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Clinical Implications of Molecular PEGylation on Therapeutic Proteins
Nandhakumar Sathyamoorthy, Dhanaraju Dasaratha Magharla*
Department of Pharmaceutics, GIET School of Pharmacy, Rajahmundry, Andhra Pradesh, India
Dr. Dhanaraju Dasaratha Magharla
Department of Pharmaceutics, GIET School of Pharmacy, NH-16 Chaitanya Knowledge City, Rajahmundry, Andhra Pradesh, India.
Citation:Nandhakumar S, Dhanaraju DM. Clinical Implications of Molecular PEGylation on Therapeutic Proteins. J Basic Clin Pharma 2017;8:87-90.
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Molecular PEGylation has redefined the clinical importance of many biomolecules by improving their pharmacodynamic and pharmacokinetic properties. From its inception, PEGylation has grown substantively into a well-established technology to facilitate the clinical translation of macromolecules by overcoming their limitations. PEGylation renders a number of benefits to therapeutic proteins, such as, increase in hydrodynamic size, extension of circulation half-life, prevention of proteolytic degradation and reduction of immunogenicity and antigenicity. The successful entrance of the PEGylated protein pharmaceuticals to the market, can be ascribed to the unique properties of poly (ethylene glycol) (PEG) conjugated to these proteins. This article aims to review the precise role of PEG in improving the therapeutic efficacy of PEG-protein conjugates approved by regulatory bodies. The data presented herein were extracted from articles published in peer reviewed journals, official websites of manufacturers and safety labeling and drug approval summary of the FDA Centre for Drug evaluation and Research (CDER).
PEGylation, proteins, poly(ethylene glycol), circulation half-life, immunogenicity
The advent of molecule-altering technologies and improved synthetic methods has led to the finding of newer proteins and peptides that resemble human proteins and peptides.[1] Although, capable of producing potential therapeutic benefits, protein molecules have serious biopharmaceutical concerns such as, poor shelf- life, rapid degradation in the physiological environment, poor solubility, immunogenicity and antigenicity.[2] These concerns can be overcome by utilizing the beneficial properties of polyethylene glycols and PEGylation. 'PEGylation' is the process of chemical attachment of PEG to bioactive proteins and peptides, to modify their pharmacokinetic and pharmacodynamic properties. Here, we present a brief summary of molecular PEGylation and PEGylated proteins currently approved for the clinical management of various conditions including oncology, infectious diseases and metabolic disorders.
The origin of PEGnology dates back to the 1960's, when Davis and his colleagues were looking for a solution to overcome the immunological reactions produced injection of foreign proteins into humans. Eventually, they found that coupling monomethoxy PEGs to therapeutic proteins yielded PEG-proteins which possessed low immunogenicity and longer circulating half-lives in comparison to their unpegylated equals.[3] Then onwards PEGylation has grown profoundly into a well-accepted and well-established technology to produce biomolecules with improved stability and potency.[4]
Molecular PEGylation
The attachment of PEG to drug molecule to alter its bio-distribution, pharmacokinetics and toxicity is termed as molecular PEGylation. [5] Molecular PEGylation is principally used to configure therapeutic proteins and enzymes, although seldom used on small drug molecules. [6] PEGylating a protein or a peptide by chemical linkage is generally intended at improving its water solubility, bioavailability, decreasing elimination rate, formation of stable linkage and augmenting the therapeutic activity.[7] The most important application of PEG conjugation is increasing the circulating half-life of proteins and peptides. Research has shown that biological half-life and bioavailability of interferon-α-2a,[8] tumor necrosis factor,[9] brain derived neurotropic factor,[10] growth hormone-releasing factor,[11] asparaginase,[12] lactoferrin,[13] interleukin-2,[14] and streptokinase[15] are improved significantly after PEGylation than the native proteins. The anticancer activity of interferon-α-2a and tumor necrosis factor increased profoundly after conjugation with PEG. Though extensive research have hovered towards the advancement in PEGylated proteins, only a few products has entered the market owing to expensive costs involved in the clinical development and regulatory approval process. [16] Of the marketed nanomedicines which got approval from the regulatory bodies, nearly 40% are based on protein-polymer conjugates and liposomal formulations.[17] The list of PEGylated proteins which are approved for clinical applications is presented in Table 1.
PEGylated drug
PEG Type and
Size (Da)
Year of approval
Adagen Pegadamase PEGylated adenosine deaminase Random, Multiple linear 5000 Da PEG, amine PEGylation Combined immunodeficiency disease caused by deficiency of? adenosine deaminase Enzon
Inc., USA FDA (1990)
Oncaspar Pegaspargase PEGylated
L-asparaginase Random, Multiple linear 5000 Da PEG, amine PEGylation Acute lymphoblastic leukemia Enzon
Somavert Pegvisomant PEGylated recombinant analogue of the human growth hormone Random, 4-6 linear 5000 Da PEGs, amine PEGylation Acromegaly Pharmacia & Upjohn Company LLC., USA FDA (2003) and EMA (2002)
PEG-ASYS Peginterferon-
a2a PEGylated interferon alfa-2a Random, branched, 40000 Da PEG, amine PEGylation Chronic hepatitis C & B Hoffmamn-La Roche Inc., USA FDA (2002) and EMA (2002)
PEG-intron Peginterferon- a2b PEGylated interferon alfa-2b Random, linear 12000 Da PEG, amine PEGylation Chronic hepatitis C Schering-Plough
Corporation, USA FDA (2001) and EMA (2001)
Macugen Pegaptanib PEGylated anti-VEGF aptamer Selective, branched 40000 Da, amine PEGylation Age-related macular degeneration OSI Pharmaceuticals Inc/Pfizer Inc., USA FDA (2004) and EMA (2006)
Cimzia Certolizumabpegol PEGylated tumor necrosis factor alpha inhibitor Selective, branched 40000 Da, Thiol PEGylation Crohn's disease UCBPharma, Belgium FDA (2008)
Neulasta Pegfilgrastim PEGylated granulocyte colony-stimulating factor analog Selective, linear 20000 Da PEG, N-terminal PEGylation Neutropenia Amgen Inc., USA FDA (2002) and EMA(2002)
Krystexxa Pegloticase PEGylated urate oxidase Random,? linear10000 Da? PEG Chronic Gout Horizon PharmaPlc, Dublin FDA (2010)
Mircera mPEG-epoetin-? PEGylated erythropoetin receptor activators Random, linear30000 Da PEG, amine PEGylation Anaemia associated with chronic kidney disease Roche Inc.,
USA FDA (2007) and EMA (2007)
EMA: European Medicines Agency; FDA: The Food and Drug Administration (USFDA)
Table 1: List of FDA approved PEG-Protein conjugate.
PEGylation-chemistry and disposition
Polyethylene glycol is considered as an ideal polymer for conjugation with proteins owing to its desirable properties such as, non-toxicity, non-immunogenicity, non-antigenicity, amphiphilic nature, FDA approval and low accumulation in the reticulo-endothelial system (RES) organs.[18] PEG is an inert polymer comprising of repetitive units of ethylene oxide, either as linear or branched chains as shown in figure 1. PEGs are commercially available in different molecular weights with functional groups present at one or more termini to facilitate conjugation. PEGs with free hydroxyl groups at both ends (-OH) or PEGs with methoxylated groups (-OCH3) at one or two ends are frequently used in conjugation, of which the latter has important application in PEGylation. Reaction conditions and PEGylation chemistry are immensely responsible for the functional properties of the conjugated proteins.[19] The PEG chemistry for amine conjugation include PEG tresylate, PEG succinimidyl carbonate, PEG succinimidyl succinate, PEG dichlorotriazine, PEG trichlorophenyl carbonate, PEG p-nitrophenyl carbonate, PEG benzotriazole carbonate and PEG carbonylimidazole. PEGylation of cystein involves the utilization of thiol reactive derivatives such as PEG iodoacetamide, PEG-maleimide, PEG orthopyridyl disulfide. PEG hydrazides are much useful in conjugating oxidized carbohydrates or N-terminal serine or threonine.[1]
Figure 1: Structure of Poly (ethylene glycol) (PEG)
A PEG derivative with suitable functional chemistry is essential to couple a peptide or protein molecule and to prolong its circulatory time. This is achieved possibly by two effects; increased protection from proteolytic degradation and decreased rate of clearance of kidney. The proteolytic degradation is prevented by the stearic hindrance created by the hydrated PEG chains, which reduce the interactive collisions between reactive domains of proteins and enzymes. The decreased rate of clearance occurs in response to the dramatic increase in the hydrodynamic volume following conjugation with PEG, which in turn reduces the glomerular filtration.[20]
The following section reviews in brief, the effect of PEGylation on the clinical aspects of therapeutic PEG-protein conjugates approved for use in patients.
Adagen
Adagen is Pegademase bovine (PEG-ADA), approved by FDA in 1990, as a placement therapy for Severe Combined Immunodeficiency Disease (SCID), a genetically inherited, fatal disorder, caused by deficiency of Adenosine deaminase (ADA).[21] Decrease in the levels of ADA results in intracellular and extracellular accumulation of toxic substances such as, adenosine (Ado) and 2'-deoxyadenosine (d-Ado) and have its intense manifestation on the immune system. The successful management of SCID involves hematopoietic stem cell transplant, gene therapy and enzyme replacement therapy by red cell transfusions. Enzyme replacement therapy using PEG-ADA is not a curative therapy, but considered as an important treatment option to promote the well-being of the patient. ADA is a cytosolic enzyme, which catalyzes the conversion of Ado and d-Ado to inosine and 2-deoxyinosine, respectively in the cell location. PEG-ADA does not reach the cellular location owing to the PEG component. It can produce the same effect on the nucleosides by diffusing through the cell. The conjugation of monomethoxy polyethylene glycol (PEG) to ADA through a lysine bridge adds immense therapeutic benefits to ADA. The circulation half-life of ADA was increased from few minutes to 24 h by resisting the neutralization by circulating antibodies. PEG also protects the enzyme from proteolytic attack and renal clearance.[22]
Oncaspar
Oncaspar, the PEG conjugated version of E-coli derived asparaginase is approved as first line treatment for childhood acute lymphoblastic leukemia (ALL), in the US. Asparaginase hydrolyses plasma asparagines into ammonia and aspartic acid. Since, ALL cells lack asparagine synthetase, they depend on plasma asparagine for intracellular synthesis of asparagines. L-asparaginase prevents the protein synthesis of lymphoblasts by depleting the plasma asparagines and consequently cause the cell death.[23] The downside in the treatment with native L-asparaginase are the adverse effect on normal protein synthesis and recurrent hypersensitivity reactions in patients. PEG-asparaginase is well tolerated in patients and the advent of severe hypersensitivity reactions is uncommon.[24] The PEG component decreases the immunogenic episodes by reducing the development of anti-asparaginase antibodies.[25] PEGylation of native L-asparaginase increase its circulation half-life from 5.5 h to 1.2 days.[26]
Pegvisomant - a genetically engineered antagonist of growth hormone (GH) approved for the treatment and management of acromegaly is another protein in which the role of PEG is well exhibited. Acromegaly is a rare hormonal disorder characterized by the excess production of growth hormone (GH) by pituitary adenoma, which leads to increased secretion of insulin like growth factor I (IGF-I). The treatment for acromegaly is reliant on removal of adenoma or regulation of GH/IGF-I levels. Pegvisomant inhibits the metabolic effects of the hypersected GH and normalizes the levels of IGF-I. Pegvisomant acquires its antagonistic effects due to one of the nine amino acids (G120K), while the rest is responsible for the binding to growth hormone receptor (GHR).[27] PEGylation of the GH analogue increase its half-life to 100 h and binding affinity to GH.[28] PEGylated GH analogue can prolong the efficacy up to 12 weeks due to the sustained suppression of IGF-I.[29]
Pegasys and Peg-intron
PEGylated Interferon α-2a (Pegasys) and α-2b (Peg-intron) were approved by FDA in 2002 and 2001, respectively, as the first line treatment for Chronic Hepatitis C infection. The infection of Hepatitis C virus (HCV) was dealt previously with Interferon-alpha (INF-α) monotherapy or with a more effective combination therapy using INF-α and broad spectrum antiviral agent, ribavirin. INF-α inhibits virus protein translation and destabilizes viral RNA by inducing interferonstimulated genes (ISG) through INF receptor- JAK/STAT mediated pathway.[30] The shortcoming of INF-α treatment in its unmodified form is its short half-life, frequent administration and fluctuating plasma levels. The plasma half-life of INF-α2a is 4-6 h which is reduced to undetectable levels within one day following subcutaneous injection, persuading the administration of three doses per week. The fluctuating levels of INF α-2a in plasma during this treatment regimen pave way for entry and replication of virus. PEGylation of INF-α2a using a branched 40 kDa PEG prolonged the half-life from 3.8 h to 65 h and delayed the clearance by 100 fold. Phase III clinical trials demonstrated that the effectiveness of PEG-INF-α2a, given subcutaneously, once a week is superior to INF-α2a, given subcutaneously 3 times per week, which could be ascribed to the increased circulation half-life and reduced existence of virus particles.[31] Similarly, PEGylation of INF- α2b increases the half-life of native protein from 7 h to 48 h and the recommended dose of administration of Peg-intron is 1 mg/kg per week for 52 weeks, due to its prolonged effect.[32]
Pegaptanib
Pegaptanib sodium is an RNA aptamer used as an anti-vascular endothelial growth factor (anti-VEGF) directed therapeutic agent for the treatment of neovascular age related macular degeneration (AMD). The degeneration of macula following metabolic stresses in AMD results in loss of central vision. Pegaptanib was approved by the US FDA in 2004 and is the first aptamer used for clinical application. Aptamers are oligonucleotides that bind biological proteins with high affinity and specificity. Aptamers are preferred over the naturally occurring DNA or RNA molecules as they interact with molecular targets using superior binding abilities and adaptive recognition capabilities even at picomolar or nanomolar concentrations.[33] VEGF is the principal regulator of vascular permeability and pathological angiogenesis and hence selected as the target for the development of pegatanib in ocular neovascular diseases.[34] Pegaptanib sodium (1 mg/3 mg) is administered by intravitreous route, every six weeks for 48 weeks. The traditional topical delivery of pegaptanib may not produce the clinical benefits in posterior chamber diseases like AMD, as they increase the therapeutic concentrations in the anterior chamber of the eye but not the posterior chamber. The intravitreal injection facilitates the drug to interact with VEGF, responsible for the choroidal neovascularization in the posterior chamber. Conjugation of PEG (40 kDa) to the aptamer reduces its binding affinity to VEGF by four folds, but prolongs the residence time and maximizes the efficacy by slowing down the diffusion out of the vitreous humor.[29] PEGylation minimizes the systemic effects and the occurrence of adverse events is transient to moderate and is mostly related to the injection procedure rather than the drug itself.
Certolizumab Pegol
Certolizumab Pegol is PEGylated anti-Tumor necrosis factor-alpha (TNF-α), approved for the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA). It is an antigen binding fragment (Fab') of a monoclonal antibody that accede to conjugation with PEG which in turn enhances the pharmacokinetic properties and reduced immunological reactions.[35] TNF-α is a cytokine involved in the pathogenesis of autoimmune diseases including CD and RA. Therefore, decreasing the levels of TNF-α could improve the conditions of the above said immunological diseases.[36] Certolizumab pegol is given alone or in combination with methotrexate in RA and as a monotherapy for CD. It neutralizes both soluble and transmembrane TNFα and produce a longer and effectual effect on the symptoms of these diseases over its TNF-α monoclonal antibody counterpart (natalizumab, adalimumab and infliximab). The better clinical outcomes of Certolizumab pegol can be due to the lack of Fc region which reduces the Fc mediated response viz., antibody dependent, cell-mediated and complementmediated cytotoxicity.[37,38] Also, the conjugation of a 40 kDa PEG molecule increases the stability of Certolizumab, which facilitate the administration of the drug by subcutaneous route instead of intravenous route. PEGylation alters the pharmacokinetics of anti- TNF-α by improving its distribution and penetration into inflamed tissues preventing the TNF-α induced inflammation.[39]
Pegfilgrastim
Cytotoxic chemotherapy induced neutropenia is a serious condition in which the host hematopoietic system is suppressed, compromising the immune mechanism of the body. Thus, neutropenia is associated with the episodes of life-threatening infections, intolerance to chemotherapy dose and impediment in the expected clinical outcomes. Neutrophils are key components of innate immunity and are responsible for the protection against infections. Chemotherapy suppresses the production of neutrophils; as a result, patients with neutropenia show reduced signs and symptoms with fever being the only sign of infections.[40] Pegfilgrastim (Neulasta) was approved in 2002, for the treatment of febrile neutropenia.. Pegfilgrastim is formed by conjugating a 20 kDa monomethoxy polyethylene glycol aldehyde to Granulocyte-Colony Stimulating Factor G-CSF.[41] PEGylation increases the half-life to 42 h against 3.6 h of non-PEGylated G-CSF, which reduce the frequency of drug administration. Pegfilgrastim offers lower elimination rate and less incidence of febrile neutropenia compared to filgrastim.[42]
Pegloticase (Krystexxa) is PEGylated mammalian urate oxidase approved in 2010 for the treatment of chronic gout in adult patients, refractory to conventional therapy. Pegloticase catalyze the oxidation of uric acid to allantoin-an inert, water soluble metabolite and thereby reduce serum uric acid levels. The inflammation and pain caused due to uricase crystal formation in plasma can be prevented by Pegloticase. It is more effective in treating gout over other available treatments.[43] The PEGylation using 20 kDa to uricase tend to reduce immunogenicity reactions and increases its half-life from eight hours to twelve days.[29]
Methoxy polyethylene glycol-epoetin beta
Anemia associated with chronic kidney disease (CKD) is a major cause of morbidity which, if untreated, can lead to more devastating conditions including deterioration of cardiac function. Frequent red cell transfusions was the only treatment available to combat anemia in CKD and hemodialysis patients, before the introduction of erythropoietin stimulating agents (ESA).[44] First generation ESAs (Human recombinant erythropoietins-alpha and beta) and second generation ESAs (darbepoetin Alfa and continuous erythropoietin receptor agonist (CERA)) have greatly improved the quality of life of CKD patients over two decades.[45] Methoxy polyethylene glycolepoetin beta (Mircera) is approved for the treatment of patients with anemia associated with CKD in 2007. It is synthesized by the addition of activated monomethoxy PEG butanoic acid to lysine 46 and 52 on erythropoietin.[46] The molecular weight of Mircera is 60 kDa, of which the polyethylene glycol moiety accounts for 30 kDa. Increase in the glycosylation by the conjugation of PEG offered longer half-life (130 h) and improved biological activity compared to first generation erythropoietins.[47] Mircera requires once monthly administration and produces negligible adverse reactions, thereby, considerably improves patient compliance than any other ESAs.[21]
Peginesatide
Peginesatide (Omontys) is an erythropoietin stimulating agent (ESA) developed by Affymax and Takeda. This functional analog of erythropoietin was approved by The US FDA in 2012, for anemia treatment associated with CKD in adult patients on dialysis. Peginesatide is a synthetic peptide consisting of 21 amino acids bonded together by a linker derived from β-alanine and iminodiacetic acid. This dimeric peptide molecule is attached to a single lysine-branched bis- (methoxypolyethylene glycol) (MW=40 kDa) to improve its biological half-life and reduce immunogenic reactions. Peginesatide binds to erythropoietin receptor and facilitates erythroblast proliferation resulting in increased reticulocyte and RBC count. The outcomes of Phase III clinical trials showed that Peginesatide is not inferior to standard ESA agents in improving hemoglobin levels within the target range. However, PEARL (Peginesatide for anemia in patients with chronic kidney disease not receiving dialysis) study demonstrated that the safety endpoint of cardiovascular events (unstable angina, and arrhythmia) and death was inferior for peginesatide than darbepoetin. The rate of renal failure was twice as high in patients receiving peginesatide. Though there is no clear justification for these adverse reactions encountered by patients, peginesatide was voluntarily recalled from the market by its manufacturer in 2013.[43]
Molecular PEGylation of small drug molecule
Research has shown that biologically active drugs, ibuprofen, aspirin, benzoylacrylic acids, and ursodeoxycholic acid, on conjugation with PEG esters exhibited better therapeutic benefits over unmodified molecules. However, the PEG-low molecular weight drug molecule conjugates are yet to be approved for clinical use. Of those that entered clinical trials, the four important products which are at various phases of clinical trials are PEG-Camptothecin (Prothecan), PEG-Naloxol (NKTR-118), PEG-Irinotecan (NKTR-102), PEG-SN38- a metabolite of irinotecan (EZN-2208). The conjugation of the PEG moiety with small organic drugs is much simpler as compared to macromolecular PEGylation. As these molecules possess less functional groups and free from conformational limitations, purification and characterization of PEGylated-drug conjugates is done at ease.[2,4]
PEGylation is a versatile technology capable of altering the properties of both bioactive molecules and drug loaded particulate carrier systems. In the former case, molecular PEGylation could impart distinguished pharmacokinetic properties and benefits to proteins and small drug molecules over their biosimilars. In the latter situation, PEGylation renders steal thing abilities to drug carriers, such as liposomes, polymeric nanoparticles, metal nanoparticles, lipid emulsions, etc. The PEG molecules adhered or grafted on the surface of these drug carriers camouflages them from interactions with plasma proteins and subsequent clearance by the mononuclear phagocytic system (MPS). Therefore, PEGylation is an essential technique to modify the physicochemical properties of the parent drug either free form or encapsulated form to improve its immunogenicity, cellular uptake, spatial placement and biological activity. The scope of PEGylation in the near future is still intensifying as it is the most reliable tool available to help the innovative medicinal products meet the clinical and regulatory standards.
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Africa ranks poorly in fostering female entrepreneurship – report
By Gabriella Mulligan on July 6, 2015 East Africa, Features, North Africa, Southern Africa, West Africa
African countries rank in the bottom half of countries globally for fostering high-potential female entrepreneurship, with access to financial services and training a critical shortcoming in Africa, according to research by the Global Entrepreneurship and Development Institute (GEDI).
The Female Entrepreneurship Index 2015 considers the extent to which 77 countries across the world foster entrepreneurship among women.
The index measures 30 indicators spanning the three categories of entrepreneurial environment, entrepreneurial ecosystem, and entrepreneurial aspirations – each of the three pillars subdivided into five pillars containing multiple factors.
The results of the 2015 index saw 61 per cent of countries surveyed fail to reach a score of 50 out of 100.
In Africa, South Africa performed the highest, ranked 36th worldwide, with a score of 44.2 out of 100. Botswana came next at number 53, scoring 36.4 points; while Africa's third highest placed country was Tunisia at number 61, scoring 30.7.
The other African countries included in the index came even lower in the rankings, with Zambia placed 64th, Egypt at 66, Algeria at 67, Angola in 68th place, Ghana in 69th, Ethiopia at 72, Uganda at 74, and – in second last place globally – Malawi at 76.
The research also made regional recommendations for the most pressing issues in need of being addressed. In Sub-Saharan Africa, the recommended focus areas for improvement are women's access to bank accounts and access to financial training programmes.
According to GEDI, research into the conditions that support female entrepreneurship is necessary, as there is "growing appreciation" that these conditions are different from those which favour male entrepreneurship.
As such, the report aims to distill the most important issues for policy makers, governmental officials, and other decision makers who are interested in improving the conditions for high potential female entrepreneurship development.
"Women entrepreneurs play a substantial role in growing their economies. When a country does not achieve its full potential, the economy suffers. Fewer 'high potential' female entrepreneurs result in fewer ideas being realized, less innovation, less export potential, and fewer jobs created," the report said.
"Through their entrepreneurial activities, high-potential female entrepreneurs increase their own economic welfare, and also improve the economic and social fabric of society through job creation, innovative products, processes, and services, and cross-border trade."
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Maria Immanuel on July 6, 2015 8:17 am
I want to find our if Namibia was part of the survey on women entrepreneurship. Kindly also send me full report

redpajama_set_name: RedPajamaCommonCrawl


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Dash If You Dare, Zombie Dash Returns to GR
Tylee Shay
The seventh annual Zombie Dash 5K returns to Grand Rapids on Saturday, Oct. 20. In this fun, role-play race, runners represent a small band of survivors who avoided a viral outbreak. In this dystopian plot, racers are on a mission to scout out the urban quarantine area at dusk and survive the ravenous zombies who roam at night. The objective is to make it 3.1 miles untouched and unscathed.
Raymond Pashier, co-race director, said each year an effort is made enhance the race with new elements. "It is local-centric to Grand Rapids, but it attracts people from all over the state and even out of state," he said.
Information for Runners
Pashier explained that the format for the race has been the same each year. "Every runner gets three life strips that they tuck into their shorts, and then there are certain areas on the course where zombies can walk and grab those life strips from the runners. The objective is to finish the race with life strips, and for each life strip remaining, time is deducted from the racers' final finish time."
There are two "feed zones" along the course where zombies may try to take racers' life strips, making them lose a life. There is no penalty for losing all three lives and you may still complete the race, however, racers who finish with any life strips remaining will have one minute per life strip deducted from their final time. Runners, who prefer not to be chased by zombies, may run without life strips.
Racers receive a custom glow in the dark t-shirt, a race bib with timing chip, a finisher's medal and refreshments. Kids 10 and under may run free with their parents. Kids are not timed and do not get a shirt, but they do receive a small kid's medal when they finish. Kids 10 and under do not have to be registered online, they just need a signed waiver and to pick up a special kids bib at registration.
The race begins and ends at Sixth Street Park at 6:45 p.m. There are no waves, so racers can start whenever they'd like, in small groups or solo. The starting line will close at 7:15 p.m. and all racers should have started their run by that time.
Age group award pickups for runners will begin at 8 p.m. No formal awards ceremony is held. The race route is flat, equipped with three refreshment stations and hundreds of slow-moving, yet deadly "zombies."
Information for Zombies
So where do the zombies come from? Zombies are members of the community who dress up and roam the streets, taunting racers, motivating them to race even faster and reach safety. The Zombie Dash is always looking for more voluntary zombies, so if you are not into running and prefer a slow shuffle, grunting and dressing like the undead, visit thezombiedash.com to become a registered zombie.
Zombies receive a free shirt and get to enjoy spooking racers all night long, and there will be a best-dressed zombie contest at the end of the night. Zombies are asked to dress in ragged attire with distressed hair and makeup, and at 8:15 p.m. after the race has closed the zombie costume awards will kick off.
Zombies are asked to remain on the 5K course for the duration of the race, from 6:45 p.m. to 8 p.m. Zombies in a "scare zone" may only scare (for safety reasons), and zombies in a "feed zone" may attempt to grab a runner's life strips at a "realistically slow pace."
Pashier said this year there will be even more zombies and additional props to set the mood. "We bring in abandoned cars and set them up on the second half of the race route. We call it Apocalypse Avenue. This makes it more interesting for the runners and zombies."
Each year, a portion of the profits from the Zombie Dash 5K goes to Michigan Blood and the Michigan Blood Stem Cell Programs.
Friends and family are encouraged to come out and watch the race. Race route maps are posted on the race website.
The Dash will happen rain or shine…or snow! In the event of a thunderstorm or tornado, the race will be postponed until conditions improve. Racers and spectators are encouraged to bring rain gear and umbrellas if necessary.
Runners and zombies can register through Oct. 18 at 7 p.m. online at thezombiedash.com. Zombies are free, but must still register online. (Note: a custom shirt is NOT guaranteed after this date/time as we put our shirt order in on October 10). For information on group discounts or military discounts, visit email racedirector@thezombiedash.com for a discount code.
Zombie Dash
Halloween themed race
5K race
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Tylee is a writer and photographer with a degree in Communications and Writing. She is published in several local and national publications, and as founder and owner of Tylee Shay, she offers content, photography, and social media services to local business and brands. She is equal parts world-traveler and homebody, has been to more countries than her age, and never turns down a glass of wine.
Harlem ballet takes center stage
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City offers winter activities


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Toyota Corolla Altis. It's better, but how much?
The Toyota Corolla Altis is one of the most popular cars in Singapore. Altis lovers will be delighted to know that their favourite car has now received a mid-life update to its 11th generation model. The changes may not seem like much at first glance, but they are more than a little nip-and-tuck exercise.
First of all, there are slight revisions to the design, as you can see from our fabulous picture. The front-end design is more streamlined, with a slimmer grille and sharper-looking LED headlights. These changes combine to give the Altis a new, more aggressive look that is guaranteed to turn heads. At least for the first few months before they start to populate our roads en-masse once more.
Inside, the changes are also slight but noticeable. The air con vents on either side of the dashboard are now round instead of rectangular - people seem to find this classier for some reason. The controls for the air con vents have been revised too, and now look and feel a touch more solid and refined.
It's the things you can't see that have been changed significantly on this face lifted Altis. For one, the car now comes with seven airbags as standard. For the protective family man, you need no longer worry about your family's safety should you ever get into a crash. In addition, the Altis now has Vehicle Stability Control (VSC) as standard, to help prevent you from getting into a crash in the first place!
Finally, under the bonnet, the engine has also been tuned to give a slight bump in power; the 1.6-litre Dual VVT-i petrol unit now produces 128bhp and 160Nm of torque. Handy for those times when you want to challenge those pesky taxi drivers at the lights.
2) What's it like now?
The Corolla Altis has always been known for being a safe, reliable car. The updated model is pretty much the same, just marginally better in all the key areas.
The extra airbags means that the car is a much safer proposition, and puts the Altis in a position to really challenge the best in its class. And the improved engine means that the car feels much more engaging to drive, with better responsiveness mated with its trademark refinement. It is no sports car, but there is plenty here to satisfy the demands of the vast majority of drivers today.
3) So is it worth my money?
If you're looking for a family sedan that ticks all the right boxes, a solid four out of five star car, then yes, the Altis is very much worth your money. And most importantly, with the extra upgrades, the car has a lot more going for it. The Corolla Altis has always been safe, dependable, frugal and generally assuring. Now it's still all of that, but 10% better in every way.
Toyota V Honda. Same Price But Which One Should You Buy?


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PRINT September 1998
Manny Farber
MANNY FARBER IS THE RAYMOND CHANDLER of American film criticism. His adrenaline prose has been pumping since 1942, when he began reviewing for The New Republic. Over the succeeding four decades, he kept his writing lean and mean, florid and furious, absolutely unique. He reviewed for Time, The Nation, The New Leader, Artforum, and a parcel of other publications. In the late '70s, his successful career as a painter increasingly took center stage, and film gradually lost an important, always surprising apologist.
I first learned of Farber's criticism about twenty years ago, at the height of my enthusiasm for the films of the B-movie producer Val Lewton, who assembled a kind of atelier for writers, directors, cameramen, and actors to churn out low-budget horror movies of extraordinary beauty and, time permitting, intelligence (including The Seventh Victim, I Walked with a Zombie, and The Curse of the Cat People). A friend gave me a copy of the 1971 edition of Farber's Negative Space, a collection of his reviews which contains a brief obituary consideration of Lewton, written in 1951 for The Nation, and I became an instant convert, as much to the energy of the writing as to the writer's opinions, which were singularly cantankerous. At the time , I was so thrilled to have encountered someone else's thinking about Lewton that I didn't notice just how elegantly parsimonious Farber was in his postmortem critique, which, typically, leads with a vice to identify a virtue. He cut to the core of Lewton's methodology, observing that the producer "hid much more of his story than any other filmmaker, and forced his crew to create drama almost abstractly with symbolic sounds, textures, and the like, which made the audience hyperconscious of sensitive craftsmanship" and that "his lighter-than-air sense of pace created a terrifically plastic camera style." Obviously, "hiding the story" in "a lighter than air sense of pace" isn't really a great asset, but it is precisely what makes Lewton's films so stunningly different from any other contribution to the American horror genre.
The newly reissued edition of Negative Space (Da Capo) includes plenty of material that was not presented in the earlier edition of the anthology, notably Farber's collaborative reviews with his wife, Patricia Patterson (written in the '60s for Artforum), which drag him kicking and, occasionally, screaming into the '70s. While spousal collaborations can be among the most truly horrible pursuits a couple can indulge each other in, Farber and Patterson actually manage to pull off a not inelegant Pat and Mike impersonation à la George Cukor (not one of Farber's favorite directors). A major source of critical conflict between them is Marguerite Duras, whose India Song strikes a deep, vibrant gong for him and is a mosquito batting against a wind chime for his wife. What's lovely about the Farber/Patterson collaborations is their shared enthusiasm for certain directors, particularly Fassbinder (whose use of color and composition they liken to "Mondrian with a sly funk twist"). And it is Fassbinder who allows Farber to visit a European aesthetic on a guilt-free pass after a good twenty years of jingoistic Americanism. Let me give you a Whitmanesque example of the latter from Farber's 1957 essay "Underground Films": "The cream on the top of a Framed or Appointment with Danger . . . is the eye-flicking action that shows the American body—arms, elbows, legs, mouths, the tension profile line—being used expediently, with grace and the suggestion of jolting hardness. " Still, the real meat of the matter is Farber flying solo with his wild prejudices and enthusiasms boldly tattooed on the wing of his little single-prop plane of cinematic advocacy.
When the American Film Institute announced the winners of its troublesome contest to nominate the one hundred best American films last June, I thought of Manny Farber. I raced through the Institute's awardees and came up with one entry I thought he might approve of. At the very least, I assumed he had to like Charlie Chaplin, but when I consulted Negative Space's index it led me to find Farber, in an interview with Richard Thompson, trying to ditch Chaplin in an attempt to champion Laurel and Hardy. I knew better than to check him on the Institute's numero uno film, Citizen Kane. Back in 1952, in an essay entitled "The Gimp," he tackled A Place in the Sun (no. 92 on the AFI list) and A Streetcar Named Desire (no. 45) and pummeled them until you could hear George Stevens and Elia Kazan screaming "Uncle" across the back lots of Hollywood. However, it was not really Stevens and Kazan that Farber was after. He was tracking much bigger game, the very agent of the chiaroscuro virus they were victims of: Orson Welles. At the core of Farber's critique was the notion that, although it was initially unsuccessful, "Citizen Kane seems to have festered in Hollywood's unconscious until after the Wylers and Hustons returned [after the war] from their government film chores; then it broke out in full force." His analysis (in "The Gimp") of Welles' first—and perhaps greatest—film is a wonderfully insightful reading of how Hollywood went about creating the postwar, A-film formula, exemplified by "a horse-drawn truckload of liberal schmaltz called The Best Years of Our Lives." Farber is relentless in his downsizing of what he calls "solemn goiters" bearing "the label of ART in every inch of their reelage." He is, at heart, a B-movie apologist. He's sensational on products like Sam Fuller's Pickup on South Street and Don Siegel's Coogan's Bluff, without ever implying that they are more than the brute propulsive unreelings that they appear to be: "a bit of John Foster Dulles, a good bit of Steve Canyon, sometimes so good as to be breathtaking." Farber also loves character actors, and much of his best writing is devoted to supporting cast members like Gene Evans in Fuller's The Steel Helmet, who "plays the hot-headed [sic] showing off, the endless chewing on a cigar stump with the blast effect of water issuing from a whale's spout, bestial and grotesque as a charm spot in a film dedicated to the U.S. Infantry." Or Elisha Cook in Howard Hawks' The Big Sleep, who as "a supporting player hit his peak and managed to dry out whatever juicy glamour and heroics were in the film so that it took on a slatelike hardness."
Farber is very much a sensitized kind of guy's guy. His writing peaks in the presence of idiosyncratic originals like Hawks and Preston Sturges, whom he assessed in a 1954 essay coauthored by W.S. Poster (entitled "Preston Sturges"), where he seems to be arguing for himself as a critic as much as for the director he is writing about. "The discrepancies in Sturges's films are due largely to the peculiar discontinuities that afflict his sensibility, although such affliction is also a general phenomenon in a country where whole eras and cultures in different stages of development exist side by side, where history along one route seems to skip over decades only to fly backward over another route and begin again in still a different period." In a rebuttal of Siegfried Kracauer's critique of Sturges' confusion of honesty and candor in The Great McGinty, Farber/Poster write: "Such criticism is about as relevant as it would be to say that Cubists were primarily interested in showing all sides of a bottle at once." The curiously parental-advisorial end of the Sturges essay can, in many ways, stand in for a self-defense tactic by Farber, for justifying his critical capriciousness. "Sturges may not be the greatest director of the last two decades; in fact, it can be argued that a certain thinness in his work—his lack of fully formed, solid, orthodox moviemaker's technique—prevents him from being included among the first few. He is, however, the most original movie talent produced in recent years: the most complex and puzzling."
It's hard to place Farber in any subdivided pantheon. He clearly adores the work of James Agee with, natch, serious reservations: "Agee was a brick wall against pretense in small movies, but, on Big Scale work, where the Boulevard is madeof National Velvet and the Limelight's as stunning as the Sierra Madre, Agee's reviews suggested a busy day at Muscle Beach: flexing words, bulging rumps of talent, pyramidal displays of filming cunning." I still love Pauline Kael, but not for a second would I put her in the ring with Farber; she simply doesn't have the chops for his kind of ham-fisted finesse. The biggest problem with his criticism is the fact that he can't always slow down long enough to frame his passionate ardor for the art form he is alternately embracing and repelling. What is exhilarating about the best of his criticism is that it moves with the speed and linear clarity of the films he loves. It is unlikely that movies will ever again get the kind of tough love that Farber dispenses with such exuberant, bruising gusto.
Richard Flood is the chief curator of the Walker Art Center in Minneapolis. He is currently at work on the exhibition "Robert Gober: Sculpture and Drawing," which opens in February 1999.


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Towards the end of the Nineteenth Century, the Great Northern Railway's (GNR) passenger locomotive stock was having difficulties keeping up with traffic developments. The single-wheelers of the day could not cope with the faster speeds and heavier loads that were being seen. With this background, on 1st November 1895 the GNR Board appointed Ivatt to replace Stirling. 75 years old, Stirling died ten days later. Although Ivatt's first locomotives were merely modifications of Stirling types (E1 2-4-0 and D4 4-4-0), it appears that he was considering the Atlantic 4-4-2 wheel arrangement before his appointment with the GNR.
He was given permission to build an experimental 4-4-2 in February 1897, and one year later No. 990 was completed. This was the first Atlantic 4-4-2 locomotive built in Britain, and quickly acquired the nickname of 'Klondike' (or 'Klondyke') after the 1896 Gold Rush in the Klondike region of the Yukon. In June 1900, No. 990 was named Henry Oakley, but the 'Klondike' name stuck and was used for the entire class throughout their existence.
No. 990 had an unusual extension ring at the front of the boiler. This 1ft 11in ring was to allow the front of the boiler to be anchored to the cylinder castings. The overall effect was for the smoke box to be 1ft 11in longer than it appeared from the outside.
Ten more Klondikes were built in 1900, followed by a four-cylinder version (No. 271) in 1902. With small cylinders, No. 271 was not a great success and was rebuilt to match the other Klondikes in 1911. Meanwhile, from 1901 the basic Klondike boiler design was being used on the new 0-8-0 goods engines (LNER Q1 & Q2), and from 1903 on the 0-8-2T (LNER R1).
The next development was No. 251 which featured a larger boiler. This would become the first of the LNER C1 class, but a further batch of ten 'Klondikes' were built in 1903.
The fitting of superheaters started in 1909, with the fitting of a Schmidt superheater to No. 988. Dr. Schmidt also insisted on the fitting of piston valves at the same time. From 1914, the fitting of Robinson superheaters to the other C2s started. This was completed by the LNER in 1925. In line with contemporary thinking, the fitting of superheaters was accompanied by a reduction in boiler pressure from 175psi to 160psi. This was compensated for, by increasing the cylinder diameter to 19in diameter. Piston valves would eventually be fitted to twelve of the Klondikes.
Gresley fitted his twin-tube superheater to No. 950 in 1916, and Nos 255 & 989 in 1919. This design had two headers: one at the top, and one at the bottom of the smokebox. These were fitted with the standard 18-element Robinson superheaters between 1927 and 1928.
In 1913, No. 252's smokebox was extended by 1ft 2.75in to act as a simple spark arrestor. All but four of the C2s were similarly altered by Grouping (1923). Two of these were converted, but Nos. 3984 & 3985 kept their short smokeboxes until they were withdrawn.
Cracked frames were often repaired by replacing one side only. Over time, the frame design was modified slightly. From 1919, the frame depth near the cylinders was increased by 2.5in, and an additional row of bolts was often added. It was not unusual for this modified design to be seen on one side of a locomotive but not the other. In fact, the preserved No. 990 has this deeper frame on the right-hand side, but keeps the older frame design on the left-hand side!
The C2 Klondykes were initially distributed between the GNR's main line sheds. In 1905, they were allocated to Kings Cross, Peterborough, Grantham, and Doncaster sheds. Their early duties consisted of the heavier expresses on the GNR main line from London to York. These services were not very fast in the early 20th Century, and the C2s could keep up even if they tended to be slow when climbing uphill.
By 1913, all of the C1s were in service, and the Klondikes tended to be seen on the easier relief expresses. However, they were still called upon to pull some heavy trains during World War 1.
By 1920, the C1s had replaced many of the C2s at Grantham and Doncaster, with the displaced C2s joining the other main line sheds. By 1923, three were allocated to Cambridge to haul the London to Hitchin passenger services. In 1924, the ex-North Eastern Railway (NER) shed at Starbeck received a C2 to haul the Ripon to Doncaster leg of the Ripon to London service. In the following year, the NE area would receive more C2s for working between Leeds, Hull, Scarborough, and Newcastle. As well as pulling secondary passenger services, the C2s often pulled fish trains during the 1920s until these duties were taken over by K2s and K3s.
Throughout the 1920s and early 1930s, the C2 Klondikes would continue to pull secondary passenger services and deputise for C1s on faster services.
In 1935, the Klondikes were in need of new boilers, but were regarded as being too weak for the current traffic needs. Withdrawals commenced immediately, but five were still in service by 1939. Withdrawals were postponed for World War 2, but the last five engines were withdrawn in 1945. No. 3990 Henry Oakley has survived into preservation.
The following details are for the locomotives with piston valves, and 18-element Robinson superheaters. Those that still had slide valves, had 19x24in cylinders and a quoted tractive effort of 15,649 lb.
At the time of Grouping (1923), No. 3271 (GNR No. 271) had two 18.5x26in inside cylinders with Stephenson valve gear and 8in piston valves. Tractive effort was quoted at 16,071 lb, with an engine weight of 58 tons 13 cwt.
Heating Surface: Total: 1370.75 sq.ft.
When No. 3990 Henry Oakley (GNR No. 990) was withdrawn at the end of 1937, it was restored to a GNR livery and placed in the York Museum in January 1938. In 1953, No. 990 was restored to running condition and ran a series of specials with C1 No. 251 celebrating the centenary of Doncaster Works. No. 990 was steamed again in 1975 for the Stockton & Darlington 150th anniversary celebrations, before entering the National Railway Museum in 1975 as a part of the National Collection. During the summer of 1977, Henry Oakley was loaned to the Keighley & Worth Valley Railway to haul passenger trains.
No. 3990 Henry Oakley is currently on loan to Bressingham Steam Museum and Gardens, where it is exhibited in a static condition.
DJH sell a whitemetal kit of the C2 'Klondike' for 4mm scale (OO gauge).
An O gauge (7mm scale) kit is available from ACE Products.
Of the twenty two C2s, only the first C2 to be built carried a name. No. 990 Henry Oakley was named in June 1900, and carried the LNER number of 3990. It had both a superheater and piston valves fitted in December 1922.
Thank you to Malcolm Peirson for the photograph of LNER No. 3258.
Thank you to Geoff Byman FRPS for the photograph of the C2 No. 3990 Henry Oakley at the Doncaster 150 celebrations.


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Q: Where do the first two numbers of Fibonacci Sequence come from? I'm trying to code a simple algorithm that prints out the $n^{th}$ Fibonacci number. However, my program requires the initial seed values $F_0 = 0$ and $F_1 = 1$, when I'm hopeful I can figure something out to not require initial seed values.
Where does $F_0$ and $F_1$ come from anyway? Recursively, $F_n = F_{n-1} + F_{n-2}$, for all $n > 1$, but is there a mathematical approach to infer $F_0$ and $F_1$? Basically, how would I approach the values $F_0$ and $F_1$ without knowing them beforehand?
edit; I wanted to add since there seems to be confusion: I'm only concerned with the below sequence.
$$0, 1, 1, 2, 3, 5, 8, ...$$
I'm curious to how the $0, 1$ is defined, because every other term can be derived recursively, but the first two cannot (or can they?).

A: The initial values $F_0 = 0$ and $F_1 = 1$ are part of the definition of the Fibonacci sequence. They can't be derived, because e.g. you could just as well pick any two numbers and apply the same recursion relation to get a different sequence. They're just the simplest numbers to start with, in a sense.
In general, any recursive definition which specifies a member of a sequence in terms of the previous $n$ members will require you to put in the first $n$ values by hand. They can be chosen arbitrarily and then you use the formula to produce further values. If you know that you want to produce a sequence with certain properties, then perhaps you can "derive" the $n$ seeds you need to come up with such a sequence (although there is not guaranteed to be any more efficient way to do so than guessing and checking), but without some constraint on the sequence you expect to end up with, nothing specifies the seeds.

A: One compelling reason for the standard definition of the fibonacci sequence is that it reveals their interesting divisibility properties, namely that they form a strong divisibility sequence, i.e.
$$\rm\ gcd(f_m,f_n)\ =\ f_{\:gcd(m,n)}$$
hence $\rm\ m\ |\ n\ \Rightarrow\ f_m\ |\ f_n\ $ etc. Analogous results hold for the more general class of Lucas-Lehmer sequences, which prove convenient when studying elementary number theory of quadratic fields, e.g. generalizations of Fermat's little theorem, Euler's $\phi$ totient function, etc. If one changed the indexing then many of these results would be greatly obfuscated.
That said, it should be emphasized that such definitions are merely conventions that prove useful in the context at hand. In other contexts - where such divisibility properties play no role - another indexing might prove more convenient.

A: There is an entire family of Fibonacci-like sequences. A cool result by Wythoff is that for integral valued Fibonacci sequences, if you "center" them properly, you can use them to make a 1 to 1 correspondence with the rationals. However, the classic Fibonacci sequence is defined that way.
http://mathworld.wolfram.com/WythoffArray.html

A: If you want to "derive" the initial conditions in some sense you could do so in the idealized biological sense of rabbit pair populations like "in the book Liber Abaci (1202) by Leonardo of Pisa, known as Fibonacci."
http://en.wikipedia.org/wiki/Fibonacci_number#Origins

A: Technically it shouldn't matter which nonzero numbers you start with. The cool thing about Fibonacci number is the limit should go to the golden ratio.
Consider the definition of Golden Ratio -
Smaller is to bigger piece, as bigger is to the whole.
As Fibonacci numbers get bigger and bigger, they get to this ratio. Intuitively speaking the original numbers matter less and less, and successive a, b, a+b patterns will go to:
a is to b, as b is to a+b.
Which gets closer and closer to the golden ratio.

redpajama_set_name: RedPajamaStackExchange


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BLF's Lindsay Maasdorp Says He Would Side with a Rapist if the Victim was White
By James Bishop on December 17, 2018 • ( 2 Comments )
Lindsay Maasdorp. Image Credit: Black Opinion.
In a debate that took place on his YouTube channel in August, Renaldo Gouws, a politician in the Democratic Alliance and political-social commentator, hosted Lindsay Maasdorp. The debate is just one of several "Sunday debates" that Gouws has hosted on his channel over the last few months.
Admittedly, often the debates appear to be more like discussions as opposed to actual formal debates with the whole process of opening speeches, rebuttals etc.. Independent of their form these debates are a good means for bringing together representatives of different ideological groups holding to quite different social and political beliefs and convictions. On the 19 of August it was Maasdorp, the national spokesperson for black supremacist group Black First Land First (BLF). Maasdorp is considered an authority in the "revolutionary" movement and is a frequent activist for its cause.
The BLF has made its disdain for white South Africans incredibly clear over the last few months. Maasdorp, for instance, stated that a white person's existence is "a crime," a view that meshes well with the party's view that all white South Africans, due to the land theft and dispossession by white people during colonization and apartheid, are settlers and are therefore all criminals who illegally possess land in South Africa (1). This year, Maasdorp also posted on his Twitter account that: "I have aspirations to kill white people, and this must be achieved!" More recently, Andile Mngxitama, the president of the BLF, asserted at a rally that "For each one person that is being killed by the taxi industry, we will kill five white people… You kill one of us, we will kill five of you. We will kill their children, we will kill their women, we will kill anything that we find on our way" (2).
Many more events fueled by a similar hatred of whiteness and white people could be mentioned, and perhaps another worth noting is from the debate with Gouws within which Maasdorp stated that he would support a rapist as long as the victim was white and the rapist was black. Here is the direct quite made by Maasdorp in the discussion:
"There is no black person in this country that we won't defend when they come into a fight with white people… Annanias Mathe, the Mozambican brother who was robbing all over the suburbs, white peoples homes, he was raping white women, that's a reality, he died I think last year or the year before… that's a reality. Me, I stand with Annanias Mathe."
For those interested in hearing him, view this short clip from the debate:
Maasdorp's condoning of such an individual as Mathe and his acts is quite illuminating particularly because Mathe was convicted of 67 of 71 counts of murder, attempted murder, rape, and armed robbery. It is clear then that Maasdorp celebrates violent and traumatic crime when whites are the victims and blacks are the perpetrators. Most strikingly this would include the rape of white women, perhaps one of the most physically, emotionally, and psychologically traumatic experiences a person could have.
For more on this see Renaldo Gouw's video. Also please like and support my Facebook page White Identity, South Africa.
1. Friedman, D. 2018. White existence is a crime, says BLF spokesperson. Available.
2. Pijoos, I. 2018. Complaints pour in over Andile Mngxitama's 'kill whites speech.' Available.
Categories: Racism, Topics & Issues
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