Thanatology
Types of transplants
Cause, Mechanism of Death
Manner of death
Anoxia
Signs of Death
Immediate Changes (Somatic Death)
Early Changes (Molecular Death)
Algor Mortis ......
Reference
Thanatology
Types of transplants
Cause, Mechanism of Death
Manner of death
Anoxia
Signs of Death
Immediate Changes (Somatic Death)
Early Changes (Molecular Death)
Algor Mortis ......
Reference
This report details the geological observations and interpretations made during a field investigation of the Kaptai Rangamati road-cut section, located in southeastern Bangladesh. The purpose of this report is to document the exposed rock units, their characteristics, and the geological structures present within the road cut.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
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.
word2vec, node2vec, graph2vec, X2vec: Towards a Theory of Vector Embeddings o...Subhajit Sahu
Below are the important points I note from the 2020 paper by Martin Grohe:
- 1-WL distinguishes almost all graphs, in a probabilistic sense
- Classical WL is two dimensional Weisfeiler-Leman
- DeepWL is an unlimited version of WL graph that runs in polynomial time.
- Knowledge graphs are essentially graphs with vertex/edge attributes
ABSTRACT:
Vector representations of graphs and relational structures, whether handcrafted feature vectors or learned representations, enable us to apply standard data analysis and machine learning techniques to the structures. A wide range of methods for generating such embeddings have been studied in the machine learning and knowledge representation literature. However, vector embeddings have received relatively little attention from a theoretical point of view.
Starting with a survey of embedding techniques that have been used in practice, in this paper we propose two theoretical approaches that we see as central for understanding the foundations of vector embeddings. We draw connections between the various approaches and suggest directions for future research.
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 .
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
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.
Richard's aventures in two entangled wonderlandsRichard 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.
Gliese 12 b, a temperate Earth-sized planet at 12 parsecs discovered with TES...Sérgio Sacani
We report on the discovery of Gliese 12 b, the nearest transiting temperate, Earth-sized planet found to date. Gliese 12 is a
bright (V = 12.6 mag, K = 7.8 mag) metal-poor M4V star only 12.162 ± 0.005 pc away from the Solar system with one of the
lowest stellar activity levels known for M-dwarfs. A planet candidate was detected by TESS based on only 3 transits in sectors
42, 43, and 57, with an ambiguity in the orbital period due to observational gaps. We performed follow-up transit observations
with CHEOPS and ground-based photometry with MINERVA-Australis, SPECULOOS, and Purple Mountain Observatory,
as well as further TESS observations in sector 70. We statistically validate Gliese 12 b as a planet with an orbital period of
12.76144 ± 0.00006 d and a radius of 1.0 ± 0.1 R⊕, resulting in an equilibrium temperature of ∼315 K. Gliese 12 b has excellent
future prospects for precise mass measurement, which may inform how planetary internal structure is affected by the stellar
compositional environment. Gliese 12 b also represents one of the best targets to study whether Earth-like planets orbiting cool
stars can retain their atmospheres, a crucial step to advance our understanding of habitability on Earth and across the galaxy.
2. Unit 1: Thanatology
Death: causes and manner of death, signs of death and changes after death. Somatic death, molecular death,
Early changes after death: algor mortis, rigor mortis, pallor mortis, livor mortis, cadaveric spasm, heat
stiffening, cold stiffening, changes in blood; Time since death by body fluid analysis; chemical changes in
cerebrospinal fluid; Changes in vitreous humour; Late changes: putrefaction: external and internal changes.
Adipocere, mummification, skeletonization
3. Thanatology, Death and its Causes
● STAGES OF DEATH
Antemortem,
Postmortem
and Perimortem
Injuries
*Agonal period
Molecular
Death
Somatic
Death
4. SUSPENDED ANIMATION (syn apparent death)
Causes
(1) Anesthesia, (2) Barbiturates, (3) Coma (4)
Cholera (5) Concussion, (6) Deep shock (7)
Drowning, (8) Electrocution, (9) Frozen state
(Hypothermia) (10) yoG is [voluntarily
induced, but may be remembered by the
student here as a memory aid], (11) Hanging
(12) Heat stroke, (13) Hypothermia, (14)
Hysteria (15)Illnesses [prolonged],
(16)Infections [Cholera, Typhoid]
(17)Newborn, (19) Opiates.
5. THE MOMENT OF DEATH
A. Classical
Criteria of
Death
Bichat’s
criteria/Atria
mortis
French physician Marie Bichat (1771 –1802).
[Latin, Gateways of death,
death’s portals of entry]
within 20 seconds
within 20 minutes
3 minutes
3 minutes
6. Tests to determine the death of
each organ Tests for circulation
• Magnus test (Hugo Magnus in 1872)
• Icard’s test: Vivid yellow (Séverin Icard of France in 1895)
• Diaphanous test: red and translucent vs. yellow and opaque
(transillumination test)
• Finger nail test: red-pale on pressure-red
Tests for respiration
• Winslow’s test: Jacques-Bénigne Winslow (1669-1760)
• Mirror test
• Feather test
Tests for brain function
(1) Blowing a strong stimulant such as hellebore or mustard into the
nose
(2) inserting a sharp instrument under the nail
(3) cauterization or incisions
(4) scalding with hot water or oil
(5) trumpeting or loud noises.
Miscellaneous tests :X-ray fluoroscopy for body movt.
Source: Agrawal, A. (2016).
.
7. Brain Death 1)Unreceptivity and
unresponsivity
2) No movements or
breathing (at least 1
Hour)
3) No reflexes (pupil,
corneal reflexes, spinal
reflexes i.e. knee jerk
4) Flat
electroencephalogram
5)Repetive test after
24hrs
Harvard criteria of Brain Death (1968)
1)Minnesota criteria of
Brain stem death
(1971) : In 1971,
Mohandas and Chou
(two neurosurgeons
from Minnesota)
2)Indian law on brain
stem death (The
Transplantation of
Human Organs and
Tissues Act, 1994)
Brain Stem Death (Modern Criteria of the
Moment of Death)
10. Minnesota criteria of Brain stem
death (1971)
(1) No spontaneous movement
(2) No spontaneous respiration
when tested for a period of 4
minutes at a time
(3) Absence of 5 major brain stem
reflexes (ref. figure)
(4) EEG not mandatory. All the
above findings must remain
unchanged for at least 12
hours
13. GORDON’S CLASSIFICATION OF DEATH
A.Anoxic Anoxia
reduced oxygen in ambient air
i.e. trap/noxious gases h2s, so2, sewer gas/ high altitude
pulmonary blood supply pulmonary gas exchange
reduced
supply of
oxygen
i.e.
mechanical
interface of
air passages
14. GORDON’S CLASSIFICATION OF DEATH
B. Anaemic
Anoxia
Oxygen carrying capacity of the blood is reduced. i.e. acute massive
hemorrhage , CO poison
15. GORDON’S CLASSIFICATION OF DEATH
C. Stagnant
Anoxia
Blood is incapable of movement
i.e. heart failure, embolism
16. GORDON’S CLASSIFICATION OF DEATH
D. Histotoxic Anoxia
1. Cellular histotoxic anoxia ( Oxygen cannot be taken up due to failure of
tissue enzyme system by poisoning, eg CN , PH3 , H2S, overdose of hypnotics and
anesthetics.
2. Pericellular histotoxic anoxia
permeability of cell membrane, eg in
nitrous oxide or halogenated
hydrocarbons [chloroform, cyclopropane,
ether, halothane, trilene].
3. Substrate histotoxic anoxia
failure of efficient cell metabolism,
eg hypoglycemia
4. Metabolite
histotoxic
anoxia
, eg CO2
poisoning,
uremia.
17. SUDDEN AND UNEXPECTED DEATH
Sudden and unexpected death is death occurring
within 24 hours of the onset of symptoms in an
individual who was not known to be suffering from any
disease, injury or poisoning.
Coronary artery disease
CVS
Acute edema of lungs / Air
embolism
(1) epilepsy (2)
hemorrhage (3)
meningitis, and (4)
tumors.
(1) Acute hemorrhagic (2)
pancreatitis (2) Appendicitis (3)
Cancer of esophagus (4)
Enlarged spleen [rupture]
18. Signs of Death and Changes Following Death
Immediate
Early
Late
1-30
minus
1hour-
Upto 36
hours
Beyond
36 hours
21. EARLY CHANGES
Within few minutes
1) Skin ashy-white,
pale and loses
elasticity
2)Changes in lips:
dry, brownish and
hard due to drying
1. Loss of corneal reflex
2. Opacity of the cornea
3. Pupils
4. Intraocular pressure (14-
3)
4. Retinal vessels
5.Biochemical changes i.e.
Potassium levels
Source: Agrawal, A. (2016).
Source: Agrawal, A. (2016).
22. EARLY CHANGES (Algor mortis)
Important points
Core temperature (after 2 hours)
Ambient temperature
Method of recording i.e rectal, sub-hepatic temperature
Formula
Factors affecting Algor Mortis
Environmental temp
Build i.e SA/BW
Physique i.e FAT/ lean
Environment i.e. air Ventilation,Humidity i.e.
water submerged, running, sewage
Position
Covering
https://stock.adobe.com/in/search?k=homeostas
ii) Average rate of fall
- (a) during summers
- 0.75°F/h (b) during
winters - 1.5°F/h.
23. Postmortem caloricity
● The increase in body temperature for the first few hours after death is called
postmortem caloricity.
● The mechanism and conditions of this phenomenon are as follows:
● (i) When the heat regulatory mechanism has been severely disturbed
before death. For example: sun stroke.
● (ii) When there is increased heat production in the muscles of the body before
death due to convulsions. For example: Tetanus, strychnine poisoning and epilepsy.
● (iii) Excessive bacterial activity during life. For example: Septicemic deaths, cholera
and other infections.
24. Postmortem Lividity (Livor mortis/Postmortem staining/postmortem lividity/postmortem hypostasis)
Development
0.5-2 hours (Appears as bluish purple mottled patches)< 4 h
(Well developed like a sheet but not fixed)< 8 h (Fixation ) <
greater than 8 h Persists till putrefaction sets in.
*Influencing factors (vol of blood/Length
of time blood remains fluid after death/More marked
in conditions where blood does not readily coagulate,
causing more accumulation to occur. Anticoagulants i.e.
Asphyxia/ CO poisoning, Septicemia
Source: Aggrawal, A. (2016).
Source: Aggrawal, A. (2016).
25.
26. Rigor mortis (cadaveric rigidity, death stiffening)
Source: Aggrawal, A. (2016).
Source: Aggrawal, A. (2016).
Influencing
factors: age fetus/
stillborn/children
and old /infections
gas gangrene, where
putrefaction begins
early] (b) cancer (c)
cholera (d) starvation
(e) tuberculosis (f)
typhoid/
electrocution,lightning/
late in neuromuscular
disease,
CO,hemmorage,
asphyxia/ (1) Onset
slow, duration long –
Cold dry weather (2)
Onset rapid, duration
short – Hot weather.
27. Cadaveric spasm [syn cataleptic rigidity, instantaneous rigidity, instantaneous
rigor, postmortem spasm, battle-field rigidity]] is a rare condition, in which the muscles that were in
contraction at the moment of death, remain in contraction after death
28.
29. IV. LATE CHANGES (DECOMPOSITION)
1)Autolysis (enzymatic
degradation)
Inc. in hot/ dec cold
Brain
(liquefaction),Stomach and
GIT, pancreases
Putrefaction (bacterial action)
(i) Color changes (ii)
Production of foul smelling
gases (iii) Liquefaction of
tissues.
*Modifications of Putrefaction
*Casper Dictim
Source: Aggrawal, A. (2016).
Source: Aggrawal, A. (2016).
30. ● • 1st external sign of decomposition is the
Greenish discoloration
(sulfmethemoglobin) in the right iliac
fossa; which becomes evident in 12–24
hours in summer and 1 to 3 days in winter.
• This color change spreads to the entire
abdomen< chest< neck< face <limbs.
• Color gradually changes to dark green
then finally black.
31. ● The putrefaction bacteria spread easily in the
body fluid and colonize in the venous system.
● The superficial veins of the limbs, chest,
abdomen and neck are stained greenish blue
due to hemolysis of red cells and stain the
walls of the vessels.
● This condition is called as “marbling” which
occurs 36 to 48 hours after death in summer
and 2 to 3 days in winter.
32. ● Evolution of foul smelling gases:
• The main gases are ammonia, carbon dioxide, hydrogen sulfide,
phosphorated hydrogen and methane.
• Due to continued accumulation of gases, there is distention of
breast in females, penis and scrotum in males< abdomen (intestines).
● • Eyes bulge out from their sockets; tongue is forced out between
the swollen lips.
● Diaphragm is pushed up compressing the lungs and heart; blood
stained frothy fluid exudes from the mouth and nostrils, which is
called “postmortem purge”.
• Involuntary urination, defecation, seminal ejaculation and delivery
of dead fetus occur at this stage.
• Gas bubbles accumulate in all the tissues; subcutaneous tissues
become emphysematous.
33. ● • Due to the formation of gas blebs,
blisters appear between the epidermis
and dermis all over the body.
• Epidermis becomes loosened (skin
slippage) producing large, fragile sacs of
clear or pink red serous fluid.
34. Liquefaction of tissues: (Colliquative putrefaction)
● begins from 5 to 10 days.
● The abdomen bursts and contents of abdomen come out of the cavity.
• All encapsulated internal organs are converted into bags of putrid fluid and
subsequently burst open into the thoracoabdominal cavity.
• The rate of putrefaction : enzyme content, water content and blood supply of the
organs: Adrenals and pancreas<stomach and intestines<spleen and liver<lungs
<heart< Kidneys and urinary bladder < Prostrate (males) and (uterus in females)
• “foamy” liver or “honey-combed” liver: accumulation of gases, multiple blisters
appear in the liver
35. References
● Aggrawal, A. (2016). Forensic Medicine and Toxicology for MBBS. Avichal
Publication Company, 325.
36. This Photo by Unknown Author is licensed under CC BY-SA
