Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
2. Motion of Waves
• 1 An oscillating or vibrating motion in
which a point or body moves back and
forth along a line about a fixed central point
produces waves.
3. Motion of Waves
• 2. Examples of waves:
• (a) Light waves are produced as a
result of vibrations of electrons in an
atom.
4. Motion of Waves
• 2. Examples of waves:
• (b)Sound waves are produced by
vibrating mechanical bodies such as
guitar strings or a tuning fork.
5. Motion of Waves
• 2. Examples of waves:
• (c) Water waves are produced by
disturbance (or vibration) on a still
water surface.
6. Propagation (Traveling) of
Waves
• 1.When a wave travels through a
medium, the particles of the medium
vibrate about their equilibrium
positions.
Direction of
waves
8. Propagation (Traveling) of
Waves
• 3 A wave transfers energy and the
momentum from the source of the
wave (the oscillating or vibrating
system) to the surroundings.
9. Propagation (Traveling) of
Waves
• Activity 1.1: To demonstrate that waves transfer
energy without transferring matter
• Apparatus:
• Radio, candle and matches.
10. Propagation (Traveling) of
Waves
• Activity 1.1: To demonstrate that waves
transfer energy without transferring matter
• Procedure
• 1. A candle is placed about 10 cm from
the speaker of a radio.
12. Propagation (Traveling) of
Waves
• Procedure
• 3. Then, the radio is turned on and the
volume of the sound is gradually increased
until a change in the movement of the
flame becomes noticeable.
14. Propagation (Traveling) of
Waves
• Discussion
• 2. This observation shows that the
propagation of the sound waves from
the vibration of the cone of the
speaker transfers energy (or
momentum) to the flame and causes
it to vibrate.
16. Wavefronts
• 1. A wave front is a line or plane on
which the vibrations of every points
on it are in phase and are at the
same distance from the source of the
wave.
Same
Phase
17.
18. Wavefronts
• 2 . Points in a wave are in phase if
they vibrate in the same direction
with the same displacement.
Same
displacement
19. Plane Wave fronts
• 1 . Figure 1.3 shows the production of
plane water waves when a wooden
bar vibrates vertically at a constant
frequency on the surface of the water.
20. Plane Wave fronts
• 2. Lines PQ, RS, TU and VW are straight
lines along the respective crests of the
waves. These lines are called wave
fronts.
21. Circular Wave fronts
• 1. When we use a fingertip to touch
the surface of water repeatedly,
circular wave fronts are produced as
shown in Figure 1.4.
22. Types of Waves
• There are two types of waves.
• (a) Transverse wave
• (b) Longitudinal wave
23. Transverse Waves
• 1. A transverse wave is a wave in
which the vibration of particles in the
medium is at right angle
(perpendicular) to the direction of
propagation of the wave.
24. Transverse Waves
• 2. A model of a transverse wave can
be produced by a slinky spring as
shown in Figure 1.6.
26. Longitudinal Waves
• 1. A longitudinal wave is a wave in
which the vibration of particles in the
medium is parallel to the direction of
propagation of the wave.
27. Longitudinal Waves
• 2. When the slinky spring is vibrated
back and forth along the direction of
propagation of the wave at a fixed
rate, a longitudinal wave is produced
as shown in Figure 1.8.
29. Amplitude, Period and Frequency of a
Wave
• 1 . The amplitude, A, of a vibrating system is
maximum displacement from its equilibrium
position. It is a measure of height of the wave crest
or depth of the wave trough.
Amplitude
30. Amplitude, Period and Frequency of a
Wave
• 2 . In Figures 1.9 (a) and (b), the distance OQ is the
amplitude, where O is the equilibrium position of the
vibrating system.
Amplitude
31. Amplitude, Period and Frequency of a
Wave
• 3 . The period, T, of a vibrating system is the time
taken to complete an oscillation.
Period
32. Amplitude, Period and Frequency of a
Wave
• 4. In the two vibrating (oscillating) systems show in
Figure 1.9, a complete oscillation are:
• (a) from P Q P or Q P Q,
• (b) from OPQO or
OQPO
33. Amplitude, Period and Frequency of a
Wave
• 5. If a vibrating system makes n
complete oscillations in a time of t
seconds, the period of oscillation, T of
the system is second
• The SI unit of period is second.
n
t
34. Amplitude, Period and
Frequency of a Wave
• 6 The frequency, f, is the number of complete
oscillations made by a vibrating system in one
second.
• The unit of frequency is hertz (Hz) or s-1
.
35. Amplitude, Period and
Frequency of a Wave
• 7 From the formulae of T and f, the relationship
between period, T and frequency, f is:
• T is inversely proportional to f and vice versa.
36. Amplitude, Period and
Frequency of a Wave
• Example 1:
• In an experiment, Aziz observes that a simple
pendulum completes 30 oscillations in 48.0 seconds.
What is
• (a) the period of oscillation?
• (b) the frequency of oscillation?
37. Amplitude, Period and
Frequency of a Wave
• Example 1:
• Solution
• (a)
s6.1
30
48.0
oscllationcompletedofnumber
takentime
Tperiod,
==
=
39. Displacement-time Graph of a
Wave
• 1. The sinusoidal graph in Figure 1.10 is
a graph of displacement, s against
time, t of a load on a spring.
40. Displacement-time Graph of a
Wave
• 2 From the graph of s against t in Figure 1.10, the
following information is obtained.
• (a) Amplitude, A = a cm
• (b) Period of oscillation, T is the time between
points:
• (i) O and F, (ii) C and G or (iii) P and Q.
41. Displacement-time Graph of a
Wave
• Example 2:
• Figure 1.11 shows the displacement-time graph of
the oscillation of a mass on a spring.
• Figure 1.11
42. Displacement-time Graph of a
Wave
• Example 2:
• From the graph,
• (a) state the amplitude,
• (b) calculate the period of the oscillation,
• (c) calculate the frequency of the oscillation.
48. Displacement-distance Graph
of a Wave
• 2. The displacement, s of each particle of the
medium at different distances can be shown in a
displacement-distance graph as shown in Figure
1.12 (c).
49. Displacement-distance Graph
of a Wave
• 3. The wavelength, λ, is the distance between
successive points of the same phase in a wave.
50. Displacement-distance Graph
of a Wave
• For example:
• (a) the distance between two successive crests or
two successive troughs in a water wave,
51. Displacement-distance Graph
of a Wave
• (b) the distance between two successive
compressions or two successive rarefactions in a
sound wave.
The SI unit of wavelength, λ , is metre (m).
52. Displacement-distance Graph
of a Wave
• Example 3:
• Figure 1.13 shows a displacement-distance
graph of a wave.
• Figure 1.13
• Find
• (a) the amplitude,
• (b) the wavelength of the wave.
55. Relationship between Speed (v),
wavelength, λ and Frequency (f)
• The relationship between speed,
wavelength and frequency can be
obtained by relating the SI unit of the
quantities.
λfv =
56. Relationship between Speed (v),
wavelength, λ and Frequency (f)
• Example 4:
• A wave of frequency 120 Hz has a
wavelength of 5.0 m. What is the
speed of the wave?
57. Relationship between Speed (v),
wavelength, λ and Frequency (f)
• Example 4:
• A wave of frequency 120 Hz has a
wavelength of 5.0 m. What is the
speed of the wave?
Solution
f = 120 Hz and λ =5.0m
Speed of wave,
v = f λ
= 120 x 5
= 600 m s-1
58. Relationship between Speed (v),
wavelength, λ and Frequency (f)
• Example 5:
• The displacement-distance graph in
Figure 1.14 shows the motion of a
transverse wave. The source of the
wave produces 10 complete waves in
one second.
• Figure 1.14
59. Relationship between Speed (v), wavelength,
λ and Frequency (f)
• Example 5:
• Calculate
• (a) the amplitude,
• (b) the wavelength, and
• (c) the speed of the wave.
60. Relationship between Speed (v),
wavelength, λ and Frequency
(f)
• Example 5:
• Solution
• (a) Amplitude, A = 6 cm
•
61. Relationship between Speed (v),
wavelength, λ and Frequency
(f)
• Example 5:
• Solution
• (b) Wavelength, = 20 cm
•
•
•
λ
1o 2o
62. Relationship between Speed (v),
wavelength, λ and Frequency
(f)
• Example 5:
• Solution
• (c) Frequency, f = 10 Hz, = 20 cm
• Speed, v = f
=10x20
• = 200 cm s-1
λ
λ
