1. The amyloid cascade hypothesis proposes that amyloid-beta (Ab) aggregation drives Alzheimer's disease pathogenesis and has guided much research for 20 years.
2. Previous phase 3 clinical trials of drugs targeting Ab failed to show efficacy, questioning the hypothesis.
3. For an Ab-directed drug to demonstrate efficacy, it remains unclear what the minimum Ab reduction threshold must be and at what disease stage treatment would be most effective. Testing the amyloid cascade hypothesis in clinical trials continues to be challenging.
Multiple alleles exist at the ABO blood group locus. There are two alleles (IA and IB) that determine the A and B antigens. The O allele is recessive to both IA and IB. There are three main blood groups - A, B, and O - determined by the interactions between the alleles. ABO blood typing is important for blood transfusions to avoid transfusion reactions.
DNA sequence can be determined through gel electrophoresis by separating DNA fragments of differing lengths. While this shows fragments of different sizes, it does not reveal the terminal nucleotides. However, if fragments with the same terminal nucleotide are grouped, it may be possible to read the entire sequence. Maxam-Gilbert and Sanger methods allow determining DNA sequence. Maxam-Gilbert uses chemical cleavage while Sanger uses a biosynthetic method incorporating chain terminating dideoxynucleotides, producing fragments of varying lengths that can then be read to reveal the sequence.
1) The ABO blood group system has multiple alleles that determine the blood type.
2) The alleles IA and IB determine the A and B antigens, while i determines the O type.
3) Crossing different ABO genotypes can determine the offspring's probable blood type.
Blogging and social networking sites may help reduce vote bank politics in India. The current state of Indian politics is problematic as it relies too heavily on vote banks. While technology is not a perfect solution, it could help address the issues in Indian politics until a better method is found.
Este documento habla sobre la esteticiología y cómo se aplica a la constitución débil y el anillo senil. La profesora Carmen M. Colón de Jorge enseña sobre estos temas de la esteticiología.
Ciencias corporales campo estetica parte 2 del 21 40 de 59 slidesCARMEN COLON DE JORGE
Este documento habla sobre probióticos y homeopatías como herramientas estéticas que integran la salud y la belleza. Explica los procesos de fermentación en el intestino grueso y cómo los probióticos convierten los almidones en aminoácidos de manera saludable. También describe cómo la putrefacción puede generar sustancias tóxicas y cómo los probióticos ayudan a prevenir esto.
This document discusses epidemiology of aging and dementia in Down syndrome. It notes that individuals with Down syndrome experience accelerated aging due to factors like shorter telomere length and earlier menopause. They are also at higher risk of dementia because the gene for amyloid precursor protein is triplicated on chromosome 21, leading to overproduction of amyloid beta, a key factor in Alzheimer's disease. The risk of developing Alzheimer's disease increases with age for those with Down syndrome and is influenced by additional genetic and medical factors like atypical karyotypes, APOE genotype, metabolic conditions, and changing levels of amyloid beta 42 in cerebrospinal fluid over time.
Samantha Budd discussed bringing effective treatments to patients with neurological and pain conditions, noting it requires a long-term commitment. She advocated for better research and technologies to predict outcomes, a better understanding of targets, patient segments, and compounds, which would give a better chance of success in translational science.
Multiple alleles exist at the ABO blood group locus. There are two alleles (IA and IB) that determine the A and B antigens. The O allele is recessive to both IA and IB. There are three main blood groups - A, B, and O - determined by the interactions between the alleles. ABO blood typing is important for blood transfusions to avoid transfusion reactions.
DNA sequence can be determined through gel electrophoresis by separating DNA fragments of differing lengths. While this shows fragments of different sizes, it does not reveal the terminal nucleotides. However, if fragments with the same terminal nucleotide are grouped, it may be possible to read the entire sequence. Maxam-Gilbert and Sanger methods allow determining DNA sequence. Maxam-Gilbert uses chemical cleavage while Sanger uses a biosynthetic method incorporating chain terminating dideoxynucleotides, producing fragments of varying lengths that can then be read to reveal the sequence.
1) The ABO blood group system has multiple alleles that determine the blood type.
2) The alleles IA and IB determine the A and B antigens, while i determines the O type.
3) Crossing different ABO genotypes can determine the offspring's probable blood type.
Blogging and social networking sites may help reduce vote bank politics in India. The current state of Indian politics is problematic as it relies too heavily on vote banks. While technology is not a perfect solution, it could help address the issues in Indian politics until a better method is found.
Este documento habla sobre la esteticiología y cómo se aplica a la constitución débil y el anillo senil. La profesora Carmen M. Colón de Jorge enseña sobre estos temas de la esteticiología.
Ciencias corporales campo estetica parte 2 del 21 40 de 59 slidesCARMEN COLON DE JORGE
Este documento habla sobre probióticos y homeopatías como herramientas estéticas que integran la salud y la belleza. Explica los procesos de fermentación en el intestino grueso y cómo los probióticos convierten los almidones en aminoácidos de manera saludable. También describe cómo la putrefacción puede generar sustancias tóxicas y cómo los probióticos ayudan a prevenir esto.
This document discusses epidemiology of aging and dementia in Down syndrome. It notes that individuals with Down syndrome experience accelerated aging due to factors like shorter telomere length and earlier menopause. They are also at higher risk of dementia because the gene for amyloid precursor protein is triplicated on chromosome 21, leading to overproduction of amyloid beta, a key factor in Alzheimer's disease. The risk of developing Alzheimer's disease increases with age for those with Down syndrome and is influenced by additional genetic and medical factors like atypical karyotypes, APOE genotype, metabolic conditions, and changing levels of amyloid beta 42 in cerebrospinal fluid over time.
Samantha Budd discussed bringing effective treatments to patients with neurological and pain conditions, noting it requires a long-term commitment. She advocated for better research and technologies to predict outcomes, a better understanding of targets, patient segments, and compounds, which would give a better chance of success in translational science.
The naval bombing of Vieques for the past 60 years has generated the suspicion that cause proliferation of multiple illness on the island of 9,000 inhabitants.
Busca version en español
The document discusses how the study of schizotypy helps advance our understanding of schizophrenia. It defines schizotypy as a latent personality organization that harbors liability for schizophrenia. Studying schizotypy offers a unifying framework as it represents a spectrum of expressions from subtle abnormalities to psychosis. Schizotypy is assessed through various approaches including genetics, laboratory measures, clinical features, and psychometric indexes. High scores on measures of schizotypy like the Perceptual Aberration Scale are associated with features like attention deficits and genetic risk factors. While schizotypy is measured dimensionally, evidence suggests it may have an underlying discontinuous nature. Longitudinal studies find that some schizotypic individuals develop psychosis over time.
The document discusses the International Consortium on Schizotypy Research which promotes research on schizotypy. The ICSR has an online workshop in September 2015 and publishes in the Schizophrenia Bulletin journal as well as maintains a website on schizotypy research.
Webinar o abeta alzforum shared slides 101311 slnicowef
The document discusses research on endogenous Aβ oligomers, including:
1. A model of endogenous oligomer production and the differential secretion of low-n oligomers in neurons and cell lines.
2. A relationship between low-n oligomers and Aβ*56 in human brain tissue.
3. The temporal accumulation of Aβ dimers in a transgenic mouse model of Alzheimer's disease.
4. Proposed models for the expression profile of oligomers in the human brain across aging and disease progression, and a model of endogenous oligomer toxicity.
The document discusses issues with the "toxic oligomer hypothesis" in Alzheimer's research. Specifically, it notes that a lack of understanding and definition of the term "toxic oligomer" allows for too much interpretation of scientific results. It outlines problems with analytical techniques used to characterize oligomers and questions what is meant by terms like "stable oligomers" and "biologically active conformation". The document calls for more standardization and characterization of oligomer preparations, as well as discussion of the weaknesses of different preparations before precise claims can be made.
Assessing risk and managing behavior may 6 2015nicowef
This document discusses the identification and management of problematic behaviors commonly seen in dementia patients, such as sundowning, wandering, and aggression. It explores potential causes of these behaviors like unmet needs, medical issues, and the patient's stage of dementia. Prevention strategies are outlined, including understanding behaviors from the patient's perspective, meeting their basic needs, and making environmental modifications.
The document provides an overview of an instructor orientation meeting for the Department of Social Services (DSS).
The agenda includes reviewing past trainings, previewing upcoming fall courses, new policies and procedures, training site locations, continuing education units, and a question and answer session. New items include online CEU applications, a department preamble, and training sites in Fairfax and Virginia Beach. Instructors shared tips for engaging learners, using icebreakers, and making the training fun and interactive. Questions from instructors addressed person-centered care regulations and the leadership program requirements.
El documento habla sobre los policrestos, que son los 30 remedios homeopáticos más utilizados. Explica que tienen un amplio espectro de acción terapéutica y que algunos son los más vendidos sin receta. Luego analiza algunos policrestos específicos como Aconitum Napellus, Belladona, Barita Carbonica y Bryonia Alba, describiendo sus características, síntomas y usos clínicos.
Care Of Hands And Arms For Computer UsersAngel Rivera
It discusses causes of fatigue and discomfort of the hands and arms while using computer keyboards and mice.
It provides recommendations on how to provide relief:
Adjusting a better posture
Taking frequent breaks
Considering ergonomic devices
Exercise
Self-massage
Reading speed fluency games were developed by Ms. Batchu to help improve reading speed and fluency. The document contains lists of high frequency words, sentences, poems and instructions to read each item from left to right and when words appear and disappear. The goal is to read quickly and smoothly.
El documento describe las técnicas del masaje Tuina, una forma tradicional de masaje chino. Explica que fue creado en 1950 en China y que los practicantes de Tuina, llamados "Chijiao Yisheng", manejan emergencias médicas y recetan tratamientos para enfermedades simples usando acupuntura, moxibustión, masaje y herbología. Luego describe varias técnicas de masaje Tuina como rodar, pulir, amasar, rotar y presionar, y sus usos para tratar lastimaduras, dol
Industrial Tech SW: Category Renewal and CreationChristian Dahlen
Every industrial revolution has created a new set of categories and a new set of players.
Multiple new technologies have emerged, but Samsara and C3.ai are only two companies which have gone public so far.
Manufacturing startups constitute the largest pipeline share of unicorns and IPO candidates in the SF Bay Area, and software startups dominate in Germany.
[To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations]
This presentation is a curated compilation of PowerPoint diagrams and templates designed to illustrate 20 different digital transformation frameworks and models. These frameworks are based on recent industry trends and best practices, ensuring that the content remains relevant and up-to-date.
Key highlights include Microsoft's Digital Transformation Framework, which focuses on driving innovation and efficiency, and McKinsey's Ten Guiding Principles, which provide strategic insights for successful digital transformation. Additionally, Forrester's framework emphasizes enhancing customer experiences and modernizing IT infrastructure, while IDC's MaturityScape helps assess and develop organizational digital maturity. MIT's framework explores cutting-edge strategies for achieving digital success.
These materials are perfect for enhancing your business or classroom presentations, offering visual aids to supplement your insights. Please note that while comprehensive, these slides are intended as supplementary resources and may not be complete for standalone instructional purposes.
Frameworks/Models included:
Microsoft’s Digital Transformation Framework
McKinsey’s Ten Guiding Principles of Digital Transformation
Forrester’s Digital Transformation Framework
IDC’s Digital Transformation MaturityScape
MIT’s Digital Transformation Framework
Gartner’s Digital Transformation Framework
Accenture’s Digital Strategy & Enterprise Frameworks
Deloitte’s Digital Industrial Transformation Framework
Capgemini’s Digital Transformation Framework
PwC’s Digital Transformation Framework
Cisco’s Digital Transformation Framework
Cognizant’s Digital Transformation Framework
DXC Technology’s Digital Transformation Framework
The BCG Strategy Palette
McKinsey’s Digital Transformation Framework
Digital Transformation Compass
Four Levels of Digital Maturity
Design Thinking Framework
Business Model Canvas
Customer Journey Map
❼❷⓿❺❻❷❽❷❼❽ Dpboss Matka Result Satta Matka Guessing Satta Fix jodi Kalyan Final ank Satta Matka Dpbos Final ank Satta Matta Matka 143 Kalyan Matka Guessing Final Matka Final ank Today Matka 420 Satta Batta Satta 143 Kalyan Chart Main Bazar Chart vip Matka Guessing Dpboss 143 Guessing Kalyan night
Storytelling is an incredibly valuable tool to share data and information. To get the most impact from stories there are a number of key ingredients. These are based on science and human nature. Using these elements in a story you can deliver information impactfully, ensure action and drive change.
[To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations]
This PowerPoint compilation offers a comprehensive overview of 20 leading innovation management frameworks and methodologies, selected for their broad applicability across various industries and organizational contexts. These frameworks are valuable resources for a wide range of users, including business professionals, educators, and consultants.
Each framework is presented with visually engaging diagrams and templates, ensuring the content is both informative and appealing. While this compilation is thorough, please note that the slides are intended as supplementary resources and may not be sufficient for standalone instructional purposes.
This compilation is ideal for anyone looking to enhance their understanding of innovation management and drive meaningful change within their organization. Whether you aim to improve product development processes, enhance customer experiences, or drive digital transformation, these frameworks offer valuable insights and tools to help you achieve your goals.
INCLUDED FRAMEWORKS/MODELS:
1. Stanford’s Design Thinking
2. IDEO’s Human-Centered Design
3. Strategyzer’s Business Model Innovation
4. Lean Startup Methodology
5. Agile Innovation Framework
6. Doblin’s Ten Types of Innovation
7. McKinsey’s Three Horizons of Growth
8. Customer Journey Map
9. Christensen’s Disruptive Innovation Theory
10. Blue Ocean Strategy
11. Strategyn’s Jobs-To-Be-Done (JTBD) Framework with Job Map
12. Design Sprint Framework
13. The Double Diamond
14. Lean Six Sigma DMAIC
15. TRIZ Problem-Solving Framework
16. Edward de Bono’s Six Thinking Hats
17. Stage-Gate Model
18. Toyota’s Six Steps of Kaizen
19. Microsoft’s Digital Transformation Framework
20. Design for Six Sigma (DFSS)
To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations
The naval bombing of Vieques for the past 60 years has generated the suspicion that cause proliferation of multiple illness on the island of 9,000 inhabitants.
Busca version en español
The document discusses how the study of schizotypy helps advance our understanding of schizophrenia. It defines schizotypy as a latent personality organization that harbors liability for schizophrenia. Studying schizotypy offers a unifying framework as it represents a spectrum of expressions from subtle abnormalities to psychosis. Schizotypy is assessed through various approaches including genetics, laboratory measures, clinical features, and psychometric indexes. High scores on measures of schizotypy like the Perceptual Aberration Scale are associated with features like attention deficits and genetic risk factors. While schizotypy is measured dimensionally, evidence suggests it may have an underlying discontinuous nature. Longitudinal studies find that some schizotypic individuals develop psychosis over time.
The document discusses the International Consortium on Schizotypy Research which promotes research on schizotypy. The ICSR has an online workshop in September 2015 and publishes in the Schizophrenia Bulletin journal as well as maintains a website on schizotypy research.
Webinar o abeta alzforum shared slides 101311 slnicowef
The document discusses research on endogenous Aβ oligomers, including:
1. A model of endogenous oligomer production and the differential secretion of low-n oligomers in neurons and cell lines.
2. A relationship between low-n oligomers and Aβ*56 in human brain tissue.
3. The temporal accumulation of Aβ dimers in a transgenic mouse model of Alzheimer's disease.
4. Proposed models for the expression profile of oligomers in the human brain across aging and disease progression, and a model of endogenous oligomer toxicity.
The document discusses issues with the "toxic oligomer hypothesis" in Alzheimer's research. Specifically, it notes that a lack of understanding and definition of the term "toxic oligomer" allows for too much interpretation of scientific results. It outlines problems with analytical techniques used to characterize oligomers and questions what is meant by terms like "stable oligomers" and "biologically active conformation". The document calls for more standardization and characterization of oligomer preparations, as well as discussion of the weaknesses of different preparations before precise claims can be made.
Assessing risk and managing behavior may 6 2015nicowef
This document discusses the identification and management of problematic behaviors commonly seen in dementia patients, such as sundowning, wandering, and aggression. It explores potential causes of these behaviors like unmet needs, medical issues, and the patient's stage of dementia. Prevention strategies are outlined, including understanding behaviors from the patient's perspective, meeting their basic needs, and making environmental modifications.
The document provides an overview of an instructor orientation meeting for the Department of Social Services (DSS).
The agenda includes reviewing past trainings, previewing upcoming fall courses, new policies and procedures, training site locations, continuing education units, and a question and answer session. New items include online CEU applications, a department preamble, and training sites in Fairfax and Virginia Beach. Instructors shared tips for engaging learners, using icebreakers, and making the training fun and interactive. Questions from instructors addressed person-centered care regulations and the leadership program requirements.
El documento habla sobre los policrestos, que son los 30 remedios homeopáticos más utilizados. Explica que tienen un amplio espectro de acción terapéutica y que algunos son los más vendidos sin receta. Luego analiza algunos policrestos específicos como Aconitum Napellus, Belladona, Barita Carbonica y Bryonia Alba, describiendo sus características, síntomas y usos clínicos.
Care Of Hands And Arms For Computer UsersAngel Rivera
It discusses causes of fatigue and discomfort of the hands and arms while using computer keyboards and mice.
It provides recommendations on how to provide relief:
Adjusting a better posture
Taking frequent breaks
Considering ergonomic devices
Exercise
Self-massage
Reading speed fluency games were developed by Ms. Batchu to help improve reading speed and fluency. The document contains lists of high frequency words, sentences, poems and instructions to read each item from left to right and when words appear and disappear. The goal is to read quickly and smoothly.
El documento describe las técnicas del masaje Tuina, una forma tradicional de masaje chino. Explica que fue creado en 1950 en China y que los practicantes de Tuina, llamados "Chijiao Yisheng", manejan emergencias médicas y recetan tratamientos para enfermedades simples usando acupuntura, moxibustión, masaje y herbología. Luego describe varias técnicas de masaje Tuina como rodar, pulir, amasar, rotar y presionar, y sus usos para tratar lastimaduras, dol
Industrial Tech SW: Category Renewal and CreationChristian Dahlen
Every industrial revolution has created a new set of categories and a new set of players.
Multiple new technologies have emerged, but Samsara and C3.ai are only two companies which have gone public so far.
Manufacturing startups constitute the largest pipeline share of unicorns and IPO candidates in the SF Bay Area, and software startups dominate in Germany.
[To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations]
This presentation is a curated compilation of PowerPoint diagrams and templates designed to illustrate 20 different digital transformation frameworks and models. These frameworks are based on recent industry trends and best practices, ensuring that the content remains relevant and up-to-date.
Key highlights include Microsoft's Digital Transformation Framework, which focuses on driving innovation and efficiency, and McKinsey's Ten Guiding Principles, which provide strategic insights for successful digital transformation. Additionally, Forrester's framework emphasizes enhancing customer experiences and modernizing IT infrastructure, while IDC's MaturityScape helps assess and develop organizational digital maturity. MIT's framework explores cutting-edge strategies for achieving digital success.
These materials are perfect for enhancing your business or classroom presentations, offering visual aids to supplement your insights. Please note that while comprehensive, these slides are intended as supplementary resources and may not be complete for standalone instructional purposes.
Frameworks/Models included:
Microsoft’s Digital Transformation Framework
McKinsey’s Ten Guiding Principles of Digital Transformation
Forrester’s Digital Transformation Framework
IDC’s Digital Transformation MaturityScape
MIT’s Digital Transformation Framework
Gartner’s Digital Transformation Framework
Accenture’s Digital Strategy & Enterprise Frameworks
Deloitte’s Digital Industrial Transformation Framework
Capgemini’s Digital Transformation Framework
PwC’s Digital Transformation Framework
Cisco’s Digital Transformation Framework
Cognizant’s Digital Transformation Framework
DXC Technology’s Digital Transformation Framework
The BCG Strategy Palette
McKinsey’s Digital Transformation Framework
Digital Transformation Compass
Four Levels of Digital Maturity
Design Thinking Framework
Business Model Canvas
Customer Journey Map
❼❷⓿❺❻❷❽❷❼❽ Dpboss Matka Result Satta Matka Guessing Satta Fix jodi Kalyan Final ank Satta Matka Dpbos Final ank Satta Matta Matka 143 Kalyan Matka Guessing Final Matka Final ank Today Matka 420 Satta Batta Satta 143 Kalyan Chart Main Bazar Chart vip Matka Guessing Dpboss 143 Guessing Kalyan night
Storytelling is an incredibly valuable tool to share data and information. To get the most impact from stories there are a number of key ingredients. These are based on science and human nature. Using these elements in a story you can deliver information impactfully, ensure action and drive change.
[To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations]
This PowerPoint compilation offers a comprehensive overview of 20 leading innovation management frameworks and methodologies, selected for their broad applicability across various industries and organizational contexts. These frameworks are valuable resources for a wide range of users, including business professionals, educators, and consultants.
Each framework is presented with visually engaging diagrams and templates, ensuring the content is both informative and appealing. While this compilation is thorough, please note that the slides are intended as supplementary resources and may not be sufficient for standalone instructional purposes.
This compilation is ideal for anyone looking to enhance their understanding of innovation management and drive meaningful change within their organization. Whether you aim to improve product development processes, enhance customer experiences, or drive digital transformation, these frameworks offer valuable insights and tools to help you achieve your goals.
INCLUDED FRAMEWORKS/MODELS:
1. Stanford’s Design Thinking
2. IDEO’s Human-Centered Design
3. Strategyzer’s Business Model Innovation
4. Lean Startup Methodology
5. Agile Innovation Framework
6. Doblin’s Ten Types of Innovation
7. McKinsey’s Three Horizons of Growth
8. Customer Journey Map
9. Christensen’s Disruptive Innovation Theory
10. Blue Ocean Strategy
11. Strategyn’s Jobs-To-Be-Done (JTBD) Framework with Job Map
12. Design Sprint Framework
13. The Double Diamond
14. Lean Six Sigma DMAIC
15. TRIZ Problem-Solving Framework
16. Edward de Bono’s Six Thinking Hats
17. Stage-Gate Model
18. Toyota’s Six Steps of Kaizen
19. Microsoft’s Digital Transformation Framework
20. Design for Six Sigma (DFSS)
To download this presentation, visit:
https://www.oeconsulting.com.sg/training-presentations
At Techbox Square, in Singapore, we're not just creative web designers and developers, we're the driving force behind your brand identity. Contact us today.
The 10 Most Influential Leaders Guiding Corporate Evolution, 2024.pdfthesiliconleaders
In the recent edition, The 10 Most Influential Leaders Guiding Corporate Evolution, 2024, The Silicon Leaders magazine gladly features Dejan Štancer, President of the Global Chamber of Business Leaders (GCBL), along with other leaders.
𝐔𝐧𝐯𝐞𝐢𝐥 𝐭𝐡𝐞 𝐅𝐮𝐭𝐮𝐫𝐞 𝐨𝐟 𝐄𝐧𝐞𝐫𝐠𝐲 𝐄𝐟𝐟𝐢𝐜𝐢𝐞𝐧𝐜𝐲 𝐰𝐢𝐭𝐡 𝐍𝐄𝐖𝐍𝐓𝐈𝐃𝐄’𝐬 𝐋𝐚𝐭𝐞𝐬𝐭 𝐎𝐟𝐟𝐞𝐫𝐢𝐧𝐠𝐬
Explore the details in our newly released product manual, which showcases NEWNTIDE's advanced heat pump technologies. Delve into our energy-efficient and eco-friendly solutions tailored for diverse global markets.
Anny Serafina Love - Letter of Recommendation by Kellen Harkins, MS.AnnySerafinaLove
This letter, written by Kellen Harkins, Course Director at Full Sail University, commends Anny Love's exemplary performance in the Video Sharing Platforms class. It highlights her dedication, willingness to challenge herself, and exceptional skills in production, editing, and marketing across various video platforms like YouTube, TikTok, and Instagram.
Discover timeless style with the 2022 Vintage Roman Numerals Men's Ring. Crafted from premium stainless steel, this 6mm wide ring embodies elegance and durability. Perfect as a gift, it seamlessly blends classic Roman numeral detailing with modern sophistication, making it an ideal accessory for any occasion.
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IMPACT Silver is a pure silver zinc producer with over $260 million in revenue since 2008 and a large 100% owned 210km Mexico land package - 2024 catalysts includes new 14% grade zinc Plomosas mine and 20,000m of fully funded exploration drilling.
The Genesis of BriansClub.cm Famous Dark WEb PlatformSabaaSudozai
BriansClub.cm, a famous platform on the dark web, has become one of the most infamous carding marketplaces, specializing in the sale of stolen credit card data.
How to Implement a Strategy: Transform Your Strategy with BSC Designer's Comp...Aleksey Savkin
The Strategy Implementation System offers a structured approach to translating stakeholder needs into actionable strategies using high-level and low-level scorecards. It involves stakeholder analysis, strategy decomposition, adoption of strategic frameworks like Balanced Scorecard or OKR, and alignment of goals, initiatives, and KPIs.
Key Components:
- Stakeholder Analysis
- Strategy Decomposition
- Adoption of Business Frameworks
- Goal Setting
- Initiatives and Action Plans
- KPIs and Performance Metrics
- Learning and Adaptation
- Alignment and Cascading of Scorecards
Benefits:
- Systematic strategy formulation and execution.
- Framework flexibility and automation.
- Enhanced alignment and strategic focus across the organization.
Top mailing list providers in the USA.pptxJeremyPeirce1
Discover the top mailing list providers in the USA, offering targeted lists, segmentation, and analytics to optimize your marketing campaigns and drive engagement.
2. The amyloid cascade hypothesis
• This has influenced much of AD research over
the past twenty years
• The hypothesis has led to several compounds
being tested in phase 3 clinical trials.
3. APP
PS1/PS2 FAD + + APP FAD mutations
mutations Trisomy 21
Ab42 aggregation
?
Soluble forms ? Amyloid
of oligomeric Ab plaque
AGGREGATE STRESS
Tau dysfunction
PHF formation
Neuronal dysfunction and death
DEMENTIA
5. Two key questions
1. By how much should Ab production be
lowered, or Ab clearance facilitated, to
mediate a therapeutic disease-modifying
effect (that can be detected in a phase 3 trial
given current clinical assessment tools)?
2. At what stage in the disease process would
an amyloid-directed therapeutic approach be
likely to show clinical efficacy?
6. More specifically….
1. What is the minimum threshold reduction in
Ab load required … and why?
2. What patient population, at which stage in
the disease process, would this minimum
reduction show clinical efficacy?
7. But the questions became
1. When and how does Ab play a role in AD?
2. When and how might an Ab-directed
therapeutic be shown to be efficacious?
3. What constitutes a test of the amyloid
cascade hypothesis?
8. APP N GF CuBD KPI Ab C
g-secretase
b-secretase
GSM
g g z e
BI GSI
EISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTS
FAD mutations NL R GK N TI AT L P
Q VAMVI
G F
Ab37/38
Benign
Effect of GSM -
shift to smaller Ab39/40
Ab species
Pathogenic Ab42/43
Effect of GSI – Effect of BI –
Ab species reduced All Ab species
but Ablonger/smaller reduced uniformly
Cleavage point GSI = g-secretase inhibitor ratio increased
GSM = g-secretase modulator
BI = BACE inhibitor
9. Anti-Ab antibodies
• Bapineuzumab
– Binds to the N-terminus of Ab
– Primary m.o.a. is binding to deposited Ab and
mediating clearance
• Solaneuzumab
– Binds to the mid-domain of Ab – does not
recognize deposited Ab
– Primary m.o.a. is peripheral sink
10. A summary consensus of the
literature
• In Alzheimer’s disease, the regional distribution and
amount of deposited Ab does not correlate well with
the extent of tangle pathology, cell loss or dementia.
• In preclinical experiments:-
– genetic and pharmacological reduction in Ab production or
facilitation of clearance does not reduce deposited Ab to
below the t=0 point, but can prevent additional
deposition.
– Reduction in Ab production can markedly delay onset of
Ab deposition
11. Effect of FAD mutations and ApoE
genotype
• Often commented that FAD mutations result
in a more ‘aggressive’ disease process
• Substantial and compelling data that the age
of onset can be brought forward very
significantly, but very little data that the
duration of the disease is shortened
thereafter
• Effect seems to be in triggering, rather than
driving the disease process
12. Age of onset versus duration of disease
Effect of FAD mutations/ApoE4 genotype
Demented
Familial Sporadic
AD AD
A=B
C<D
A B
Normal
20 C 40 Age/Years 60 D 80
Age of Age of
Death Death
onset onset
13. Testing the amyloid cascade hypothesis –
which scenario is ‘right’?
Tau pathology Ab pathology
Ab Ab Ab
L3 trigger threshold driver
O O P
L3*
L2
Arbitrary Ab trigger
/threshold level
O P P
L2*
L1
P P P
L1*
Ab therapeutic slows or halts AD progression
P by lowering brain Ab from
Lx to Lx*.
40 Years 60 80
Ab therapeutic does not affect AD
O progression by lowering brain Ab from Lx to
Lx*.
14. Hypothetical effect of an early therapeutic intervention
Ab
Tau Small increase in Ablonger/shorter Small decrease in Ablonger/shorter
ratio caused by FAD mutation ratio or amount of Ablonger pathology
pathology
mediated by therapeutic.
Familial Sporadic AD –
AD AD onset
delayed
FAD mutation
Ab therapeutic
0 40 60 80 100 120
Age/Years
Clinical Clinical Clinical
symptoms symptoms symptoms
15. Conclusion
• The amyloid cascade hypothesis needs to be
tested in the clinic.
• How to test the hypothesis depends on your
view of the role that Ab plays in the disease:
trigger, threshold or driver?
• It might be that treating early in the disease
process with an Ab therapeutic is not ‘better’
but a prerequisite for demonstrating efficacy.