It explaines DNA repair mechanisms with perfect GIF Videos
DNA Damage and DNA repair mechanism in Space
DNA repair systems in Both prokaryotes and eukaryotes
It explaines DNA repair mechanisms with perfect GIF Videos
DNA Damage and DNA repair mechanism in Space
DNA repair systems in Both prokaryotes and eukaryotes
Molecular Mechanisms of Radiation Damage. Dmitri Popov
Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005).
Conclusion: Specific antibodies – possible antagonists of Toll like receptors and can inhibit massive activation of lysosomal hydrolytic enzymes and prevent radiation toxicity after high doses of Radiation.
The Effect of Gamma Irradiation on the Radiofrequency Dielectric Dispersion P...theijes
The International Journal of Engineering & Science is aimed at providing a platform for researchers, engineers, scientists, or educators to publish their original research results, to exchange new ideas, to disseminate information in innovative designs, engineering experiences and technological skills. It is also the Journal's objective to promote engineering and technology education. All papers submitted to the Journal will be blind peer-reviewed. Only original articles will be published.
Molecular Mechanisms of Radiation Damage. Dmitri Popov
Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005).
Conclusion: Specific antibodies – possible antagonists of Toll like receptors and can inhibit massive activation of lysosomal hydrolytic enzymes and prevent radiation toxicity after high doses of Radiation.
The Effect of Gamma Irradiation on the Radiofrequency Dielectric Dispersion P...theijes
The International Journal of Engineering & Science is aimed at providing a platform for researchers, engineers, scientists, or educators to publish their original research results, to exchange new ideas, to disseminate information in innovative designs, engineering experiences and technological skills. It is also the Journal's objective to promote engineering and technology education. All papers submitted to the Journal will be blind peer-reviewed. Only original articles will be published.
DK Group secured the first order from a European shipowner for 4xVLBC of USD 100m each
The order is a significant step towards proof of concept and confirms that the shipping market is ready and willing to order new ships with the ACS technology
Project pipeline established leading to new orders
DK Group received an important classification of the ACS technology (Germanischer Lloyd)
The ACS demonstrator vessel was acquired and reconstructed
The project is supported by key industry players
Shipowners have shown willingness to compensate for development cost, reducing CAPEX per project
DK Group received significant political and industrial interest
DK Group raised first round venture capital in a private placement process
DK Group appointed a professional non-executive board of directors
Creative Responses to Artificial IntelligenceLuba Elliott
This presentation was delivered by Murray Shanahan at the Creative AI meetup #3 in London on the 18th January 2017.
Science fiction has long offered a philosophical critique of the prospect of artificial intelligence. But now that AI technologies are increasingly real rather than fictional the wider world of culture and the arts is beginning to respond. I will offer my personal perpective on this based on my experience working with the film Ex Machina, and collaborating with artist collective Random International.
Murray Shanahan is Professor of Cognitive Robotics in the Dept. of Computing at Imperial College London, where he heads the Neurodynamics Group. Educated at Imperial College and Cambridge University (King’s College), he became a full professor in 2006. His publications span artificial intelligence, robotics, logic, dynamical systems, computational neuroscience, and philosophy of mind. He was scientific advisor to the film Ex Machina, and regularly appears in the media to comment on artificial intelligence and robotics. His books include “Embodiment and the Inner Life” (2010), and “The Technological Singularity” (2015).
Les Français et l'Hôpital du Futur - Sondage OpinionWay pour le Groupe Conflu...MTaveau
Sondage OpinionWay réalisé en novembre 2016 pour le Groupe Confluent, auprès d'un échantillon de 1023 personnes représentatif de la population française âgées de 18 ans et plus.
Radiosurgery is a discipline that utilizes externally generated ionizing radiation in certain cases to inactivate or eradicate a defined target(s) in the head or spine without the need to make an incision. Its uses in Neurosurgery is immense.
It explaines DNA repair mechanisms with perfect GIF Videos
DNA Damage and DNA repair mechanism in Space
DNA repair systems in Both prokaryotes and eukaryotes
Warm
Low
density
Cool
High
density
Warm
Platinum
film
Spin
current
a
b
c
Electric field
Electric field
Chemical
potential m
m↓
m↑
Ferromagnet
Magnetic
field (’spin-up’)
Ferromagnet
Metal bar
Cool
Warm Cool
process. In the rest frame of the electron, the
charged impurity rushing towards it consti-
tutes a current filament, so the electron ‘sees’ a
weak magnetic field circling the filament. This
non-uniform magnetic field imparts a force
on the electron along a direction that depends
on its spin orientation3,4. The net result is that
spin-up electrons are pushed to the right of
the impurity whereas spin-down electrons are
pushed to its left.
In effect, each impurity acts like a spin filter
that selectively kicks electrons to one side or
the other, depending on their spin. As shown
in Figure 1c, the excess spin-up population
in the incident beam results in more charge
accumulating on the far face than on the near
face of the platinum film. The voltage differ-
ence between the two faces is observable as
a Hall signal. The asymmetric scattering of
electrons is especially large in materials with
a high atomic number, such as platinum. Fol-
lowing its prediction3,4, the spin Hall effect was
first observed by applying purely optical tech-
niques to semiconductors5,6, and was later
detected electrically in metals7,8.
In a series of tests, Uchida et al.2 convincingly
show that the Hall voltage in the platinum film
arises from the spin voltage. The Hall signal in
the platinum film tracks both the magnitude
and the direction of the magnetization in the
nickel–iron film. Moreover, by moving the
platinum film along the length of the nickel–
iron film, they show that the spin voltage varies
linearly over the 6-mm length of the sample.
In demonstrating that the spin Seebeck effect
can produce a large, calibrated spin-voltage
source that can be ‘tapped’ anywhere along
the length of the ferromagnet, Uchida and
colleagues have added an important tool to the
spintronics toolbox. ■
N. P. Ong is in the Department of Physics,
Princeton University, Princeton, New Jersey
08544, USA.
e-mail: [email protected]
1. Gregg, J. F. in Spin Electronics (eds Ziese, M. & Thornton,
M. J.) 3–31 (Springer, 2001).
2. Uchida, K. et al. Nature 455, 778–781 (2008).
3. D’yakonov, M. I. & Perel, V. I. Phys. Lett. A 35, 459–460
(1971).
4. Hirsch, J. E. Phys. Rev. Lett. 83, 1834–1837 (1999).
5. Kato, Y. K., Myers, R. C., Gossard, A. C. & Awschalom, D. D.
Science 306, 1910–1913 (2004).
6. Wunderlich, J., Kaestner, B., Sinova, J. & Jungwirth, T.
Phys. Rev. Lett. 94, 047204 (2005).
7. Valenzuela, S. O. & Tinkham, M. Nature 442, 176–179
(2006).
8. Kimura, T., Otani, Y., Sato, T., Takahashi, S. & Maekawa, S.
Phys. Rev. Lett. 98, 156601 (2007).
Figure 1 | The spin Seebeck effect. a, In
the ordinary Seebeck effect, a temperature
gradient in a metal bar causes more electrons to
accumulate at the cool end, producing a ti.
Protection of humans during long space flight. using cannabis to reduce biol...Dmitri Popov
Protection of humans during long space flight. using cannabis to reduce biological consequences of high doses of radiation, treat stress, anxiety, and depression Associated with Long-term Space Flight to Mars.
Theralase Technologies Inc., founded in 1995, designs, develops, manufactures and markets patented, superpulsed laser technology utilized in biostimulation and biodestruction applications. Theralase technology is safe and effective in treating pain, inflammation and for tissue regeneration of neuro musculoskeletal conditions and wound healing. Theralase is currently developing proprietary Photo Dynamic Compounds (PDCs) that are able to target and destroy cancers, bacteria and viruses when light activated by Theralase’s proprietary and patented laser technology.
Characterizing the Effect of Static Magnetic Fields on C. elegans Using Micro...Iowa State University
In nature, several organisms possess a magnetic compass to navigate or migrate them to desired locations. It is thought that these organisms may use biogenic magnetic matter or light-sensitive photoreceptors to sense and orient themselves in magnetic fields. To unravel the underlying principles of magnetosensitivity and magnetoreception, previous experiments have been conducted on bacteria, vertebrates, crustaceans, and insects. In this study, the model organism, C. elegans, is used to test their response and sensitivity to static magnetic fields in the range of 5 milli Tesla to 120 milli Tesla. Single wild-type C. elegans are put in microfluidic channels and exposed to permanent magnets for five cycles of thirty-second time intervals. The worm movement is recorded and analyzed with custom software to calculate the average velocity and the percentage of turning and curling. Contrary to some published studies, our results did not show a significant difference compared to control experiments. This suggests that C. elegans may not sense static magnetic fields in the range of field strengths that we tested.
Effect of Static Magnetic Field on Parasitic Worms in MicroChipsIowa State University
This study uses the model organism, C. elegans, to investigate its sensitivity and response to static magnetic fields. Wild-type C. elegans are put into microfluidic channels and exposed to permanent magnets for five cycles of thirty-second time intervals at field strengths ranging from 5 milli Tesla to 120 milli Tesla. Recorded and analyzed with custom software, the results of the worm's movement - the average velocity, turning and curling percentage - were compared to control experiments. Surprisingly, the results did not show any significant difference, indicating that C. elegans may not be able to sense static magnetic fields at the range of field strengths tested.
Njus, Z. , Feldmann, D. , Brien, R. , Kong, T. , Kalwa, U. and Pandey, S. (2015) Characterizing the Effect of Static Magnetic Fields on C. elegans Using Microfluidics. Advances in Bioscience and Biotechnology, 6, 583-591.
doi: 10.4236/abb.2015.69061.
https://www.scirp.org/journal/paperinformation.aspx?paperid=59434
It’s a moral and strategic imperative that humanity gets to space, and does so soon. We have a ticking time bomb on our hands, but we don’t know when the clock is going to run out. In short, we are overdue for an extinction-level event.
As we’ve dug deeper into the Space Startup market over the 6 months since our original Space as a Platform thesis post in mid-2016, we’ve come to a frightening realization.
There are not enough people investing their time nor dollars into the required areas of space to enable us as a species to get there. It’s simply not going to happen, folks.
Nearly 900 investors from 700 VC firms responded to the mid-2016 survey covering Deal Sourcing, Investment Decisions, Valuations, Deal Structures, Post-Investment Value Adds, Exits, Org Structures of VCs, LP Relationships.
This document describes the results.
Nervana was just acquired by Intel for their capabilities and platform focused on Deep Learning and Artificial Intelligence. This is an overview deck of what they do.
This White Paper outlines dramatic advances in content discovery, search and recommendation that will improve the business prospects for service providers, broadcasters and other content owners. It explains the revolution in metadata technology and processes that underpin these advances. It demonstrates clearly how an advanced content metadata system improves the user experience and helps to drive loyalty, differentiation and revenues for both broadcast and digital services.
The future of online video, or, where the puck is heading. Whether you're an MCN, a social celebrity or YouTube/Vine star, or maybe an up and coming Instagram "millennial", you have the choice to build the tech yourself, or partner, but you still need to monetize it and acquire an audience. If you build it, they may never come. Niche content is the future. Act now, before Netflix steals your thunder.
Medical Technology Tackles New Health Care Demand - Research Report - March 2...pchutichetpong
M Capital Group (“MCG”) predicts that with, against, despite, and even without the global pandemic, the medical technology (MedTech) industry shows signs of continuous healthy growth, driven by smaller, faster, and cheaper devices, growing demand for home-based applications, technological innovation, strategic acquisitions, investments, and SPAC listings. MCG predicts that this should reflects itself in annual growth of over 6%, well beyond 2028.
According to Chris Mouchabhani, Managing Partner at M Capital Group, “Despite all economic scenarios that one may consider, beyond overall economic shocks, medical technology should remain one of the most promising and robust sectors over the short to medium term and well beyond 2028.”
There is a movement towards home-based care for the elderly, next generation scanning and MRI devices, wearable technology, artificial intelligence incorporation, and online connectivity. Experts also see a focus on predictive, preventive, personalized, participatory, and precision medicine, with rising levels of integration of home care and technological innovation.
The average cost of treatment has been rising across the board, creating additional financial burdens to governments, healthcare providers and insurance companies. According to MCG, cost-per-inpatient-stay in the United States alone rose on average annually by over 13% between 2014 to 2021, leading MedTech to focus research efforts on optimized medical equipment at lower price points, whilst emphasizing portability and ease of use. Namely, 46% of the 1,008 medical technology companies in the 2021 MedTech Innovator (“MTI”) database are focusing on prevention, wellness, detection, or diagnosis, signaling a clear push for preventive care to also tackle costs.
In addition, there has also been a lasting impact on consumer and medical demand for home care, supported by the pandemic. Lockdowns, closure of care facilities, and healthcare systems subjected to capacity pressure, accelerated demand away from traditional inpatient care. Now, outpatient care solutions are driving industry production, with nearly 70% of recent diagnostics start-up companies producing products in areas such as ambulatory clinics, at-home care, and self-administered diagnostics.
Struggling with intense fears that disrupt your life? At Renew Life Hypnosis, we offer specialized hypnosis to overcome fear. Phobias are exaggerated fears, often stemming from past traumas or learned behaviors. Hypnotherapy addresses these deep-seated fears by accessing the subconscious mind, helping you change your reactions to phobic triggers. Our expert therapists guide you into a state of deep relaxation, allowing you to transform your responses and reduce anxiety. Experience increased confidence and freedom from phobias with our personalized approach. Ready to live a fear-free life? Visit us at Renew Life Hypnosis..
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
Leading the Way in Nephrology: Dr. David Greene's Work with Stem Cells for Ki...Dr. David Greene Arizona
As we watch Dr. Greene's continued efforts and research in Arizona, it's clear that stem cell therapy holds a promising key to unlocking new doors in the treatment of kidney disease. With each study and trial, we step closer to a world where kidney disease is no longer a life sentence but a treatable condition, thanks to pioneers like Dr. David Greene.
Navigating the Health Insurance Market_ Understanding Trends and Options.pdfEnterprise Wired
From navigating policy options to staying informed about industry trends, this comprehensive guide explores everything you need to know about the health insurance market.
Navigating the Health Insurance Market_ Understanding Trends and Options.pdf
Neurological Effects of Space Radiation
1. Gravitational and Space Biology 22(2) September 2009 33
NEUROLOGICAL EFFECTS OF SPACE RADIATION
Gregory A. Nelson, Ph.D.
Loma Linda University, Loma Linda, CA
ABSTRACT
In this brief review, several aspects of radiation effects on the
central nervous system are considered. Low to moderate levels
(~ 1 to 2 Gy) of charged particle radiation exposure will
characterize the environment experienced by astronauts on long-
term space missions. These doses are well below those
associated with gross pathological changes and tissue
breakdown; however, they may cause persistent functional
changes. The intrinsic membrane properties of mature neurons
appear be stable to space-like radiation exposures but their
connectivity and information processing properties are
persistently altered. These alterations result in altered
excitability with reductions in synaptic remodeling for many
months post irradiation. Changes in information processing due
to synaptic changes as well as depletion of neural precursor cells
may in turn lead to reduced cognitive abilities. Supporting this
idea, behavioral studies on irradiated rodents and human
children have shown that performance decrements do occur in
the space operations dose range. An analysis of charged particle
track interactions with neuron structure suggests that nearly
every nerve cell’s dendritic or axonal arborizations will be
traversed by multiple cosmic rays during a long duration space
mission. The functional changes observed experimentally are
associated with the complex arborizations of nerve cells and
their structural specializations. Although the data for charged
particle radiation exposures are sparse, the available
observations from all exposure regimens point to a credible risk
of cognitive or performance decrements during long term space
missions.
KEYWORDS
Central nervous system, hippocampus, neurogenesis,
space radiation, synapse.
INTRODUCTION
The effects of radiation on the central nervous system
(CNS) have been investigated for many years, but
primarily in the context of radiotherapy. In this context,
survival of cells is the key indicator as the emphasis is on
tumor control, while minimizing side effects to normal
tissue. Most of these studies have employed gamma rays
or X-rays and typically, high doses (> 20 Gy) are applied
to local areas. This results in steep dose response curves
for white matter degeneration in either cortex
(leukencephalopathy) or the spinal cord (myelopathy)
which appears after a substantial time lag of many months
(Debus et al., 2003). This may be accompanied by
edema, breakdown of the blood-brain barrier, swelling of
vessels (telangiaectasia), inflammatory reactions and
sometimes necrosis. In this literature, there has been an
active debate about whether vascular endothelial cells or
parenchymal cells (especially oligodendrocytes) are the
dose limiting cells of the tissue which is characterized
overall by low rates of cell division and replacement.
Three excellent reviews of this literature are: Wong and
Van der Kogel, 2004; Tofilon and Fike, 2000; Schultheiss
et al.,1995. Many of the mainstream opinions about CNS
radiation responses are derived from results that result
from high dose exposures. These may not extrapolate
well to effects of the space environment in which the
relevant exposures are in the dose range of < 2 Gy
delivered slowly to the whole body by mixed fields of
charged particles. In this exposure regime there is much
less known, and NASA’s interest is in establishing
whether: 1) there are acute risks that could lead to mission
compromising performance impairments, and 2) whether
the severity and onset of neurodegenerative conditions
later in life may be enhanced or accelerated. The
following presentation will consider some selected studies
that address this lower dose regime, with emphasis on
charged particle effects if known.
Charged Particle Radiation
The unique properties of charged particles are associated
with their track structure. Unlike X-rays and gamma rays
which are absorbed in an exponential fashion with depth
in tissue, charged particles have a defined range and
deposit their energy at an increasing rate until they reach
the end of their range. This rate of energy loss is termed
the linear energy transfer or LET and is commonly used
as a measure of the quality of the radiation or its
ionization density. Charged particle interactions with
electrons in the target material are primarily electrostatic
rather than through processes such as Compton scattering.
Because the particles have significant mass, they travel in
relatively straight lines and about half of the energy they
deposit is confined to a narrow cylinder (track core) about
20 nm in diameter along the track. The other half of their
energy is deposited through radially scattered electrons
around the track core. These properties tend to
concentrate damage along the track rather than in the
more diffuse damage patterns produced by X-ray and
gamma ray exposures. Unique DNA damage,
genotoxicity and tissue responses have been described for
such densely ionizing radiation and many of these
properties have been reviewed in volume 16 of this
Bulletin (Nelson, 2003).
Cellular Level Responses
The first level of biological organization to explore is the
neuron with its excitable membrane that is the basic
____________________
* Correspondence to: Gregory A. Nelson
Radiobiology Program
Loma Linda University
Loma Linda, CA 92354
Email: gnelson@dominion.llumc.edu
Phone: 909-558-8364; Fax: 909-558-0825
2. G.A. Nelson — Neurological Effects of Space Radiation
34 Gravitational and Space Biology 22(2) September 2009
functional unit of the nervous system. It might be
expected that radiation-induced lipid peroxidation
reactions would compromise neuronal electrochemical
gradients, membrane receptors and ion channels
Extensive studies of membrane fluidity, cell leakage and
activities of Na+
/K+
ATPases and acetylcholinsterases
show that only doses in excess of 100 Gy are significantly
deleterious, although lipid chain shortening is observed at
lower dose (Benderitter et al., 2003; Krokosz and
Szweda-Lewandowska,2005). However, isolated rat
synaptosomes show decreased 22
Na+
uptake after 1 Gy of
gamma rays (Mullin et al., 1986) and some tissue culture
cells exhibit alterations in Ca2+
transport after 1-4 Gy of
electrons (Todd and Mikkelsen, 1994) suggesting
sensitivity of ion channels. Direct measurements of
charged particle-induced lipid peroxidation of liposomes
shows that they are much less effective than X-rays
(Ziegler & Wessels, 1998).
In early studies, the conduction velocities of compound
action potentials along isolated frog and rabbit sciatic
nerves was found to be very resistant to radiation,
requiring in excess of 500 Gy to show conduction block
(Gerstner et al., 1955). Recent studies using patch clamp
recordings from mouse hippocampal slices indicate that
intrinsic membrane properties of pyramidal neurons are
resistant to change after 1-4 Gy of iron ions or 1-8 Gy of
protons (NSCOR, unpublished). Together these results
emphasize the stability of nerve functional properties to
radiation exposure. By contrast, the survival of cultured
NT2 human neural precursor cells is quite sensitive to
charged particles and shows significant LET-dependent
apoptosis and necrotic death at doses < 0.5 Gy (Guida et
al. 2005). Growth of new processes (neuritogenesis)
from neurons in chick retinal explants is also sensitive to
iron ions at doses below 0.5 Gy (Vazquez et al., 1994).
So, survival, growth and different-tiation properties of
neurons are radio-sensitive in the space radiation dose
range while the functional integrity of fully differentiated
neurons appears to be relatively stable.
Electrical Output of Nerve Ensembles
The primary function of systems of nerves is to generate
output signals in response to input from other neurons and
environmental cues. Early experiments using implanted
microelectrodes in rabbits measured spontaneous
electrical activity from a number of brain locations
including hippocampus, thalamus and cortex. Significant
decreases in the frequency and amplitude of spikes were
observed in most brain regions after 4 – 5 Gy at times up
to 6 hr, but the hippocampus exhibited hyperexcitability
along with changes in spike train organization that may be
associated with inhibitory neuron malfunction (Monnier
and Krupp, 1962). At higher doses (9 Gy) all activity was
suppressed. Visually-evoked potentials in mice irradiated
with 20 MeV deuterons exhibited spike amplitude and
firing pattern modifications after 5 Gy (Ordy et al., 1968)
and the pedal-pleural ganglion of the sea slug Aplysia
exhibited increased excitability after 10 Gy of 137
Cs
gamma rays (Clatworthy et al., 1999). Pellmar and
collaborators performed recordings on Guinea Pig
hippocampal slices during or shortly after irradiation and
demonstrated increases in synaptic efficacy (dendritic
response) while population spikes (somatic response)
were inhibited at gamma ray doses above 30 Gy (Pellmar
et al., 1990; 1993). All of the above observations
demonstrate that changes in output may occur within
hours after > 4 Gy of low LET radiation but do not
address late changes or responses to high LET radiation.
Recent field recording experiments conducted by
Vlkolinsky et al. (2007) under NASA funding (NSCOR,
unpublished) examined mouse hippocampal slices
isolated from 1 to 18 months following 0 to 4 Gy of
accelerated iron ions or protons. These demonstrated that
synaptic efficacy was increased long after irradiation and
led to hyperexcitability. However, in the simple long
term potentiation (LTP) model of memory, synaptic
remodeling between pyramidal neurons was inhibited
months after 1-2 Gy of iron ions. LTP is correlated with
hippocampus functions in spatial memory and learning
using behavioral measures. These electrophysiological
paradigms report alterations in the number and strength of
synapses as well as glutamate receptor function and are
mostly post-synaptic in their anatomical distribution.
Observations on the important neural adhesion molecule
NCAM, which regulates synaptic plasticity, show that it is
down-regulated after doses of 2.5 Gy of 1 GeV/n iron
ions in rats (Casadesus et al., 2005) and > 0.5 Gy of iron
ions in mice (NSCOR, unpublished). These observations
suggest that the output of systems of neurons (and their
associated glia) is altered after irradiation at the level of
connectivity between cells in the networks. Further, these
systems are vulnerable to charged particle doses of the
same order as predicted for long term space missions and
exhibit defects in information processing that underlies all
CNS functions. The observed hyperexcitability may also
indicate an enhanced susceptibility to seizures.
Neural Precursor Cells
The most radiosensitive cells of the CNS are neural
precursor cells (NPC). These astrocyte-like stem cells
located in the linings of the ventricles and in the
subgranular layer of the hippocampus continue to divide
throughout life in mammals. They differentiate into
astrocytes, oligodendrocytes and neurons which become
incorporated into neuronal circuits and contribute to
learning and memory. J.R. Fike and others have
demonstrated that X-ray doses of 2-5 Gy cause substantial
apoptosis of NPCs and continued reduction in the
production of immature neurons (Mizamatsu et al., 2003;
Rola et al., 2004). Lower doses of ~1 Gy iron ions result
in similar elimination of NPCs (NSCOR, unpublished).
Further, irradiation causes remodeling of the CNS
microenvironment resulting in a state that inhibits
differentiation of resident NPC descendents (or grafted
unirradiated NPCs) and the continued elevated production
of reactive oxygen species (Monje et al., 2002; Limoli et
al., 2007) and chronic activation of microglia (Rola et al.,
2004). Iron ions are much more effective than 250 MeV
3. G.A. Nelson — Neurological Effects of Space Radiation
Gravitational and Space Biology 22(2) September 2009 35
protons or X-rays (NSCOR, unpublished). The loss of
NPC regenerative capacity may lead to accelerated
learning and memory decline with age.
Behavioral and Cognitive Effects
Electrophysiological and neurogenesis experiments are
consistent with behavioral observations on rats and mice
irradiated with charged particles. Morris water maze and
Barnes maze experiments indicate that spatial memory
and learning are inhibited by doses as low as 0.1 Gy of
iron ions (Shukitt-Hale et al., 2000; Raber et al., 2004).
These behaviors are believed to be largely associated with
the hippocampus. Conditioned taste aversion to
amphetamine (but not lithium) in rats is inhibited at doses
of >0.1 – 0.8 Gy iron ions in rats implicating dopamine
pathways. Ascending scale operant conditioning studies
(food reward after lever pressing) also indicate that, in
rodents, cognitive abilities may be susceptible to low
doses of charged particles (2 Gy iron ions) (Rabin et al.,
2004).
But are humans susceptible to radiation in the low dose
regime? Adult radiotherapy patients treated for head,
neck and brain tumors have commonly reported
depression, confusion and lethargy; but these are
individuals receiving high localized doses and who have
underlying medical conditions. There are, however,
observations on human children that have shown
sensitivity of still-developing nervous systems to low
LET radiation. In Israel, a large cohort of children
(~20,000 of average age 7 years) were treated with a
mean dose of 1.3 Gy X-rays to cause depilation of the
scalp in order to facilitate treatment of tinea capitis fungal
infections. These children later showed poorer outcomes
in high school aptitude and IQ performance and more
frequent psychiatric disturbances in later life. (Ron et al.,
1982). A group of 6-18 month-old Swedish children
treated for cutaneous hemangioma (strawberry
birthmarks) on the head were followed-up at the time of
comprehensive testing prior to military enlistment (age 18
– 19 years). They showed cognitive impairments at doses
above 0.1 Gy and up to 32% decreases in high school
attendance (corrected for social influences) after frontal
lobe X-ray doses > 0.25 Gy (Hall et al., 2004). So,
human CNS tissue that is still undergoing growth and
differentiation is susceptible to space-like doses of low
LET radiation. Together with animal behavioral studies
this suggests that low doses of charged particles may be
of concern in adults, especially with respect to brain
regions or processes dependent on continued
neurogenesis.
Fluence-Based Assessment of the Cellular Target
In estimating risks from fields of charged particles,
especially at low doses, it has been useful to consider the
fluence of particles rather than the dose The planar
fluence is the number of particles that traverse a unit area
and dose is proportional to fluence and LET. In this way
the contributions from different particles expressed as the
probability of exhibiting an endpoint (such as mutation or
cell death) per particle type can be summed to estimate
the total probability. Using this strategy, Curtis et al.
have estimated the number of traversals of cell nuclei or
soma in different CNS structures for a reference 3-year
Mars mission (Curtis et al., 1998). They showed that
approximately 46% of cell somas (areas from 180 – 486
µm2
) and 7.6% of cell nuclei (areas 40 – 100 µm2
) in
human hippocampal cells would be traversed by at least
one particle of atomic number Z ≥ 15. By extension,
16,000 cells in the retinal macula, 2x107
cells of the
hippocampus, and 850,000 cells of the thalamus would be
“hit” by such heavy ions. These calculations were
motivated by cell survival as the significant endpoint but
experiments suggest that fully differentiated cells are
radioresistant for survival. Extensive modeling of
network failure modes in the hippocampus have shown
that a very high proportion of cells in the hilar region
must be lost before there are significant changes in
connectivity (Dyhrfjeld-Johnsen et al., 2007). This
suggests that minor cell loss would not lead to major
functional changes. The situation may be different for
radiosensitive NPCs, however. If they are preferentially
incorporated into new memories, then lower fractions of
cell loss may be significant.
From the discussion above on functional output, it can be
argued that dendritic and axonal arborizations may be the
more relevant cellular targets, so a re-examination of the
impact of fluence is in order. Neuroanatomical studies
have characterized the number and topology of neuronal
processes; from these studies, the properties of
hippocampal CA1 (subfield cornu ammonis 1) pyramidal
neurons are summarized below for the rat (Pyapali et al.,
1998; The Hippocampus Book, 2007):
• Cell soma diameter: 15 µm with cross sectional
area = 193 µm2
• Total dendritic length per cell: 1.2 – 1.3 cm at
1.0 to 2.5 µm diameter.
• Total axon length per cell: ~ 0.2 cm and diameter
< 1 µm.
• Total dendritic spines per cell: ~30,000.
• Total spine synapses per cell: 10,000 – 30,000
(of which only 16-26 need to fire
synchronously to generate action potentials).
From these dimensions and three dimensional
reconstructions of cells it was possible to calculate the
cross sectional area of a typical pyramidal cell at 11,800
+/- 3,200 µm2
(N=11) and the number density of
synapses at between 1 and 2 per µm3
. Using these areas
and the estimated Mars mission fluences from Curtis et al.
(1998), Poisson distribution calculations yield the
following. At solar minimum, with a fluence for Z ≥ 15
ions of 107,000/cm2
, each cell body would be traversed,
on average, by 0.21 particles (1 out of 5 cells) whereas
each arbor area would be traversed by 12.8 particles (a
128-fold greater value). At solar maximum, with a Z ≥ 15
fluence of 59,300/cm2
, the values are 0.14 hits per soma
and 7.1 hits per arbor (a 71-fold greater value). Thus,
essentially every cell will be traversed multiple times and
4. G.A. Nelson — Neurological Effects of Space Radiation
36 Gravitational and Space Biology 22(2) September 2009
the high interconnectivity of neurons is likely to spread
the influence of each traversal to many cells.
Another estimate can be made from the track structure of
the particles. Chatterjee and collaborators (Chatterjee and
Schaefer, 1976) employed a model for particle tracks that
describes the local dose as a function of radial distance
from the track axis. Applying their model to 600 MeV/n
iron ions or 250 MeV/n protons (which are relevant
energies for accelerator experiments, cosmic rays and
solar particle events) one may estimate that cylindrical
regions within 4.5 µm of an iron ion track axis will
receive ≥ 1 cGy dose and regions within 2 µm will receive
at least 5 cGy. For protons the corresponding radial
distances are 0.32 and 0.05 µm. At 2 synapses per µm3
this means that for iron ions, 25,132 synapses per
millimeter track length receive ≥ 5 cGy dose and
127,235/mm receive ≥ 1 cGy. For protons the values are
16/mm and 643/mm, respectively. If only 16-26 synapses
must be activated to initiate an action potential (The
Hippocampus Book, 2007), and if 5 cGy has a 10%
chance of activating a synapse, then for each millimeter of
iron track length, approximately 2500 synapses could be
activated and could, in turn, result in 100 action potentials
in interconnected neurons participating in the same
pathway or local circuit. Sufficient activation might
mimic the effects of high frequency (tetanic) stimulation
to neuron ensembles leading to persistent changes in their
synaptic strengths and efficacies. Perhaps the light
flashes perceived by astronauts during to the passage of
charged particles through their retinas reflect such
activation processes.
SUMMARY
In this brief review, several aspects of radiation effects on
the central nervous system were considered. It was
shown that although major necrotic and demyelinating
changes are not expected from exposures to space
radiation, there may still be enduring functional
consequences. While the excitability properties of mature
neurons are expected to be stable, their connectivity and
information processing properties may be persistently
altered. These alterations result in hyperexcitability,
perhaps with attendant seizure risks. Changes in
information processing due to synaptic changes and/or
depletion of newly-born neurons may also lead to reduced
cognitive abilities. Radiation-induced alterations in the
CNS microenvironment could stabilize an unfavorable
milieu for cell function and replacement possibly through
oxidative stress and inflammatory mechanisms.
Behavioral studies on young adult rodents exposed to
charged particles and observations of human children
exposed to photons have shown that performance
decrements can occur in the dose range associated with
space operations. Finally, a reconsideration of how
charged particle tracks interact with neuron structure
suggests that nearly every nerve cell’s dendritic or axonal
arborizations will be traversed by multiple cosmic rays
during a long duration space mission. Thus, earlier
estimates focusing on cell survival alone may
underestimate the potential for deleterious functional
changes.
ACKNOWLEDGEMENTS
The author wishes to thank the many co-investigators on
the NSCOR program project investigating the effects of
charged particles on the mouse hippocampus for
providing focus and perspective on the properties of the
central nervous system. Funding for this effort was
provided by NASA grant NNJ04HC90G.
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