Circadian rhythms are 24-hour cycles in biological processes regulated by an internal biological clock. Chronopharmacology studies how biological rhythms impact drug effects. Optimizing drug administration times based on disease symptoms and molecular rhythms can increase efficacy and reduce toxicity. For example, statins given in the evening are more effective due to circadian cholesterol synthesis patterns, and cancer drugs given at night target fast-dividing tumor cells. Understanding chronopharmacology allows personalized, rhythm-based drug therapy.
Target Validation
Introduction,Drug discovery, Target identification and validation, Target validation and techniques
By
Ms. B. Mary Vishali
Department of Pharmacology
Role of nuclicacid microarray &protein micro array for drug discovery processmohamed abusalih
role of nuclic acid microarray and protein microarray for drug discovery process
1.introduction about microarray technique and genomics
2.process of drug discovery
3.microarray techiques
4.microarray analysis in drug discovery
5.steps involved in the micro array analysis
Introduction to chronology, chronotherapy, and chronopharmacology.
How chronopharmacology involved in asthma and helps to manage asthma?.
Biological rhythms in bronchial asthma.
Factors associated with nocturnal exacerbation of bronchial asthma.
Introduction to asthma and their symptoms.
Introduction to Antiasthmatic drugs like beta-blockers, leukotriene antagonists, steroids, etc.
Chronopharmacology division & their examples.
Advantages and disadvantages of chronopharmacology.
Marketed preparation and their images along with the price in India.
Role of Target Identification and Target Validation in Drug Discovery ProcessPallavi Duggal
Target identification and Validation tells about the how target is neccesary for new drug discovery and its development to reach into market for rare diseases.
Target Validation
Introduction,Drug discovery, Target identification and validation, Target validation and techniques
By
Ms. B. Mary Vishali
Department of Pharmacology
Role of nuclicacid microarray &protein micro array for drug discovery processmohamed abusalih
role of nuclic acid microarray and protein microarray for drug discovery process
1.introduction about microarray technique and genomics
2.process of drug discovery
3.microarray techiques
4.microarray analysis in drug discovery
5.steps involved in the micro array analysis
Introduction to chronology, chronotherapy, and chronopharmacology.
How chronopharmacology involved in asthma and helps to manage asthma?.
Biological rhythms in bronchial asthma.
Factors associated with nocturnal exacerbation of bronchial asthma.
Introduction to asthma and their symptoms.
Introduction to Antiasthmatic drugs like beta-blockers, leukotriene antagonists, steroids, etc.
Chronopharmacology division & their examples.
Advantages and disadvantages of chronopharmacology.
Marketed preparation and their images along with the price in India.
Role of Target Identification and Target Validation in Drug Discovery ProcessPallavi Duggal
Target identification and Validation tells about the how target is neccesary for new drug discovery and its development to reach into market for rare diseases.
Chronobiology is a field of biology that examines periodic phenomena in living organisms and their adaptation to solar- and lunar-related rhythms.
These cycles are known as biological rhythms.
Chronobiology comes from the ancient Greek word (chrónos, meaning "time"), and biology, which pertains to the study, or science, of life.
Chronobiology is the science of biological rhythms, more specifically the impact of the 24- hour light- dark cycle on our biochemistry and therefore behaviors.
It is defined as the periodic component of temporal series of biological data whose waveform profile has been analytically validated.
In other words, biological rhythm is a bio-signal whose period of oscillation has been validated by analytical models of periodic regression using one or more harmonic components.
Examples : Heart beat, breathing, hormone secretion, menstrual cycle, body temperature and sleep/wake cycle.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
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.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
3. INTRODUCTION
• Chronology : The arrangement of events according to the time of occurrence.
• These events occur after particular time interval called Rhythm.
CHRONOBIOLOGY
• The science dealing with the phenomenon of rhythmicity in living organisms.
• In medicines three disciplines take into account with the influence of time:-
CHRONOPHYSIOLOGY
CHRONOPATHOLOGY
CHRONOPHARMACOLOGY
5. CIRCADIAN RHYTHM
CIRCA-AROUND DIAM- A DAY
• A circadian rhythm is a 24 hour cycle of physiological and biological processes of living
beings including plants, animals, fungi and cyanobacteria.
• Circadian rhythms are endogenously generated, although they can be modulated by external
factors such as sunlight and temperature.
• It also important in sleeping and feeding patterns of all animals, including human beings.
• Brain wave activity, hormone production, cell regeneration and other biological activities
linked to this daily cycle.
CONTI…….
6. • An internal biological clock is located in mammals, in the suprachiasmatic
nucleus of the hypothalamus (SCN), delivering its message of time throughout the
body i.e. is responsible for circadian rhythms.
• It is also known as the master clock of our body.
• The SCN uses its connections with the autonomic nervous system for spreading its
time-of-day message, either by setting the sensitivity of endocrine glands i.e.,
thyroid, adrenal, ovary) or by directly controlling an endocrine output of pineal
gland i.e. melatonin.
7. SCN Cells contain a newly discovered protein (eg.
clock protein) that regulates gene function and
which shows 24-hr variations in cellular levels.
Anterior Portion of the Hypothalamus (SCN)
Superior to optic chiasm, receives input from optic nerves
(RHT); this input synchronizes the “clock” in the SCN to
the exterior day-night cycle
Fig-:Saggittal section of brain
• When light falls on the eye, afferent nerves arising from the
retina of the eye transmit the light signals directly through
retinal hypothalamic tract to the paired suprachiasmatic
nuclei situated in the hypothalamus and pineal gland.
• Biological clock since found is represented by
suprachiasmatic nuclei , which creates biological rhythms
under control of clock genes
11. • The study of rhythmic, predictable-in-time differences in the effects of
drugs both in experimental animals and in men.
• It investigates the effects/side effects of drugs upon temporal changes in
biological functions or symptoms of a disease as well as drug effects as
a function of biologic timing.
• It is defined as an investigative science concerned with the biological
rhythm dependencies of medication.
CONT….
Definition ????
12. • Chronopharmacolgy subdivided into 4 categories:-
Chrono pharmacokinetics(ADME)
Chronotoxicity (The toxic effect of drug on the organism, which is
undesirable and affects the rhythmic system.)
Chronesthesy(doseing schedule of drugs according to the biological
rhythm/clock)
Chronotherapy(whole therapy of particular disease depending upon
biological rhythum)
14. CHRONOPHARMAKINETICS
• Chronopharmacokinetics deals with the study of the temporal changes
in absorption, distribution, metabolism and elimination and thus takes
into account the influence of time of administration on these different
steps.
• The main aim of chronokinetic studies is to control the time of
administration which can be responsible for variations of drug kinetics
but also may explain chronopharmacological effects observed with
certain drugs.
15. NEED OF CHRONOKINETIC STUDY
• When possible daily variations in pharmacokinetics may be responsible for time
dependent variations in drug effects (e.g. some antimicrobial agents are more
effective at a specific time of day),
• When drugs have a narrow therapeutic range .
• When symptoms of a disease are clearly circadian phase-dependent (e.g.
nocturnal asthma, angina pectoris, myocardial infarction, ulcer disease).
• When drug plasma concentrations are well correlated to the therapeutic effect in
case the latter is circadian phase dependant.
18. DRUGS UNDERGOING CHRONOKINETICS:
Antibiotics :
• Important aspect of chronokinetics in antibiotics is that not only the efficacy of
the drug may increase but also the toxicity of certain drugs may decrease at
different time of day.
Aminoglycosides:
• Renal toxicity of aminoglycosides can be reduced by giving the drug as a single
daily injection when patients are active (at day time or in other words in the
activity period)
Eg: gentamycin, tobramycin, amikacin
19. CVS
Myocardial infarction,
acute cardiac arrest ,
transient myocardial
ischemia
Onset – early morning –
34% events
Reason – release of
catecholamines, cortisol,
increase in platelet
aggregation, vascular tone,
heart rate surge.
MORNING HOURS
INCREASED PLASMA
NOREPINEPHRINE ,
CORTISOL AND RENIN
ACTIVITY
INCREASED
SYMPATHETIC TONE
INCREASED PLATELET
AGGREGABILIGY AND
DECREASED
FIBRINOLYTIC
ACTIVITY
20. Objective- To deliver drug in high concentration when its great need
required.
ACE inhibitors
Nifedipine
Amlodipine
Night
21. Anti hyperlipidemic drugs
• More Cholesterol systhesis takes place in the evening than in the
morning.
• The enzyme HMG Co-A Reductase is required to reduce hydroxy 3-
methyl glutaryl Co-A to mevalonate in the synthesis of cholesterol.
• This enzyme is competitively inhibited by HMG Co-A Reductase
inhibitors (Statins)
• Hence statins should be administered at evening rather than at
morning for increased efficacy.
22. Antiasthmatic drugs :
• Asthma is attacked more frequently in night hours.
• Lungs are more sensitive to bronchoconstrictor substances such as
Acetylcholine, Histamine, house mite dust, grass propellers, at night time
than day time. It is treated by antiasthmatic drugs.
Ex:-Theophylline, beta sympathomimetics.
• Theophylline must be given in higher doses during the night time than day
time.
Antiulcer drugs :
• Gastric acid secretion is highest at early night or late afternoon.
• H2 blockers like Ranitidine ,cimetidine ,famotidine should be taken once a
day in the late afternoon or early night when acid secretion is more.
24. Cancer cells are considered to have lost internal time keeping mechanism.
Tumor cells and normal cells differ in their chronobiological cycles.
(The basis for the chronopharmacotherapy of cancers.)
The DNA synthesis in the normal human bone marrow cells has a peak
around noon while the peak of DNA synthesis in lymphoma cells is near
midnight.
So, an s-phase active cytotoxic therapy at late nights should be more
advantageous.
conti….
25. A comparison study* included 118 children received maintenance chemotherapy
of mercaptopurine and methotrexate around the period from 1976 to 1984
It was found that the risk of relapse was 2.56 times higher in children who
received chemotherapy in the morning than in those receiving in the evening.
*Circadian time dependent response of childhood lymphoblastic leukemia to chemotherapy: A long-term follow-up study of survival.
Chronobiology International, 10(3): 201-4.
26. NSAID’s & Arthritis
• Patients with osteoarthritis tend to have less pain in the morning and
more at night; while those with rheumatoid arthritis, have pain that usually
peaks in the morning and decreases throughout the day.
• Chronotherapy for all forms of arthritis using NSAID’s such as ibuprofen
should be timed to ensure that the highest blood levels of the drug
coincide with peak pain.
• For osteoarthritis sufferers, the optimal time for a non- steroidal anti-
inflammatory drug such as ibuprofen would be around noon or mid-
afternoon.
• The same drug would be more effective for people with rheumatoid
arthritis when taken after the evening meal.
27. Opiod analgesics
• Stronger analgesic effects were observed when tramadol and
dihydrocodeine were applied in the evening to relieve painful stimuli.
• Peak morphine use occurred at 9 a.m. and least use at 3 a.m.
28. Melatonin – secreted at night by pineal gland.
Function – synchronizes sleep wake cycle with circadian
rhythm.
Melatonin agonist [Ramelteon] – hypnotic for sleep onset
insomnia.
Reduces Jet lag symptoms.
Bedtime administration of hypnotics- more
effective.
29.
30.
31. Effectiveness and toxicity of a drug are not constant over 24 hr period.
Understanding the biological rhythms can optimize and individualize drug
therapy to a great extent. Thus it can help to decrease the drug related toxicity
and enhance effectiveness.
To monitor rhythmic markers such as clock genes it may be useful to choose
the most appropriate time of day for administration of drugs that may increase
their therapeutic effects and reduce their side effects.