Introduction: cell will die. Adopted from: https://www.researchgate.net/publication/315849444/figure/fig3/AS:[email protected]/Illustration-showing-the-production-route-of-hybridoma-technology-Monoclonal-antibodies.png Hybridoma

Introduction: In 1975 Monoclonal antibody was first produced by Kohler and Milstein.

When antibodies are made by identical immune cells which are clones of parent cell is called monoclonal antibody. For the production of monoclonal antibody hybridoma technology is used where B-cell is made immortal by fusing them with Myeloma cell. The fused cell is known as hybridoma.Principle: To produce monoclonal antibody, hybridoma technology is very important. B cell is involved here which can produce an antibody that have single specificity, Production of B cell or plasma cell can be impelled by the immunization of an animal with an antigen. The B cells produce specific antibodies for different epitopes of the antigen. But it is quite difficult to maintain these cells in culture medium, which prohibit production of MAbs.

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In this technology to make B cell immortal it is fused with myeloma cell which is an artificial medium. It can overcome the death of plasma cells in culture medium but not possible to control the cell become malignant, and the anitbody which produced are useless. Hybrid cell formation by the fusion of normal and malignant cell can solve the problem. These hybrids were named as heterokaryons.Sendai virus was helped for this fusion but more efficient fusogen is PEG (Polyethylene Glycol).

In the medium all other cells except the fused hybrid cell will die. Adopted from: https://www.researchgate.net/publication/315849444/figure/fig3/AS:[email protected]/Illustration-showing-the-production-route-of-hybridoma-technology-Monoclonal-antibodies.pngHybridoma Production of Monoclonal Antibody: In monoclonal antibody production by hybridoma technology there are some following methods-1.

Immunization: Immunogen is injected into the laboratory mice. It is mixed with suitable adjuvant and injected intradermally or subcutaneously. This injection procedure should be in repeated manner. Blood sample is taken and assayed for the presence of the desired antibody. If the antibody is present and is in desired amount then the mice is sacrificed and it’s spleen is disintegrated into spleenocytes. 2.

Cell Fusion: In this step the acquired spleenocytes are fused with plasmacytoma cells. This fusion takes place in a suitable medium like PEG (Polyethylene Glycol). The concentration of the medium must be high (about 50%). This mixture will later form the hybridoma.3.

Selection: In the selection step the fused cells are incubated in HAT medium (Hypoxanthine-Aminopterin-Thymidine medium) for kind of 10 to 14 days. The viable hybridoma cells are formed in this medium. Afterwards they are transferred to a regular culture medium. The incubated medium is then diluted into multi-properly plates (96-well plastic culture plate) to such an volume that every well contain only one cell. The medium in each well is examined periodically.

4. Screening: The next step is a speedy primary screening system, in which the most effective hybridomas that produce antibodies of suitable specificity are identified. This screening is done by ELISA test.

Antigen is applied in the bottom of the well of the culture plates. Samples of produced antibody is incubated in the wells. Antigen-antibody bind together. So, if the desired antibody is present in the sample then it’ll bind with the antigen and stay in the plates. While washing the bound materials are retained and the unbound materials are washed away. 5. Cloning: The B cell that produces the desired antibodies can be cloned to produce many same daughter clones.

The cloning techniques are Limiting Dilution Method and Soft Agar Method. They can be used individually but most of the cases combined. In limiting dilution method, 96-well plastic culture plate is used for cloning. The hybridoma cells are diluted and each cell is planted in each well. This process is repeated and it ensured that monoclonality is attained. In the alternative method hybridoma cells are cloned in a single plate containing soft agar medium where the cells form spherical colonies. 6. Characterization and Storage: The monoclonality of the antibodies is established by biomedical and biophysical characterization of the antibodies using spectrometric, electrophoretic and chromatographic methods.

The suitability and stability of the antibodies for therapeutic and diagnostic purpose is determined through this process. Antibodies are preserved in frozen liquid nitrogen. Some are stored for running the further cloning process. REFERENCEKulkami, G. (2002). Biotechnology and its applications in pharmacy, New Delhi: Jaypee Bros Medical Publishers.

Introduction: of art we try to see

Introduction:Art is an “expression of the human creative skill and imagination, typically in a visual form such as painting or sculpture.” Art captures time and is presented by many standpoints that have been expressed in a visual form for us to interpret. Art teaches us perspective as we look at a work of art we try to see into the minds of artists and why has the artist used specific color schemes or shapes to represent what he was thinking of the time. Many artists use their form of artwork to pass along their views and feelings hence the images produced by them can express an innovative way of seeing the world from their perspectives.

In my essay, I will be focusing the art movement of “Surrealism”. It is a style in art and literature in which ideas, images, and objects are combined in a strange way, like in a dream. The Surrealists attempt to channel their unconscious state of mind as a means to unlock their power of the imagination. Therefore this topic boils down to one question, How Did Female Surrealists Aim to Subvert the Male Gaze within Surrealist Photography? Surrealism began in Paris in 1924 and was later moved to Mexico and the United States and it had a huge impact on women artists. The tale of surrealism in the United States started by including two women artists, Lee Miller and Rosa Rolanda, who appeared from different sides of the country (New York and California, respectively) and discovered themselves in 1920s Paris modeling for an artist and photographer Man Ray (the United States, 1890–1976). Both women were decided to build their own uniqueness, and they used innovative methods in photography to begin an investigation of their imaginary worlds and themselves.Unconsciously, surrealism became the beginning of two tides of creativity: the imagined, which arose from intelligence and was created originally by men, and the intuited, which arose from the artist’s experience and was generated mostly by women. The women’s art reflected the female psyche as beauty and it surprisingly began a new conversation between the different artists that increasingly modified the relationship between the genders.

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Although the male surrealists in Paris during the 1920s examined the unconscious within dreams and their paintings did not significantly expose the individual experiences. In this, the women differed considerably from their male counterparts, as their art often reflected personal wounds and tortures. For them, surrealism became a means of increasing self-awareness, searching their inner thoughts and feelings, dealing with their experiences, and discovering or building their true identities. (1, lamca)The themes that dominated the work of women surrealists in Mexico and the United States reflected the artists’ past experiences, present-day situations, fears, hopes, and desires.

The feminine exchange between the self and the other was distinguished from the male surrealists’ outward projection of their motives. Femininities transformed the female body into a site of protection, psychic power, and creative energy. They also improved set the stage for the feminist evolution by creating art that inspired social institutions and gender boundaries.Since the time of the Egyptians, portraits have served as reports that record an individual’s likeness at a particular moment in time. While conventional portraiture provided information and hints about the sitter’s characteristics, interests, social status, or history, because many of the art of women surrealists were self-referential in nature, portraiture was an ideal vehicle for exploring identity. (1, lamca)Objectification of women in Male Surrealist art depicted the male gaze in its darkest form, through the ideas of the uncanny, obsession, and convulsive beauty. Women were treated as objects throughout Surrealist photography and painting instead of as human subjects. Their femininity and beauty were valued to the extent of held belief that a woman’s destiny is to be beautiful and be present for the male gaze.

Women Surrealists have gained notoriety in the last sixty years for their presence in the Surrealist movement and for their perseverance in providing the female perspective in opposition to the male perspective.Surrealism was a gated realm created exclusively for male artists, the majority of whom objectified and fetish zed women. For a female artist to unlock this gate, she had to fulfill the male artists’ need for narrowing the role of women down to an object of male desire. This conception of women blinded male Surrealists to the fact that women were individuals with multi-faceted characters, who wanted to be more than their inspirations. Because of their blindness to women’s capabilities, women “functioned within male Surrealist works at best as an idealized other, at worst as an object for the projection of unresolved anxieties.

” (3, frieze)Being a part of the movement as a female artist did not prove the same amount of respect, which was given to their male equivalents. Due to these problems, artists Frida Kahlo and Claude Cahun, despite exhibiting with the Surrealists and using their visual vocabulary, never became official members of the group. They used Surrealist practices, such as having dream-like images and mirrors in their art, but rather than using such practices to objectify women, they used these techniques to overcome ‘the subject-object split’, which was one of the core tenets of Surrealism. The male Surrealists were not able to defeat this duality due to their fascination with “seeking transformation through a female representational object, which paradoxically reinforced the subject-object split that Surrealism was dedicated to overcoming.” Kahlo and Cahun, on the other hand, defeated this duality by practising their art as a venue to characterise themselves as subjects, and not objects. Despite being females and not being a part of the movement, Frida Kahlo and Claude Cahun used one of Surrealism’s base assumptions to knock the male artists at their own game.Due to her life-long argument against female objectification, Kahlo is an inspiration for women to break out of gender stipulations. By rectifying her body and apprehending it in the paint, she still summons and flouts the roles and rules society placed on her.

Through her art, even after death, she refuses to let her individuality be boxed, wrapped and ribboned by anyone, and does not remain silent about her uniqueness. In her work, her gaze is never tractable. Even when subjugated, it speaks against the compact, pleasurable descriptions that women are forced into. Kahlo’s self-portraits “do not employ the traditionally gendered symbolism of establishment but subvert them to overthrow the binary-driven hierarchies of art and the colonizer-colonized.” By putting the colonizer and the colonized, the male and the female, into the same space without any boundaries, Kahlo overwhelms the subject-object split that previously divided these entities.

With this act, she interjects women to the fact that gender should not be inhibiting them from raising their social status to the same level as men’s. (5, scholarcompass)

Introduction: next in rank to the first

Introduction:Prostate cancer is considered to be next in rank to the first reason of cancer throughout the whole globe.

According to a research 29,000 men was predicted to be dead due to prostate cancer in 2014. It was found that testosterone suppression with hormone therapy paved a milestone in the treatment of patients who were having severe metastatic disease. The initial attempt to reduce the amount of testosterone and modifying the AR axis was believed to be a controlling factor for this disease. (Sternberg, Petrylak, Madan & Parker, 2014)Being the second purpose of death prostate cancer is common mainly in male. The scopes of treatment for such cancer are ADT (Androgen deprivation therapy) or castrating surgically or chemically.

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Though these treatment options are highly effective but after some times CRPC is seen in the patients. Because of the CRPC implementations of other therapies have been made and androgen axis can be blocked. So, this has made the androgens and AR signaling pathway a very significant in prostate cancer advancement. In addition to their effects on the prostate tumor cells the ADTs show impact on the immune system too. (Gamat & McNeel, 2017)For the treatment of repeated prostate cancer the ADTs are the basic options. The ADTs have systemic immunomodulatory effect and cases thymopoiesis.

In the modern time the combination of ADTs with immunotherapy has been showing the ability to improve the output of prostate cancer immunotherapy. Clinical trials of such combination therapies are already being investigated but there remain some doubts on 1) the best androgen-targeted-agents, 2) best series of therapies and 3) the applicability of these combination therapies. It is expected that within the next 5-10 years we might be able to clarify these doubts and ultimately it will lead us to design a safer and sustainable treatment therapy of prostate cancer. (Gamat & McNeel, 2017)?Objectives: The core objectives of this particular study on “Anti-androgen therapies in prostate cancer” are:• To have an insight of prostate cancer.• To understand how anti-androgen therapies are given.

• To know the pharmacokinetics of anti-androgens.• To know about ongoing researches.• To know about few cases. ?Prostate Cancer:The androgen testosterone are the elementary agonists for the AR while the DHT( dihydrotestosterone) being the most useful one. These can attach on the AR-LBD and can cause a conformational change and as a result the foldsome can be moved to a new location and the AR can dislocate inside the nucleus. Then dimerization of the AR takes place and the AR interact with DNA androgen-responsive elements(AREs) and finally cell proliferation takes place. (cano et al.

, 2013). The additional transactivation of AR can be done through growth factors and cytokines. The sophisticated activity and biology of the AR is also related with AR signaling that is started from the MISS which are the binding sites and the plasma membrane being the location of the MISS. The MISS can be further explained in multiple cell lines, even the cells produced from prostate cancer and it is separable from the observable effects that are related to the NISS.

According to Pelekanou et al. it is stated that “membrane androgen binding sites have been described in cell lines and prostate specimens, even in the absence of the full length receptor FL-AR.” (Pelekanou & Castanas, 2016)Though there’s been a major improvement in the drug development of prostate cancer castration resistance disease in found in the majority of the cancer patients of prostate cancer.

Firstly we need to understand what CPRC is. CPRC can be defined as a condition where the androgen signaling remains prominent by the cells and in addition to that they can evade cell death or apoptosis even under the ADT. In order to elucidate the disease condition such term CPRC is applied even if the testosterone level in the circulation persists in castration range (50 ng/dl, alternative to 280-1100 ng/dl which is considered as normal in males), on the other hand tumor growth remains at large due to the AR signaling.

According to few researches the castration resistance can be done based few mechanisms such as, 1) AR and ligand dependency, 2) AR dependency and ligand independency, 3) AR and ligand independency. (Pelekanou ; Castanas, 2016)?The imprimatur of abiraterone and enzalutamide has been a break through event in the medication of advanced CRPC which in turn pushed the level of management of prostate cancer to a whole new level. And the advantages were found to be in the recoil of the disease, clinical profit, and better tolerance. Even though with this much huge advancement the ADT resistance is being a significant problem for the enzalutamide and abiramide. According to Narayanan et al,. a study from 2016 stated that, “nevertheless, these two drugs have provided strong evidence on the importance of AR targeting, even under castration resistance”. Abiraterone and enzalutamide both have been able to show elevated containment of this cancer and such facts obvious.

These two drugs have been able to provide the mechanisms that refer to the AR axis, drug resistance improvements, tumor cell anointment even under the ADT. (Pelekanou ; Castanas, 2016) Among the other achievements that these two drugs have earned are:• Influencing glucocorticoids with AR.• Differentiating treatment induced-neuroendocrine.• Activating AR variants steadily. ? Figure: AR signaling axis and mechanisms of AR targeted inhibition. Here we can see the mechanism of AR signaling and how the prostate cancer is being developed and several AR target inhibitors. The CYP17A1 is the main thing that is causing the conversion of androgen precursors to DHEA and the AD is made from DHEA and this is done by HSD3?1. Testosterone is made from AD with the help of AKR1C3 and ultimately testosterone is converted into DHT by 5?-reductase.

When the AR is activated by the DHT a structural modification is seen at the location where the dimerization of AR takes place and after that the translocation of AR occurs towards the nucleus.And in the nucleus the AR binds with the DNA and then the DNA under goes transcription which results in biologic responses such elevated growth of the prostate, increasing the PSA and the survival rate of the cancer cells.?Anti-androgens:Anti-androgens are the name given to a diverse group of medicines that counteract the effects of the male sex hormones, testosterone and dihydrotestosterone. The basic principle is some anti-androgens work by lowering the body’s production of androgens while others block androgen receptors, limiting the body’s ability to make use of the androgens produced.The term ADT is referred to the decrease or inhibition of the gonadal androgen manufacture or signaling. It has been 70 years since this has been a portion of the norm of endeavor for prostate cancer patient.

(Huggins and Hodges, 2002). In the early stages medical castration done and after that GnRH agonists were used. Deduction of LH, FSH secretion and testicular testosterone production are the most known disadvantage of such agonists. In addition to that glucocorticoids are used in order to suppress androgen synthesis. Through the invention of AR antagonists which are also known as anti-androgens the activity of androgens can be inhibited. Bicalutamide, flutamide, nilutamide being the first gen antagonists while the enzalutamide is the second gen antagonist.

It is seen that Ketoconazole can also block the Cytochrome P450 enzymes by which the testosterone is biosynthesized. Because of being most accurate and powerful blocker of androgen synthesis Abiraterone is being used even though it has been established newly. The synthesis of androgens can be contained in the testes, besides in the cancer cells of prostate gland by Abiraterone.

(Pelekanou ; Castanas, 2016)Enzalutamide:Among the anti-androgens Enzalutamide belongs to the second generation of drugs and acts of several steps in the AR signaling pathway. Its main action is to inhibit the androgen from attaching to AR and this inhibition in don in competitive manner. The major advantages of Enzalutamide over the 1st gen of anti-androgens are that the translocation of AR can also be blocked by it as well as DNA attachment and co-activator recruitment. The identification of Enzalutamide was made through the quest of finding nonsteroidal anti-androgens that can show activity even when the AR expression amount is very high. (Rodriguez-Vida, Chowdhury, Sternberg, Rudman ; Galazi, 2018)Confocal microscopy that was done in live LNCaP cells by researchers found that when enzalutamide was used the ratio of nuclear versus cytoplasmic AR was decreased to about fivefold comparing to bicalutamide. They also demonstrated that impairment of nuclear translocation of AR was also done by Enzalutamide.

Another study was also done, in this case a VCap cell lines having endogenous AR gene enhancement and CRPC were used. The results were quite good relative to bicalutamide. Apoptosis and growth were found to be subdue by enzalutamide which tells us that enzalutamide was able to show the blocked effect on AR even in CRPC containing situations. (Rodriguez-Vida, Chowdhury, Sternberg, Rudman ; Galazi, 2018) Figure: Mechanism of action of enzalutamide in the androgen receptor signaling pathway. Obtained from: http://dx.

doi.org/10.2147/DDDT.S69433Here we can see how enzalutamide is giving its anti-androgen effect. Firstly it is competitively inhibiting the testosterone to bind with the AR.

The secondly it is inhibiting the nuclear translocation of the AR into the nucleus. Then again lastly enzalutamide is also inhibiting the transcription process of DNA which ultimately leading to the death of the cancer cells.

INTRODUCTION: factors result in the politics and the

INTRODUCTION:Geopolitics is the analysis of how geographical factors result in the politics and the economics of the country The term geography is evolved by introducing borders between different regions. These borders are introduced mainly to ensure security and to protect the culture. Some of the other factors that brought borders on the globe are to gain some economic benefits such as foreign direct investment, imports/exports. In addition to this there are also some natural borders such as oceans, mountains, rivers etc.

Some of the examples for physical borders are:- pyrenees mountains which separate france and spain- ural mountains which divide asia and Europe- niagara river which separate Canada and usa- himalayas which separate india and china The factors that affect geopolitics are population, natural resources, military power, currency value of the country, cultural values of the country, GDP of the country. There are two forms of powers in geopolitics. they are: 1> hard power 2>soft powerWhere hard power involves military power and economic power. The different forms are nuclear weapons, eligibility to spread military power across the globe and Soft power involves cultural power.

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There are different forms of powers in all the countries where some of the countries use hard power and some other countries use soft power. There are countries which also adopt smart power that is use of both smart power and hard power. Hence the above mentioned are the factors that made geopolitics into existence and following on are the different powers in geopolitics.RISE OF GEOPOLITICS:The word geopolitics was originally driven by Swedish political scientist Rudolf kjellen and it was got into existence in Europe during world war 1 and world war 2. Later it was spread throughout the world.

Mahans study of rise of the british empire was intial stage of geopolitics which resulted in the formation of geopolitical thought which contains of heartland theory and rimland theory. HEARTLAND THEORY: This theory was given by mackinder in 1904 which is also known as geographical pivot of history. Mackinder described that there were continuous wars for land and water. He also explained that earth has huge landmass which is included of Asia, Africa and Europe. So mackinder divided the earth into three different parts. They are:The heartland The inner and marginal crescentThe outer and insular crescent THE HEARTLAND: It includes the area of interior and arctic drainage of the eastern Europe which is surrounded by mountains on the three sides and arctic on the other.THE INNER AND MARGINAL CRESCENT: It includes the area of Europe and Asia joining heartland and Africa, north of sahara. THE OUTER AND INSULAR CRESCENT: It includes north and south America, south of sahara and Australia.

Besides to this it also includes the japan and Great Britain. According to Mackinder the one with control over heartland will have impeccable position with control over the world. Then he later changed the theory by adding some of the regions like Baltic sea, black sea, lower and middle Volga, Persia, Tibet, magnolia and then named it as strategic heartland in 1919. In the mids of 1920’s he changed his focus onto north America and western Europe. Then he added eastern united states, north Atlantic and western Europe and given name midland basin. Later on the theory was put into consideration in world war 2 where Germany was defeated and the heartland become more powerful and ruled over the world island.Thus Mackinder resulted to the formation of heartland theory and rimland theory which brought control over the world island. This was geopolitical thought in the history of geopolitics.

IMPACT OF GEOPOLITICS ON INTERNATIONAL BUSINESS: Geopolitics play an important role in the international business among the globe. This has been started in the early days where goods were exchanged in return of other goods between countries. For example India used to export agricultural products in return of agricultural machines and some equipment related to agriculture to UK in 1600. Followingly imports and exports were done with the exchange of gold, which is called as golden era. And then the US dollars were introduced where exchange of trade was done in terms of dollars, where dollarization is done everywhere for trade between different countries. And later on many currencies were introduced which brought an advantage among many countries. This is how business was started among different countries in the olden days.

Some of the great impacts of geopolitics on international business are:Oil for food programLafargeInternational SOSa;travel risksb;medical risks OIL FOR FOOD PROGRAM: In this program Iraq was to export more oil in return of goods to meet the basic needs of the people. This lead to a fine of 750,000 euros for corrupting official in the program.LAFARGE: It is one the important investments in Syria. This brought up a cement factory in jalabiya. Later on ISIS took control over the roads and cities near the factory. It has to taxes about 20000 dollars to ISIS for each month to protect its cement business in Syria.

TRAVEL RISKS: It is one of the risks identified by company called international SOS which is good at medical and security. It has many centres all over the globe. It has complete assistance over the employees work and travel internationally. This tracking keeps informing the travellers the risks they will get through. Thus there are some packages for the employees which protect them all over the trip. These are some of the risks of geopolitics on international business in history.CONCLUSION: Thus we can conclude that geopolitics play a key role in the international business between different countries around the globe.

There are many barriers for trade with the foreign in the olden days when as compared to know. Presently there are somewhat less barriers to trade such as taxes for imports and exports, cultural barriers, lack of resources in the home country. For example apple gadgets are manufactured in china due to the less labour cost and more availability of the employees in china compared to that of USA. Thus many countries take time zone advantage also to make business easier.

The example for it is the scanning reports of hospitals in America are done on the day time of other foreign countries and the reports are available for the very next day. In addition to this they also take place advantage where surgeries in America are more costlier compared to that of a foreign countries such as India. Most of the people travel to other places to save their money. Thus geopolitics has both advantages and disadvantages in the international business over the globe. The term geopolitics was born to fight for the natural resources available around their region.

Some of the other factors are cultural factors, different languages in different regions. Thus many countries fought for the survival due to the disputes that are occurred through geopolitics. One of main conflict risen in Europe was immigration crisis where many individuals migrate to Europe considering the advantage of currency value. There are about 1 million migrants in France. Not only in previous days but there are also migrants from different places in recent times. So we can conclude that geopolitics has brought many conflicts among different countries on the globe in history and now also.REFERENCES:https://www.britannica.com/topic/geopoliticshttp://www.psbedu.net/cours.html#https://www.quora.com/What-is-Mackinders-heartland-theoryhttps://www.researchgate.net/publication/263659477_Geopolitics_and_its_Impacts_on_International_Business_Decisions_A_Framework_for_a_Geopolitical_Paradigm_of_International_Business

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