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HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI)

Correspondence Address:
Sergio Canavero
Turin Advanced Neuromodulation Group, Turin, Italy

DOI:10.4103/2152-7806.113444

Copyright: c 2013 Canavero S This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Canavero S. HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI). Surg Neurol Int 13-Jun-2013;4:

How to cite this URL: Canavero S. HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI). Surg Neurol Int 13-Jun-2013;4:. Available from:

In 1970, the first cephalosomatic linkage was achieved in the monkey. However, the technology did not exist for reconnecting the spinal cord, and this line of research was no longer pursued. In this paper, an outline for the first total cephalic exchange in man is provided and spinal reconnection is described. The use of fusogens, special membrane-fusion substances, is discussed in view of the first human cord linkage. Several human diseases without cure might benefit from the procedure.

Keywords: Fusogens, head transplantation, spinal cord reconstruction

In 1970, Robert White and his colleagues successfully transplanted the head of a rhesus monkey on the body of another one, whose head had simultaneously been removed. The monkey lived 8 days and was, by all measures, normal, having suffered no complications.[ 28 ] A few years later, he wrote: ȡWhat has been accomplished in the animal model – prolonged hypothermic preservation and cephalic transplantation, is fully accomplishable in the human sphere. Whether such dramatic procedures will ever be justified in the human area must wait not only upon the continued advance of medical science but more appropriately the moral and social justification of such procedural undertakings.[ 29 ] In 1999, he predicted that ȡwhat has always been the stuff of science fiction - the Frankenstein legend, in which an entire human being is constructed by sewing various body parts together – will become a clinical reality early in the 21st century brain transplantation, at least initially, will really be head transplantation – or body transplantation, depending on your perspective with the significant improvements in surgical techniques and postoperative management since then, it is now possible to consider adapting the head-transplant technique to humans.[ 30 ]

The greatest technical hurdle to such endeavor is of course the reconnection of the donor (D)'s and recipient (R)'s spinal cords. It is my contention that the technology only now exists for such linkage. This paper sketches out a possible human scenario and outlines the technology to reconnect the severed cord (project GEMINI). It is argued that several up to now hopeless medical conditions might benefit from such procedure.

HYPOTHERMIA PROTOCOL
The only way to perform a cephalic exchange in man is to cool the body-recipient (R)'s head to such a low temperature to allow the surgeons to disconnect and reconnect it to the donor (D)'s body, whose head has been removed in the same operating theater by a second surgical team. Once R's head has been detached, it must be joined to D's body, that is, it must be reconnected to the circulatory flow of D, within the hour.[ 29 30 31 ] Mammals can be sustained without blood flow for 1 hour at most when cooled to the accepted safe lower limit of 12-15C: At a temperature of 15C, the cerebral metabolic rate in man is 10% of normal. Recovery following circulatory arrest for as long as 1 hour has been reported at <20C temperatures since the 1950s.[ 13 15 ] Profound hypothermia (PH) curtails the onset of global ischemia and give time to the surgeons to reconnect the bodies.

Clinical experience in cardiac surgery has demonstrated that total circulatory arrest under deep hypothermia (18C) for 45 minutes produces virtually no discernible neurological damage, with a slight increase on approaching the hour.[ 16 34 ] Experience with surgical clipping of aneurysms shows the safety of the procedure.[ 22 ]

R's blood subjected to PH tends to become coagulopathic: Accordingly, R's head will be exsanguinated before linkage, and flushed with iced (4C) Ringer's lactate.[ 2 13 ]

Hypothermia can be achieved in several ways,[ 2 ] but, in this particular endeavor, it will not involve total body extracorporeal circulation (TBEC), in order to avoid the attendant ill effects (brain damage and coagulopathy), and make the procedure as simple and as cheap as possible.

White developed a special form of PH, which he named autocerebral hypothermic perfusion (ACHP).[ 32 ] No pumps or oxygenators are called for [ Figure 1 ]. The first patient submitted to this protocol was operated on in November 1968 for removal of a brain lesion. Here follows a short description.

Figure 1
Drawing depicting White's autocerebral hypothermic perfusion in place (from White 1978)

SNI-4-335-g001

After induction of anesthesia and intubation, and insertion of a cerebral 21G thermistor into the right parietal lobe and appropriate exposure, the common carotid arteries and their bifurcations were exposed. The two vertebral arteries were uncovered on each side of the neck as they coursed toward their body canals just caudal to the C6 body. Silk ligatures were passed around each individual artery and threaded through a short glass tube with a narrow opening and capped with a rubber tip for temporary nontraumatic occlusion. Following total body heparizination, the left femoral (F) artery and both common carotid (C) arteries were cannulated with small slightly curved metal cannulas (single carotid cannulation had been found to be unsafe in that it did not afford homogeneous bi-hemispheric cooling in monkeys). These were connected to each other via a pediatric Brown-Harrison high-efficiency heat-exchanger. Fluids of varying temperatures were circulated into the cylinder chamber around the tube containing the perfusing blood from a plastic reservoir using a sump pump. Under electroencephalography (EEG) control and with the F-C shunt open, each cervical artery was occluded beginning with the external carotids and ending with the closure of the vertebrals. With the demonstration that the shunt could maintain a normal EEG at normothermia, ACHP was instituted by altering the temperature of the fluid entering the heat-exchanger: After 48 minutes of perfusion, the intracerebral temperature had reached 11.4C. Electrocortical activity invariably ceases with cortical temperatures below 20C making the subject brain dead. Brain rewarming could be significantly retarded during the ischemic period by surrounding the head with ice. The patient made an uneventful recovery.

White[ 29 31 ] also experimented with biventricular cooling [ Figure 2 ]. Here, two 18G ventricular cannulas are inserted in the anterior horn of each lateral ventricle through small burr holes in the skull and fixed with acrylic cement; a similar cannula is inserted percutaneously in the cisterna magna for egress of the perfusate. Sodium chloride (NaCl) solution (154 mmol/) at 2C is perfused through both ventricular cannulas at a pressure of 80 cm/H2O and a flow of approximately 65 ml/min: <20C can be achieved in about 30 minutes. This technique has been employed in man: It is rapid and easy and obviates vascular cannulation, extracorporeal routing of the circulation, and total body anticoagulation. No damage to the brain has been reported.

Figure 2
Drawing depicting biventricular cooling for deep brain hypothermia in a monkey (from White 1978)

SNI-4-335-g002

Commercial cooling helmets are widely available[ 2 ] and similar contraptions helped White to lower and sustain brain temperature below 10C consistently. With pressure maintained at >80 mmHg through catecholamines infusion, 15C was achieved in <30 in White's Rhesus experiments. No neurologic deficit was detected.

In HEAVEN, once D's circulation starts flowing into R's exsanguinated head, normal temperatures will be reached within minutes. A thermistor in the brain can be replaced by one placed in the temporalis muscle (TM), as this closely correlates with intraparenchymal brain temperature.[ 26 ] The anesthesiological management during hypothermia is outlined elsewhere.[ 34 ]

D's spinal cord will be selectively cooled, that is, no systemic PH will be necessary. With custom-built units,[ 1 24 ] the spinal subdural and epidural spaces can be perfused with cold solutions at 4-15C, with rapid cooling and easily maintained at 10-15C for several hours without neurologic sequelae [ Figure 3 ]. Segmental hypothermia of the cervical cord produced no measurable temperature change of the brain.

Figure 3
Depiction of various ways to locally cord the spinal cord (from Negrin 1973)

SNI-4-335-g003

In the seminal experiment,[ 28 ] a Rhesus monkey [ Figure 4 ] was sedated, tracheotomized and mechanically respired, then transected at C4-C5 vertebral level. Surgical isolation was accomplished stepwise, under antibiotic coverage: - See more at: 

Figure 4
Drawing depicting the first total cephalosomatic exchange in a monkey (from White et al. 1971)

SNI-4-335-g004

Circumferential soft tissue and muscle were divided around the entire surface of the cervical vertebra with ligation and transection of the trachea and esophagus following appropriate intubation

Cervical laminectomy was performed at C4-C6 vertebral level with ligation and division of the spinal cord and its vasculature at C5-6. Following spinal cord division, an infusion of catecholamine was begun to counteract the hypotension of ensuing spinal shock with the maintenance of mean arterial pressure (MAP) 80-100 mmHg. Mechanical respiration was begun and continued throughout the experiment

The vertebral sinus was obliterated with judicious use of cautery and intravascular injection of fast-setting celloidin

Intraosseous destruction of the vertebral arteries was carried out

The vertebral body or interspace was transected. At this point, the head and body were completely separated save for the two neurovascular bundles

Each carotid artery and jugular vein in turn was divided and reconnected by means of a suitable sized tubing arranged in loops during constant EEG surveillance. Prior to cannulation, the preparation was heparinized and the vagi sectioned under ECG monitoring

For vascular transference of the cephalon to the new isolated body, the individual cannulas were occluded and withdrawn from the parent body carotid arteries and jugular veins (in sequence, allowing for continuous cerebral perfusion from one set of cannulas during the exchange) and replaced into the appropriate somatic vessel under EEG observation

Following successful cannula-vascular transfer, direct suture anastomosis of the carotid arteries and jugular veins was undertaken (silk 6-0 and 7-0, respectively) under the operating microscope. This permitted discontinuance of purposeful anticoagulation. Fresh monkey blood was available if significant losses were encountered under prolonged heparizination.

The monkey survived, neurologically intact, for 36 hours, having reacquired awareness within 3-4 hours.

With time, some blood loss was encountered from the muscles at the surfaces of surgical transection, due to chronic heparinization. The initial attempt to suture the vessels directly and thus eliminate the necessity of anticoagulation was only partially successful because of the constriction that developed in the jugular vein at the suture line, impeding venous return from the head.

No evidence of cellular changes compatible with a hyper-rejection reaction in cerebral tissue was seen on pathological examination up to 3 postoperative days.[ 29 31 ] The conclusion was that direct vascular suture will eliminate the long-term need for anticoagulation.

During the GEMINI procedure, the surgeons will cut the cooled spinal cords with an ultra-sharp blade: This is of course totally different from what happens in clinical spinal cord injury, where gross damage and scarring hinder regeneration. It is this clean cut the key to spinal cord fusion, in that it allows proximally severed axons to be fused with their distal counterparts. This fusion exploits so-called fusogens/sealants.

Several families of inorganic polymers (polyethylene glycol [PEG], nonionic detergents triblock copolymers, i.e., polymers of a PEG–propylene glycol–PEG structure: Poloxamers – e.g., poloxamer 188, 1107 – and poloxamines) are able to immediately reconstitute (fuse/repair) cell membranes damaged by mechanical injury, independently of any known endogenous sealing mechanism.[ 7 ] PEG (independent of molecular weight, 400-5000 being all equally effective) is both water-soluble and nontoxic in man; it can also seal the endothelium and wounds simply go dry during experimental laminectomy procedures.[ 20 ]

Originally, this fusogenic potential was exploited to induce the formation of hybridomas during the production of monoclonal antibodies as well as facilitating vesicular fusion in model membrane studies. Membrane fusion and attendant mixing of the cytoplasm of fused cells occurs when adjacent membranes touch in the presence of PEG or similar compound. Acute dehydration of the fusing plasmalemmas permits glycol/protein/lipid structures to resolve into each other at the outer membrane leaflet first and the inner membrane leaflet subsequently.[ 21 ] In other words, dehydration of the membrane facilitates the hydrophobic core of the lamellae to become continuous; rehydration after PEG exposure permits the polar forces associated with the water phase to help reorganize the structure of transmembrane elements. PEG is dislodged once the membrane is sealed. This reorganization of cellular water is believed to result from the strongly hydrophilic structure of PEG.

In contrast, triblock copolymers, which are mainly composed of PEG side chains around a high molecular mass hydrophobic core, act differently, namely, the hydrophobic head group inserts itself into the membrane breach, seal-plugging it.

The diameter of injured axons does not affect their susceptibility to repair by PEG: Both myelinated and unmyelinated axons are equally susceptible, but also neurons.

PEG is easy to administer and has a strong safety record in man, often employed as vehicle to clinically injected therapeutic agents.[ 33 ] P188 has also been utilized clinically in man without ill effects. Yet, the lower the molecular weight of PEG, the more toxic might be the by-products of degradation in the body (the monomer is very toxic) and thus only a molecular weight >1000 is totally safe in man.

Bittner et al.[ 5 ] were the first to show axonal fusion after complete axonal transection and data accrued since 1999 strongly point to the actual possibility of functional reconnection of the severed spinal cord.[ 7 12 ] In these experiments, immediate (within 2 minutes and in no case more than 3 minutes of disconnection) topical application to isolated severed (transected and reattached) guinea pig spinal cord white matter in vitro and both immediate topical or intravenous (IV) application of PEG in vivo reversed physiological conduction block and dramatically increased the number of surviving axons (i.e., the overall amount of spared white matter) to a similar degree. This was associated with an extremely rapid electrophysiological (100%) and/or behavioral (93%) recovery in mammals: The first action potentials are evident within 5-15.[ 7 12 ] In neurologically complete spinal cord injuries (SCI) in dogs, there was a significant and rapid recovery of conduction, ambulation, and sensibility.[ 7 12 ] Recovery is stable for at least a month and actually improves with time. In both dogs and guinea pigs, IV PEG still had effects, respectively, 72 and 8 hours after SCI (instead, rats could be salvaged at 2 and 4 hours, but not 6 hours, after brain injury: There was actually a worsening), but it should be stressed how IV injection of 30% PEG only increased the locomotor rating score by 0.7 out of a 21-point-scale compared with the controls receiving saline, partly due to the difficulty in delivering sufficient amount of agents to the injured site via systemic circulation. This is a clear indication for the need to use a topical approach. In any case, PEG appears to be superior to poloxamer 188. A successful phase I human trial of PEG on human volunteers has been completed.[ 12 ]

To sum up, no more than 2 minutes of application of PEG can fuse previously severed myelinated axons in completely transected spinal cords, enough to permit the diffusion of intracellular markers throughout the reconnected segments and immediate recover of conduction of compound action potentials lost after injury. Injected PEG crosses the blood–brain barrier and spontaneously targets areas of neural injury, without accumulating or lingering in undamaged tissues. Similarly, PEG injected beneath the perineural sheath near the lesion in peripheral nerves is effective in functional repair.[ 7 12 ]

Certainly, PEG-mediated plasma membrane resealing is incomplete: Compound action potentials are only 20% strong, owing to either leakiness to K+ or inability of PEG to target paranodal regions of clustered K+ channels likely exposed to demyelination. However, this can be partially offset by the administration of a specific agent, 4-AminoPyridine, a drug in clinical use, with doubling of recovered strength (40%).[ 12 ]

Fortunately, better ways to deliver PEG have been developed.

One involves self-assembled monomethoxy poly(ethylene glycol)-poly(D, L-lactic acid) [mPEG (2000)-PDLLA] di-block copolymer micelles (60 nm diameter), in which a PEG shell surrounds a hydrophobic inner core. These polymeric micelles, sizing from 10 to 100 nm, possess unique properties such as biocompatibility and long blood residence time, and have been widely investigated as nano-carriers of water-insoluble drugs.[ 12 ] Injured spinal tissue incubated with micelles showed rapid restoration of compound action potential into axons. Much lower micelle concentration is required for treatment than pure PEG. Injected mPEG-PDLLA micelles are significantly more effective than high-concentration PEG in functional recovery of SCI, likely due to prolonged blood residence of mPEG-PDLLA micelles.

Another way exploits monodispersed, mesoporous spherical PEG-decorated silica nanoparticles: These are hydrophilic, biocompatible, nontoxic, and stable. This colloid-based PEG derivative may do an even better job compared with polymer solution by controlling the density of PEG molecules at cord level.[ 12 ] Recovery of SSEP conduction after 15-20 following injection was seen in guinea pigs with transected cords.[ 25 ]

An alternative, possible better way to fuse severed axons has been described.[ 6 ] Methylene Blue is applied in hypotonic Ca++free saline to open cut axonal ends and inhibit their plasmalemmal sealing. Then, a hypotonic solution of PEG (500 mM) is applied to open closely apposed axonal ends to induce their membranes to rapidly flow into each other (PEG-fusion). Finally, Ca++-containing isotonic saline is applied to remove PEG and to induce endogenous sealing of any remaining plasmalemmal holes by Ca++-induced accumulation and fusion of vesicles. This technique has been applied to experimentally cut sciatic nerves in rats with excellent results.

Better agents than PEG have been identified and are available. Chitosan (poly--(1 4)-D-glucosamine) is a positively charged natural polymer that can be prepared by de-N-acetylation of chitin, a widely found natural biopolymer (crustaceans, fungi). It is biocompatible, biodegradable, and nontoxic. It is normally used as clinical hemostatic and wound healing agent in both gauze and granules. Chitosan appears superior to PEG: Chitosan in sterile saline (or otherwise nanoengineered nano/micro particles) can act as a potent membrane sealer and neuroprotector, being endowed with significant targeting ability.[ 12 ] Chitosan is capable of forming large phospholipid aggregates by inducing the fusion of small dipalmitoyl phosphatidylcholine (DPPC) bilayers, a major component of the plasma membrane.

Combining the actions of both chitosan and PEG leads to a newly developed hydrogel based on photo-cross-linkable chitosan (Az-C), prepared by partial conjugation of 4-azidobenzoic acid (ABA) to chitosan.[ 3 ] Chitosan hydrogel is attractive for use in GEMINI, due to its simplicity of application, tissue adhesiveness, safety, and biocompatibility. The Az-C network is reinforced by adding PEG (Az-C/PEG gel). Low-molecular-weight PEG with a nonreactive terminal group would be best. This gel can be applied as a viscous liquid that flows around the damaged cord temporarily held together. The gel precursor solution can be quickly cross-linked in situ by short-term UV illumination, covering the tubular part of the nerves and providing a reliable linkage during the healing process. The composite gels of PEG and Az-C have higher storage moduli and shorter gelation times than an Az-C gel or fibrin glue, and nerves anastomosed with an Az-C/PEG gel tolerate a higher force than those with fibrin glue prior to failure. These effects are likely due to the formation of a semi-IPN network, where PEG interpenetrates the covalent Az-C network and physically reinforces the network. Az-C/PEG gels are compatible with nerve tissues and cells. PEG is slowly released over a prolonged period, providing additional fusogenic potential.

A possible objection to GEMINI involves the supposed need for proper mechanical alignment (abutment) of the severed axons. The behavioral results of the PEG experiments, however, make a strong point that, while the number of axons reconnected to be expected is unknown, the results are nonetheless clinically meaningful, as highlighted by Bittner et al.[ 6 ] It is relevant to note how as little as 10% of descending spinal tracts are sufficient for some voluntary control of locomotion in man.[ 4 ] It is equally important to remark how the gray matter in this paradigm remains basically unscathed and functional. Here, interneuronal chains can function as a relay between the supraspinal input and the lower motor circuitry, given proper active training and provision of sensory cues in order to promote plasticity. Interneurons may act as central pattern generator for movement in man, and treatment strategies that promote their sprouting and reconnection of interneurons have great potential in promoting functional recovery.[ 17 ] One way to achieve this is by electrical stimulation: Electrical stimulation is known to promote plasticity and regeneration in patients (e.g., 20 Hz continuous stimulation.[ 8 14 ] In GEMINI, this would be achieved by installing an epidural spinal cord stimulating (SCS) apparatus, a commonly employed, safe way to treat neurological conditions. Parenthetically, these interneuronal chains can be set into operation by nonpatterned stimulation delivered via intact segmental input pathways: SCS has proved effective in this regard too in humans.[ 23 ] Another attractive way to supply electrical stimulation is by oscillating field stimulation.[ 27 ] Interestingly, electricity can be exploited to achieve axonal fusion (electrofusion): This method is at the moment not a suitable alternative for GEMINI, but it should be explored in this context.[ 11 ]

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ȸ Surgical Neurology International





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McDonald's cheeseburger left in doctors' surgery for 2 YEARS - can you guess what happens to it?

Jan 08, 2015 12:09

Two chiropractors in Michigan left a sandwich and a chicken taco on the counter of their surgery to make people think about what they are putting into their bodies

PAY-Fast-food-left-out-in-the-open-for-2-years

Dinnertime: The two-year-old cheeseburger seems mostly unchanged What happens when you leave a McDonald's cheeseburger unattended in the open air for two years?

The answer is nothing, really. No mould, nasty smells or ants.

It just sits there uneaten as people walk past.

PAY-Fast-food-left-out-in-the-open-for-2-years (1)

Fast food: The taco and the burger seem quite close to edible, thanks to preservatives Two chiropractors in Waterford, Michigan, US, left the sandwich and a Taco Bell chicken taco on the counter of their surgery to see what would happen to them.

Dr Jacqueline Vaughn hopes it will make people think about what they are putting into their bodies every time they make a trip to their local fast food restaurant.

It comes just a few weeks after a similar experiment in which another man drank 10 cans of Coca-Cola a day for a month to show the effects of the sugary drink.

Over almost two years, the meals appear unchanged - apart from the cheese on the burger turning a darker brown and the taco's lettuce greying slightly.

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"There's no smell from it, it's basically mummified. You can pick it up, turn it over and still see the cheese and pickle in the burger ," Dr Vaughn told MailOnline.

"Even in the summer when we get ants, the bugs won't go near it."

Dr Vaughn says she intends to leave the fast food on display "forever", although anyone expecting a dramatic transformation will most probably be disappointed.

McDonalds-cheeseburger

The beginning: A fresh McDonald's cheeseburger Yafan Zhang, professor of food science at Wayne State University, says a preservative called calcium probinate keeps the food looking near-edible for a long time.

He told CBS the non-toxic substance is used in a range of products to keep them fresh, including bread, cakes and processed meat.

The product is safe to use and eat. Although it can sometimes cause inflammation of the stomach, it is fine unless it is eaten every day.

ȸ mirror


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ȸ McDonald's hamburger looks the same after 14 years

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դǥȤƺҤ35ˤ̾ؤǡּʤлߤ衣ʥդǼڤפȶ

ּʤлߤץȶ

2014/11/26 18:37
 
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2013ǯ120518:29
 
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̩ݸˡƤˤĤơΰդʰդΥ롼פ񸫤ԤΥץ饤Хʤʤ붲줬ȤѰƤȤ褦ޤ

֤ɤ줬̩ʤΤʬʤΤϡ桹ˤȤäƤ˺סʿδ ʰա

ֲ̩ʤΤȤȤ̩ȡ̱Τ̤Ū˳ᤵ롣ɬǤסʽͦ ա

񸫤򳫤Τ̳ƻ鲭ޤǡǣͤޤΰդʰդǺ륰롼פǤդΥ롼פϡ̩ݸˡƤˤĤơֲ̩ȤΤϰϤΤǤʤʬʿĤԤƤʤפȤơˡƤؤȿФɽޤ

ξǡԤ̩򰷤̳ʤɤ硢ѤƤʤɥץ饤Х˴ؤˤĤơؤ󶡤פ붲줬ꡢʿ͸˷Ҥ꤫ͤʤȤѰƤȤ褦˵ޤ

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̩ݸˡơȿФ̱դ˽ֶԺη衢ȿСѤΤסƱˡƤΰѰǶԺη褵줿Τä̱֤ʤ̵פܤȯ
̩ݸˡơۣ壴Ϳ¦ηƧڤꡢ桢̱Ϳޤλ¿Dzķ衡ɽִνξ󱣤ˡΧ
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ھ׷۸̻Τɡ򼺤ä ա֤Ǥɡޤ礦 ǤɡޤʾС

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ѤϡµΤʤɤǿΤ»ȤˡγѤ򸵤᤹ѤΤȤǤ롣ޡ󥿡ͥåȾ򸫤ʤѤܤƤ롣

ʤȡɡ򼺤äΤǤɡ䤷ȤΤϡùǤ̤ǤʤΤǤɡϡɡɡ¤Ǵ¸ߤΩɤɡʤΤʤʤȤˡ

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ɡѷˤꡢϢˤϥ륮©ξɾФ褦ˤʤäƤޤäѤäƤޤäʬλѤ˶줷ߡƵۤ˴٤뤳Ȥ⡣

ϢϤ󤶤Ǻ̡ĤɡηѤԤȤˤɡϤǤˡŪɡηѤǤ֤ǤϤʤäǡŤ˸ƤŤ̡ͤդϡ֤ǤɡƤפȤФ

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ѤγפϤޤǤ򹭤Ĥɡλ٤ˤʤܿˤϾϢϾȤ줿Ʒդ۴Ĥ͹Ǵܿξɤɡ򳫤롣ޤǤǡ9פȤϺǸĴԤǤɡڤꡢɡΰ֤˰ܿѽλޤǤȰǤ롣

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ޤǸιĤäƤ뤬줿ϢɡϡǤˤĤƤȤơޤäΤΤǤ롣ޤǤɡƤ֤ʤΤdzлˤϤޥ˹ҤɬܤϢϡ֤Ϥ䤯ޥ褫줿Ϥ䤯ѤäƸƵۤǤ褦ˤʤꤿפäƤ롣

ΤܿͤȿȤäѤϵȿʤΤŪȸƤ롣ޤǤɡܤƤޤȤϡġķѤϡΤεǽǤʤΥˤĤʤȸ뼣ŤѤϤȰ칩ĤäƤ뤬褬Ǥ褯ʤ褦鷺ˤϤʤ

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