Retroviruses can be used as tools in cell biology. They contain an RNA genome and reverse transcriptase enzyme, which allows them to insert their DNA into the host cell genome. Their life cycle involves reverse transcribing their RNA into DNA within the cell. This proviral DNA may then remain latent or produce new viral particles. Retroviral vectors can be engineered to express genes of interest by removing viral genes and adding the gene of interest, allowing them to integrate and persist long-term in infected cells. These vectors have been used to label and study tumor cells, brain development, and the effects of gene expression.
Adenoviridae is a group of medium sized, non-enveloped, double stranded DNA viruses that replicate and produce disease in the eye and in the respiratory, gastrointestinal and urinary tracts;
Adenoviridae is a group of medium sized, non-enveloped, double stranded DNA viruses that replicate and produce disease in the eye and in the respiratory, gastrointestinal and urinary tracts;
It is believed that HERVs are the result of ancient viral infections. A number of HERVs have maintained some functionality and still contain intact open reading frames (ORF’s) which code for fully functional proteins. HERV-W is one of these endogenous retroviruses. Over the last few years several research projects have suggested that HERV-W may be involved with multiple sclerosis, bipolar disorder, schizophrenia, autism, and various tumors. The presence of HERV-W RNAs, proteins, and virions has been detected in association with these diseases. This power point presentation was created to be used in conjunction with the associated paper.
A detailed description of HIV covering virology, morphology, pathogenesis, clinical stages and manifestations, laboratory diagnosis, and diagnostic strategy, and therapeutic options and prevention.
Ques-7Viruses contain DNA (deoxyribonucleic acid) or RNA (ribonuc.pdfaquacare2008
Ques-7:
Viruses contain DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) as their genetic
material, and they reproduce in the host cells. Bacteriophage is a type of virus that can infect
bacteria and inject its genome into the host, the bacteria then produces dozens of viral lineages.
Retrovirus such as HIV (human immune deficiency virus) reproduces in a different way, as they
contain reverse transcriptase enzyme. In this, a complementary DNA is transcribed from the
RNA genome, and it is called as DNA provirus.
The rate of evolution in RNA-based viruses (microcosm), like HIV-1 has million times higher
mutation rate when compared to that of DNA-based organisms (bacteria humans etc). It can
rapidly changes its genome components under biological conditions to acquire adaptations for
survival (resistance against drugs, immune components) in the biological host cell medium
compared to the DNA based organisms in which lower rate of evolutionary adaptations were
observed. This property of high genomic mutation rate in HIV-1 retrovirus is due to the
following mechanisms.
Viral genome transcribe via reverse transcription finally proved HIV-1 mRNA (after splicing)
with Rev 350 nucleotide sequences. These Rev produced once the viral mRNA transferred to the
cytoplasm from the nucleus for translation. Virulence is the factor of causing extensive damage
to the host cell and infecting new host cell in which pathogen is going to undergo extensive rate
of reproduction & phase variation along with genome modification to defend host immune
system. This is the main basis of evolution and an example ahs described below.
Several mutated viral lineages are produced due to the nucleotide integration into the host cells
& change their genome finally code for the enzymatic proteins such as reverse transcriptase,
ribonuclease, and integrase in order to promote severe multiplication of integrated host genome
with viral protein predominanlty result in several lineages (multiple capies of virions).
For example: Viral evolution mechanism with new genome & producetion of several viral
lineages
1. After viral particle entry, viral genome integrates into the host cell genome and replicate
followed by expression. Later the novel synthesized viral proteins are going to be transported to
specific sites for assembly into progeny virus thereby-----> more assembly/progeny
2. Even though viral assembly is going to takes place in the host cell plasma membrane, but a
variety of viral genomes initiate assembly in intracellular organelles or nucleus predominantly.
Thereby further particle/plaque forming units associate with exocytosis of the viral and host cell
integrated genome after lysis. Finally again mature viral lineages are going to target new cells.
Reverse transcriptase induced complementary DNA synthesis followed by mRNA synthesis for
viral protein -coding repoitre. This enzyme enables to produce more viral genome particle by
integrating into the host cell followed by vir.
This lecture is about Virology of HCV presented by Dr. Mahmoud Elzalabany, Internal Medicine Resident, Ahmed Maher Teaching Hospital.
The lecture was presented in the scientific meeting of Internal and Tropical Medicine departments, Ahmed Maher Teaching Hospital titled (Towards Eradication of HCV in Egypt) in celebration of World Hepatitis Day on July 28, 2016.
https://www.facebook.com/AMTH.IM
https://www.facebook.com/events/1072758396145209/
http://www.no4c.com
Epistemic Interaction - tuning interfaces to provide information for AI supportAlan Dix
Paper presented at SYNERGY workshop at AVI 2024, Genoa, Italy. 3rd June 2024
https://alandix.com/academic/papers/synergy2024-epistemic/
As machine learning integrates deeper into human-computer interactions, the concept of epistemic interaction emerges, aiming to refine these interactions to enhance system adaptability. This approach encourages minor, intentional adjustments in user behaviour to enrich the data available for system learning. This paper introduces epistemic interaction within the context of human-system communication, illustrating how deliberate interaction design can improve system understanding and adaptation. Through concrete examples, we demonstrate the potential of epistemic interaction to significantly advance human-computer interaction by leveraging intuitive human communication strategies to inform system design and functionality, offering a novel pathway for enriching user-system engagements.
Neuro-symbolic is not enough, we need neuro-*semantic*Frank van Harmelen
Neuro-symbolic (NeSy) AI is on the rise. However, simply machine learning on just any symbolic structure is not sufficient to really harvest the gains of NeSy. These will only be gained when the symbolic structures have an actual semantics. I give an operational definition of semantics as “predictable inference”.
All of this illustrated with link prediction over knowledge graphs, but the argument is general.
Dev Dives: Train smarter, not harder – active learning and UiPath LLMs for do...UiPathCommunity
💥 Speed, accuracy, and scaling – discover the superpowers of GenAI in action with UiPath Document Understanding and Communications Mining™:
See how to accelerate model training and optimize model performance with active learning
Learn about the latest enhancements to out-of-the-box document processing – with little to no training required
Get an exclusive demo of the new family of UiPath LLMs – GenAI models specialized for processing different types of documents and messages
This is a hands-on session specifically designed for automation developers and AI enthusiasts seeking to enhance their knowledge in leveraging the latest intelligent document processing capabilities offered by UiPath.
Speakers:
👨🏫 Andras Palfi, Senior Product Manager, UiPath
👩🏫 Lenka Dulovicova, Product Program Manager, UiPath
Kubernetes & AI - Beauty and the Beast !?! @KCD Istanbul 2024Tobias Schneck
As AI technology is pushing into IT I was wondering myself, as an “infrastructure container kubernetes guy”, how get this fancy AI technology get managed from an infrastructure operational view? Is it possible to apply our lovely cloud native principals as well? What benefit’s both technologies could bring to each other?
Let me take this questions and provide you a short journey through existing deployment models and use cases for AI software. On practical examples, we discuss what cloud/on-premise strategy we may need for applying it to our own infrastructure to get it to work from an enterprise perspective. I want to give an overview about infrastructure requirements and technologies, what could be beneficial or limiting your AI use cases in an enterprise environment. An interactive Demo will give you some insides, what approaches I got already working for real.
GraphRAG is All You need? LLM & Knowledge GraphGuy Korland
Guy Korland, CEO and Co-founder of FalkorDB, will review two articles on the integration of language models with knowledge graphs.
1. Unifying Large Language Models and Knowledge Graphs: A Roadmap.
https://arxiv.org/abs/2306.08302
2. Microsoft Research's GraphRAG paper and a review paper on various uses of knowledge graphs:
https://www.microsoft.com/en-us/research/blog/graphrag-unlocking-llm-discovery-on-narrative-private-data/
Smart TV Buyer Insights Survey 2024 by 91mobiles.pdf91mobiles
91mobiles recently conducted a Smart TV Buyer Insights Survey in which we asked over 3,000 respondents about the TV they own, aspects they look at on a new TV, and their TV buying preferences.
Connector Corner: Automate dynamic content and events by pushing a buttonDianaGray10
Here is something new! In our next Connector Corner webinar, we will demonstrate how you can use a single workflow to:
Create a campaign using Mailchimp with merge tags/fields
Send an interactive Slack channel message (using buttons)
Have the message received by managers and peers along with a test email for review
But there’s more:
In a second workflow supporting the same use case, you’ll see:
Your campaign sent to target colleagues for approval
If the “Approve” button is clicked, a Jira/Zendesk ticket is created for the marketing design team
But—if the “Reject” button is pushed, colleagues will be alerted via Slack message
Join us to learn more about this new, human-in-the-loop capability, brought to you by Integration Service connectors.
And...
Speakers:
Akshay Agnihotri, Product Manager
Charlie Greenberg, Host
DevOps and Testing slides at DASA ConnectKari Kakkonen
My and Rik Marselis slides at 30.5.2024 DASA Connect conference. We discuss about what is testing, then what is agile testing and finally what is Testing in DevOps. Finally we had lovely workshop with the participants trying to find out different ways to think about quality and testing in different parts of the DevOps infinity loop.
Key Trends Shaping the Future of Infrastructure.pdfCheryl Hung
Keynote at DIGIT West Expo, Glasgow on 29 May 2024.
Cheryl Hung, ochery.com
Sr Director, Infrastructure Ecosystem, Arm.
The key trends across hardware, cloud and open-source; exploring how these areas are likely to mature and develop over the short and long-term, and then considering how organisations can position themselves to adapt and thrive.
Slack (or Teams) Automation for Bonterra Impact Management (fka Social Soluti...Jeffrey Haguewood
Sidekick Solutions uses Bonterra Impact Management (fka Social Solutions Apricot) and automation solutions to integrate data for business workflows.
We believe integration and automation are essential to user experience and the promise of efficient work through technology. Automation is the critical ingredient to realizing that full vision. We develop integration products and services for Bonterra Case Management software to support the deployment of automations for a variety of use cases.
This video focuses on the notifications, alerts, and approval requests using Slack for Bonterra Impact Management. The solutions covered in this webinar can also be deployed for Microsoft Teams.
Interested in deploying notification automations for Bonterra Impact Management? Contact us at sales@sidekicksolutionsllc.com to discuss next steps.
Essentials of Automations: Optimizing FME Workflows with ParametersSafe Software
Are you looking to streamline your workflows and boost your projects’ efficiency? Do you find yourself searching for ways to add flexibility and control over your FME workflows? If so, you’re in the right place.
Join us for an insightful dive into the world of FME parameters, a critical element in optimizing workflow efficiency. This webinar marks the beginning of our three-part “Essentials of Automation” series. This first webinar is designed to equip you with the knowledge and skills to utilize parameters effectively: enhancing the flexibility, maintainability, and user control of your FME projects.
Here’s what you’ll gain:
- Essentials of FME Parameters: Understand the pivotal role of parameters, including Reader/Writer, Transformer, User, and FME Flow categories. Discover how they are the key to unlocking automation and optimization within your workflows.
- Practical Applications in FME Form: Delve into key user parameter types including choice, connections, and file URLs. Allow users to control how a workflow runs, making your workflows more reusable. Learn to import values and deliver the best user experience for your workflows while enhancing accuracy.
- Optimization Strategies in FME Flow: Explore the creation and strategic deployment of parameters in FME Flow, including the use of deployment and geometry parameters, to maximize workflow efficiency.
- Pro Tips for Success: Gain insights on parameterizing connections and leveraging new features like Conditional Visibility for clarity and simplicity.
We’ll wrap up with a glimpse into future webinars, followed by a Q&A session to address your specific questions surrounding this topic.
Don’t miss this opportunity to elevate your FME expertise and drive your projects to new heights of efficiency.
Builder.ai Founder Sachin Dev Duggal's Strategic Approach to Create an Innova...Ramesh Iyer
In today's fast-changing business world, Companies that adapt and embrace new ideas often need help to keep up with the competition. However, fostering a culture of innovation takes much work. It takes vision, leadership and willingness to take risks in the right proportion. Sachin Dev Duggal, co-founder of Builder.ai, has perfected the art of this balance, creating a company culture where creativity and growth are nurtured at each stage.
The Art of the Pitch: WordPress Relationships and SalesLaura Byrne
Clients don’t know what they don’t know. What web solutions are right for them? How does WordPress come into the picture? How do you make sure you understand scope and timeline? What do you do if sometime changes?
All these questions and more will be explored as we talk about matching clients’ needs with what your agency offers without pulling teeth or pulling your hair out. Practical tips, and strategies for successful relationship building that leads to closing the deal.
GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using Deplo...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
2. Electron micrograph of HIV. Cone-shaped cores are sectioned in various orientations. Viral genomic RNA is located in the electron-dense wide end of core.
3. Retroviruses are infectious particles consisting of an RNA genome packaged in a protein capsid , surrounded by a lipid envelope . This lipid envelope contains polypeptide chains including receptor binding proteins which link to the membrane receptors of the host cell, initiating the process of infection. Retroviruses contain RNA as the hereditary material in place of the more common DNA. In addition to RNA, retrovirus particles also contain the enzyme reverse transcriptase (or RTase) , which causes synthesis of a complementary DNA molecule (cDNA) using virus RNA as a template.
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6. Genetic organization Each retrovirus contains at least the following genetic sequence : LTR-GAG-POL-ENV-LTR This sequence is in the integrated provirus (DNA). LTR : Long Terminal Repeats ; in the viral DNA genes are bracketed by long terminal repeats (LTR), identical sequences that can be divided into three elements, including a promoter. These sequences are needed for successful transcription. GAG : G roup-specific A nti G en ; gene of the structural proteins (e.g. p24 and p17) POL : POL ymerase gene ; codes for protease, reverse transcriptase and integrase ENV : ENV elope gene ; codes for membrane proteins gp41 and gp120 Most Lentivirusses, including HIV-1, also have the following accessory genes : vif : viral infectivity factor vpr : viral protein R vpu : viral protein U rev : regulator of viral gene expression tat : trans-activator of transcription nef : negative effector These accessory genes are located downstream from POL. Some retroviruses (like RSV) carry an oncogene (like src).
8. In a addition to the nine proteins derived from GAG, POL and ENV, there are six other proteins made by HIV. Three of these are incorporated into the virus (Vif, Vpr and Nef) while the others are not found in the mature virus: Tat and Rev are regulatory proteins and Vpu indirectly assists in assembly. The genes that encode these proteins are known by three letter names that are derived as follows: TAT: T rans- A ctivator of T ranscription REV: Re gulator of V irion protein expression NEF: N e gative R egulatory F actor VIF: V irion I nfectivity F actor VPU: V iral P rotein U VPR: V iral P rotein R
9. The typical retrovirus genome consists of a single-stranded RNA of about 8500 nucleotides. The enzyme reverse transcriptase is a multifunctional enzyme that first makes a DNA copy of the viral RNA molecule. It then acts as a nuclease to remove the RNA, and then makes a second DNA strand, generating a double-stranded DNA copy of the RNA genome. The integration of this DNA into the host chromosome, catalyzed by a viral protein called integrase , is required for the synthesis of new viral RNA molecules by the host cell RNA polymerase. Retroviruses are examples of enveloped viruses , in which the protein shell is further enclosed by an outer lipid bilayer membrane. The envelope contains proteins that enable the virus to bind to cells, and that aid its entry into a cell. As indicated, the lipid membrane is acquired when the virus is released from the cell by a process of budding from the plasma membrane, taking some of the plasma membrane with it. The budding process is reversed when the virus reinfects a cell. Retrovirus Life Cycle
10. The retroviral life cycle begins in the nucleus of an infected cell. At this stage of the life cycle the retroviral genome is a DNA element integrated into and covalently attached to the DNA of the host cell. The genome of the virus is of approximately 8-12 kb of DNA (depending upon the retroviral species). Full-length genomic mRNA is made initiating at the beginning of the R (repeat) at the 5' LTR (Long Terminal Repeat). The free particle can infect new cells by binding to a cell surface receptor. The specificity of the virus-cell interaction is determined largely by the envelope protein(s) of the retrovirus. Infection leads to injection of the virus nucleoprotein core (consisting mostly of gag-derived proteins, full-length genomic RNA, and the reverse transcriptase protein). LTR LTR
13. Retroviruses contain viral RNA and several copies of reverse transcriptase (DNA polymerase). After infecting a cell, the reverse transcriptase is used to make the initial copies of viral DNA from viral RNA. Once a DNA strand has been synthesized, a complementary viral DNA strand is made. These double strand copies of viral DNA are inserted into the host-cell chromosome and host-cell RNA polymerase is used to make virus-related RNA. These RNA strands serve as templates for making new copies of the viral chromosomal RNA and serve also as mRNA. mRNA is translated into viral proteins that are used to make the virus envelope. New viral particles are assembled, bud from the plasma membrane, and are released. An example of this process is illustrated in the replication of the retrovirus, HIV (human immunodeficiency virus).
14. HIV infection begins with the interaction of the HIV glycoprotein gp120 with the CD4 molecule on the surface of the target cell. Following CD4 binding, a change in the HIV gp120/ gp 41 complex is induced by interaction of gp120 with the chemokine receptors CCR5 or CXCR4 . This change in confirmation exposes gp41 allowing it to initiate fusion of the membranes. The significant role of CCR5 in this process has been revealed upon the observation that individuals homozygous for mutations within CCR5 are resistant to infection by HIV-1. HIV Infection
15. As the virus fuses with the cell, internalization of the viral core with the associated RNA occurs. Partial uncoating of the viral core occurs to expose the viral RNA. Once in the cell cytoplasm, the conversion of the viral RNA into double-stranded DNA commences as the viral reverse transcriptase becomes active. HIV Infection
16. Reverse transcriptase synthesizes a double-stranded DNA copy of the single-stranded viral RNA generating a provirus . The viral DNA migrates to and enters the host cell nucleus (facilitated by HIV proteins vpr and MA ) and becomes integrated into the cell DNA with the help of the enzyme integrase . The provirus can then remain latent or be active, generating products for the generation of new virions. HIV Infection
17. Inside the nucleus, RNA polymerase II transcribes viral DNA into mRNA. The 9kb (genomic) mRNA is used for: 1. synthesis of the gag and gag-pol polyproteins 2. as the genetic material for the new virons formed. The 9kb mRNA can be spliced to yield 4kb and 2kb mRNAs. The 4kb viral mRNA is used to synthesize: 1. gp 120 2. gp 41 3. 3 regulating proteins - vif, vpr, and vpu. The 2kb viral mRNA is used to synthesize 3 regulatory proteins: tat, rev, and nef. HIV Infection
18. 1) The viral mRNA leaves the nucleus. The translation of the viral mRNA results in the synthesis of three polyproteins : 2) ENV gp 160 - containing gp 120 and gp 41 3) GAG p55 - containing MA (matrix), CA (capsid), and NC (nucleocapsid protein) GAG-POL p 160 - containing MA (matrix), CA (capsid), PR (proteinase), (RT) reverse transcriptase, and INT (integrase) p55 and p160 are generated from the same mRNA strand by the process of ribosome frame shifting. The env gp160 proteins pass through the E.R. and Golgi apparatus to be processed into gp120 and gp41 HIV envelope proteins. During movement through the Golgi apparatus, glycosylation of gp120 occurs. RV Protein Processing
19. The gag and gag-pol polyproteins associate with the inner surface of the plasma membrane and interact with gp41 present in the plasma membrane. Some of the 9 kb viral RNA interacts with the nucleocapsid portion of p55. As p55 and p160 accumulate on the inner surface of the plasma membrane, they aggregate and commence assembly to form the viron. As assembly continues, the structure extrudes from the cell. Budding
20. As the virus buds from the cell, it acquires a lipid coat , carrying the gp120 and gp41 proteins. The virus is extruded into extra-cellular space in this immature state . During (or soon after) the budding of the new HIV particle from the host cell membrane, the viral proteinase in p160 becomes active, resulting in the cleavage of p160 and p55 into the various subunits and generating the mature form of HIV. This processing of p160 and p55 by the viral proteinase is essential for the generation of infectious virus. Budding and Maturation
21. Assembly of the virus occurs at the surface membrane of the cell. Viral Assembly gp41 p55 p160
22. The virus buds and the protease cuts itself free of the GAG-POL polyprotein . p55 gp120 p160 gp41 free protease
24. The necessity for CD4 antigen expression for entry of HIV into a human cell. HeLa and most other cells do not have CD4 antigen and are not infected. Cells transfected with CD4 gene can be infected with HIV. CD4 antigen gp120 CD4
25. Virus titer , CD4 cell number and anti-gp120 titer during the course of HIV infection. Time course of HIV infection
26. Wild-type retrovirus life cycle. 1) Viral particle with RNA genome binds to cell and is endocytosed. 2) Virus uncoats and RNA is reverse-transcribed into dsDNA. 3) dsDNA integrates into the infected cell’s genome irreversibly. 4) Viral genes are transcribed and translated into proteins. 5) New infectious viral particles assemble and bud from cell surface.
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28. Retroviral Vectors Retroviruses can be used to express two genes of interest in infected cells. pLZ10/LZ14 gag lacZ AATAAA pLZIS gag lacZ v- src IRES pBH1210 gag pol env pLZIS SH2 gag lacZ v- src SH2 IRES gag lacZ v- src SH3 IRES pLZIS SH3
29. lacZ only v-src v-src SH2 v-src SH3 Effects of v-src expression on developing brain cells Early developing brains were infected with retroviral vectors encoding only the lacZ marker gene , or lacZ along with different forms of the v-src tyrosine kinase. LacZ-expressing cells turn blue when incubated in X-gal.
30. Retroviral vector tumor cell marking 1) C6 rat glioma brain tumor cells were infected with a lacZ-containing retroviral vector. 2) Cells were injected into chick embryo brains and made tumors. 3) When tissue was incubated in X-gal, the tumor cells turned blue , so they are easy to find. White brain tissue, blue tumor cells.
35. Normal “clones” of brain cells that came from single infected progenitor cells. The cells migrated radially in the developing brain along radial glia.
36. Chick embryo brains were infected with a mixture of 2 retroviral vectors. One encoded regular lacZ (right). The other (left) encoded lacZ that was fused to a nuclear localization signal sequence , so that the lacZ protein that was translated would enter and accumulate in the nucleus.
37. Migration of Clonal Cohorts Mechanism: Are integrins involved in radial migration? E3 E6 E7.5 E9 VZ VZ IZ MZ TP VZ
38. Antisense retroviral vectors Instead of expressing a second gene, like v-src, retroviral vectors can be used to mark cells (via lacZ) and shut down expression of a protein using antisense sequences . Essentially, this is a negative copy of a gene that is expressed by the retroviral vector, and it hybridizes to the cell’s mRNA to block it from being translated into protein. Therefore, you get specific attenuation of a gene. Here, antisense integrin 1 subunit sequences were used.
39. E 7 Clones lacZ RV 1) Antisense 1 integrin RV 2) Antisense 8 integrin RV 8 1 integrin is required for radial migration and cell survival. Antisense clones die E8- E12.