Hubble Ultra-Deep Field

IDL TIFF file

Arguably HUBBLE’s most important image to date

The Hubble Space Telescope aimed its lens at a very small region of space, about 1/10 of the size of the moon as viewed from Earth, where initially there was nothing to see but darkness. NASA aimed the telescope in an area of apparent darkness in an attempt to look for bright, distant objects. The telescope collected light from this region of the sky for over three months (September 24, 2003 through January 16, 2004). The HUDF was taken in a region of the sky with a low density of bright stars in the near field, allowing for better viewing of dimmer, more distant objects. The Hubble captured and recorded light in the full range from ultra violet to near-infrared spectrum. Looking back approximately 13 billion years the HUDF image shows objects that existed between only 400 million and 800 million years after the big bang. That is, the light from these galaxies were emitted 13 billion years ago, about 8.5 billion years before our Earth had even formed. These photons have been essentially traveling through the universe for the entire history of (space) time. There are approximately 10,000 galaxies in the image. With the exception of four stars (you can see them twinkle), virtually every spec of light visible is an entire galaxy containing anywhere from a thousand (10^3) to a trillion stars (10^12) each. These galaxies are some of the very first to form, indeed able to form in our universe. Interestingly, to observe the entire sky with the same sensitivity, the Hubble would need to observe continuously for a million years.

 

The Ten Most Popular South Jersey hikes!!!

South Jersey Trails

At the moment, we have 96 trails posted in South Jersey, which is a lot!  The saying goes that people vote with their feet (drumroll crash!), but which trails have the most views this year?  We celebrate 2 1/2 years as a blog by taking this completely unscientific look at the most popular hiking trails in South Jersey as chosen purely on page hits in 2015 on this terrible, terrible blog!

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Is Scientific Literature too difficult to understand?

Here is a summary of chapter 3.7 entitled “The Minicolumnopathy of Autism Spectrum Disorders” from the book The Neuroscience of Autism Spectrum Disorders by  Manuel F. Casanova. I was instructed to read this for a class entitled, “Capstone of Neuroscience”.

Cortical development arises from the epistatic interaction of multiple gene polymorphisms and transcriptional programs, their epigenetic modifications, expression patterns of morphogens and other small molecules, and incipient patterns of synaptic activity, all subject to developmental noise. These mechanisms exhibit redundancy and crosstalk so that a stable phenotypic distribution is maintained in the face of stochastic effects and (epi-)genetic perturbations. The resulting constrained programs of differentiation, migration, and neuronal development provide a basis for emergent patterns of information flow within the developing minicolumn, which may in turn feed back to further refine the formation of its circuits. In autism, our research has shown the existence of supernumerary columns with significant diminution in their peripheral neuropil. This finding, along with descriptions of ‘epigenetic’ heterotopias, suggests a dysregulation of periventricular germinal cell divisions. The heterochronicity of periventricular cell divisions provides an uncoupling between the radial migrating system and the tangential migration of inhibitory elements.

 

WHAT?!

I have studied neuroscience for years and I can hardly understand the summary above.I seriously doubt anyone who isn’t very familiar with mini columns or isn’t an expert on Autism could gain much of anything after reading that paragraph.Is there a problem with this? is it necessary? There has long been a debate about whether scientific journals use too much scientific jargon. Using this jargon makes it easier for trained scientists to know precisely what the author is describing. Although, it renders the research and its conclusions all but impossible for the average person.

The Beauty of the Pre-Telephone Writers: With Concentration on Einstein

A short piece I forgot I wrote…

6/6/15 Reading this Einstein book (Einsteins bibliography by Walter Isaacson) I was shocked by the beauty in which the people of his time wrote with. I could not understand why they could write with such fluidity and elegance. Indeed, every letter that Isaacson includes in the biography (mostly Einsteins) is written so well and it is quite apparent the care that each writer took. After reading the first 200+ pages I realized they were just excellent writers back then simply because that was the only was to communicate long distance. They had, therefore, been writing their entire lives. The beauty of an ordinary letter, perhaps a birthday card, took me by surprise, let alone a love letter written by a 16 year old Einstein to his beloved Mileva. It seems, because of technology, that the written (and spoken?) word has all but been extinguished in comparison to those who lived pre telephone. With ease we can contact anyone anywhere without writing a thing and as great an innovation as this, it is not without a loss, one in which our society, and our world, has largely lost the ability to write beautifully. There are of course many current writers who can write very well, but on average, the style of an everyday man or woman has been lost to innovation. We have destroyed our ability to write. Because there was such an abundance of written letters back then, it is easy to get a direct glimpse, straight from the source of what people were really like, not a secondhand account or a retelling. I urge you to at least explore the written world pre-1876 which in fact was not invented by Alexander Graham Bell, at least not independently and possible not at all. Additionally I urge you to read the Albert Einstein biography by the great and talented Walter Isaacson which is as close to being exhaustive as a biography of a dead man can be. Isaacson also has written what I imagine are tremendous biographies on Benjamin Franklin and Steve Jobs although I have not yet read them.

Why I am Not A Super Patriotic American

Let me first define what I mean by SUPER-patriotic…

SUPER-Patriotic : An American citizen that believes America and its citizens’s (humans) better than every other country and their citizen’s (humans) on Earth and is willing to go to absurd lengths to prove it.

I am an American, I have been for 23+ years and I doubt that I’ll ever not be. I love America, although I’m not proud of everything She has done. I have nothing but the utmost respect for my Father’s and his Father’s generation for sacrificing everything in the World War’s, the Vietnam War, the Korean War and every instance of freedom being defended, that which all too often necessitates violence and death. I am a patriotic citizen of the USA but I’m not SUPER-patriotic. Please, allow me to defend myself and explain just what I mean.

The US has a long and complex history, but I would like to focus on the present times, or maybe the last 30-40 years. Like I said I love America. I love it for defending Freedom at all costs. I love it for giving millions of people the chance to make a better life for themselves (whether the “American Dream” is still alive, or the possibility that it exists for one race of Americans and not the other is a discussion for another time). However, I believe that being super patriotic can have some bad and sometimes deadly consequences. If we assert that America is the best country in the world, better than all the rest, then we are already standing on a very slippery slope. It is much easier to dehumanize and thus kill another person if you believe that you are better than them. In fact, I would argue that it isn’t possible to dehumanize someone, or some nation or some race if you believe, honestly, that you are equal to them. We need not go back very far to see how blacks were (and still are albeit to a lesser degree in most places) dehumanized and thus oppressed, assaulted and murdered. Take a look at the middle east. I, myself, find it hard not to look down upon a Muslim when I’m in the city even though I know that the percentage of radical Islamists is a very small, small percentage of Muslims world wide. This dehumanizing thing, saying that WE are better than THEM has been around since man walked out of the trees. It is easier to hurt others when you believe they are subhuman is what I’m trying to say. And while you can be super patriotic and be a decent person, it is dangerous to believe this, mainly because there are very few years on record that man has not been systematically killing each other. This brings me to my zeitgeist on nationalism: It is fine to have, but can be very dangerous in excess. And, now I would like to share a couple quotes by the immortal Einstein, who it turns out hated Nationalism so much he denounced his German citizenship and refused to fight in WWII.

“Nationalism is an infantile disease. It is the measles of mankind.”

and  a personal favorite:

 

“The worst outcrop of herd life [is] the military system, which I abhor.  That a man can take pleasure in marching in fours to the strains of a band is enough to make me despise him.  He has only been given his big brain by mistake; unprotected spinal marrow was all he needed.  This plague-spot of civilization ought to be abolished with all possible speed.  Heroism on command, senseless violence, and all the loathsome nonsense that goes by the name of patriotism – how passionately I hate them!  How vile and despicable war seems to me!  I would rather be hacked in pieces than take part in such an abominable business.”

– Albert Einstein

 

Additionally, if you have ever read any Kurt Vonnegut you will notice he adds in many themes related to this post, Slaughterhouse-5 is one of the greatest books I have ever read.

I would like to reiterate the fact that I love America and our mixed national blood, I love the fact that for many Americans we consider our selves as One, regardless of race, religion, sex or ethnicity. And lastly, thank you to all the men women and children, (17 is a child right?) of the past, present and future who have served to keep us safe. I would also like to thank even African-American who served his or her country even at a time when their country didn’t serve them all that well. I’ll leave you with a quote that really pulls at the heart…

 

“And When he gets to heaven,
To Saint Peter he will tell;
One more Soldier reporting, sir.
I’ve served my time in Hell”

 

An Excerpt from Despair: (By The Greatest Writer to ever live: A Look at Faith)

An Excerpt from Nabokov’s Despair

The nonexistence of God is simple to prove. Impossible to concede for example, that a serious Jah, all wise and almighty, could employ his time in such inane fashion as playing with manikins, and—what is still more incongruous—should restrict his game to the dreadfully trite laws of mechanics, chemistry, mathematics, and never-mind you, never!—show his face, but allow surreptitious peeps and circumlocutions, and the sneaky whispering (revelations, indeed!) of contentious truths from behind the back of some gentle hysteric.

All this divine business is, I presume, a huge hoax for which priests are certainly not to blame; priests themselves are its victims. The idea of God was invented in the small hours of history by a scamp who had genius; it somehow reeks too much of humanity, that idea, to make its azure origin plausible; by which I do not mean it is the fruit of crass ignorance; that scamp of mine was skilled in celestial lore—and really I wonder which variation of Heaven is best: that dazzle of argus-eyed angels fanning their wings, or that curved mirror in which a self-complacent professor of physics recedes, getting ever smaller and smaller. There is yet another reason why I cannot, nor wish to, believe in God: the fairy tale about him is not really mine, it belongs to strangers, to all men; it is soaked through by the evil-smelling effluvia of millions of other souls who have spun about a little under the sun and then burst; it swarms with primordial fears; there echoes in it a confused choir of numberless voices striving to drown one another out; I hear it in the boom and pant of the organ, the roar of the orthodox deacon, the croon of the cantor, Negroes wailing, the flowing eloquency of the Protestant preacher, gongs, thunderclaps, spasms of epileptic women; I see shining through it the pallid pages of all philosophies like the foam of long-spent waves; it is foreign to me, and odious and absolutely useless.

If I am not master of my own life, not sultan of my own being, then no man’s logic and no man’s ecstatic fits may force me to find less silly my impossibly silly position: that of God’s slave; no, not his slave even, but just a match which is aimlessly struck and then blown out by some inquisitive child, the terror of his toys. There are, however, no grounds for anxiety: God does not exist, as neither does our hereafter, that second bogey being as easily disposed of as the first. Indeed, imagine yourself dead—and suddenly wide awake in Paradise where, wreathed in smiles, your dear dead welcome you.

Now tell me, please, what guarantee do you possess that those beloved guests are genuine; that it is really your dear dead mother and not some petty demon mystifying you, masked as your mother and impersonating her with consummate art and naturalness? There is the rub, there is the horror; the more so as the acting will go on, endlessly; never, never, never will your soul in that other world be quite sure that the sweet gentle spirits crowding about it are not friends in disguise, and forever, and forever, and forever shall your soul remain in doubt, expecting every moment some awful change, some diabolical sneer to disfigure the dear face bending over you.

That is the reason why I am ready to accept all, come what may, the burly executioner in his top hat, and then the hollow hum of blank eternity; but I refuse to undergo the tortures of everlasting life, I do not want those cold white little dogs. Let me go, I will not stand the least token of tenderness, I warn you, for all is deceit, a low conjuring trick. I do not trust anything or anyone—and when the dearest being I know in this world meets me in the next and the arms I know stretch out to embrace me, I shall emit a yell of sheer horror, I shall collapse on the paradisian turf, writhing. . . oh, I know not what I shall do! No, let the strangers not be admitted to the land of the blessed.

Still, despite me lack of faith, I am by nature neither sullen nor wicked. When I returned from Tarnitz to Berlin and drew up an inventory of my soul’s belongings, I rejoiced like a child over the small but certain riches found therein, and I had the sensation that, renovated, refreshed, released, I was entering, as the saying goes, upon a new period of life…in short I was bursting with fierce energy which I did not know how to apply.

 

—Vladimir Nabokov, writing from the view of Hermann in his seventh novel, originally written in Russian (in which he translated into English himself). I am unsure whether or not Nabokov shares the same view as his character but something tells me he does, although that is not an important issue for me, rather his beautiful style of writing is what transfixes me. I, along with scores of others regard Nabokov as the greatest, most talented writer to ever live. The book was written in Russian in 1934 and translated to English in 1937. However, during World War II German bombs destroyed most/all of the 1937 English editions of the book. The Russian version was again translated to English by the author in 1965, the ’65 version being the only English version around today. Indeed, my version of the novel, although it’s pages are brittle and falling out, is dated Copyright 1965-66.

 

A Plea for Help at The Alamo

Addressed to “The People of Texas & All Americans in the World”,

“I am besieged, by a thousand or more of the Mexicans under Santa Anna—I have sustained a continual Bombardment & cannonade for 24 hours & have not lost a man. The enemy has demanded a surrender at discretion, otherwise the garrison are to put to the sword, if the fort is taken—I have answered the demand with a cannon shot, & our flag still waves proudly from the walls—I shall never surrender or retreat. Then, I call on you in the name of Liberty, patriotism & everything dear to the American character, to come to our aid, with all dispatch—The enemy is receiving reinforcements daily & will no doubt increase to three or four thousand in four to five days. If this call is neglected, I am determined to sustain myself & die like a soldier who never forgets what is due to his own honor & that of his country—Victory or Death.”

—William Barrett Travis with Davie Crockett and James Bowie under siege by Antonio Lopez de Santa Anna at The Alamo (in San Antonio, TX) on February 24^th, 1836. All three men died just twelve days later on March 6.

You can read more about The Alamo in the book I found this quote in titled, ” Three Roads to the Alamo”. You can also read the wikipedia page here.

Infinity and Beyond?

There once lived a man named George Cantor (1845-1918), and if you do not recognize the name and if you are not familiar with his work this may be irrefutable proof that you are a normal person.  Nevertheless, in the world of mathematics Cantor is extremely important, specifically for his work involving infinity. He invented set theory, which I won’t get into except to say that a revelation he had about something called one-to-one correspondence (between numbers of a set) lead him to very profound conclusions. I am not a mathematician so I am not going to embarrass myself trying to get into the details. The main conclusion Cantor drew was that some infinities can be larger than others. When I first heard (or read) this I almost dropped the book (ok, not really). It sounds ridiculous, does it not? Cantor’s reasoning went something like this…

Take your good old infinity, the integers {1,2,3,4,5…}. This series of numbers can of course go on forever, hence infinity. Although, this series of endless integers can in fact be counted (a job for a motivated undergrad!). This type of infinite set is known as either a countable set or denumerable sets.

In accordance with 1-to-1 correspondence, Cantor envisioned a set of numbers that included decimals. For example, (if you are not familiar with decimals) {1.0, 1.1, 1.2, 1.3, 1.4……}. However, as you probably know, you can add decimals to make your number more accurate, indeed you can add infinite decimals if you so choose. So, imagine a set of numbers like this: {1.1, 1.12, 1.123, 1.1234, 1.12345, 1.123456…}. This type of set is said to be uncountable or nondenumerable. Because you can really never make progress with this second set of numbers, it is said to be a larger infinity than the first. Cantor apparently proved this mathematically although I am not even going to look at his proof.

One thing (many things really) does not make sense to me. I have heard that there are as many odd integers as theres are integers. If you keep track of all the odd numbers and normal numbers, there will always be another odd number to correspond with the normal number (normal numbers just means odd and even numbers ex: 1,2,3,4,5,6…).  Of course the odd numbers will grow larger (it will approach 2x as large I think) but who cares, it’s infinite. But this fact seems to contradict Cantors notion of infinities of different sizes.

 

Why is it not the case that the countable infinity can just add another integer in its list to correspond to the uncountable series? The countable series will also grow bigger (infinitely bigger??) than the uncountable series. The answer to this most likely lies in the proof Cantor wrote which is why I am having difficulty grasping the concept. Another titan of this realm of mathematics named David Hilbert came up with something called Hilbert’s Hotel which aims at explaining this concept of infinities in a more concrete way.

I will consult with the infinitely intelligence over at Reddit and report what I find.You can read more about Cantor’s life and work at his wikipedia page here.

An NIH grant proposal I wrote for a Regenerative Engineering class

 

A Combinatorial Treatment for Spinal Cord Injury: A Research Proposal

Specific Aims

Spinal cord injury (SCI) is a traumatic and complex condition that often results in chronic sensory and motor paralysis below the level of injury. There are approximately 17,000 new SCIs in the U.S. each year and on average 62% of these injuries have been incomplete [28]. However, basic research has focused more attention on treating motor complete SCI for a number of reasons. Many reactionary cellular mechanisms alter the microenvironment following acute SCI inhibiting functional nerve regeneration. Mechanisms including robust inflammation and glutamatergic excitotoxicity cause massive cell death. Formation of an astroglial scar and myeline accumulation inhibit the growth and reconnectivity of axons [22].

There are many types of therapies aimed at various mechanisms although two recent therapies have been shown to be very promising. Bioscaffolds that bridge the cavity caused by SCI can be seeded with stem cells and neurotrophic factors to induce axonal growth, guidance and regeneration [12].

In addition, several recent studies have shown that applying electrical stimulation to the spinal cord can induce involuntarily and ultimately voluntary step-like movements in motor complete SCI patients. These same studies claim that residual effects such as the ability to activate lower extremity muscle groups are seen even after the stimulation is turned off [5].

This proposal will investigate the efficacy of a bioscaffold seeded with appropriate stem cells and neurotrophic factors implanted at the time of spinal fusion following incomplete SCI. We will then determine how a specific therapeutic regiment focused on noninvasive electrical stimulation can enhance the regenerative capacity of the spinal cord.

 

Aim 1: To engineer a bioscaffold seeded with stem cells and neurotrophic factors to induce axonal growth and guidance

Our goal is to design a neurospinal scaffold that will facilitate axonal growth and guidance. The scaffold will be optimized for biocompatibility, biodegradation, morphology and ultimately SCI specific nerve regeneration. The propriospinal interneuron network (PN) will be targeted as a possible regenerative substrate. Because the PN contains neurons that sprout laterally into grey matter as well as neurons that connect spinal cord segments together, it is a very promising target for complete and incomplete SCI regeneration [6].

Aim 2: To use noninvasive electrical stimulation to neuromodulate the lumbosacral spinal cord circuitry to induce step-like movements

Targeting the lumbosacral circuitry with electrical stimulation has been shown to induce involuntary step-like movements in both healthy individuals and individuals who have suffered motor complete SCIs [9]. We believe that electrical stimulation may activate dormant pathways that project supraspinally to the lumbosacral central pattern generator (CPG). This will be the first human trial to test noninvasive electrical stimulation on patients with incomplete SCI.

Significance

While treatment of motor complete paralysis is important for providing proof of concept it is considered to be by far the most difficult type of SCI to treat clinically. On the other hand, incomplete SCIs hold far more potential for regeneration and functional recovery which is why we are proposing to treat this population with our multifaceted approach first.

If successful this strategy will be completely noninvasive, aside from the obvious spinal fusion following SCI, and will not be as intense as current SCI therapy paradigms. Furthermore, if patients reach our predicted goal it will enhance the health and quality of life while reducing the degree of disability for thousands of children and adults who have been paralyzed due to SCI.

 

Innovation

Due to the novelty of both technologies there has never been a study designed to determine the synergistic effects of a surgically implanted bioscaffold and noninvasive electrical stimulation on SCI regeneration. Our approach is unique in that we are attempting to bridge the spinal cord lesion as well as stimulate motor circuits below the level of injury. We believe that treating SCI from the top-down and from the bottom-up holds more potential for regeneration than either method alone. With the success of recent electrical stimulation of complete SCI we believe there is reason to have very high expectations for patients with incomplete SCI.

Preliminary Data: Bioscaffolds

Scaffolds offer the advantage of concentrating appropriate factors at a specific site and enhancing neural regeneration through contact mediated axonal guidance [17]. Scaffolds can also be seeded with stem cells, neurotrophic factors, nucleic acids material and other pharmacological drugs as needed. This method of delivery is aimed at improving efficiency of the drug or stem cell delivered and reducing the side effects of conventional drug delivery such as multiple injections [4]. SCI leaves a very hostile environment that is not conducive to axonal growth or regeneration as stated above. Using a bioscaffold can help in the physical and chemical reorganization that is needed to promote proper growth and reconnection of spinal cord axons [13, 15]. Scaffolds have been used in every area of tissue engineering for a long time however, neurospinal scaffolds are the most complicated and least studied due to the intrinsic complexity of the CNS. Still, there have been many studies investigating how a neurospinal scaffold should be engineered with positive results [12].

 

 

The figures above describe the data that were collected from a number of behavioral tests administered to rats who were given a unilateral (incomplete) SCI. Groups were assigned as such, one with a bioscaffold seeded with neural stem cells (NSCs), one with only a bioscaffold, one with only NSCs and one control group. (A) Data from the BBB open-field walking test for the ipsilateral side of SCI shows that the bioscaffold+NSC group scored significantly higher than both the bioscaffold only and NSC only groups. (B) BBB open-field walking test for the contralateral forelimb showing very similar data. (C) Data from an inclined plane test where the upward orientation was not altered significantly but the downward orientation was. The bioscaffold+NSC group improved significantly from day 14 onward. (D) Represents the righting reflex results. The bioscaffold+NSC group shows a significantly higher percentage of righting compared to other groups. (E) Represents the percentage of animals with a normal pain response. (F) Represents the percentage of animals with a spastic response to the same painful stimuli. Figures were taken from [23], description was adapted from [23].

Preliminary Data: Non-invasive Electrical Stimulation

A recent study [5] have successfully induced step-like movements using an invasive epidural stimulation device in four complete SCI patients. The patients regained the ability to move their legs after several weeks, and in one case several months of training with the electrical stimulation. However, the epidural device had to be surgically implanted along the patients’ lumbar spinal vertebrae. In addition, leg movement was only seen when the epidural stimulation device was on, no residual effects were seen. Instead of an invasive stimulation a new form of noninvasive electrical stimulation is suggested instead of the epidural device. This non-invasive method is known as transcutaneous electrical nerve stimulation (TENS). TENS is not new in itself but applying this method of stimulation to the spinal cord is relatively new. TENS works by strategically placing electrodes onto the skin above the spinal cord, specifically at the lumbosacral junction in humans. In a more recent study [5] five motor complete SCI patients who were at least two years post injury were able to move their legs in a gravity neutral position while the TENS unit was activated. Surprisingly, after a number of training sessions each of the five patients showed some degree of movement without the TENS unit turned on. Because this study was done in motor complete SCI patients who were at least two years post injury we have every reason to believe that an acute, incomplete SCI patient will respond even better to the TENS stimulation

Lower extremity EMG activity during voluntary movement occurred only with epidural stimulation in four individuals with motor complete spinal cord injury.

Lower extremity EMG activity during voluntary movement occurred only with epidural stimulation in four individuals with motor complete spinal cord injury. EMG activity during attempts of ankle dorsiflexion (A) without stimulation and (B) with stimulation. Force was not collected for Patient B07. Electrode representation for each subject denotes the stimulation configuration used. Although stimulation was applied throughout the time shown in B, in all four subjects EMG bursts were synchronized with the intent to move. Grey boxes are cathodes and black boxes are anodes, white boxes are inactive electrodes. Stimulation frequency varied from 25 to 30 Hz.

Figure and Description were taken directly from [9].

Approach: Bioscaffold Design           

Several conditions must be met in order to maximize reconnectivity and subsequent functional recovery. Biocompatibility is the most important characteristic to consider when designing a SCI model scaffold due to the risk of inflammation which could cause further neurological damage [8]. Furthermore, biodegradability is crucial, especially in the SCI model where removal of a non-degradable scaffold would warrant secondary surgery which may result in unnecessary complications. After the scaffold has assisted in axonal growth it should degrade through endogenous enzymatic activity. Another quality to consider is that of mechanical strength. The SCI scaffold will not have to stretch or expand but it will need to be able to withstand a certain amount of pressure caused by inflammation. The morphology of a bioscaffold for SCI should also be highly porous and contain large pore sizes, allowing for cell attachment and axonal growth.

For the reasons stated above, a chitosan scaffold with collagen hydrogel as a filler is proposed. Chitosan is a natural, biodegradable polymer used extensively by tissue engineers. The scaffold will contain the extra cellular matrix proteins fibronectin and laminin which have been shown to improve cell adhesion and axonal guidance [8]. Furthermore, evidence has shown that axons and axonal growth are extremely sensitive to the surface and architecture of scaffolds. Specifically, microchannels have proved successful in extending neurite growth with an optimal channel diameter of 20-30 nanometers [16]. For this reason the chitosan scaffold will be a solid conduit instead of an injectable scaffold. The scaffold will also be seeded with appropriate cells and neurotrophic factors that can modulate regeneration.In most cases after SCI the axons of the injured neurons will retract proximally and distally from the site of injury leaving a gap or cavity in the spinal cord [10]. Therefore, it will be beneficial to seed the bioscaffold with stem cells that will directly replace the cells that died. A popular stem cell line used for inducing spinal cord regeneration are neural stem cells (NSCs). NSCs are stem cells that are committed to becoming neural cells and are believed to facilitate spinal cord regeneration by differentiating into, and thus directly replacing, lost neurons and glial cells (Iwanami et al., 2005). Another advantage of NSCs is that they are believed to facilitate host axonal growth, that is, axons that survived the SCI, by secreting neurotrophic factors. For these reasons we are choosing NSCs to seed our chitosan bioscaffold. Several neurotrophic factors have been identified as playing important roles specific to the propriospinal interneuron network (PN) in axonal regeneration and plasticity. Brain-derived neurotrophic factor (BDNF) contributes to regeneration by promoting plasticity and increasing remyelination (Fouad et al., 2012). Specifically, BDNF administered to the cortex resulted in a greater number of propriospinal axon sprouting and a more complete preservation of corticospinal tract (CST) axons [26]. Additionally, ciliary-derived neurotrophic factor (CDNF) prevents degeneration of axons after axotomy [26] and glial derived neurotrophic factor (GDNF) has been shown to promote plasticity of the PN directly [10]. Other members of the neurotrophin family, including NT-3 and NT-4 are known for promoting axonal sprouting and growth [19]. These five neurotrophic growth factors are among some the most extensively studied and are well described in spinal cord regenerative literature [2]. Therefore, they will constitute the basis of the neurotrophic factors that will be seeded into the bioscaffold.

Approach: Noninvasive Electrical Stimulation Design

As soon as our recruited patients would be able to begin conventional physical therapy following a SCI we will instead start them on a therapeutic plan centered on noninvasive electrical stimulation. We will work with Thomas Jefferson University Hospital in Philadelphia, PA to recruit eight individuals who have recently suffered an incomplete SCI. We are attempting to recruit two groups of four, each group being comprised of similar injuries (ie. Level, type and severity of injury). We will begin our study by applying the TENS at the lumbosacral junction tonically for 45 minutes at a time or as long as the patient can stand the stimulation. We will have two sessions a day, five days a week for 90 days. The default stimulation parameters we will use will be adapted from Edgerton et al. from his 2015 study which are 8v at 15Hz. We will also record EMG data at three time points (d=30,d=60,d=90) from three groups of muscle synergies including hip, knee and ankle. The hip flexor, quadriceps and hamstring muscles. From the ankle we will record from the plantar flexor and plantar extensor. We will compare the data we collect from incomplete controls.

Potential Problems

The bioscaffold approach may result in a number of clinical issues. It will be difficult to personalize the bioscaffold to each SCI until we have a much better understanding of the different types of SCI and how different types of bioscaffolds work in each environment. Also, the solid conduit bioscaffold has a higher risk of causing inflammation and further neurological damage in comparison to an injectable scaffold. However, the bioscaffold allows for much more effective targeting of stem cells and neurotrophic factors and thus a higher potential for successful regeneration. The balance between the regeneration and inflammation of the solid conduit and injectable scaffold needs to be investigated further. There are a few potential problems with the TENS therapy. Patients may not be able to tolerate an intensity of electrical stimulation that is sufficient to provide the response needed for regeneration. Also, some patients will undoubtedly be able to tolerate higher levels of stimulation which may make interpreting results complicated. Some patients may need longer and more frequent electrical stimulation which may render the noninvasive method pointless at which point the patient may want to

End Goals

At the end of 90 days our goal is that at least 6 out of 8 of our patients will be able to take a few steps with the help of parallel bars, a walker or crutches. We expect that 6 out of 8 of our patients will be able to bear at least 75% of their body weight. We believe that being treated with a bioscaffold and training for 90 days with the TENS unit these SCI patients will improve significantly relative to controls. Further studies may want to address the relevancy of Lokomat training in addition to TENS therapy. Although at least one study determined that Lokomat training was no more beneficial than conventional physical therapy there may be reason to investigate the effect of the TENS with the Lokomat training. This may be a promising combination because TENS stimulation is thought to stimulate a central pattern generator and the Lokomat helps the patient to generate rhythmic walking motion.

 

 

References

1. Aigner, L., Arber, S., Kapfhammer, J. P., Laux, T., Schneider, C., Botteri, F., … & Caroni, P. (1995). Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice. Cell, 83(2), 269-278.
2. Bregman, B. S., McAtee, M., Dai, H. N., & Kuhn, P. L. (1997). Neurotrophic factors increase axonal growth after spinal cord injury and transplantation in the adult rat. Experimental neurology, 148(2), 475-494.
3. Carrade, D. D., Affolter, V. K., Outerbridge, C. A., Watson, J. L., Galuppo, L.D. Buerchler, S., … & Borjesson, D. L. (2011). Intradermal injections of equine allogeneic umbilical cord-derived mesenchymal stem cells are well tolerated and do not elicit immediate or delayed hypersensitivity reactions. Cytotherapy, 13(10), 1180-1192.
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We are not so small

Here’s the thing though… we aren’t small in the grand scheme of things. We are everything in the grand scheme of things.

There either is God or there is not. There is either some sort of higher power responsible for everything, or there is not. In the case of God, humans are everything in the grand scheme (pretty much no matter the religion). However, if everything that exists is a cosmic accident, we are also everything, because in that case there is no grand scheme and as best we can tell the rest of the universe is a desolate wasteland mostly filled with rocks and gas (besides all the nothing). In that case, Earth, and humanity, is a shining beacon in a sea of nothing.

Drilling down even further, to those in your Sphere of Influence and Perception, you mean more than all the nothingness in the universe. And those in your Sphere mean more to you in some way than all the rest of the universe. Your co-worker dying means more to you than an entire solar system imploding somewhere out there.

The very fact that you can appreciate the moon makes you more important than the entire lifeless universe. It’s only because of humanity that the moon means anything at all.

Edit: Yes, yes, “but aliens”. Replace “humanity” with “intelligent life” and we’re still part of an astonishingly elite club in the universe.

 

 

Taken from /u/Man_or_Monster on a reddit thread.