA endonuclease that serves as “molecular scissors” cutting double stranded DNA at specific locations.
  • The CRISPR nuclease Cas9 is targeted by a short guide RNA that recognizes the target DNA via Watson-Crick base pairing. This guide RNA sequence, CRISPR RNAs (crRNAs) is complementary to the phage sequence or plasmid sequence constituting the natural mechanism for CRISPR antiviral defense. Guide RNA will bind to the complementary phage sequence and cas 9 endonuclease degrade phage DNA or RNA thus preventing phage gene insertion. A small portion of  phage DNA is retained as spacer DNA to recognize the phage easily when it attacks next time. This guide RNA can be easily replaced by a sequence of interest to retarget the Cas9 nuclease.
  • In  type I CRISPR locus of Escherichia coli, CRISPR arrays are transcribed and converted into
  • small crRNAs containing individual spacers to guide Cas nuclease activity (crRNA-directed RNA cleavage activity)
  • The point is we can design guide RNAs to precisely target our desired genes to preferred locations within a genome using cas9.
  • Even multiple guide RNAs can also be used to target several genes at once.
Fact 5: Applications and future prospects?
CRISPR-Cas9 technology applications

  • Genome editing using CRISPR-Cas9 has been successfully carried out in a variety of species including human cell lines.
  • For example, Streptococcus pyogenes Cas9 (SpCas9) has been widely used to achieve efficient genome editing in a variety of species and cell types, including human cell lines, bacteria, zebra fish, yeast, mouse, fruit fly, roundworm, rat, common crops, pig, and monkey.
  • SpCas9 is also dramatically expanding the catalog of genetically tractable model organisms, for example, by enabling the introduction of multiplex mutations in cynomolgus monkeys.
Current research and future prospects
  • Improving CRISPR-Cas9 target recognition fidelity
  • CRISPR-based interference, or CRISPRi, works well in prokaryotic genomes but is less effective in eukaryotic cells. CRISPR based transcription repression or gene silencing needs to be further improved.
  • Development of versatile delivery and expression systems for applications of cas9
  • Cas9 as a therapeutic molecule for treating genetic disorders. For a monogenic recessive disorder due to loss-of-function mutations (such as cystic fibrosis, sickle-cell anemia, or Duchenne muscular dystrophy), Cas9 may be used to correct the causative mutation.
  • The multiplexing capabilities (introduction of many mutations simultaneously) of Cas9 offer a promising approach for studying common human diseases such as diabetes, heart disease, schizophrenia, and autism—that are typically polygenic.
  • Use of CRISPR-Cas9 technology for editing germ line cells is highly controversial. It is illegal and prohibited by law in most countries due to ethical reasons as germ line editing will be passed on from generation to generation. Anyway, gene editing in somatic cells is uncontroversial.
Reference:
  1. Hsu, P. D., Lander, E. S., & Zhang, F. (2014). Development and applications of CRISPR-Cas9 for genome engineering. Cell157(6), 1262-1278. (Images from this review)
  2. Sander, J. D., & Joung, J. K. (2014). CRISPR-Cas systems for editing, regulating and targeting genomes. Nature biotechnology32(4), 347-355.
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CSIR UGC NET JRF December 2016 Notification Apply Online

CSIR will hold   the Joint CSIR-UGC Test on 18th December, 2016 for determining the eligibility of the Indian National  candidates for the award of Junior Research Fellowships (JRF) and for determining eligibility for appointment of  Lecturers (NET) in certain subject areas falling under the faculty of Science & Technology. The award of Junior Research  Fellowship (JRF) to the successful eligible candidates will depend on their finding admission/placement in a university/  national laboratory/ institution of higher learning and research, as applicable
Exam DateCSIR-UGC JRF(Junior Research Fellowship) & NET (Eligibility for Lectureship) 
:18th December, 2016.
Important Dates:
Age Limit & Relaxation:
  • For Junior Research Fellowships  (JRF):Maximum 28 years as on 01-07-2016 (upper age limit may be relaxed up to 5 years in case of candidates belonging to SC/ST/OBC, Physically handicapped/Visually handicapped and female applicants).
  • For LS (NET): No upper age limit.
                                                          Exam Opportunities after Post Graduation in Life Sciences
Educational Qualification:
  • BS-4 years program/BE/BTech/BPharma/MBBS/Integrated BS-MS/MSc or equivalent degree with at least 55% marks for general and OBC (50% for SC/ST candidates, physically and Visually Handicapped candidates).
  • Candidates enrolled for M.Sc or having completed 10+2+3 years of the above qualifying examination are also eligible to apply in the above subject under the Result Awaited (RA) category on the condition that they complete the qualifying degree with requisite percentage of marks within the validity period of two years to
    avail the fellowship from the effective date of award.
    Such candidates will have to submit the attestation format (Given at the reverse of the application form) duly certified by the Head of the Department/Institute from where the candidate is appearing or has appeared.
  • BSc (Hons) or equivalent degree holders or students enrolled in Integrated MS-PhD program with at least 55% marks for general and OBC candidates; 50% marks for SC/ST candidates, physically and visually handicapped candidates are also eligible to apply.Candidates with bachelor’s degree, whether Science, engineering or any other discipline, will be eligible for fellowship only after getting registered/enrolled for PhD/Integrated PhD program within the validity period of two years.
  • The eligibility for lectureship of NET qualified candidates will be subject to fulfilling the criteria laid down by UGC. PhD degree holders who have passed Master’s degree prior to 19th September 1991, with at least 50% marks are eligible to apply for Lectureship only.
    Syllabus
    The question paper shall be divided into three parts, (A, B & C) as per syllabus & Scheme of Exam.
    Part 'A' shall be common to all subjects including Engineering Sciences. This part shall contain questions pertaining to General Aptitude with emphasis on logical reasoning, graphical analysis, analytical and numerical ability, quantitative comparison, series formation, puzzles etc.
    Part 'B' shall contain subject-related conventional Multiple Choice questions (MCQs), generally covering the topics given in the syllabus.
    Part 'C' shall contain higher value questions that may test the candidate's knowledge of scientific concepts and/or application of the scientific concepts. The questions shall be of analytical nature where a candidate is expected to apply the scientific knowledge to arrive at the solution to the given scientific problem.
    Negative marking for wrong answers, wherever required, shall be applicable as per subject wise scheme of Exam.
    Examination fee:

    Examination Centres: Bangalore, Bhavnagar, Bhopal, Bhubaneshwar, Chandigarh, Chennai, Cochin, Delhi, Guntur, Guwahati, Hyderabad, Imphal, Jammu, Jamshedpur, Karaikudi, Kolkata, Lucknow, Nagpur, Pilani, Pune, Raipur, Roorkee, Srinagar, Thiruvananthapuram, Udaipur and Varanasi.
    Exam Result& Validity period of fellowship:
    The final result of this Single MCQ test may be declared sometime in the month of March/April, 2016 and fellowship to successful candidates will be effective from 1 st January 2017 with the validity period of 2 years for joining the fellowship under CSIR Scheme.
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    Riboswitches: Definition, Structure, Mechanism and Applications

    Definition: Riboswitches are structured noncoding RNA domains that selectively bind metabolites and control gene expression (Roth and Breaker, 2009).

    Riboswitches are mRNA elements that bind metabolites or metal ions as ligands* and regulate mRNA expression by forming alternative structures in response to this ligand binding (Winkler, 2005)
    what are riboswitches? 
    • The term riboswitch was used to define RNAs that control gene expression by binding metabolites without the need for protein factors or a protein-independent gene regulation mechanism.
    • Riboswitches form highly specific binding pockets for the target metabolite and undergo allosteric changes in structure
    • Transcription termination in bacteria is a classical example of riboswitch in action.
    • The most widespread riboswitch class discovered to date responds to the coenzyme thiamin pyrophosphate (TPP). This riboswitch is quite common in plants and fungi.
    • Common ligands that are sensed by riboswitches; includes magnesium ions, nucleic acid precursors, enzyme cofactors, and amino acid residues
    Location:
    ·         Riboswitches are most often located in the 5' untranslated region (5' UTR; a stretch of RNA that precedes the translation start site) of bacterial mRNA.
    Structure of riboswitches
    Structure of riboswitches
    ·         Riboswitches are composed of two domains: the aptamer domain (ligand binding domain) and the expression platform. The aptamer domain acts as a receptor that specifically binds a ligand.
    ·         The expression platform regulates gene expression through its ability to toggle between two different secondary structures in response to ligand binding (Figure 1, blue).
    ·         Common to both domains is something called the switching sequence, (that can pair with both aptamer domain or the expression platform) and its placement or pairing in the aptamer domain or the expression platform ultimately dictates the expression outcome of the mRNA.

         Mechanism:
    Riboswitches mechanisms of action
    Established or predicted mechanisms of riboswitch-mediated gene regulation. The most common mechanisms are (A) transcription termination, (B) translation initiation, and (C) splicing control (in eukaryotes). More rare mechanisms observed or predicted in some bacterial species include (D) transcription interference or possibly antisense action, (E) dual transcription and translation control, and (F) ligand-dependent self-cleaving ribozyme action. The numbers in a identify steps that are important for kinetically driven riboswitches (Wickiser et al. 2005a,bGilbert et al. 2006). Numbers represent (1) folding of the aptamer, (2) docking of the ligand, (3) folding of the expression platform, and (4) speed of RNA polymerase (RNAP). In B, Rho represents the transcriptional terminator protein (Skordalakes and Berger 2003).
    ·         Riboswitches that control transcriptional repression have a switching sequence that directs formation of a Rho-independent transcriptional terminator, a short stem-loop structure (followed by six or more uridine residues) that signals RNA polymerase to stop transcription.
    Riboswitches in translation

    ·         Riboswitches that regulate translational initiation utilize a switching sequence that can expose ribosome-binding site (called theShine-Dalgarno sequence) in bacteria.

    How Are Riboswitches Categorized?

    Example, families and classes of riboswitches


    • Riboswitches are organized into families and classes based on two features: the type of ligand they bind, and their secondary structure.
    • A family of riboswitches is typically a group of RNAs that recognizes a specific ligand.
    • Example, the SAM riboswitch family recognizes the compound S-adenosylmethionine (SAM). The family is further divided into distinct classes of riboswitches, based on the common sequence pattern that usually defines the ligand-binding pocket, as well as features required for folding the RNA into a three-dimensional shape.
    • The SAM riboswitch family contains at least five known classes. These classes are distinguished from one another by their specific secondary structure or domain features. For example, the SAM-I class forms a four-way helical junction, SAM-II forms a classic (H-type) pseudoknot, and SAM-III is defined by a three-way junction.
    Applications:
    • Novel Riboswitch-Based Therapeutics to control bacterial infection. Riboswitches are not reported in mammals therefore unlikely to interact with mammalian mRNA
    • Analogs of riboswitch ligands can be used to deregulate key metabolic pathways in bacteria, and thus may serve as new classes of antibiotics 
    • Reverse engineering of natural riboswitches could help guide the creation of designer riboswitches to expand the tools available for genetics studies
    Ligand*: Any molecule that binds to the receptor or binding site
    Reference:
    • The structural and functional diversity of metabolite-binding riboswitches.Roth A, Breaker RR. Annu Rev Biochem. 2009; 78():305-34.
    • Breaker, R. R. (2012). Riboswitches and the RNA World. Cold Spring Harbor Perspectives in Biology, 4(2), a003566.
    • Garst, A. D., Edwards, A. L., & Batey, R. T. (2011). Riboswitches: Structures and mechanisms. Cold Spring Harbor Perspectives in Biology, 3(6), a003533.
    • http://www.nature.com/scitable/topicpage/riboswitches-a-common-rna-regulatory-element-14262702
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    Lugdunin, Newest powerful antibiotic isolated from nose bacterium Staphylococcus lugdunensis

    Discoverers: A team of scientist led by Andreas Peschel at University of Tubingen, Germany.
    Lugdunin, Newest powerful antibiotic isolated from nose bacterium Staphylococcus lugdunensis

    Summary of the work:
    Lugdunin, an antibiotic  produced by  Staphylococcus lugdunensis, a bacterium found in human nasal swab has been found to effective against many pathogenic bacteria especially potentially dangerous drug-resistant forms such as methicillin resistant Staphylococcus aureus (MRSA). Many bacterial species including Staphylococcus are found in the human nose, but the presence of pathogenic S.aureus inhibits the growth of other bacterial species.
    Objective:
    Screening of Staphylococcus species of nasal swabs for antimicrobial activity against S. aureus
    Methedology:
    • In vitro microbial culture studies
    •  In vivo studies in mice and cotton rats
    • Compound identification:  NMR spectra of the natural product lugdunin.
    • Structure elucidation by multistage tandem and electrospray ionization high-resolution   mass spectrometry
    • Clinical studies using nasal swabs of 187 hospitalized patients
    Summary of results:
    • Staphylococcus lugdunensis bacterial strain significantly inhibits the growth of S. aureus in culture studies, in vivo and also in clinical studies
    •  On further study of nasal S. lugdunensis, the team identified the compound that prohibits colonization by S. aureus and called it lugdunin
    • Structural elucidation revealed that the compound is a thiazolidine-containing cyclic peptide, first known example of peptide antibiotic
    •  Lugdunin is effective against many pathogenic bacterial strains.
    • S. aureus infected mice, when treated with Lugdunin for 24, 30 and 42 hours proved to be very effective in clearing all viable S. aureus from the surface  and deeper layers of the skin
    • S. aureus and S. lugdunensis were introduced into the cotton rat nose and found out that lugdunin of  S. lugdunensis effectively prohibits the colonization of S. aureus
    • Clinical studies: The nasal swabs of 187 hospitalized patients were tested for the presence of S. aureus and S. lugdunensis. The presence of S. lugdunensis significantly lowered (nearly six times) the colonization of S. aureus compared to the patients with S. aureus alone.
    Future prospects:
    Lugdunin is bactericidal against many major pathogenic bacterial strains and not prone to causing development of resistance in S. aureus. The results suggest that lugdunin or lugdunin-producing commensals* could be valuable for preventing staphylococcal infections.
    *Commensalism: relationship between two organisms where one receives a benefit or benefits from the other and the other is not affected by it.
    Reference:
    Original Paper
    Zipperer A, Konnerth M, Laux C, Berscheid A, Janek D, Weidenmaier ,5, Burian M, Schilling N, Slavetinsky C, Marschal M, Willmann M, Kalbacher H, Schittek B, Brötz-Oesterhelt H, Grond S, Peschel A, Krismer B. “Human commensals producing a novel antibiotic impair pathogen colonization”. Nature. 2016 Jul 27;535(7613):511-6. doi: 10.1038/nature18634.
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    Summary of Fluid Mosaic Model of Plasma Membrane by Singer and Nicolson 1972

    Proposed by S J Singer and Garth L Nicolson
    Published in the journal “Science’’ in 1972.
    Composition: Cell membrane is made up of lipid, protein and small amount of carbohydrate.

    Properties:
          Membrane is quasi fluid with components held together mostly by non-covalent interaction
          The fluidity of the membrane is α chain length and unsaturation of fatty acids
          The more the un-saturation (no. of double bonds), the more the fluidity of the membrane
          Increased fatty acid chain length decreases fluidity.
          Increased amount of cholesterol decreases fluidity at 37oC
    1. Phospholipid bilayer
          Consists of polar hydrophilic (water loving) phosphate head group
          Non polar hydrophobic fatty acid chain
          Forms the structural backbone of the membrane that serves as a barrier to regulate the passage of substances
          Cholesterol  bound with phospholipids makes membrane stable and  highly impermeable to polar molecules
    2. Proteins mostly globular
          A) Extrinsic or peripheral proteins are loosely attached to the lipid bi layer and are hydrophilic
          B) Intrinsic, integral or transmembarne proteins may serve as transport channels (permeases, translocases), receptor molecules, antigens etc. It forms about 70% of total membrane proteins
    3. Carbohydrates are present on the outer side or extracellular side of the plasma membrane
          Present as glycoprotein or glycoli
          pid (carbohydrates bound to protein or lipid)
          Function : helps in cell recognition, cell interaction and cell adhesion
          As receptors, antigens etc
    Reference:

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    Why is genetic code a triplet code? Logical Explanation

    The logic behind triplet genetic code or why is the genetic code a triplet code instead of a singlet or doublet?
    There are four nitrogenous bases in our DNA. Upon transcription, bases in mRNA are (Adenine A, Guanine G, Uracil U and Cytosine C) and transcribed mRNA codes for proteins. As we already know there are 20 amino acids (essential amino acids) that are coded by these four bases. Let's us consider the following possibilities. 
    Genetic code singlet doublet triplet logic diagram

    Case I
    Now if we consider the genetic code to be singlet then it would be impossible as there are only four bases and that cannot code for 20 amino acids.  If codon is a singlet code then it can code for 4 amino acids only.
    Genetic code, possible permutations
    Case II:
    If the genetic code is a doublet code; that is, an amino acid is coded by 2-nitrogeneous bases on mRNA in a specific sequence, then it can form 16 codons (42=4x4=16), still not sufficient enough to code 20 amino acids, so the genetic code can’t be of two letters. 
    Case III: 
    If the genetic code is a triplet code, that is, an amino acid is coded by 3-nitrogeneous bases, and then it can form 64 codons (43=4x4x4=64). But we have only 20 amino acids so codons are in excess. Then the possibility is some amino acids may be coded by more than one triplet code.
     Case IV: 
    If the genetic code is a 4 letter code, that is, an amino acid is coded by 4-nitrogeneous bases then it can form 256 codons (44=4x4x4x4=256). But we have only 20 amino acid which is way too more. So it can't be 4.
    Final verdict:
    So the best possibility is for the codon to have 3 nitrogenous bases or each codon is a triplet code. George Gamow (1954) postulated each codon is a triplet code and is encoding the 20 standard amino acids of proteins used by living cells. Moreover, all the codon are specific, they will code for a single amino acid. Several triplets have the same letters but in different sequences and these code for different amino acids. Later by in vitro synthesis, scientists elucidated the triplet codons for all twenty amino acids.
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    ICAR NET 2016 Notification

    The Agricultural Scientists Recruitment Board (ASRB) shall hold  NET-2016 Examination in Online mode at 23 Centres across India in a staggered slot-wise examination.
    •  NET-2016 Examination during 01.08.2016 to 06.08.2016
    Age limit:
    • For NET-2016 A candidate must have attained the age of 21 years as on 01.08.2016. There is no upper age limit for the National Eligibility Test.

    Application Form available on the website: http://www.asrb.org.in.
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