1. The document discusses delivering AAV2 gene therapy for Parkinson's disease through convection-enhanced delivery (CED), which uses a syringe pump to generate pressure and spread the vector throughout the targeted striatal area.
2. It examines delivering different doses of AAV2-hAADC, ranging from 6 to 500 units per hemisphere, to animal models and evaluating clinical responses and vector distribution up to 6 months later using various analysis methods.
3. The highest dosage group showed large discrepancies and no antibody response was detected, suggesting a potential delivery problem rather than immunogenicity issues.
Synthetic biology towards gene therapy: synthetic repressors in Huntington's ...Laura Berry
Presented at the 3rd Synthetic Biology Congress in London. To find out more, visit: www.global-engage.com
Mark Isalan, Reader in Gene Network Engineering at Imperial College London, presents results of applying lessons learnt from synthetic biology to the treatment of Huntington’s disease.
Watch the full presentation at: blog.globalengage.co.uk/synthetic-biology-applications-huntingtons-disease
IMATINIB IS A PDGF receptor antagonist ..used in idiopathic pulmonary HTN of 61 yr old patient,with positive family h/o
this article is prsented in NEJM SEP 2005
Synthetic biology towards gene therapy: synthetic repressors in Huntington's ...Laura Berry
Presented at the 3rd Synthetic Biology Congress in London. To find out more, visit: www.global-engage.com
Mark Isalan, Reader in Gene Network Engineering at Imperial College London, presents results of applying lessons learnt from synthetic biology to the treatment of Huntington’s disease.
Watch the full presentation at: blog.globalengage.co.uk/synthetic-biology-applications-huntingtons-disease
IMATINIB IS A PDGF receptor antagonist ..used in idiopathic pulmonary HTN of 61 yr old patient,with positive family h/o
this article is prsented in NEJM SEP 2005
Yearly Clinical Review of a Patient’s WGS Results Leads to a New Gene Candida...Golden Helix
The rapid evolution of genetic disease understanding and expanding genetic databases behooves clinician specialists to regularly review the status of clinical genetic test panels, reevaluating the status of identified variants. With the increasing use of WES and WGS sequencing, these results likely also need regular review.
We present a four-generation family affected by sudden cardiac arrests, ventricular tachycardia and (within the last 2 generations) documented left ventricular non-compaction. An affected member underwent a 38-gene pan-cardiomyopathy clinical genetic panel with no identified pathogenic variants. Therefore, affected members from three surviving generations (*) agreed to undergo genetic testing by whole genome sequencing in 2016. Analysis with Golden Helix SVS identified 69 shared, rare (MAF≤0.00005) coding variants in 40 genes, but none were identified to be associated with cardiac phenotypes.
At clinical follow-up of the youngest family member in 2019, we elected to review our WGS results again. A recent review of the genetics and genomics of dilated cardiomyopathy now identifies the SRA1 gene as being potentially involved in this phenotype, although no human cases have yet been reported. Upon review of this families previous WGS sequencing using SVS, we identified a SRA1 c.328_329 ins GAC (p.Val110delinsGlyLeu) rare shared variant. This variant is only present in 2 of 142724 alleles in the gnomAD database and inserts an additional amino acid into a partially conserved two amino acid region within an otherwise highly conserved protein region.
Friedrichs and colleagues previously identified SRA1 as one of 3 genes within a 600kb haploblock associated with cardiomyopathy in three independent Caucasian populations. In zebrafish, sra1 morphants display severe pericardial edema. The human SRA1 region also encodes a long noncoding RNA, lnc-SRA1-2, that is modulated in heart failure, attenuates hypoxia-induced injury in experimental cardiomyocytes through PPARγ/NF-κB signalling, and promotes the activation of cardiac myofibroblasts. SRA1 knockdown in C2C12 mouse myoblast cells prevented proper muscle gene expression and cell differentiation.
Cardiac genetics assessments by whole genome or whole exome sequencing also need regular review, which can be easily performed by Golden Helix SVS software. Links to new and frequently updated gene tracks and other genetic databases facilitate these reviews.
Genome-wide survey and characterization of AP2/ERF and HSP 90 gene family in ...ICRISAT
APETALA2/Ethylene Response Factor (AP2/ERF) and Heat Shock Protein 90 (HSP90) are important classes of transcription factor and chaperone proteins known to play a significant role under stress. Productivity and yield of legume crops are severely affected by environmental and pathogen stresses.
24 June 2015
Western Blot Antibody Customer Review for Anti-GPR18 antibody (STJ93370)St John's Laboratory Ltd
N-arachidonyl glycine receptor also known as G-protein coupled receptor 18 (GPR18) is a protein that in humans is encoded by the GPR18 gene. Along with the other previously "orphan" receptors GPR55 and GPR119, GPR18 has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to cannabinoid receptors. Research supports the hypothesis that GPR18 is the abnormal cannabidiol receptor and N-arachidonoyl glycine, the endogenous lipid metabolite of anandamide, initiates directed microglial migration in the CNS through activation of GPR18.
Anti-GPR18 - http://www.stjohnslabs.com/gpr18-antibody-p-96212?filter_name=STJ93370
Join our Antibody Validation Project - http://www.stjohnslabs.com/services/antibody-validation
Integrative Medicine and Experimental Pharmacogenomic Therapy in a Child with...Sophia's Garden Foundation
A 34-month female with Niemann-Pick Disease, Type A (NPD-A) is presented. NPD-A is a rare autosomal recessive, hereditary lysosomal storage disease caused by reduced acid sphingomyelinase (ASM) activity. Reduced sphingomyelinase activity resulting in impaired sphingomyelin turnover leads to cellular lipid and lysosomal storage (foam cells), hepatosplenomegaly, delay and loss of developmental milestones, and degenerative neurologic deficits. Death occurs in infancy or early childhood, with the usual life span being 2-3 years. No effective treatment for NPD-A is known, although bone marrow transplantation and enzyme replacement therapy with ASM have been attempted. [Both have been tried for NPD-B, but I do not know if either of these techniques have been tried for NPD-A. This is true that no successful treatment has been demonstrated for humans with NPD-A, yet the Genzyme studies using adeno viruses were successful for mice.
See <http://www.genzyme.co.uk/corp/news/all_news/GENL%20PR-060503.asp>. Stem cell and gene therapy research is being investigated in animal models. This child is known to have an unusual stop-codon mutation. Aminoglycosides have been found in animal and small-scale human studies to cause read-through in translation effectively skipping the “stop-codon” and are in clinical trials in other genetic diseases with similar mutations. It was hypothesized that gentamicin would cause read-through in translation in this patient, and thereby increase production of acid sphingomyelinase. After presentation to the Ethics Committee of Lucile Salter Packard Children’s Hospital at Stanford University, the child was treated with an experimental protocol using intranasal gentamicin. This is the first case of NPD-A in which this has been tried.
This patient has also been treated with Traditional Chinese Medicine including acupuncture and botanicals, massage therapy, nutritional measures, homeopathy, energy healing and compassionate intention in an Integrative Medicine approach. Disease characteristics, clinical features and course will be described.
Behavioral and Biochemical Studies of Piperidine Related Adrenolytic Compound...IJRESJOURNAL
ABSTRACT: The present study concerns behavioral and biochemical effects of 4 amino methyl piperidine substituted 2-bromo ethyl benzene derivative compounds. With intraperitoneal injection in rats, locomotor activity was significantly decreased in open field experiment, anxiolytic effect observed in light and dark apparatus significantly increased while stimulatory activity of compound monitor in home cage apparatussignificantly decreased. Moreover, blood glucose and cholesterol level also examined. Presentsynthetic compound decreases blood glucose level and also decreases the total serum cholesterol, suggested that these 4 amino methyl piperidine substituted 2-bromo ethyl benzene compounds may be effective as a drug for treatment of anxiety, enhancement of locomotion. It is also beneficial for cardiac and diabetic patient.
Yearly Clinical Review of a Patient’s WGS Results Leads to a New Gene Candida...Golden Helix
The rapid evolution of genetic disease understanding and expanding genetic databases behooves clinician specialists to regularly review the status of clinical genetic test panels, reevaluating the status of identified variants. With the increasing use of WES and WGS sequencing, these results likely also need regular review.
We present a four-generation family affected by sudden cardiac arrests, ventricular tachycardia and (within the last 2 generations) documented left ventricular non-compaction. An affected member underwent a 38-gene pan-cardiomyopathy clinical genetic panel with no identified pathogenic variants. Therefore, affected members from three surviving generations (*) agreed to undergo genetic testing by whole genome sequencing in 2016. Analysis with Golden Helix SVS identified 69 shared, rare (MAF≤0.00005) coding variants in 40 genes, but none were identified to be associated with cardiac phenotypes.
At clinical follow-up of the youngest family member in 2019, we elected to review our WGS results again. A recent review of the genetics and genomics of dilated cardiomyopathy now identifies the SRA1 gene as being potentially involved in this phenotype, although no human cases have yet been reported. Upon review of this families previous WGS sequencing using SVS, we identified a SRA1 c.328_329 ins GAC (p.Val110delinsGlyLeu) rare shared variant. This variant is only present in 2 of 142724 alleles in the gnomAD database and inserts an additional amino acid into a partially conserved two amino acid region within an otherwise highly conserved protein region.
Friedrichs and colleagues previously identified SRA1 as one of 3 genes within a 600kb haploblock associated with cardiomyopathy in three independent Caucasian populations. In zebrafish, sra1 morphants display severe pericardial edema. The human SRA1 region also encodes a long noncoding RNA, lnc-SRA1-2, that is modulated in heart failure, attenuates hypoxia-induced injury in experimental cardiomyocytes through PPARγ/NF-κB signalling, and promotes the activation of cardiac myofibroblasts. SRA1 knockdown in C2C12 mouse myoblast cells prevented proper muscle gene expression and cell differentiation.
Cardiac genetics assessments by whole genome or whole exome sequencing also need regular review, which can be easily performed by Golden Helix SVS software. Links to new and frequently updated gene tracks and other genetic databases facilitate these reviews.
Genome-wide survey and characterization of AP2/ERF and HSP 90 gene family in ...ICRISAT
APETALA2/Ethylene Response Factor (AP2/ERF) and Heat Shock Protein 90 (HSP90) are important classes of transcription factor and chaperone proteins known to play a significant role under stress. Productivity and yield of legume crops are severely affected by environmental and pathogen stresses.
24 June 2015
Western Blot Antibody Customer Review for Anti-GPR18 antibody (STJ93370)St John's Laboratory Ltd
N-arachidonyl glycine receptor also known as G-protein coupled receptor 18 (GPR18) is a protein that in humans is encoded by the GPR18 gene. Along with the other previously "orphan" receptors GPR55 and GPR119, GPR18 has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to cannabinoid receptors. Research supports the hypothesis that GPR18 is the abnormal cannabidiol receptor and N-arachidonoyl glycine, the endogenous lipid metabolite of anandamide, initiates directed microglial migration in the CNS through activation of GPR18.
Anti-GPR18 - http://www.stjohnslabs.com/gpr18-antibody-p-96212?filter_name=STJ93370
Join our Antibody Validation Project - http://www.stjohnslabs.com/services/antibody-validation
Integrative Medicine and Experimental Pharmacogenomic Therapy in a Child with...Sophia's Garden Foundation
A 34-month female with Niemann-Pick Disease, Type A (NPD-A) is presented. NPD-A is a rare autosomal recessive, hereditary lysosomal storage disease caused by reduced acid sphingomyelinase (ASM) activity. Reduced sphingomyelinase activity resulting in impaired sphingomyelin turnover leads to cellular lipid and lysosomal storage (foam cells), hepatosplenomegaly, delay and loss of developmental milestones, and degenerative neurologic deficits. Death occurs in infancy or early childhood, with the usual life span being 2-3 years. No effective treatment for NPD-A is known, although bone marrow transplantation and enzyme replacement therapy with ASM have been attempted. [Both have been tried for NPD-B, but I do not know if either of these techniques have been tried for NPD-A. This is true that no successful treatment has been demonstrated for humans with NPD-A, yet the Genzyme studies using adeno viruses were successful for mice.
See <http://www.genzyme.co.uk/corp/news/all_news/GENL%20PR-060503.asp>. Stem cell and gene therapy research is being investigated in animal models. This child is known to have an unusual stop-codon mutation. Aminoglycosides have been found in animal and small-scale human studies to cause read-through in translation effectively skipping the “stop-codon” and are in clinical trials in other genetic diseases with similar mutations. It was hypothesized that gentamicin would cause read-through in translation in this patient, and thereby increase production of acid sphingomyelinase. After presentation to the Ethics Committee of Lucile Salter Packard Children’s Hospital at Stanford University, the child was treated with an experimental protocol using intranasal gentamicin. This is the first case of NPD-A in which this has been tried.
This patient has also been treated with Traditional Chinese Medicine including acupuncture and botanicals, massage therapy, nutritional measures, homeopathy, energy healing and compassionate intention in an Integrative Medicine approach. Disease characteristics, clinical features and course will be described.
Behavioral and Biochemical Studies of Piperidine Related Adrenolytic Compound...IJRESJOURNAL
ABSTRACT: The present study concerns behavioral and biochemical effects of 4 amino methyl piperidine substituted 2-bromo ethyl benzene derivative compounds. With intraperitoneal injection in rats, locomotor activity was significantly decreased in open field experiment, anxiolytic effect observed in light and dark apparatus significantly increased while stimulatory activity of compound monitor in home cage apparatussignificantly decreased. Moreover, blood glucose and cholesterol level also examined. Presentsynthetic compound decreases blood glucose level and also decreases the total serum cholesterol, suggested that these 4 amino methyl piperidine substituted 2-bromo ethyl benzene compounds may be effective as a drug for treatment of anxiety, enhancement of locomotion. It is also beneficial for cardiac and diabetic patient.
Next-generation small molecule neuro regeneration therapy
Dual actions of increasing endogenous stem cells and suppressing glial differentiation of neural stem cells to regenerate neurons by peripheral administration of low molecular weight compounds.
Next-generation hair regenerative medicine
Hair regrowth by a low molecular weight compound that stimulates the proliferation of hair follicle stem cells.
Next-generation small molecule neuro regeneration therapy
Dual actions of increasing endogenous stem cells and
suppressing glial differentiation of neural stem cells to
regenerate neurons by peripheral administration of low
molecular weight compounds.
UiPath Test Automation using UiPath Test Suite series, part 3DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 3. In this session, we will cover desktop automation along with UI automation.
Topics covered:
UI automation Introduction,
UI automation Sample
Desktop automation flow
Pradeep Chinnala, Senior Consultant Automation Developer @WonderBotz and UiPath MVP
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
Software Delivery At the Speed of AI: Inflectra Invests In AI-Powered QualityInflectra
In this insightful webinar, Inflectra explores how artificial intelligence (AI) is transforming software development and testing. Discover how AI-powered tools are revolutionizing every stage of the software development lifecycle (SDLC), from design and prototyping to testing, deployment, and monitoring.
Learn about:
• The Future of Testing: How AI is shifting testing towards verification, analysis, and higher-level skills, while reducing repetitive tasks.
• Test Automation: How AI-powered test case generation, optimization, and self-healing tests are making testing more efficient and effective.
• Visual Testing: Explore the emerging capabilities of AI in visual testing and how it's set to revolutionize UI verification.
• Inflectra's AI Solutions: See demonstrations of Inflectra's cutting-edge AI tools like the ChatGPT plugin and Azure Open AI platform, designed to streamline your testing process.
Whether you're a developer, tester, or QA professional, this webinar will give you valuable insights into how AI is shaping the future of software delivery.
"Impact of front-end architecture on development cost", Viktor TurskyiFwdays
I have heard many times that architecture is not important for the front-end. Also, many times I have seen how developers implement features on the front-end just following the standard rules for a framework and think that this is enough to successfully launch the project, and then the project fails. How to prevent this and what approach to choose? I have launched dozens of complex projects and during the talk we will analyze which approaches have worked for me and which have not.
LF Energy Webinar: Electrical Grid Modelling and Simulation Through PowSyBl -...DanBrown980551
Do you want to learn how to model and simulate an electrical network from scratch in under an hour?
Then welcome to this PowSyBl workshop, hosted by Rte, the French Transmission System Operator (TSO)!
During the webinar, you will discover the PowSyBl ecosystem as well as handle and study an electrical network through an interactive Python notebook.
PowSyBl is an open source project hosted by LF Energy, which offers a comprehensive set of features for electrical grid modelling and simulation. Among other advanced features, PowSyBl provides:
- A fully editable and extendable library for grid component modelling;
- Visualization tools to display your network;
- Grid simulation tools, such as power flows, security analyses (with or without remedial actions) and sensitivity analyses;
The framework is mostly written in Java, with a Python binding so that Python developers can access PowSyBl functionalities as well.
What you will learn during the webinar:
- For beginners: discover PowSyBl's functionalities through a quick general presentation and the notebook, without needing any expert coding skills;
- For advanced developers: master the skills to efficiently apply PowSyBl functionalities to your real-world scenarios.
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/
UiPath Test Automation using UiPath Test Suite series, part 4DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 4. In this session, we will cover Test Manager overview along with SAP heatmap.
The UiPath Test Manager overview with SAP heatmap webinar offers a concise yet comprehensive exploration of the role of a Test Manager within SAP environments, coupled with the utilization of heatmaps for effective testing strategies.
Participants will gain insights into the responsibilities, challenges, and best practices associated with test management in SAP projects. Additionally, the webinar delves into the significance of heatmaps as a visual aid for identifying testing priorities, areas of risk, and resource allocation within SAP landscapes. Through this session, attendees can expect to enhance their understanding of test management principles while learning practical approaches to optimize testing processes in SAP environments using heatmap visualization techniques
What will you get from this session?
1. Insights into SAP testing best practices
2. Heatmap utilization for testing
3. Optimization of testing processes
4. Demo
Topics covered:
Execution from the test manager
Orchestrator execution result
Defect reporting
SAP heatmap example with demo
Speaker:
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
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.
Let's dive deeper into the world of ODC! Ricardo Alves (OutSystems) will join us to tell all about the new Data Fabric. After that, Sezen de Bruijn (OutSystems) will get into the details on how to best design a sturdy architecture within ODC.
Accelerate your Kubernetes clusters with Varnish CachingThijs Feryn
A presentation about the usage and availability of Varnish on Kubernetes. This talk explores the capabilities of Varnish caching and shows how to use the Varnish Helm chart to deploy it to Kubernetes.
This presentation was delivered at K8SUG Singapore. See https://feryn.eu/presentations/accelerate-your-kubernetes-clusters-with-varnish-caching-k8sug-singapore-28-2024 for more details.
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.
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.
5. Provides insight into vector trafficking in brain and peripheral tissues after intraputamenal delivery and relationship with dosage
6. Ten animals in five dose groups received bilateral intraputamenal infusions
7. (2/hemisphere; 4/brain) of AAV2-hAADC at doses of 6, 18, 55, 170, and 500 U/hemisphere. Two control animals were similarly infused with AAV2-GFP at doses of 1,000 U/brain (1 U = 1 . 10 9 vector genomes)
![AAV2 delivery through CED ,[object Object]](https://image.slidesharecdn.com/case-091207121933-phpapp02/85/Case-1-320.jpg)
