Medullary Thyroid Carcinoma (MTC) originates from mutations in calcitonin-producing parafollicular C cells of the thyroid, is a rare malignancy, accounting for 3-4% of all thyroid carcinomas. It occurs in a hereditary form (HMTC, 25%) or in a sporadic form (SMTC, 75%). The prognosis for patients with MTC is poor, as the tumor metastasizes at early stages; and the only curative therapeutic option so far is radical surgery. Genetic analysis helps identify inherited cases at a stage where prophylactic surgery can be offered to carriers of such mutations to prevent the disease. This approach may also be used to determine better treatment options for patients who are already diagnosed with MTC.

The goal of this project was to develop a comprehensive mutational panel for the detection of clinically relevant mutations in MTC samples. A total of 143 mutations (nucleic acid variations) in 8 human genes were selected from numerous papers and public databases and included into the MTC mutational panel. The selection criteria were based on the coding mutations (mutations that occur in the coding area of the genes) that were reported to occur in MTC patients and considered functionally relevant. Some of the mutations included into the MTC mutational panel (such as BRAF gene V600E mutation) were also described in other types of thyroid cancer, but most of the mutations were unique to MTC (such as all RET gene mutations). The entire assay design was carried out using Sequenom's online design tools (ProxSNP and PreXTEND (https://www.mysequenom.com/Tools) and Assay Design software (v. 3.1)).

The final file comprised from 115 assays corresponding to all 143 mutations included into the MTC panel. This file will be further processed using the SEQUENOM® Mass-ARRAY iPLEX® platform for DNA genotyping of clinical samples by the cancer research scientists at the Abramson Cancer Center of the University of Pennsylvania

            Save for Anaplastic Thyroid Carcinoma (ATC), MTC is the second most aggressive type of thyroid cancer. Hereditary mutations that could lead to HMTC need to be found as rapidly as possible, as the onset age is only 5. This Mutational Panel is one of the best ways to diagnose any type of MTC, be it hereditary or sporadic, and give a small beam of hope to the poor person diagnosed with the mutation.

            The decision to make this panel was a hard one, as at the time that I started it, I was going to take pre-calculus in Drexel University. It was an insane amount of work, but I managed to compile the list of mutations over the summer, and continue the analysis during autumn. The actually write-up was finished much later, when I decided that I could use that project as my capstone.

            Simply put, the project was not easy. It took me a long time to understand the basics, and even a longer time to be able to manipulate small details, but in the end, the project was amazing. I have to say, that out of all the work I did while I was in SLA, this capstone project is the one I am proud of the most!

Development of a Comprehensive Mutational Pannel as an Effective Tool for Personalized Diagnostic of Medullary Thyroid Carcinomas

Medullary Thyroid Carcinoma (MTC) originates from mutations in calcitonin-producing parafollicular C cells of the thyroid, is a rare malignancy, accounting for 3-4% of all thyroid carcinomas. It occurs in a hereditary form (HMTC, 25%) or in a sporadic form (SMTC, 75%). The prognosis for patients with MTC is poor, as the tumor metastasizes at early stages; and the only curative therapeutic option so far is radical surgery. Genetic analysis helps identify inherited cases at a stage where prophylactic surgery can be offered to carriers of such mutations to prevent the disease. This approach may also be used to determine better treatment options for patients who are already diagnosed with MTC.

The goal of this project was to develop a comprehensive mutational panel for the detection of clinically relevant mutations in MTC samples. A total of 143 mutations (nucleic acid variations) in 8 human genes were selected from numerous papers and public databases and included into the MTC mutational panel. The selection criteria were based on the coding mutations (mutations that occur in the coding area of the genes) that were reported to occur in MTC patients and considered functionally relevant. Some of the mutations included into the MTC mutational panel (such as BRAF gene V600E mutation) were also described in other types of thyroid cancer, but most of the mutations were unique to MTC (such as all RET gene mutations). The entire assay design was carried out using Sequenom's online design tools (ProxSNP and PreXTEND (https://www.mysequenom.com/Tools) and Assay Design software (v. 3.1)).

The final file comprised from 115 assays corresponding to all 143 mutations included into the MTC panel. This file will be further processed using the SEQUENOM® Mass-ARRAY iPLEX® platform for DNA genotyping of clinical samples by the cancer research scientists at the Abramson Cancer Center of the University of Pennsylvania.

References:

1. Millis, M. (2011, Summer). Medium-Throughput SNP Genotyping Using Mass Spectrometry: Multiplex SNP Genotyping Using the iPLEX® Gold Assay. Springer Protocols, 700. Retrieved August 20, 2012, from http://link.springer.com/protocol/10.1007%2F978-1-61737-954-3_5

This paper discusses and explains the basics of genotyping with the using MALDI-TOF Mass Spectrometry. This was the first paper that I have read right after being given the project. After fully interpreting this paper, I realized that I am going to be able to finish the project on my own. This paper served as a guide to me throughout the process of doing this project, as well as while writing the entire research report. In addition, this paper was used to make sure that I am not saying something that is factually incorrect.

2. Gabriel, S., Ziaugra, L., & Tabbaa, D. (2009, January 1). UNIT 2.12 SNP Genotyping Using the Sequenom MassARRAY iPLEX Platform. Current Protocols in Human Genetics.

This paper describes in details the SNP genotyping method based on the Sequenom MassARRAY platform. It includes two step protocol (initial locus-specific PCR reaction, followed by single base extension using mass-modified dideoxynucleotide terminators) an assay structure and how using MALDI-TOF mass spectrometry identify the SNP allele. The paper is mentioned in the corresponded section of the Introduction.

3.      Ricarte-Filho, J., Ryder, M., Ghossein, R., Fagin, J., Chitale, D., Rivera, M., et al. (2009, June 1). Mutational Profile of Advanced Primary and Metastatic Radioactive Iodine-Refractory Thyroid Cancers Reveals Distinct Pathogenetic Roles for BRAF, PIK3CA, and AKT1. CANCER RESEARCH. Retrieved July 1, 2012, from

http://cancerres.aacrjournals.org/content/69

The paper describes profiling of 111 mutations in RET, BRAF, NRAS, HRAS, KRAS, PIK3CA, AKT1 genes in clinical poorly differentiated, anaplastic and radioactive iodine-refractory differentiated thyroid cancers. The genotyping method is based on the Sequenom MassARRAY platform. It was shown that RAS mutations were prevalent in primary PDTC, whereas BRAF was more common in metastatic PDTC and ATC. PIK3CA or AKT1 mutations were rare. The paper is mentioned in the corresponded section of the Introduction.

4. MEN2 Database. (n.d.). AURP Scientific Resource for Research and Education.. Retrieved July 12, 2012, from http://arup.utah.edu/database/MEN2/MEN2_display.php

This database was only used for its mutations list during the collection phase of the project.

5. Human BLAT Search. (n.d.). UCSC Genome Browser. Retrieved August 17, 2012, from http://genome.ucsc.edu/cgi-bin/hgBlat

The Human BLAT database was used for alignment of nucleic sequences. The sequences retrieved from COSMIC were inputted in the BLAT Database to be aligned with the rest of the nucleic sequence, as only a small part of it could be gathered from COSMIC.

6. Catalogue of Somatic Mutations in Cancer - COSMIC. (n.d.). Wellcome Trust Sanger Institute. Retrieved July 10, 2012, from http://www.sanger.ac.uk/genetics/CGP/cosmic/

This database was used to retrieve the nucleic sequences that were used as the base to be inputted in the BLAT database. As it is impossible to use BLAT database with only knowing the position of the mutation, COSMIC was used to retrieve the minimal part of the sequence required to find the full nucleic sequence for any particular gene.

7. Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®). (n.d.). National Cancer Institute. Retrieved July 12, 2012, from http://www.cancer.gov/cancertopics/pdq/genetics/medullarythyroid/HealthProfessional/Table4

This database was only used for its mutations list during the collection phase of the project.

8. OMIM Entry - # 171400 - MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIA; MEN2A . (n.d.). OMIM - Online Mendelian Inheritance in Man . Retrieved July 19, 2012, from http://omim.org/entry/171400

This entry was used as the basis of understanding of the MEN 2A syndrome. It talks about the relationship between MTC and diseases such as pheochromocytoma, and about the basics of what MEN 2A syndrome actually is. In addition, it talks about what mutations are associated with the syndrome. It was specifically used for comparison with the MEN 2B and FMTC.

9. Jimenez, C., Hu, M. I., & Gagel, R. (2008, Spring). Management of Medullary Thyroid Carcinoma. Elsevier Saunders, ?, 15.

This MTC review was the first of many that I have read in the duration of this project. This review provided me with the basic information about MTC without which any attempt at actually finishing this project would have been obsolete. Many parts of the introduction are referred to this paper, as it was very influential. Similarly to many other sources, mutations were taken from this publication during the first phase of the project.

10. MacConaill, L Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples. PLoS ONE (2009). http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007887

This publication was one of many that were used only for its mutations. No part, except for the abstract, which contributed to the overall idea of the research report, has been read.

11. Ehsan Alvandi, Seyed Mohammad Akrami, Mohsen Chiani, Mehdi Hedayati, Babak Noori Nayer, Mohammad Reza Mohajeri Tehrani,et al. (2011, April 5). Molecular Analysis of the RET Proto-Oncogene Key Exons in Patients with Medullary Thyroid Carcinoma: A Comprehensive Study of the Iranian Population. Thyroid, 1. Retrieved September 1, 2012, from http://online.liebertpub.com/doi/abs/10.10

This publication was one of many that were used only for its mutations, and or one small piece of information. No part, except for the abstract, which contributed to the overall idea of the research report, has been read.

12. Moura, M., Cavaco, B., Pinto, A., & Leite, V. (2011, February 16). High Prevalence of RAS Mutations in RET-Negative Sporadic Medullary Thyroid Carcinomas. JCEM ONLINE, 95, 6.

This paper has shown a study where 64% of the patients that had Sporadic MTC were found to have a BRAF mutation in position 600. This is very unusual as this mutation is considered to be PTC specific. In addition, this publication has given additional context to this research report. Similarly to many other sources, mutations were taken from this publication during the first phase of the project.

13. OMIM Entry - # 162300 - MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB; MEN2B . (n.d.). OMIM - Online Mendelian Inheritance in Man . Retrieved June 19, 2012, from http://omim.org/entry/162300 

This entry was used as the basis of understanding of the MEN 2B syndrome. It talks about the relationship between MTC and diseases such as pheochromocytoma, and about the basics of what MEN 2B syndrome actually is. In addition, this entry talks about what mutations are associated with the syndrome. It was specifically used for comparison with the MEN 2A and FMTC.

14. hybridization, f. i., & (1989), I. e. (n.d.). OMIM Entry - + 164761 - REARRANGED DURING TRANSFECTION PROTOONCOGENE; RET . OMIM - Online Mendelian Inheritance in Man . Retrieved July 19, 2012, from http://omim.org/entry/164761

This entry was used as the basis of understanding MTC, and why the mutations RET gene are found in so many cases of MTC. Unfortunately, as with many other publications, no definitive answer was given. This entry was also used as a guide, to make sure that what I say about mutations in RET gene is factually correct.

15. RT-PCR., & (2003), M. e. (n.d.). OMIM Entry - # 155240 - THYROID CARCINOMA, FAMILIAL MEDULLARY; MTC . OMIM - Online Mendelian Inheritance in Man. Retrieved July 19, 2012, from http://omim.org/entry/155240

This entry was used as the basis of understanding of the FMTC syndrome. It talks about the relationship between MTC and diseases such as pheochromocytoma, and about the basics of what FMTC syndrome actually is. In addition, this entry talks about what mutations are associated with the syndrome. It was specifically used for comparison with the MEN 2B and MEN 2A.

16. Hazard, J., Hawk, W., & Crile, G. (1959, January 1). MEDULLARY (SOLID) CARCINOMA OF THE THYROID—A CLINICOPATHOLOGIC ENTITY. JCEM, 19. Retrieved June 26, 2012, from http://jcem.endojournals.org/content/19/1/152

This publication was the first time MTC was classified. The paper itself was not read by this applicant, however, due to its historic relevance, it was referred to in the first paragraph of the introduction.

17. Cakir, M., & Grossman, A. (2009, May 25). Medullary Thyroid Cancer: Molecular Biology and Novel Molecular Therapies. Neuro Endocrinology, 25.

This publication, alongside many MTC reviews, was used as the guideline for this research report. Many facts, such as information about Sporadic and Hereditary MTC were confirmed by this publication. Similarly to many other sources, mutations were taken from this publication during the first phase of the project.

1.    Who you spoke with and why you chose that partner:

- SharedTalk; Miki

What did you learn about them? What did you learn from them?

He is my old friend, one of the people that I talked to on sharedtalk before. I know enough about him, such as how he learned English, and it was really through sharedtalk which is a fun fact, but also, he asked me to help him out a bit with a problem, and I did, but all I have from that conversation is a small ss, because interned decided to turn off for a bit.

2.    /How did this interaction help you move towards achieving your personal goals?

Again, he learned English on Sharedtalk, which is awesome, and really fits my goal of learning how others learn English.

3.    What specifically did you do well according to your goals/expectations? What specifically to you need to improve on?

I think that the best thing that I did was helping him out, which really felt nice, but as for my goals, figuring out that Ecuadorian people speak English and call white guys Gringo!!!!!

What specifically do you need to improve on? (Quote specific things you said or did and what you would have done or said if you could do it again)rc

I think I improved a lot overall, so I would say that our conversation was on a pretty high level.

Who did I speak with and why did I choose that person?
I spoke to Marco. He is cool I guess, and we had a long discussion, but I was only able to ss one small part of our discussion.

What did you learn about them? What did you learn from them?
I learned that he learned English for two years and Russian for a little while, I learned how he did it, his reasons and…. Then we just talked about our lives in both languages.

How did this interaction help you move towards achieving your personal goal?
My goal was and is to find out about people’s language skills, which means that this one obviously helped a lot.

What specifically did you do well according to your goals/expectations?

I… simply learned about him. I did not follow my goal too much, but for a good chunk of our discussion, I did, so… yea!

·       Who did I speak with and why did I choose that person?

I talked to a Charles in my conversation, and obviously I chose him because he responded.

·       What did you learn about them? What did you learn from them?

I learned that he loves anime, and speaks English pretty darn well.

·       How did this interaction help you move towards achieving your personal goal?

He is the first one to correct me, so it helped me in more then one way!

·       What specifically did you do well according to your goals/expectations?
Since my goal was to learn about him and life there, I’d say that this Dominican republic guy was pretty helpful!

·       Who did I speak with and why did I choose that person?
Talked to Nayeli, and I chose her, because she is a cool girl, and likes chess (I found that one out later.

·       What did you learn about them? What did you learn from them?

It seems that she loves to play chess, and have been learning English for some time on her own, and a bit in special classes. She is actually quite an interesting person.

·       How did this interaction help you move towards achieving your personal goal?

Since my personal goal is to find out more about how people learn different languages, I believe learning about her way of “learning” is quite interesting and helpful!

·       What specifically did you do well according to your goals/expectations?

I actually hadn’t used translator all that much, and like I said, I have learned about her way of learning English.

·       What specifically do you need to improve on? (Quote specific things you said or did and what you would have done or said if you could do it again)

My grammar unquestionably.

o   Who you spoke with and why you chose that partner

The girl’s name was Astrid, and I talked to her because she actually responded!

o   What did you learn about them? What did you learn from them?

We didn’t get a chance to finish our conversation, but I know that she is about my age, a bit older, and she is learning English on her own, which is really hard!

o   How did this interaction help you move towards achieving your personal goals?

My new goal is to find out about people’s abilities to speak languages that are not their own (having me as the test subject as well) I am pretty happy with this discussion.

o   What specifically did you do well according to your goals/expectations? What specifically to you need to improve on? (Quote specific things you said or did and what you would have done or said if you could do it again)

o   I am pretty sure that if I could do this again, I would do it the same way.

• Who did I speak with and why did I choose that person?

  My guy was guillermo from argentina, and... we just talked around, he in english, me in spanish, and each of us was correcting each other when needed, kind of a mutual help discussion thingy going on between the two of us!

• What did you learn about them? What did you learn from them?

  He is a cool guy who wants to go to england or USA, and maybe Canada. He is pretty darn good at english, and, obviously, really good at spanish! 

• How did this interaction help you move towards achieving your personal goal?

  My personal goal was to improve my verb conjugation skills, and I think I got that covered pretty gosh darn well!

• What specifically did you do well according to your goals/expectations?

  I think that instead of conjugating verbs incorrectly, I did it correctly!

• What specifically do you need to improve on? (Quote specific things you said or did and what you would have done or said if you could do it again)rc

  It is kind of hard to specify what I was bad at, my best guess would be sentence structure, and I think that I would think about saying things twice before saying them next time!
  
  

For my group’s project we had to debate a lot of things. First of all, one of the most important debates that we had, was what particular way of presenting we will do, and while it wasn’t a large debate since we all are obviously stronger with websites than any other way of presenting, we still argued a bit, over what we should do. After that, came the actual debates. I wanted to have a lot of things some of them being very important, like wanting the color of the font not to be black, however, since all three of my group mates said that black will be the very best color, we have decided to go with the black color, and things like that.

After all of the debates were over (well, not all, there were more to come) we have decided to go with the Iweb, black font, psa the way it is, and having to work with my least favorite type of website maker, however, I grew to like it after this project. I found that it is a lot easier to use than any other type of website maker. However, after the whole website was done, and we were ready to upload, we couldn’t publish it, and thus we decided to move back to the weebly.com idea.

Through a lot of debating and not knowing what, why and how to do and or start this particular project, we ended up with what we have right now, and it actually turned out to be very good. We were also debating on how we should implement it, and the best way that we found was to publish it, and twitter/facebook/myspace people about it, and make sure that people know about it, thus if some people know about it, others will come around, and so on, in a never-ending circle of social websites, this website will be the light in the end of the tunnel for the students that are in danger of dropping out.

Choosing a topic is a very important part of any one project. I however, already had an idea of a research in mind, before I even learned about NHD. One of my old history teachers from Russia (that I still am in contact) was making fun of me, because I did not know the basics of my own country’s history. At that point in time, I had decided to pick an event, and find out about it, as much as I can. I picked up a book that was written by Leo Trotski about 1917 democratic and communist revolutions. Little did I knew, that on the next day, my history teacher was going to tell us about the NHD.

            My research started from the book that was mentioned above. I wanted to educate myself about that time period, and so within that week, I almost finished the first half of that book. After my teacher told me about this project, I decided to stop at the point that I had gotten to, and look for specifics about events online. I was searching throughout the internet for websites and diaries that could explain me, what drove people to come out to the streets, forsake their very lives, and fight for what they believed was equality. People like that deserve to be praised, and not squished into one event by a powerful compressor which is history.

            The category selection was the hardest thing to choose for me. I was unsure of what my biggest strength is, but in the end I choose a website, because in it, I had the opportunity to express my opinion on paper, and also support it with as many claims as are needed. While a research paper would have a similar concept, I felt a lot more comfortable with actually having an opportunity to have a website that is a bit more interactive than a paper can possibly be.

            When I was doing a project, I had a very important choice to make. I could have choose one particular revolution, and while concentrating on that, I would be able to explain everything in a lot more details, however I felt that it would not be as strong of a project. I decided to combine 3 revolutions, and I am claiming that the true change in them was not as simple as the cosmetic change from one government to the other. I decided to attempt to show that the way people behaved changed, and while their reasons were the same, and all of the reforms were simply cosmetic, throughout those 3 events, the true reform occurred inside of everybody who was inspired to go out, and sacrifice his own life for what he believed.

What did you learn from doing this project?  

How do you feel about your final product?

If you could do your project all over again, what would you do differently/the same?

·       Mi grupo y yo hicimos un PSA sobre...My group and I did a PSA about...

·       Mi grupo hicimos un PSA sobre arbolas!!!!!

·       Por crear el PSA, la cosa más importante que aprendí fue...By creating this PSA, the most important thing I learned was...

·       Por crear el PSA, la cosa mas importante que aprendi fue arboles muy importante con enviromente, porque CO2 es no bueno, y O es muy bueno!!

·       Me gusta el PSA de mi group porque... Ellos en muy comica, pero muy “hard” a trabajo y completa proyectos, es possible, pero “hard”

·       Si pudiera hacer el proyecto otra vez, yo cambiaría...If I could do the project again, I would change...

·       Si puduera hacer el proyecto otry vez, yo cambiaria pasado frases, porque los frases no es bueno.

Algunos cosas son fácil,

Yo no me gusto desconocido

No me gusto

No me gusto

Yo duermo en la cama

Y yo pienso sobre Rusia

Yo me gusto nieve perpetuas

En el invierno

Yo me gusto calido verano,

Aunque el es muy corto

Y también, yo no me gusto presidente

Algunos cosas son difícil,

Algunos cosas son fácil,

Yo no me gusto desconocido

No me gusto

No me gusto

Yo sentarse en mi silla

Y pienso sobre USA

Yo me gusto los gentes

Que vienen desde todas partes

Y me gusto los películas

Que son hicieron en “Hollywood”

¡Y también, no me gusto la futbol Americana!

Algunos cosas son difícil,

Algunos cosas son fácil,

Yo no me gusto desconocido

No me gusto

No me gusto

Y me gusta USA!

Porque me gusta los paises?

Yo no se!

"Maybe you should shut the hell up before I kick you!"

"And who is going to do it, your mommy?"

"No, I will personally do it!"

"I hate you so much, I will ***"...

            Arguing with Ilia, and cursing pretty badly at each other, I did not notice my mom walking towards me on the street. She was shocked. I always was a very polite person at home, never cursed, and practically was a different person then she saw just now. Unfortunately for myself, I used to lie about the fact that I never curse, but after seeing that, she understood that it all.

"Sergey Kuznetsov, I can't believe what I am hearing!"

"Am... mom? What are you doing here, I thought that you weren't going to the store today, how much did you hear?"

"I have heard enough, you both are in so much trouble! You yourself are grounded, and Ilia's mother is going to hear about this as well!"

"Mom, please, we didn't mean what we said, it was just a joke!"

"Maybe you should have thought of it before, lets go!"

She didn't even want to talk to me after it. Even up until now, I am trying to understand why I used to change the way I talked with people so drastically, but no matter how I approach the problem, I can't. Changing the way I speak still helps me drastically, but while I am growing older, I start changing a lot less, and acting more similarly everywhere.

It is very possible that one of the reasons that I have spoke that way, was because I accidentally entered the reverse speech stage. It sometimes happens to me, when I go to extremes with my feelings, and at that moment I have really been disappointed about what happened. As was said by By Kathy J. Jeffries "the Reverse Speech of a person indicates their subconscious or unconscious thoughts. The Reverse Speech of a person indicates truthful responses or thoughts. The subconscious cannot lie. These thoughts can be on a conscious level, contradicting or confirming the forward speech. This would be the first level of Reverse Speech. The second level of Reverse Speech reveal a persons personality make-up, emotions and thoughts that are not on a conscious level. These reversals use metaphors to communicate the messages from our unconscious mind. The third level of Reverse Speech indicates emotions and feelings from within our deep self. Third level reversals use archetypes as well as metaphors to describe ones' innermost beliefs. As third level reversals come from the very core of ones' being, they are very powerful in their meaning." When I spoke to my friend, I have been only in only in first level of reverse speech. If my mom hadn't stopped me however, I might have even entered the 2'd or 3'd stage, which would probably cause a break of our friendship to occur. The hard thing is to know when to stop, when you enter the first stage. Anyone can enter those stages, but the ones that may actually hurt from them are politicians. If they accidentally say something to the press that they should not hear, then their life would be destroyed.

            Code switching also is a very big issue, especially when people are starting to learn a new language. (Author unknown, Power of code switching) "Professionals studying code-switching continue to debate about the advantages and disadvantages of code-switching for second language learners. Some arguments against code-switching say it is not a true language; one is not fluent enough in either language if code-switching is necessary; or, code-switching is not academically appropriate. On the other hand, there seem to be more arguments in support of code-switching." This person states that there are two sides of the coin in code switching. If both are taken in consideration, it is neither  good nor bad. It makes people harder to understand, but at the same time, if a very literate person is trying to say a metaphor in English, but only knows how to say it in his native language, he or she should be able to say it in English, and if they get a bad reaction, then they may explain what they have mean.

"Serge, are we not late?"

"No, it's only 4 PM, we still have 3 hours."

"How did you know, did you look at the clock when I didn't notice?"

"No, my organism works like clocks!"

"What do you mean?"

"Well it means that I can feel what time it is, and approximate, apparently this time I was correct."

"Hm, If you say so."