The Czech scientist Jan Svoboda was a pioneer of Rous sarcoma virus (RSV). In the 1960s, before the discovery of reverse transcriptase, he demonstrated the long-term persistence of the viral genome in non-productive mammalian cells, and he supported the DNA provirus hypothesis of Howard Temin. He showed how the virus can be rescued in the infectious form and elucidated the replication-competent nature of the Prague strain of RSV later used for the identification of the src oncogene. His studies straddled molecular oncology and virology, and he remained an active contributor to the field until his death last year. Throughout the 50 years that I was privileged to know Svoboda as my mentor and friend, I admired his depth of scientific inquiry and his steadfast integrity in the face of political oppression.
Foucault has been criticized for overlooking the similarities among Platonism, Christianity and Stoicism, and overstating Stoicism's distinctness. However, an examination of Stoic theories of truth shows that the Stoics sought out a particular kind of knowledge, and that this knowledge was necessarily sought by means of a certain circular process, to which Foucault himself vaguely alludes. This accounts for many of Foucault's observations, and explains why, even when Stoics speak about such topics as self-knowledge and self-renunciation in ways that recall Platonism and Christianity, their approach is rightly characterized as differing from that of their Platonic and Christian counterparts. Ultimately, this sheds light on Stoicism's import for politics. In short, only by the Stoic will the search for truth be carried out in such a way that the individual's identity will neither reinforce, nor be reinforced by his or her grasp of the truth; and this will uniquely prepare the Stoic to enter the political domain and to be recognized there as someone who speaks the truth.
Fifty years ago, the age-old scourge of infectious disease was receding in the developed world in response to improved public health measures, while the advent of antibiotics, better vaccines, insecticides and improved surveillance held the promise of eradicating residual problems. By the late twentieth century, however, an increase in the emergence and reemergence of infectious diseases was evident in many parts of the world. This upturn looms as the fourth major transition in human-microbe relationships since the advent of agriculture around 10,000 years ago. About 30 new diseases have been identified, including Legionnaires' disease, human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis C, bovine spongiform encephalopathy (BSE)/variant Creutzfeldt-Jakob disease (vCJD), Nipah virus, several viral hemorrhagic fevers and, most recently, severe acute respiratory syndrome (SARS) and avian influenza. The emergence of these diseases, and resurgence of old ones like tuberculosis and cholera, reflects various changes in human ecology: rural-to-urban migration resulting in high-density peri-urban slums; increasing long-distance mobility and trade; the social disruption of war and conflict; changes in personal behavior; and, increasingly, human-induced global changes, including widespread forest clearance and climate change. Political ignorance, denial and obduracy (as with HIV/AIDS) further compound the risks. The use and misuse of medical technology also pose risks, such as drug-resistant microbes and contaminated equipment or biological medicines. A better understanding of the evolving social dynamics of emerging infectious diseases ought to help us to anticipate and hopefully ameliorate current and future risks.
Fifty years ago, the age-old scourge of infectious disease was receding in the developed world in response to improved public health measures, while the advent of antibiotics, better vaccines, insecticides and improved surveillance held the promise of eradicating residual problems. By the late twentieth century, however, an increase in the emergence and reemergence of infectious diseases was evident in many parts of the world. This upturn looms as the fourth major transition in human-microbe relationships since the advent of agriculture around 10,000 years ago. About 30 new diseases have been identified, including Legionnaires' disease, human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), hepatitis C, bovine spongiform encephalopathy (BSE)/variant Creutzfeldt-Jakob disease (vCJD), Nipah virus, several viral hemorrhagic fevers and, most recently, severe acute respiratory syndrome (SARS) and avian influenza. The emergence of these diseases, and resurgence of old ones like tuberculosis and cholera, reflects various changes in human ecology: rural-to-urban migration resulting in high-density peri-urban slums; increasing long-distance mobility and trade; the social disruption of war and conflict; changes in personal behavior; and, increasingly, human-induced global changes, including widespread forest clearance and climate change. Political ignorance, denial and obduracy (as with HIV/AIDS) further compound the risks. The use and misuse of medical technology also pose risks, such as drug-resistant microbes and contaminated equipment or biological medicines. A better understanding of the evolving social dynamics of emerging infectious diseases ought to help us to anticipate and hopefully ameliorate current and future risks.
For efficient prevention of viral infections and cross protection, simultaneous targeting of multiple viral epitopes is a powerful strategy. Llama heavy chain antibody fragments (VHH) against the trimeric envelope proteins of Respiratory Syncytial Virus (Fusion protein), Rabies virus (Glycoprotein) and H5N1 Influenza (Hemagglutinin 5) were selected from llama derived immune libraries by phage display. Neutralizing VHH recognizing different epitopes in the receptor binding sites on the spikes with affinities in the low nanomolar range were identified for all the three viruses by viral neutralization assays. By fusion of VHH with variable linker lengths, multimeric constructs were made that improved neutralization potencies up to 4,000-fold for RSV, 1,500-fold for Rabies virus and 75-fold for Influenza H5N1. The potencies of the VHH constructs were similar or better than best performing monoclonal antibodies. The cross protection capacity against different viral strains was also improved for all three viruses, both by multivalent (two or three identical VHH) and biparatopic (two different VHH) constructs. By combining a VHH neutralizing RSV subtype A, but not subtype B with a poorly neutralizing VHH with high affinity for subtype B, a biparatopic construct was made with low nanomolar neutralizing potency against both subtypes. Trivalent anti-H5N1 VHH neutralized both Influenza H5N1 clade1 and 2 in a pseudotype assay and was very potent in neutralizing the NIBRG-14 Influenza H5N1 strain with IC(50) of 9 picomolar. Bivalent and biparatopic constructs against Rabies virus cross neutralized both 10 different Genotype 1 strains and Genotype 5.The results show that multimerization of VHH fragments targeting multiple epitopes on a viral trimeric spike protein is a powerful tool for anti-viral therapy to achieve "best-in-class" and broader neutralization capacity. ; Funding was provided by an IWT grant (Institute for the Promotion of Innovation by Science and Technology in Flanders, IWT70050) from the Flemish government. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding was also provided by Ablynx NV which had a significant input on the design and execution of the research. ; Sí
