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132-760: Ebolaviruses were first described after outbreaks of EVD in southern Sudan in June 1976 and in Zaire in August 1976. The name Ebolavirus is derived from the Ebola River in Zaire (now the Democratic Republic of the Congo ), near the location of the 1976 outbreak, and the taxonomic suffix -virus (denoting a viral genus). This genus was introduced in 1998 as the "Ebola-like viruses". In 2002,

264-568: A Neolithic culture had settled into a sedentary way of life there in fortified mudbrick villages, where they supplemented hunting and fishing on the Nile with grain gathering and cattle herding. Neolithic peoples created cemeteries such as R12 . During the fifth millennium BC, migrations from the drying Sahara brought neolithic people into the Nile Valley along with agriculture. The population that resulted from this cultural and genetic mixing developed

396-464: A coup d'état on 11 April 2019 and Bashir's imprisonment. Sudan is currently embroiled in a civil war between two rival factions, the Sudanese Armed Forces (SAF), and the paramilitary Rapid Support Forces (RSF). Islam was Sudan's state religion and Islamic laws were applied from 1983 until 2020 when the country became a secular state . Sudan is a least developed country and among

528-554: A 0.45 μm filter. These large particles can cause a phenomenon called membrane fouling in later purification steps. In addition, the concentration of product in the sample may not be sufficient, especially in cases where the desired antibody is produced by a low-secreting cell line. The sample is therefore concentrated by ultrafiltration or dialysis . Most of the charged impurities are usually anions such as nucleic acids and endotoxins. These can be separated by ion exchange chromatography . Either cation exchange chromatography

660-460: A 30-year-long military dictatorship led by Omar al-Bashir ruled Sudan and committed widespread human rights abuses , including torture, persecution of minorities, alleged sponsorship of global terrorism , and ethnic genocide in Darfur from 2003–2020. Overall, the regime killed an estimated 300,000 to 400,000 people. Protests erupted in 2018, demanding Bashir's resignation, which resulted in

792-413: A 90% fatality rate. It can only be explored in a BSL-4 laboratory which is very selective. In order for it to be studied more widely, BSL-2 laboratories have been able to use systems that are substitutes for the actual infectious virus. Scientists have used pseudo types that have the same glycoprotein on the surface that is used for entry into the host cell. They also use noninfectious Ebola-like particles as

924-683: A dynastic change, while another one in 1761–1762 resulted in the Hamaj Regency , where the Hamaj (a people from the Ethiopian borderlands) effectively ruled while the Funj sultans were their mere puppets. Shortly afterwards the sultanate began to fragment; by the early 19th century it was essentially restricted to the Gezira. The coup of 1718 kicked off a policy of pursuing a more orthodox Islam, which in turn promoted

1056-552: A free vote on whether they wished independence or a British withdrawal. A polling process was carried out resulting in the composition of a democratic parliament and Ismail al-Azhari was elected first Prime Minister and led the first modern Sudanese government. On 1 January 1956, in a special ceremony held at the People's Palace, the Egyptian and British flags were lowered and the new Sudanese flag, composed of green, blue and yellow stripes,

1188-461: A given antigen . In 1973, Jerrold Schwaber described the production of monoclonal antibodies using human–mouse hybrid cells. This work remains widely cited among those using human-derived hybridomas . In 1975, Georges Köhler and César Milstein succeeded in making fusions of myeloma cell lines with B cells to create hybridomas that could produce antibodies, specific to known antigens and that were immortalized. They and Niels Kaj Jerne shared

1320-609: A key province of the New Kingdom, economically, politically, and spiritually. Indeed, major pharaonic ceremonies were held at Jebel Barkal near Napata. As an Egyptian colony from the 16th century BC, Nubia ("Kush") was governed by an Egyptian Viceroy of Kush . Resistance to the early eighteenth Dynasty Egyptian rule by neighboring Kush is evidenced in the writings of Ahmose, son of Ebana , an Egyptian warrior who served under Nebpehtrya Ahmose (1539–1514 BC), Djeserkara Amenhotep I (1514–1493 BC), and Aakheperkara Thutmose I (1493–1481 BC). At

1452-495: A media sample of cultured hybridomas or a sample of ascites fluid, the desired antibodies must be extracted. Cell culture sample contaminants consist primarily of media components such as growth factors, hormones and transferrins . In contrast, the in vivo sample is likely to have host antibodies, proteases , nucleases , nucleic acids and viruses . In both cases, other secretions by the hybridomas such as cytokines may be present. There may also be bacterial contamination and, as

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1584-499: A monoclonal antibody drug, received an emergency use authorization from the US FDA for use as pre-exposure prophylaxis to protect certain moderately to severely immunocompromised individuals against COVID-19. Several monoclonal antibodies, such as bevacizumab and cetuximab , can cause different kinds of side effects. These side effects can be categorized into common and serious side effects. Some common side effects include: Among

1716-570: A petty kingdom. After the prosperous reign of king Joel ( fl. 1463–1484) Makuria collapsed. Coastal areas from southern Sudan up to the port city of Suakin was succeeded by the Adal Sultanate in the fifteenth century. To the south, the kingdom of Alodia fell to either the Arabs, commanded by tribal leader Abdallah Jamma , or the Funj , an African people originating from the south. Datings range from

1848-515: A priority of the revolutionary government. The following year, under Egyptian and Sudanese pressure, the British agreed to Egypt's demand for both governments to terminate their shared sovereignty over Sudan and to grant Sudan independence. On 1 January 1956, Sudan was duly declared an independent state. After Sudan became independent, the Gaafar Nimeiry regime began Islamist rule. This exacerbated

1980-400: A proposal (2010.010bV) to formally recognize these names, as they do not designate names for subtypes, variants, strains, or other subspecies level groupings. As such, the widely used common names are not formally recognized as part of the taxonomic nomenclature. In particular, "Ebola virus" does not have an official meaning recognized by ICTV, and rather they continue to use and recommend only

2112-445: A protein has no net charge. When the pH > pI, a protein has a net negative charge, and when the pH < pI, a protein has a net positive charge. For example, albumin has a pI of 4.8, which is significantly lower than that of most monoclonal antibodies, which have a pI of 6.1. Thus, at a pH between 4.8 and 6.1, the average charge of albumin molecules is likely to be more negative, while mAbs molecules are positively charged and hence it

2244-521: A replacement system to study. The search for a vaccine for Ebola began immediately after it was first discovered in 1976. There are currently only two FDA approved drugs. In October 2020 Immazab was officially approved and in December 2020, Ebanga was also officially approved. The difference between the two treatments is that Immazeb uses three monoclonal antibodies whereas Ebanga only has one monoclonal antibody. Both of these treatments are designed to attack

2376-410: A result, endotoxins that are secreted by the bacteria. Depending on the complexity of the media required in cell culture and thus the contaminants, one or the other method ( in vivo or in vitro ) may be preferable. The sample is first conditioned, or prepared for purification. Cells, cell debris, lipids, and clotted material are first removed, typically by centrifugation followed by filtration with

2508-710: A revival of the Nubian Empire, which rather continued in the form of a smaller kingdom centred on Napata . The city was raided by the Egyptian c. 590 BC, and sometime soon after to the late-3rd century BC, the Kushite resettled in Meroë . On the turn of the fifth century the Blemmyes established a short-lived state in Upper Egypt and Lower Nubia, probably centred around Talmis ( Kalabsha ), but before 450 they were already driven out of

2640-569: A sizable, populous empire rivaling Egypt. Mentuhotep II , the 21st century BC founder of the Middle Kingdom , is recorded to have undertaken campaigns against Kush in the 29th and 31st years of his reign. This is the earliest Egyptian reference to Kush ; the Nubian region had gone by other names in the Old Kingdom. Under Thutmose I , Egypt made several campaigns south. The Egyptians ruled Kush in

2772-587: A social hierarchy over the next centuries which became the Kingdom of Kerma at 2500 BC. Anthropological and archaeological research indicates that during the predynastic period Nubia and Nagadan Upper Egypt were ethnically and culturally nearly identical, and thus, simultaneously evolved systems of pharaonic kingship by 3300 BC. The Kerma culture was an early civilization centered in Kerma , Sudan. It flourished from around 2500 BC to 1500 BC in ancient Nubia . The Kerma culture

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2904-553: A substance in either frozen tissue section or live cells. Antibodies can also be used to purify their target compounds from mixtures, using the method of immunoprecipitation . Therapeutic monoclonal antibodies act through multiple mechanisms, such as blocking of targeted molecule functions, inducing apoptosis in cells which express the target, or by modulating signalling pathways. One possible treatment for cancer involves monoclonal antibodies that bind only to cancer-cell-specific antigens and induce an immune response against

3036-564: A suburb of modern-day Khartoum). Still in the sixth century they converted to Christianity. In the seventh century, probably at some point between 628 and 642, Nobatia was incorporated into Makuria. Between 639 and 641 the Muslim Arabs of the Rashidun Caliphate conquered Byzantine Egypt. In 641 or 642 and again in 652 they invaded Nubia but were repelled, making the Nubians one of

3168-399: A unique parent cell. Monoclonal antibodies can have monovalent affinity, binding only to the same epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different antibody-secreting plasma cell lineages. Bispecific monoclonal antibodies can also be engineered, by increasing

3300-468: Is protein A/G affinity chromatography . The antibody selectively binds to protein A/G, so a high level of purity (generally >80%) is obtained. The generally harsh conditions of this method may damage easily damaged antibodies. A low pH can break the bonds to remove the antibody from the column. In addition to possibly affecting the product, low pH can cause protein A/G itself to leak off the column and appear in

3432-531: Is able to subvert the host immune response increasing the EBOV pathogenesis. NP contains both the filoviral genome and the antigenome. NP oligomerization is responsible for the NC (helical nucleocapsid) formation which allows the -ssRNA genome to be protected against host cell degradation by endonucleases and host immune response. NP is also shown to recruit host cell proteins to facilitate virus transcription and replication within

3564-657: Is about $ 100,000 higher in oncology and hematology than in other disease states", comparing them on a per patient basis, to those for cardiovascular or metabolic disorders, immunology, infectious diseases, allergy, and ophthalmology. Once monoclonal antibodies for a given substance have been produced, they can be used to detect the presence of this substance. Proteins can be detected using the Western blot and immuno dot blot tests. In immunohistochemistry , monoclonal antibodies can be used to detect antigens in fixed tissue sections, and similarly, immunofluorescence can be used to detect

3696-488: Is actually used. They discovered that Ebolavirus uses macropinocytosis to enter the host cells. Induction of macropinocytosis leads to the formation of macropinocytosis-specific endosomes (macropinosomes), which are large enough to accommodate Ebola virions. This discovery was proven by the fact that Ebolavirus co-localizes with sorting nexin 5 (SNX5), which consists of a large family of peripheral membrane proteins that associate with newly formed macropinosomes. Also, blocking

3828-474: Is also sometimes referred to as North Sudan to distinguish it from South Sudan . Affad 23 is an archaeological site located in the Affad region of southern Dongola Reach in northern Sudan, which hosts "the well-preserved remains of prehistoric camps (relics of the oldest open-air hut in the world) and diverse hunting and gathering loci some 50,000 years old". By the eighth millennium BC, people of

3960-449: Is always to be capitalized , italicized , never abbreviated, and to be preceded by the word "genus". The names of its members (ebolaviruses) are to be written in lower case, are not italicized, and used without articles . A virus of the family Filoviridae is a member of the genus Ebolavirus if The genera Ebolavirus and Marburgvirus were originally classified as the species of the now-obsolete genus Filovirus . In March 1998,

4092-779: Is mentioned in the Bible as having saved the Israelites from the wrath of the Assyrians, although disease among the besiegers might have been one of the reasons for the failure to take the city. The war that took place between Pharaoh Taharqa and the Assyrian king Sennacherib was a decisive event in western history, with the Nubians being defeated in their attempts to gain a foothold in the Near East by Assyria. Sennacherib's successor Esarhaddon went further and invaded Egypt itself to secure his control of

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4224-588: Is now known as South Kordofan to the Sinai. Pharaoh Piye attempted to expand the empire into the Near East but was thwarted by the Assyrian king Sargon II . Between 800 BCE and 100 AD the Nubian pyramids were built, among them can be named El-Kurru , Kashta , Piye , Tantamani , Shabaka , Pyramids of Gebel Barkal , Pyramids of Meroe (Begarawiyah) , the Sedeinga pyramids , and Pyramids of Nuri . The Kingdom of Kush

4356-416: Is observed. Mutation of both Rab5 and Rab7 GTPases additionally inhibits viral entry. After trafficking to late endosomes, Ebola virus binds the intracellular receptor Neimann-Pick C1 (NPC1) and the viral membrane fuses with the endosomal membrane, allowing the virus to release its genome into the cytoplasm. The main reason that there are not many available treatments is that Ebola is such a severe virus, with

4488-921: Is passed through a column, where it selectively binds and can be retained while impurities are washed away. An elution with a low pH buffer or a more gentle, high salt elution buffer is then used to recover purified antibody from the support. Product heterogeneity is common in monoclonal antibodies and other recombinant biological products and is typically introduced either upstream during expression or downstream during manufacturing. These variants are typically aggregates, deamidation products, glycosylation variants, oxidized amino acid side chains, as well as amino and carboxyl terminal amino acid additions. These seemingly minute structural changes can affect preclinical stability and process optimization as well as therapeutic product potency, bioavailability and immunogenicity . The generally accepted purification method of process streams for monoclonal antibodies includes capture of

4620-674: Is possible to separate them. Transferrin, on the other hand, has a pI of 5.9, so it cannot be easily separated by this method. A difference in pI of at least 1 is necessary for a good separation. Transferrin can instead be removed by size exclusion chromatography . This method is one of the more reliable chromatography techniques. Since we are dealing with proteins, properties such as charge and affinity are not consistent and vary with pH as molecules are protonated and deprotonated, while size stays relatively constant. Nonetheless, it has drawbacks such as low resolution, low capacity and low elution times. A much quicker, single-step method of separation

4752-401: Is then selected for future use. The hybridomas can be grown indefinitely in a suitable cell culture medium. They can also be injected into mice (in the peritoneal cavity , surrounding the gut). There, they produce tumors secreting an antibody-rich fluid called ascites fluid. The medium must be enriched during in vitro selection to further favour hybridoma growth. This can be achieved by

4884-412: Is used at a low enough pH that the desired antibody binds to the column while anions flow through, or anion exchange chromatography is used at a high enough pH that the desired antibody flows through the column while anions bind to it. Various proteins can also be separated along with the anions based on their isoelectric point (pI). In proteins, the isoelectric point (pI) is defined as the pH at which

5016-453: Is useful in treating moderate-to-severe allergic asthma . Monoclonal antibodies for research applications can be found directly from antibody suppliers, or through use of a specialist search engine like CiteAb . Below are examples of clinically important monoclonal antibodies. casirivimab/imdevimab In 2020, the monoclonal antibody therapies bamlanivimab/etesevimab and casirivimab/imdevimab were given emergency use authorizations by

5148-573: The 'Urabi revolt , which threatened the Khedive's survival. Tewfik appealed for help to the British, who subsequently occupied Egypt in 1882. Sudan was left in the hands of the Khedivial government, and the mismanagement and corruption of its officials. During the Khedivial period, dissent had spread due to harsh taxes imposed on most activities. Taxation on irrigation wells and farming lands were so high most farmers abandoned their farms and livestock. During

5280-532: The 9th century after the Hijra ( c. 1396–1494), the late 15th century, 1504 to 1509. An alodian rump state might have survived in the form of the kingdom of Fazughli , lasting until 1685. In 1504 the Funj are recorded to have founded the Kingdom of Sennar , in which Abdallah Jamma's realm was incorporated. By 1523, when Jewish traveller David Reubeni visited Sudan, the Funj state already extended as far north as Dongola. Meanwhile, Islam began to be preached on

5412-577: The Arabisation of the state. To legitimise their rule over their Arab subjects the Funj began to propagate an Umayyad descend . North of the confluence of the Blue and White Niles, as far downstream as Al Dabbah , the Nubians adopted the tribal identity of the Arab Jaalin . Until the 19th century Arabic had succeeded in becoming the dominant language of central riverine Sudan and most of Kordofan. West of

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5544-714: The Bronze Age collapse and the disintegration of the New Kingdom of Egypt ; it was centred at Napata in its early phase. After King Kashta ("the Kushite") invaded Egypt in the eighth century BC, the Kushite kings ruled as pharaohs of the Twenty-fifth Dynasty of Egypt for nearly a century before being defeated and driven out by the Assyrians . At the height of their glory, the Kushites conquered an empire that stretched from what

5676-448: The Coptic alphabet , while also using Greek , Coptic and Arabic . Women enjoyed high social status: they had access to education, could own, buy and sell land and often used their wealth to endow churches and church paintings. Even the royal succession was matrilineal , with the son of the king's sister being the rightful heir. From the late 11th/12th century, Makuria's capital Dongola

5808-518: The Middle Assyrian Empire (1365–1020 BC), and then the resurgent Neo-Assyrian Empire (935–605 BC). The Assyrians , from the tenth century BC onwards, had once more expanded from northern Mesopotamia , and conquered a vast empire, including the whole of the Near East , and much of Anatolia , the eastern Mediterranean , the Caucasus and early Iron Age Iran . According to Josephus Flavius,

5940-514: The Nobel Prize in Physiology or Medicine in 1984 for the discovery. In 1988, Gregory Winter and his team pioneered the techniques to humanize monoclonal antibodies, eliminating the reactions that many monoclonal antibodies caused in some patients. By the 1990s research was making progress in using monoclonal antibodies therapeutically, and in 2018, James P. Allison and Tasuku Honjo received

6072-633: The Sudan Defence Force played an active part in responding to incursions early in World War Two. Italian troops occupied Kassala and other border areas from Italian Somaliland during 1940. In 1942, the SDF also played a part in the invasion of the Italian colony by British and Commonwealth forces. The last British governor-general was Robert George Howe . The Egyptian revolution of 1952 finally heralded

6204-728: The Sudanese Communist Party . Several days later, anti-communist military elements restored Nimeiry to power. In 1972, the Addis Ababa Agreement led to a cessation of the north–south civil war and a degree of self-rule. This led to ten years hiatus in the civil war but an end to American investment in the Jonglei Canal project. This had been considered absolutely essential to irrigate the Upper Nile region and to prevent an environmental catastrophe and wide-scale famine among

6336-581: The United Nations , Arab League , African Union , COMESA , Non-Aligned Movement and the Organisation of Islamic Cooperation . The country's name Sudan is a name given historically to the large Sahel region of West Africa to the immediate west of modern-day Sudan. Historically, Sudan referred to both the geographical region , stretching from Senegal on the Atlantic Coast to Northeast Africa and

6468-703: The Vali of Egypt under the Ottoman Empire , Muhammad Ali styled himself as Khedive of a virtually independent Egypt. Seeking to add Sudan to his domains, he sent his third son Ismail (not to be confused with Ismaʻil Pasha mentioned later) to conquer the country, and subsequently incorporate it into Egypt. With the exception of the Shaiqiya and the Darfur sultanate in Kordofan, he was met without resistance. The Egyptian policy of conquest

6600-422: The strain from the 1995 Kikwit outbreak. However, paleoviruses of filoviruses found in mammals indicate that the family itself is at least tens of millions of years old. The genus Ebolavirus has been organized into six species; however, the nomenclature has proven somewhat controversial, with many authors continuing to use common names rather than species names when referring to these viruses. In particular,

6732-402: The "-like viruses" to "-virus" resulting in today's Ebolavirus and Marburgvirus . Five characterised species of the genus Ebolavirus are: Rates of genetic change are 8*10 per site per year and are thus one fourth as fast as influenza A in humans. Extrapolating backwards , Ebolavirus and Marburgvirus probably diverged several thousand years ago. A study done in 1995 and 1996 found that

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6864-525: The 1870s, European initiatives against the slave trade had an adverse impact on the economy of northern Sudan, precipitating the rise of Mahdist forces. Muhammad Ahmad ibn Abd Allah , the Mahdi (Guided One), offered to the ansars (his followers) and those who surrendered to him a choice between adopting Islam or being killed. The Mahdiyah (Mahdist regime) imposed traditional Sharia Islamic laws . On 12 August 1881, an incident occurred at Aba Island , sparking

6996-401: The 1908 Nobel Prize for Physiology or Medicine for providing the theoretical basis for immunology. By the 1970s, lymphocytes producing a single antibody were known, in the form of multiple myeloma – a cancer affecting B-cells . These abnormal antibodies or paraproteins were used to study the structure of antibodies, but it was not yet possible to produce identical antibodies specific to

7128-598: The Ansar at Tushkah. The failure of the Egyptian invasion broke the spell of the Ansar's invincibility. The Belgians prevented the Mahdi's men from conquering Equatoria , and in 1893, the Italians repelled an Ansar attack at Agordat (in Eritrea ) and forced the Ansar to withdraw from Ethiopia. In the 1890s, the British sought to re-establish their control over Sudan, once more officially in

7260-634: The Bedoin of Asia, he sailed upstream to Upper Nubia to destroy the Nubian bowmen." The tomb writings contain two other references to the Nubian bowmen of Kush. By 1200 BC, Egyptian involvement in the Dongola Reach was nonexistent. Egypt's international prestige had declined considerably towards the end of the Third Intermediate Period . Its historical allies, the inhabitants of Canaan , had fallen to

7392-519: The British had a policy of running Sudan as two essentially separate territories; the north and south. The assassination of a Governor-General of Anglo-Egyptian Sudan in Cairo was the causative factor; it brought demands of the newly elected Wafd government from colonial forces. A permanent establishment of two battalions in Khartoum was renamed the Sudan Defence Force acting as under the government, replacing

7524-665: The Great Depression. Cotton and gum exports were dwarfed by the necessity to import almost everything from Britain leading to a balance of payments deficit at Khartoum. In July 1936 the Liberal Constitutional leader, Muhammed Mahmoud was persuaded to bring Wafd delegates to London to sign the Anglo-Egyptian Treaty, "the beginning of a new stage in Anglo-Egyptian relations", wrote Anthony Eden . The British Army

7656-570: The Levant. This succeeded, as he managed to expel Taharqa from Lower Egypt. Taharqa fled back to Upper Egypt and Nubia, where he died two years later. Lower Egypt came under Assyrian vassalage but proved unruly, unsuccessfully rebelling against the Assyrians. Then, the king Tantamani , a successor of Taharqa, made a final determined attempt to regain Lower Egypt from the newly reinstated Assyrian vassal Necho I . He managed to retake Memphis killing Necho in

7788-422: The Mahdist War. In 1899, Britain and Egypt reached an agreement under which Sudan was run by a governor-general appointed by Egypt with British consent. In reality, Sudan was effectively administered as a Crown colony . The British were keen to reverse the process, started under Muhammad Ali Pasha , of uniting the Nile Valley under Egyptian leadership and sought to frustrate all efforts aimed at further uniting

7920-464: The Mahdiyah period, largely because of the Khalifa's brutal methods to extend his rule throughout the country. In 1887, a 60,000-man Ansar army invaded Ethiopia , penetrating as far as Gondar . In March 1889, king Yohannes IV of Ethiopia marched on Metemma ; however, after Yohannes fell in battle, the Ethiopian forces withdrew. Abd ar-Rahman an-Nujumi, the Khalifa's general, attempted an invasion of Egypt in 1889, but British-led Egyptian troops defeated

8052-456: The New kingdom beginning when the Egyptian King Thutmose I occupied Kush and destroyed its capital, Kerma. This eventually resulted in their annexation of Nubia c.  1504 BC . Around 1500 BC, Nubia was absorbed into the New Kingdom of Egypt , but rebellions continued for centuries. After the conquest, Kerma culture was increasingly Egyptianized, yet rebellions continued for 220 years until c.  1300 BC . Nubia nevertheless became

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8184-450: The Nile Valley by the Nobatians. The latter eventually founded a kingdom on their own, Nobatia . By the sixth century there were in total three Nubian kingdoms: Nobatia in the north, which had its capital at Pachoras ( Faras ); the central kingdom, Makuria centred at Tungul ( Old Dongola ), about 13 kilometres (8 miles) south of modern Dongola ; and Alodia , in the heartland of the old Kushitic kingdom, which had its capital at Soba (now

8316-412: The Nile by Sufi holy men who settled there in the 15th and 16th centuries and by David Reubeni's visit king Amara Dunqas , previously a Pagan or nominal Christian, was recorded to be Muslim. However, the Funj would retain un-Islamic customs like the divine kingship or the consumption of alcohol until the 18th century. Sudanese folk Islam preserved many rituals stemming from Christian traditions until

8448-400: The Nile to safeguard a planned irrigation dam at Aswan . Herbert Kitchener led military campaigns against the Mahdist Sudan from 1896 to 1898. Kitchener's campaigns culminated in a decisive victory in the Battle of Omdurman on 2 September 1898. A year later, the Battle of Umm Diwaykarat on 25 November 1899 resulted in the death of Abdallahi ibn Muhammad , subsequently bringing to an end

8580-409: The Nile, in Darfur , the Islamic period saw at first the rise of the Tunjur kingdom , which replaced the old Daju kingdom in the 15th century and extended as far west as Wadai . The Tunjur people were probably Arabised Berbers and, their ruling elite at least, Muslims. In the 17th century the Tunjur were driven from power by the Fur Keira sultanate . The Keira state, nominally Muslim since

8712-421: The Nobel Prize in Physiology or Medicine for their discovery of cancer therapy by inhibition of negative immune regulation, using monoclonal antibodies that prevent inhibitory linkages. The translational work needed to implement these ideas is credited to Lee Nadler. As explained in an NIH article, "He was the first to discover monoclonal antibodies directed against human B-cell–specific antigens and, in fact, all

8844-428: The Ottoman invasion saw the attempted usurpation of Ajib , a minor king of northern Nubia. While the Funj eventually killed him in 1611/1612 his successors, the Abdallab , were granted to govern everything north of the confluence of Blue and White Niles with considerable autonomy. During the 17th century the Funj state reached its widest extent, but in the following century it began to decline. A coup in 1718 brought

8976-454: The Sudan , is a country in Northeast Africa . It borders the Central African Republic to the southwest, Chad to the west, Libya to the northwest, Egypt to the north, the Red Sea to the east, Eritrea and Ethiopia to the southeast, and South Sudan to the south. Sudan has a population of 50 million people as of 2024 and occupies 1,886,068 square kilometres (728,215 square miles), making it Africa's third-largest country by area and

9108-399: The US Food and Drug Administration to reduce the number of hospitalizations, emergency room visits, and deaths because of COVID-19 . In September 2021, the Biden administration purchased US$ 2.9   billion worth of Regeneron monoclonal antibodies at $ 2,100 per dose to curb the shortage. As of December 2021, in vitro neutralization tests indicate monoclonal antibody therapies (with

9240-405: The United Kingdom as a condominium . In effect, Sudan was governed as a British possession. The Egyptian revolution of 1952 toppled the monarchy and demanded the withdrawal of British forces from all of Egypt and Sudan. Muhammad Naguib , one of the two co-leaders of the revolution and Egypt's first President, was half-Sudanese and had been raised in Sudan. He made securing Sudanese independence

9372-404: The Vertebrate Virus Subcommittee proposed in the International Committee on Taxonomy of Viruses (ICTV) to change the genus Filovirus to the family Filoviridae with two specific genera: Ebola-like viruses and Marburg-like viruses . This proposal was implemented in Washington, D.C., as of April 2001 and in Paris as of July 2002. In 2000, another proposal was made in Washington, D.C., to change

9504-407: The antigen used to generate the antibody is covalently attached to an agarose support. If the antigen is a peptide , it is commonly synthesized with a terminal cysteine , which allows selective attachment to a carrier protein, such as KLH during development and to support purification. The antibody-containing medium is then incubated with the immobilized antigen, either in batch or as the antibody

9636-491: The beginning of the march towards Sudanese independence. Having abolished the monarchy in 1953, Egypt's new leaders, Mohammed Naguib , whose mother was Sudanese, and later Gamal Abdel Nasser , believed the only way to end British domination in Sudan was for Egypt to officially abandon its claims of sovereignty. In addition, Nasser knew it would be difficult for Egypt to govern an impoverished Sudan after its independence. The British on

9768-559: The biblical Moses led the Egyptian army in a siege of the Kushite city of Meroe. To end the siege Princess Tharbis was given to Moses as a (diplomatic) bride, and thus the Egyptian army retreated back to Egypt. The Kingdom of Kush was an ancient Nubian state centred on the confluences of the Blue Nile and White Nile , and the Atbarah River and the Nile River . It was established after

9900-632: The binding portion of a monoclonal antibody was merged with human antibody-producing DNA in living cells. The expression of this " chimeric " or "humanised" DNA through cell culture yielded part-mouse, part-human antibodies. Ever since the discovery that monoclonal antibodies could be generated, scientists have targeted the creation of fully human products to reduce the side effects of humanised or chimeric antibodies. Several successful approaches have been proposed: transgenic mice , phage display and single B cell cloning. Monoclonal antibodies are more expensive to manufacture than small molecules due to

10032-539: The complex processes involved and the general size of the molecules, all in addition to the enormous research and development costs involved in bringing a new chemical entity to patients. They are priced to enable manufacturers to recoup the typically large investment costs, and where there are no price controls, such as the United States, prices can be higher if they provide great value. Seven University of Pittsburgh researchers concluded, "The annual price of mAb therapies

10164-592: The country and slaves being transported to Egypt and the Ottoman Empire . From the 19th century, the entirety of Sudan was conquered by the Egyptians under the Muhammad Ali dynasty . Religious-nationalist fervour erupted in the Mahdist Uprising in which Mahdist forces were eventually defeated by a joint Egyptian-British military force. In 1899, under British pressure, Egypt agreed to share sovereignty over Sudan with

10296-477: The cytoplasm. Researchers have found evidence of Ebola infection in three species of fruit bat. The bats show no symptoms of the disease, indicating that they may be the main natural reservoirs of the Ebolavirus. It is possible that there are other reservoirs and vectors. Understanding where the virus incubates between outbreaks and how it is transmitted between species will help protect humans and other primates from

10428-550: The de novo pathway and become fully auxotrophic for nucleic acids , thus requiring supplementation to survive. The selective culture medium is called HAT medium because it contains hypoxanthine , aminopterin and thymidine . This medium is selective for fused ( hybridoma ) cells. Unfused myeloma cells cannot grow because they lack HGPRT and thus cannot replicate their DNA. Unfused spleen cells cannot grow indefinitely because of their limited life span. Only fused hybrid cells referred to as hybridomas, are able to grow indefinitely in

10560-431: The differences between them were sufficient to invoke an immune response when murine monoclonal antibodies were injected into humans, resulting in their rapid removal from the blood, as well as systemic inflammatory effects and the production of human anti-mouse antibodies (HAMA). Recombinant DNA has been explored since the late 1980s to increase residence times. In one approach called "CDR grafting", mouse DNA encoding

10692-426: The eluted sample. Gentle elution buffer systems that employ high salt concentrations are available to avoid exposing sensitive antibodies to low pH. Cost is also an important consideration with this method because immobilized protein A/G is a more expensive resin. To achieve maximum purity in a single step, affinity purification can be performed, using the antigen to provide specificity for the antibody. In this method,

10824-670: The end of the Second Intermediate Period (mid-sixteenth century BC), Egypt faced the twin existential threats—the Hyksos in the North and the Kushites in the South. Taken from the autobiographical inscriptions on the walls of his tomb-chapel, the Egyptians undertook campaigns to defeat Kush and conquer Nubia under the rule of Amenhotep I (1514–1493 BC). In Ahmose's writings, the Kushites are described as archers , "Now after his Majesty had slain

10956-574: The exception of sotrovimab and tixagevimab/cilgavimab ) were not likely to be active against the Omicron variant. Over 2021–22, two Cochrane reviews found insufficient evidence for using neutralizing monoclonal antibodies to treat COVID-19 infections. The reviews applied only to people who were unvaccinated against COVID‐19, and only to the COVID-19 variants existing during the studies, not to newer variants, such as Omicron. In March 2024, pemivibart ,

11088-523: The few who managed to defeat the Arabs during the Islamic expansion . Afterward the Makurian king and the Arabs agreed on a unique non-aggression pact that also included an annual exchange of gifts , thus acknowledging Makuria's independence. While the Arabs failed to conquer Nubia they began to settle east of the Nile, where they eventually founded several port towns and intermarried with the local Beja . From

11220-499: The filoviruses in Asia. A recent alignment-free analysis of Ebola virus genomes from the current outbreak reveals the presence of three short DNA sequences that appear nowhere in the human genome, suggesting that the identification of specific species sequences may prove to be useful for the development of both diagnosis and therapeutics. Sudan Sudan , officially the Republic of

11352-622: The former garrison of Egyptian army soldiers, saw action afterward during the Walwal Incident . The Wafdist parliamentary majority had rejected Sarwat Pasha 's accommodation plan with Austen Chamberlain in London; yet Cairo still needed the money. The Sudanese Government's revenue had reached a peak in 1928 at £6.6 million, thereafter the Wafdist disruptions, and Italian borders incursions from Somaliland, London decided to reduce expenditure during

11484-498: The generic term "Ebola virus" is widely used to refer specifically to members of the species Zaire ebolavirus . Consequently, in 2010, a group of researchers recommended that the name "Ebola virus" be adopted for a subclassification within the species Zaire ebolavirus and that similar common names be formally adopted for other Ebolavirus species. In 2011, the International Committee on Taxonomy of Viruses (ICTV) rejected

11616-462: The genes of Ebolavirus and Marburgvirus differed by about 55% at the nucleotide level, and at least 67% at the amino acid level. The same study found that the strains of Ebolavirus differed by about 37–41% across the nucleotide level and 34–43% across the amino acid level. The EBOV strain was found to have an almost 2% change in the nucleotide level from the original 1976 strain from the Yambuki outbreak and

11748-472: The glycoprotein in order to prevent the virus from entering a new host cell and replicating. Besides these two drugs, there is more general treatment care such as managing symptoms that are caused by Ebola such as vomiting, fever, diarrhea, and any pain. According to the rules for taxon naming established by the International Committee on Taxonomy of Viruses (ICTV), the name of the genus Ebolavirus

11880-539: The help primarily of the Baggara of western Sudan, overcame the opposition of the others and emerged as the unchallenged leader of the Mahdiyah. After consolidating his power, Abdallahi ibn Muhammad assumed the title of Khalifa (successor) of the Mahdi, instituted an administration, and appointed Ansar (who were usually Baggara ) as emirs over each of the several provinces. Regional relations remained tense throughout much of

12012-405: The known human B-cell–specific antigens were discovered in his laboratory. He is a true translational investigator, since he used these monoclonal antibodies to classify human B-cell leukemia and lymphomas as well as to create therapeutic agents for patients. . . More importantly, he was the first in the world to administer a monoclonal antibody to a human (a patient with B-cell lymphoma)." Much of

12144-509: The local tribes, most especially the Dinka. In the civil war that followed their homeland was raided, looted, pillaged, and burned. Many of the tribe were murdered in a bloody civil war that raged for over 20 years. Monoclonal antibody A monoclonal antibody ( mAb , more rarely called moAb ) is an antibody produced from a cell lineage made by cloning a unique white blood cell . All subsequent antibodies derived this way trace back to

12276-550: The macropinocytosis pathway has been proven to stop Ebolavirus from entering the cells. Four different macropinocytosis specific inhibitors were tested: cytochalasin D (depolymerizing agent), wortmannin (Wort), LY-294002 (both are inhibitors of PI3K) and EIPA (5-(N-ethyl-N-isopropyl) amiloride), an inhibitor of the Na+/H+ exchanger specific for pinocytosis. Then, internalized EBOV particles are transported to late endosomes and, there, co-localization with GTPase Rab7 (marker of late endosomes)

12408-463: The medieval Nubians has been described as " Afro-Byzantine ", but was also increasingly influenced by Arab culture. The state organisation was extremely centralised, being based on the Byzantine bureaucracy of the sixth and seventh centuries. Arts flourished in the form of pottery paintings and especially wall paintings. The Nubians developed an alphabet for their language, Old Nobiin , basing it on

12540-472: The medium because the spleen cell partner supplies HGPRT and the myeloma partner has traits that make it immortal (similar to a cancer cell). This mixture of cells is then diluted and clones are grown from single parent cells on microtitre wells. The antibodies secreted by the different clones are then assayed for their ability to bind to the antigen (with a test such as ELISA or antigen microarray assay) or immuno- dot blot . The most productive and stable clone

12672-431: The mid eighth to mid eleventh century the political power and cultural development of Christian Nubia peaked. In 747 Makuria invaded Egypt, which at this time belonged to the declining Umayyads , and it did so again in the early 960s, when it pushed as far north as Akhmim . Makuria maintained close dynastic ties with Alodia, perhaps resulting in the temporary unification of the two kingdoms into one state. The culture of

12804-519: The modern Sudan. The name derives from the Arabic bilād as-sūdān ( بلاد السودان ), or "The Land of the Blacks ". The name is one of various toponyms sharing similar etymologies , in reference to the very dark skin of the indigenous people. Prior to this, Sudan was known as Nubia and Ta Nehesi or Ta Seti by Ancient Egyptians named for the Nubian and Medjay archers or bowmen. Since 2011, Sudan

12936-508: The name of the Egyptian Khedive, but in actuality treating the country as a British colony. By the early 1890s, British, French, and Belgian claims had converged at the Nile headwaters. Britain feared that the other powers would take advantage of Sudan's instability to acquire territory previously annexed to Egypt. Apart from these political considerations, Britain wanted to establish control over

13068-493: The name was changed to Ebolavirus and in 2010, the genus was emended. Ebolaviruses are closely related to marburgviruses . Ebolavirus is a filamentous, enveloped virus within the order Mononegavirales which also contains rabies and measles viruses. This order is characterized by non-segmented, single-stranded negative-sense RNA (-ssRNA) genomes that are surrounded by a helical nucleocapsid. Filoviruses encode seven different proteins that include: NP (nucleoprotein), VP35 (part of

13200-400: The newer technologies use molecular biology techniques to amplify the heavy and light chains of the antibody genes by PCR and produce in either bacterial or mammalian systems with recombinant technology. One of the advantages of the new technologies is applicable to multiple animals, such as rabbit, llama, chicken and other common experimental animals in the laboratory. After obtaining either

13332-535: The other hand continued their political and financial support for the Mahdist successor, Abd al-Rahman al-Mahdi , who it was believed would resist Egyptian pressure for Sudanese independence. Abd al-Rahman was capable of this, but his regime was plagued by political ineptitude, which garnered a colossal loss of support in northern and central Sudan. Both Egypt and Britain sensed a great instability fomenting, and thus opted to allow both Sudanese regions, north and south to have

13464-698: The outbreak of what became the Mahdist War . From his announcement of the Mahdiyya in June 1881 until the fall of Khartoum in January 1885, Muhammad Ahmad led a successful military campaign against the Turco-Egyptian government of the Sudan, known as the Turkiyah . Muhammad Ahmad died on 22 June 1885, a mere six months after the conquest of Khartoum. After a power struggle amongst his deputies, Abdallahi ibn Muhammad , with

13596-503: The polymerase complex), VP40 (matrix protein), GP (glycoprotein spike), VP30 (transcription activator), VP42 (second matrix protein), and L (RdRp). Of these proteins, GP and NP proteins are crucial for viral entry and replication. GP is the protein responsible for pathogenic differences among ebolaviruses. GP encodes two glycoproteins, one of which is sGP (soluble glycoprotein) which has a role in Ebola pathogenesis. Research has suggested that sGP

13728-470: The poorest countries in the world, ranking 170th on the Human Development Index as of 2024 and 185th by nominal GDP per capita . Its economy largely relies on agriculture due to international sanctions and isolation, as well as a history of internal instability and factional violence. The large majority of Sudan is dry and over 60% of Sudan's population lives in poverty. Sudan is a member of

13860-639: The preclinical development phase is critical for enhanced product quality understanding and provides a basis for risk management and increased regulatory flexibility. The recent Food and Drug Administration's Quality by Design initiative attempts to provide guidance on development and to facilitate design of products and processes that maximizes efficacy and safety profile while enhancing product manufacturability. The production of recombinant monoclonal antibodies involves repertoire cloning , CRISPR/Cas9 , or phage display / yeast display technologies. Recombinant antibody engineering involves antibody production by

13992-510: The process and besieged cities in the Nile Delta. Ashurbanipal , who had succeeded Esarhaddon, sent a large army in Egypt to regain control. He routed Tantamani near Memphis and, pursuing him, sacked Thebes . Although the Assyrians immediately departed Upper Egypt after these events, weakened, Thebes peacefully submitted itself to Necho's son Psamtik I less than a decade later. This ended all hopes of

14124-440: The product target with protein A , elution, acidification to inactivate potential mammalian viruses, followed by ion chromatography , first with anion beads and then with cation beads. Displacement chromatography has been used to identify and characterize these often unseen variants in quantities that are suitable for subsequent preclinical evaluation regimens such as animal pharmacokinetic studies. Knowledge gained during

14256-477: The recent past. Soon the Funj came in conflict with the Ottomans , who had occupied Suakin c.  1526 and eventually pushed south along the Nile, reaching the third Nile cataract area in 1583/1584. A subsequent Ottoman attempt to capture Dongola was repelled by the Funj in 1585. Afterwards, Hannik , located just south of the third cataract, would mark the border between the two states. The aftermath of

14388-637: The region, which was thin on the ground. The British ambassador blocked Italian attempts to secure a Non-Aggression Treaty with Egypt-Sudan. But Mahmoud was a supporter of the Grand Mufti of Jerusalem ; the region was caught between the Empire's efforts to save the Jews, and moderate Arab calls to halt migration. The Sudanese Government was directly involved militarily in the East African Campaign . Formed in 1925,

14520-558: The reign of Sulayman Solong (r. c. 1660–1680), was initially a small kingdom in northern Jebel Marra , but expanded west- and northwards in the early 18th century and eastwards under the rule of Muhammad Tayrab (r. 1751–1786), peaking in the conquest of Kordofan in 1785. The apogee of this empire, now roughly the size of present-day Nigeria , would last until 1821. In 1821, the Ottoman ruler of Egypt, Muhammad Ali of Egypt , invaded and conquered northern Sudan. Although technically

14652-690: The rift between the Islamic North, the seat of the government, and the Animists and Christians in the South. Differences in language, religion, and political power erupted in a civil war between government forces, influenced by the National Islamic Front (NIF), and the southern rebels, whose most influential faction was the Sudan People's Liberation Army (SPLA), which eventually led to the independence of South Sudan in 2011. Between 1989 and 2019,

14784-747: The species designation Zaire ebolavirus . The threshold for putting isolates into different species is usually a difference of more than 30% at the nucleotide level, compared to the type strain . If a virus is in a given species but differs from the type strain by more than 10% at the nucleotide level, it is proposed that it be named as a new virus. As of 2019, none of the Ebolavirus species contain members divergent enough to receive more than one "virus" designation. A 2013 study isolated antibodies from fruit bats in Bangladesh, against Ebola Zaire and Reston viruses , thus identifying potential virus hosts and signs of

14916-533: The success rate is low, so a selective medium in which only fused cells can grow is used. This is possible because myeloma cells have lost the ability to synthesize hypoxanthine-guanine-phosphoribosyl transferase (HGPRT), an enzyme necessary for the salvage synthesis of nucleic acids. The absence of HGPRT is not a problem for these cells unless the de novo purine synthesis pathway is also disrupted. Exposing cells to aminopterin (a folic acid analogue which inhibits dihydrofolate reductase ) makes them unable to use

15048-902: The target cancer cell. Such mAbs can be modified for delivery of a toxin , radioisotope , cytokine or other active conjugate or to design bispecific antibodies that can bind with their Fab regions both to target antigen and to a conjugate or effector cell. Every intact antibody can bind to cell receptors or other proteins with its Fc region . MAbs approved by the FDA for cancer include: Monoclonal antibodies used for autoimmune diseases include infliximab and adalimumab , which are effective in rheumatoid arthritis , Crohn's disease , ulcerative colitis and ankylosing spondylitis by their ability to bind to and inhibit TNF-α . Basiliximab and daclizumab inhibit IL-2 on activated T cells and thereby help prevent acute rejection of kidney transplants. Omalizumab inhibits human immunoglobulin E (IgE) and

15180-451: The therapeutic targets of one monoclonal antibody to two epitopes. It is possible to produce monoclonal antibodies that specifically bind to almost any suitable substance; they can then serve to detect or purify it. This capability has become an investigative tool in biochemistry , molecular biology , and medicine . Monoclonal antibodies are used in the diagnosis of illnesses such as cancer and infections and are used therapeutically in

15312-674: The third-largest by area in the Arab League . It was the largest country by area in Africa and the Arab League until the secession of South Sudan in 2011 ; since then both titles have been held by Algeria . Sudan's capital and most populous city is Khartoum . The area that is now Sudan witnessed the Khormusan ( c. 40000–16000 BC), Halfan culture ( c. 20500–17000 BC), Sebilian ( c. 13000–10000 BC), Qadan culture ( c. 15000–5000 BC),

15444-419: The treatment of e.g. cancer and inflammatory diseases. In the early 1900s, immunologist Paul Ehrlich proposed the idea of a Zauberkugel – " magic bullet ", conceived of as a compound which selectively targeted a disease-causing organism, and could deliver a toxin for that organism. This underpinned the concept of monoclonal antibodies and monoclonal drug conjugates. Ehrlich and Élie Metchnikoff received

15576-562: The two countries. Under the Delimitation, Sudan's border with Abyssinia was contested by raiding tribesmen trading slaves, breaching boundaries of the law. In 1905 local chieftain Sultan Yambio, reluctant to the end, gave up the struggle with British forces that had occupied the Kordofan region, finally ending the lawlessness. Ordinances published by Britain enacted a system of taxation. This

15708-707: The use of viruses or yeast , rather than mice. These techniques rely on rapid cloning of immunoglobulin gene segments to create libraries of antibodies with slightly different amino acid sequences from which antibodies with desired specificities can be selected. The phage antibody libraries are a variant of phage antigen libraries. These techniques can be used to enhance the specificity with which antibodies recognize antigens, their stability in various environmental conditions, their therapeutic efficacy and their detectability in diagnostic applications. Fermentation chambers have been used for large scale antibody production. While mouse and human antibodies are structurally similar,

15840-593: The use of a layer of feeder fibrocyte cells or supplement medium such as briclone. Culture-media conditioned by macrophages can be used. Production in cell culture is usually preferred as the ascites technique is painful to the animal. Where alternate techniques exist, ascites is considered unethical . Several monoclonal antibody technologies have been developed recently, such as phage display , single B cell culture, single cell amplification from various B cell populations and single plasma cell interrogation technologies. Different from traditional hybridoma technology,

15972-431: The virus. The researchers found that bats of three species – Franquet's epauletted fruit bat ( Epomops franqueti ), the hammer-headed bat ( Hypsignathus monstrosus ) and the little collared fruit bat ( Myonycteris torquata ) – had either genetic material from the Ebola virus, known as RNA sequences, or evidence of an immune response to the disease. The bats showed no symptoms themselves. The Bombali ebolavirus (BOMV)

16104-541: The war of Jebel Sahaba , the earliest known war in the world, around 11500 BC, A-Group culture (c. 3800–3100 BC), Kingdom of Kerma ( c. 2500–1500 BC), the Egyptian New Kingdom ( c. 1500–1070 BC), and the Kingdom of Kush ( c. 785 BC – 350 AD). After the fall of Kush, the Nubians formed the three Christian kingdoms of Nobatia , Makuria , and Alodia . Between the 14th and 15th centuries, most of Sudan

16236-399: The work behind production of monoclonal antibodies is rooted in the production of hybridomas, which involves identifying antigen-specific plasma/plasmablast cells that produce antibodies specific to an antigen of interest and fusing these cells with myeloma cells. Rabbit B-cells can be used to form a rabbit hybridoma . Polyethylene glycol is used to fuse adjacent plasma membranes, but

16368-753: Was allowed to return to Sudan to protect the Canal Zone. They were able to find training facilities, and the RAF was free to fly over Egyptian territory. It did not, however, resolve the problem of Sudan: the Sudanese Intelligentsia agitated for a return to metropolitan rule, conspiring with Germany's agents. Italian fascist leader Benito Mussolini made it clear that he could not invade Abyssinia without first conquering Egypt and Sudan; they intended unification of Italian Libya with Italian East Africa . The British Imperial General Staff prepared for military defence of

16500-526: Was based in the southern part of Nubia, or " Upper Nubia " (in parts of present-day northern and central Sudan), and later extended its reach northward into Lower Nubia and the border of Egypt. The polity seems to have been one of several Nile Valley states during the Middle Kingdom of Egypt . In the Kingdom of Kerma's latest phase, lasting from about 1700–1500 BC, it absorbed the Sudanese kingdom of Saï and became

16632-523: Was expanded and intensified by Ibrahim Pasha 's son, Ismaʻil, under whose reign most of the remainder of modern-day Sudan was conquered. The Egyptian authorities made significant improvements to the Sudanese infrastructure (mainly in the north), especially with regard to irrigation and cotton production. In 1879, the Great Powers forced the removal of Ismail and established his son Tewfik Pasha in his place. Tewfik's corruption and mismanagement resulted in

16764-467: Was following the precedent set by the Khalifa. The main taxes were recognized. These taxes were on land, herds, and date-palms. The continued British administration of Sudan fuelled an increasingly strident nationalist backlash, with Egyptian nationalist leaders determined to force Britain to recognise a single independent union of Egypt and Sudan. With a formal end to Ottoman rule in 1914, Sir Reginald Wingate

16896-519: Was gradually settled by Arab nomads . From the 16th to the 19th centuries, central and eastern Sudan were dominated by the Funj sultanate , while Darfur ruled the west and the Ottomans the east. In 1811, Mamluks established a state at Dunqulah as a base for their slave trading . Under Turco-Egyptian rule of Sudan after the 1820s, the practice of trading slaves was entrenched along a north–south axis, with slave raids taking place in southern parts of

17028-548: Was in decline, and Alodia's capital declined in the 12th century as well. In the 14th and 15th centuries Bedouin tribes overran most of Sudan, migrating to the Butana , the Gezira , Kordofan and Darfur . In 1365 a civil war forced the Makurian court to flee to Gebel Adda in Lower Nubia , while Dongola was destroyed and left to the Arabs. Afterwards Makuria continued to exist only as

17160-540: Was isolated from the little free-tailed bat ( Chaerephon pumilus ) and the Angolan free-tailed bat ( Mops condylurus ) in Sierra Leone . The entry pathway that the virus uses is a key step in its cycle. Several pathways have been suggested for Ebolavirus such as phagocytosis and clathrin and caveolin mediated endocytosis. However, Nanbo et al. (2010) and Saeed et al. (2010) independently proved that neither of these pathways

17292-467: Was raised in their place by the prime minister Ismail al-Azhari . Dissatisfaction culminated in a coup d'état on 25 May 1969. The coup leader, Col. Gaafar Nimeiry , became prime minister, and the new regime abolished parliament and outlawed all political parties. Disputes between Marxist and non-Marxist elements within the ruling military coalition resulted in a briefly successful coup in July 1971 , led by

17424-568: Was sent that December to occupy Sudan as the new Military Governor. Hussein Kamel was declared Sultan of Egypt and Sudan , as was his brother and successor, Fuad I . They continued upon their insistence of a single Egyptian-Sudanese state even when the Sultanate of Egypt was retitled as the Kingdom of Egypt and Sudan , but it was Saad Zaghloul who continued to be frustrated in the ambitions until his death in 1927. From 1924 until independence in 1956,

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