Abstract: The human immunodeficiency virus (HIV) integrates its genome into that of the human host to cause a persistent infection that can be controlled by antiviral drugs, but that cannot be cured. CRISPR-Cas endonucleases can be instructed to cleave and inactivate the integrated proviral DNA genome. We observed many surprise findings along this route. For instance, it turned out that HIV escape is promoted by the cellular DNA repair machinery, which introduces small indels at the target site that trigger subsequent viral escape. When two HIV targets are attacked to realize excision of a large HIV segment, we observed instead that a regular indel is introduced at both targets. To explain this, we reasoned that the two cuts are not present simultaneously because of fast DNA repair. Novel kinetic experiments support this idea. Another surprise finding is that we can score a fair number of very large genome deletions that extend beyond the integrated HIV genome and that are potentially dangerous because of oncogene activation. Most studies will miss such products because of the used PCR-based detection methods. We will also discuss some technological developments, e.g. the development of novel expression cassettes for guide RNAs, Pol-III driven transcription units and novel lentivirus vector designs.

Keywords: HIV, CRISPR-Cas, Cure

Biography: Ben Berkhout studied molecular biology at Leiden University and obtained his PhD in 1986 on translational control by means of RNA structure in bacteriophages. He performed postdoctoral research at the Dana Farber Cancer Institute (Harvard Medical School) and the National Institutes of Health (USA). He became Head of the Laboratory of Experimental Virology and was appointed Professor of Human Retrovirology the University of Amsterdam in 2002. He supervised 55 PhD students and published over 600 manuscripts on HIV-1 replication, virus evolution, virus discovery and new antiviral therapeutic strategies. BB sits on many international science panels (e.g. ERC, RGC Hong Kong, NMRC Singapore), and is editor-in-chief of Virus Research and editor for several journals (e.g. Retrovirology).

Abstract:

• Ultrahigh field (7 Tesla) due to higher spatial resolution and higher sensitivity to susceptibility effects (SWI) improves Central Vein Sign (CVS) in MS lesions at 3T: 45%, 7T: 87% visibility. The CVS is an excellent differential diagnostic criterium between MS lesion and lesions of vascular origin and MS mimics.


• A subgroup of MS lesions (40%) show iron rim lesions (IRL). IRLs are composed of proinflammatory iron containing microglia cells and macrophages and are present in all MS stages with a peak in late RRMS and early SPMS phase. IRL gradually increase in size and fuse with neighbouring IRL within years. Whereas non-IRL shrink over time. Lesions with iron rim are slowly expanding lesions. Therefore IRL are suggested to label a subset of chronic active lesions and are worse in prognosis for IRL comared to non-IRL. IRL correlate with clinical disability. Only one-third of IRL seen at 7T can be seen at 3T. High-resolution MRSI at 7T in Multiple Sclerosis


• 7 Tesla allows higher spectral resolution and high-resolution spectroscopic imaging (MRSI) in shorter scan times compared to 3T. In normal-appearing white matter neurochemical changes can already be seen with Myo- Inositol (mIns) increase to be an earlier imaging biomarker for neuroinflammation compared to conventional MR. Mean mIns/NAA ratios correlated significantly with Clinical Disability measured with the EDSS score. In summary MRSI at 7T allows detection of early lesion development and their activity, evaluation of disease progression and sensitive monitoring under therapy as well as monitoring of new treatment trials.

Biography: Univ. Prof. Dr. Siegfried Trattnig graduated from the University of Vienna Medical School in 1985. He trained in Radiology and subsequently served as Assistant Medical Director and Acting Medical Director for the Section of Neuroradiology in the Department of Radiology, Medical University of Vienna. He was appointed as an Associate Professor in Radiology 1993 becoming the Acting Medical Director at the Clinical Magnetic Resonance Institute at the University of Vienna. Since 2003 Prof Trattnig has the position of the Medical Director of the Centre of Excellence in high-field MR at the Medical University of Vienna. In 2010 he was appointed as a full Professor for Radiology with special focus on High field MR. Prof. Trattnig has pioneered the field of multi parametric or biochemical MR imaging of cartilage and in particular cartilage repair. Together with Stefan Marlovits he has developed the semiquantitative MR Observation of Cartilage Repair Tissue Score (MOCART) 1.0 and 2.0 which is now widely accepted by the orthopedic community and the authorities such as the FDA. He is currently the lead researcher on the clinical 7T & 3T projects at the Medical University in Vienna. Based on the results of clinical comparison studies between 3 and 7T his Center of Excellence for High Field MR was appointed as the international Reference Center for 7 Tesla by Siemens Healthcare, the leader in the ultra-high field MR.
He is or has been editorial board member of 8 scientific journals, member of 35 committees and working groups within the ISMRM, ESR, ESMRMB and the ICRS among the Executive Board member of the ESMRMB, member of the ESR Research Committee Board and Chairperson of the ESR Subcommittee Imaging Biomarker. He is an author of 648 articles in peer reviewed scientific journals and contributed to 25 scientific books. His h-Index is 79. Additionally he has held 26 peer reviewed scientific grants with a total of funding money of 14.5 Mio €, received 12 scientific awards and is a reviewer for 34 scientific journals. In 2019 he was awarded with the Senior Fellowship of the ESMRMB and in 2021 with the Senior Fellowship of the ISMRM.

Abstract: Currently, there are numerous systems and models for the upper human body that aim, in some cases, to enhance object grasping and, in others, to perform repetitive grasping in manufacturing operations or loading and unloading processes within the industrial sector. On the other hand, there is the sophistication of robotic hands (a term used here to generalize the concept), which feature varying numbers of degrees of freedom and control systems of differing complexity for these degrees of freedom. But what happens when a hand disability arises, such as one caused by a stroke or paraplegia? In these instances, replacing the hand is unnecessary; instead, the priority is the restoration of hand functionality, with the goal of enabling the affected individual to carry out daily life activities as normally as possible.

Indeed, for all these scenarios, the most thorough understanding possible of the human hand is essential. To this end, the academic literature already includes several proposals for virtual models of the human hand. What is presented here is the outcome of several years of research on this topic: a proposed virtual model of the human hand featuring 29 degrees of freedom for the hand itself, plus an additional 9 degrees of freedom for the wrist.

Through the simulation of the human hand, the aim is twofold: on one hand, to provide tools for physicians and physiotherapists, enabling them to design personalized rehabilitation systems; on the other hand, to develop more accurate robotic hand models.

Biography: Esteban Peña Pitarch holds a doctorate in the UPC. He has carried out his teaching work at the Technical College of Manresa (EPSEM), since 1988 and belongs to the department of mechanical engineering. He collaborates with the Institute of Industrial and Control Engineering (IOC), UPC, since 2008, in the robotics division. His research is focused on rehabilitation and simulation of stroke survivors, the creation of medical devices and the application of kinematics and dynamics to the human body by way of mathematical tools used in robotics. He manages a group with doctors specialized in physical medicine, rehabilitation, and engineers from a number of different fields. This group has published articles in magazines and congresses and owns two patents relating to medical apparatus. Esteban Peña Pitarch belongs to the Service and Industrial Robotics (SIR) research team and is currently working on two competitive projects as the main researcher of one and collaborating in the other. He is a professor and ex-dean of college Escola Politècnica Superior d'Enginyeria de Manresa (EPSEM) at the Universitat Politècnica de Catalunya (UPC). His teaching expertise are in Kinematics and Dynamics, and Machinery Design for Undergraduate and Graduate degree for more than 30 years. He has two patents and more than 100 papers on international journals and conferences. Research interests are in Virtual Human Modeling, Rehabilitation, and Human Exoskeleton Construction.