Motorcycle Bluetooth speakers have revolutionized the way riders experience their journeys. Whether you enjoy listening to music, receiving GPS directions, or making hands-free calls, these speakers provide convenience and entertainment on the road. In this comprehensive guide, we will explore the key factors to consider when choosing the perfect motorcycle Bluetooth speakers that meet your needs and enhance your riding experience.
Sound Quality: Immersive Audio on Two Wheels
When selecting motorcycle Bluetooth speakers, sound quality should be a top priority. Look for speakers that offer clear and crisp audio, allowing you to enjoy your favorite music without any distortion. Opt for models that deliver immersive sound, ensuring you don’t miss a beat while riding. Superior sound quality enhances the enjoyment of your journey, making it an unforgettable experience.
Weather Resistance: Durability in Challenging Conditions
As motorcycles are exposed to various weather conditions, it is crucial to choose Bluetooth speakers that are weather-resistant. Look for models that are built to withstand rain, dust, and vibrations commonly experienced during rides. Ensure the speakers have an IPX rating of at least 5 or higher to provide reliable protection against water ingress. Weather-resistant speakers guarantee durability, ensuring they can handle the elements and last for many rides to come.
Mounting Options: Secure and Convenient Installation
Mounting options play a vital role in the usability of motorcycle Bluetooth speakers. Look for speakers that offer versatile mounting solutions, allowing you to attach them securely to your motorcycle. Common mounting options include handlebar mounts, mirror mounts, or helmet mounts. Ensure that the mounting system is sturdy and easy to install, providing a secure attachment for the speakers while riding.
Battery Life: Extended Riding Sessions
To enjoy uninterrupted music or communication during long rides, opt for Bluetooth speakers with a long-lasting battery life. Look for models that offer a minimum of 8-10 hours of playback time on a single charge. This ensures that the speakers won’t run out of battery midway through your journey. Additionally, consider speakers with quick charging capabilities, allowing you to recharge them swiftly for subsequent rides.
Connectivity: Seamless Integration with Your Devices
Bluetooth connectivity is a crucial feature when choosing motorcycle speakers. Look for models that offer stable and long-range Bluetooth connectivity, ensuring a seamless connection between your speakers and devices. This enables you to wirelessly stream music, receive GPS directions, and answer calls without the hassle of tangled wires. Ensure that the speakers have Bluetooth compatibility with your smartphone or GPS device for easy integration.
Hands-Free Calling: Safety on the Road
Motorcycle Bluetooth speakers with built-in microphone capabilities allow for hands-free calling while riding. This feature ensures your safety on the road, enabling you to answer calls without taking your hands off the handlebars. Look for speakers with clear voice transmission and noise cancellation technology to provide crystal-clear phone conversations, even in noisy riding environments.
User-Friendly Controls: Easy Operation on the Go
When selecting motorcycle Bluetooth speakers, consider their ease of use and user-friendly controls. Look for speakers with intuitive buttons or touch controls that can be operated effortlessly, even while wearing gloves. This allows you to adjust volume, change tracks, or answer calls without distractions, ensuring a smooth and enjoyable riding experience.
Customer Reviews: Insights from Fellow Riders
Before making a final decision, it is advisable to read customer reviews of the motorcycle Bluetooth speakers you are considering. Genuine user feedback provides valuable insights into the speakers’ performance, durability, and overall satisfaction. Look for speakers with positive reviews and high ratings, as they are likely to meet your expectations and deliver an exceptional riding experience.
Motorcycle Bluetooth speakers have become an essential accessory for riders seeking entertainment, convenience, and safety on the road. By considering factors such as sound quality, weather resistance, mounting options, battery life, connectivity, hands-free calling, user-friendly controls, and customer reviews, you can select the perfect motorcycle Bluetooth speakers for your needs. These speakers will enhance your riding experience by providing high-quality sound, seamless connectivity, and convenient controls while ensuring durability and safety in various weather conditions.


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When it comes to historical dramas, the liberal luvvies are determined to out as LGBT as many folks as possible even if those folks are manifestly straight. Ask any school kid today what they know about Queen Anne and the few who have the foggiest will tell you, following the movie, The Favourite, that she was a rampant lesbian. Maybe the odd kid will say that Queen Anne was a racist because she was involved in slavery.
That slavery thing would in fact be a lucky guess which is correct as I noted HERE. But then school kids today are taught that everyone in the old days was involved in slavery and was an out and out racist so maybe it is not such a lucky guess after all. As I noted a while back, Queen Anne became pregnant 17 times by her husband in between all that completely non-existent rampant lesbianism.
And that brings us to Anne Boleyn who cannot be guilty of racism or indeed homophobia because she was a black bisexual. Well I never. The things that I was never taught at school.
We discover this in a new drama series on Channel 5 which covers the last months of Anne’s life in 1536 and features her snogging the next Queen after her, Jane Seymour. Anne is played by an actress of colour. The Independent says that it is “debatable whether the series as a whole truly adds anything new to its heroine’s legacy.”
That is somewhat of an understatement. It is a drama but it is fiction, not history. The trouble is that kids today do not study real history. At GCSE, it is the history of medicine, the Wild West and, of course, the Nazis. At A Level, it is more Nazis and something else. And thus, for many kids, the closest they will come to studying the period which made England protestant and so shaped our entire history is watching a TV series which shows that Anne Boleyn was a black lesbian.

domain: history


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Liverpool report debt increase of £21.8m and 10-month loss of £40.5m
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Can Emre Can replace Steven Gerrard as Liverpool's star midfielder?
15th December 2014 @ 05:33pm
Will Emre Can be able to take over from Steven Gerrard as Liverpool's star midfielder once the Englishman leaves Liverpool?
Adam Lallana the key to Liverpool's title hopes?
24th September 2014 @ 07:42pm
Adam Lallana has returned from injury and could be the key to getting Liverpool's title hopes back on track
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Can Fernando Torres re-find his form under Rafa Benitez?
28th November 2012 @ 01:34pm
Chelsea’s £50m Spanish striker Fernando Torres has been regularly criticised since joining the club in 2011, as his form has certainly not warranted ...
Rosie Huntington-Whiteley doing her modelling thing ahead of Mad Max: Fury Road release
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One night last spring, Trina Fair's phone rang. It was Jim Boeheim.
"I was surprised,'' she said. "I didn't know he had my number.''
Boeheim had called to talk to her about whether C.J. should enter the NBA Draft or return to school. Later, Boeheim would talk to Fair.
Fair's return would make Syracuse a much better team, which would benefit Boeheim. But the Hall of Fame coach had earned the Fair family's trust over the years. It started five years ago when Boeheim put his trust in former Syracuse assistant Rob Murphy.
In 2008, Fair had just finished his sophomore year of high school at Baltimore City College. In April of that year, Murphy got his first look at Fair during an AAU event in Pittsburgh. Fair stood about 6-foot-5 then. He possessed a smooth, left-handed shooting stroke. He could handle the ball. And Murphy saw potential.
"He was playing the two,'' Murphy said. "I figured he'd grow two or three more inches and be the perfect 3-man at Syracuse because Coach (Boeheim) loves versatile forwards.''
In 2008, Fair, playing in a pickup game after his sophomore year, tore the ACL in his left knee.
At the end of the summer, Murphy still liked Fair better than any other forwards he had seen. Murphy told Boeheim that the Orange should not only continue recruiting Fair, but they should offer him a scholarship. But due to the timing of Fair's injury, Boeheim had never seen him play.
"A lot of schools backed off, but Syracuse didn't,'' Fair said. "Coach Murphy stayed in contact with me. He stuck with me.''
Fair committed to Syracuse after visiting the SU campus with his parents in October of 2008.
"Coach Murphy and Coach Boeheim stayed in constant contact with him,'' Trina Fair said.
After showing so much faith in Fair back then, Fair trusted Boeheim and Murphy all the more last spring.
Murphy told Fair that there was nothing wrong with going back to school, getting his degree and leaving SU as one of the greatest players in the school's history.
"I think his trust in Coach Murphy and Coach Boeheim was also a major part of his decision,'' Trina Fair said.
Said C.J. Fair, "I know Coach Boeheim was thinking of what was best for my career.''

domain: sports


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Tuesday, February 18, 2014
A Couple of Pieces Finished
Here is a pedestal we did of a great coues buck taken by Waylon Pettet of Arizona Groundpounders. Waylon's buck grosses in the mid 120s. The lion was taken by Matthew Phillips while hunting with the Arizona Groundpounder crew.


This product is a dual purpose tool: a test pencil + a screwdriver
Screwdriver Pole material is chrome vanadium alloy steel.
Screwdriver head through the hardening treatment make it rugged and durable.
Handle granular anti slip design conforms to human engineering design standards.
It can test 1000V voltage.
Handle material is ABS insulation material, safe not electric shock.
The handle whit a power warning light when the higher the voltage, the light will be bright.
Item Name: Screwdriver Test Pencil
Material: Chrome vanadium steel
Test Range: 1000V
Features: Multifunction, Test Pencil, Cross Slotted Screwdriver,


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Are you planning an event that deserves a culinary experience to remember?
Indulge your guests with a feast for the senses, meticulously crafted by our team of culinary experts. From mouthwatering appetizers to decadent desserts, we specialize in creating unforgettable dining experiences tailored to your unique event.
Ready to elevate your event with supreme culinary delights?
Copyright © 2024 Full Cup Catering - All Rights Reserved.

domain: food


Burton Men's [ak] LZ Gore-Tex Down 2L Jacket True Black 2024
Hurry up! Sales Ends In
Hurry! Only 3 Left in Stock!
Stormproof Warmth for the Coldest Days.
Why let cold and stormy slow you down. You don't have to worry about how cold or deep it is. Just zip up the men's Burton [ak] LZ Down Jacket, buckle your bindings, and ride the day away. We're talking proven waterproof coverage and our warmest down puffy all in one. It adds [ak]-level details, so you have all the mobility you need to slash and carve at will.
- GORE-TEX 2-Layer Nylon 70D Ripstop Weave Fabric Blocked with GORE-TEX 2-Layer Nylon 200D Plain Weave Fabric [Side Panels]
- Living Lining® Mapped with Lightweight 30D Ripstop Down Proof Water-Repellent Coated Fabric
- Regular articulated fit is just right: Not too tight or too baggy, with shaping at the elbows and shoulders for easy movement
- GORE-TEX two-layer fabric is windproof, waterproof, breathable, and durable: It's the versatile solution to staying warm and dry while moving outside; GORE-TEX fabric is GUARANTEED TO KEEP YOU DRY™; GORE-TEX seam tape provides durable seam protection for a completely weather and waterproof design
- Offers breathability for medium-intensity activities with moderate sweat management for quick-drying comfort with the durability of a GORE-TEX membrane for reliable weatherproofing. Zip vents enhance breathability during more intense activity and in warmer conditions.
- 90/10 RSD down 800 fill provides lightweight high-loft warmth; Ergonomic water-repellent zip-out stretch waist gaiter with jacket-to-pant interface; Living Lining® provides consistent temperature regulation without adding bulk or weight
- StormForm attached hood with drop construction and Cohaesive embedded cinch and hood length adjustment; Mesh-lined, no-snag Pit Zip vents; No-lift underarm gusset
- Power mesh wrist gaiters; 200D nylon side panels provide durability; RECCO® reflector; YKK® water-resistant zippers
For more information, please visit our Returns and Exchanges Page.


Wireless interference from Power Line Communication in Japan
How a controlled test demonstrated that Power Line Communication (PLC) turns the power lines along the streets into unintended antennas. This test was instrumental in keeping restrictions on PLC in Japan.
Keywords: power line communication, interference, radio communication, radio astronomy
Power line communication (PLC) is a method to transmit data using the existing electrical grid instead of fiber optic cables, telephone lines, dedicated lines or wireless communications. PLC can be used to bring internet services to households, for communication with smart electrical meters, or other uses.
The various PLC systems all work by injecting signals onto the electrical wires, which are then picked up elsewhere. The concern is that these added signals turn the electrical wires into unintentional antennas.
With many miles of power lines turned into antennas, even weak signals can have a substantial reach.
Early on, the authorities in Japan limited PLC systems to frequencies below 450 kHz. This limit was set as higher frequencies are used for civilian and military telecommunications, as well as by radio astronomy. These uses are not disturbed by radio noise below the 450 kHz. However, this limit was set as a precaution; it was originally not known whether there really would be a problem.
In the early 2000s, the PLC industry applied for permission to use frequencies up to 30 MHz, i.e. just below the VHF band. The ministry responsible for the wireless spectrum (Ministry of Public Management, Home Affairs, Post and Telecommunications) created a study group to look into the issue.
Testing PLC radio interference
An experiment was conducted by eight scientists from two universities, a space research center and the Japanese National Astronomical Observatory.
They created a test site on Mt. Akagi in a rural area of Japan. They had three power poles erected in a straight line, to simulate a small section of a residential power line.
Then they set up a small PLC network, using two laptop computers and PLC modems. One computer was connected to the middle pole on the simulated power line. The other computer was placed inside a shielded shed to simulate a house.
Five different PLC modems were used, covering the frequencies from 3.8 MHz to 20.9 MHz. To receive the signals radiating from the simulated power line, antennas, receivers and spectrum analyzers were used. The receiving antennas were placed from 35 meters (110 ft) to 180 meters (560 ft) from the power line.
The scientists could clearly detect the PLC radiation from the simulated power line. The report states:
many broadcasting signals were interfered [with] and some of them completely masked by the PLC noise.
They also noted that the PLC emissions were at least 30 dB above the cosmic radiation throughout the 4–30 MHz band.
As radio astronomy is very interested in the UHF band (300 MHz – 3 GHz), the study also looked at possible interference above 300 MHz. Even though the PLC systems all operated at frequencies below 21 MHz, they had a demonstrated spillover effect (harmonics) that clearly showed up at much higher frequencies.
The report concluded that a radio observatory must be located at least 4 km (2.5 miles) from the test site in order not to be disturbed. If PLC systems came into general use, using miles of power lines, a radio observatory must be located much further from populated areas. This would be impossible in densely populated Japan.
The conclusion was that PLC systems should not be allowed to use the requested frequencies, as it would interfere with telecommunication and science. The Ministry did not grant the permission.
Measurements of Harmful Interference in the HF-UHF Bands Caused by Extension of Power Line Communication Bandwidth, Fuminori Tsuchiya et al, IVS CRL-TDC News, No. 21, November 2002.
For the Grid and Through the Grid: The Role of Power Line Communications in the Smart Grid, Stefano Galli et al, Proceedings of the IEEE, June 2011.


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34 CFR 400.6 - What are the requirements for establishing a State Committee of Practitioners?
(1) Local school officials representing eligible recipients;
(2) Representatives of -
(i) Organized labor;
(iv) Community-based organizations;
(vi) State councils;
(viii) Special populations; and
(ix) Correctional institutions;
(3) The administrator appointed under 34 CFR 403.13(a);
(5) The State administrator of programs assisted under chapter 1;
(7) Guidance counselors.
(b)Committee selection. The State shall select the Committee from nominees solicited from -
(1) State organizations representing school administrators;
(4) Members of local boards of education; and
(5) Appropriate representatives of institutions of higher education.
(1)Committee membership. The Committee must consist of -
(i) Representatives of local educational agencies, who must constitute a majority of the members of the committee;
(ii) School administrators;
(v) Members of local boards of education;
(vi) Representatives of institutions of higher education; and
(2) School administrators, teachers, and members of local boards of education may be counted as representatives of LEAs for purposes of paragraph (c)(1)(i) of this section.

domain: law


In a new and incredible video series by W Magazine called “Casting Call,” actors are asked to recite famous movie lines that are usually delivered by someone of the opposite sex. This time, a slew of 29 actors including Amy Schumer, Kristen Wiig, Eddie Redmayne and Samuel L. Jackson, deliver lines from the classic southern movie “Gone with the Wind” and it’s awesome.
The two lines the actors are asked to act out are what most would consider to be the two most famous lines in the movie — “Frankly dear I don’t give a damn” and “If you go, where shall I go? What shall I do?”
These actors take this infamous, industry altering movie and make it, well, something of their very own.
Image Source: YouTube


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September 11, 2012
Return to the battlefield or fight for the first time with Battlefield 3 Premium Edition for Xbox 360. This first-person shooter (FPS) game offers all new missions, awesome vehicles like jets and tanks, and support for multi-player action online with up to 24 players. Created using the Frostbite 2 game engine and with High Dynamic Range audio, Battlefield 3 builds on past versions to become the most stunning Battlefield warfare game yet. This premium version includes 5 expansion packs with dozens of new maps, vehicles, weapons and game modes. Rated M for mature users ages 17 and up.
- Online Item #: 14766167
- Store Item Number (DPCI): 207-22-0785
- Made in the USA or Imported

domain: entertainment


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Receptor-mediated calcium signaling in axons of mouse and rat optic nerves was examined by selectively staining the axonal population with a calcium indicator. Nicotine (1-50 μM) induced an axonal calcium elevation that was eliminated when calcium was removed from the bath, suggesting that nicotine induces calcium influx into axons. The nicotine response was blocked by d-tubocurarine and mecamylamine but not α-bungarotoxin, indicating the presence of calcium permeable, non-α7 nicotinic acetylcholine receptor (nAChR) subtype. Agonist efficacy order for eliciting the axonal nAChR calcium response was cytisine ∼ nicotine >> acetylcholine. The nicotine-mediated calcium response was attenuated during the process of normal myelination, decreasing by approximately 10-fold from P1 (premyelinated) to P30 (myelinated). Nicotine also caused a rapid reduction in the compound action potential in neonatal optic nerves, consistent with a shunting of the membrane after opening of the nonspecific cationic nicotinic channels. Voltagegated calcium channels contributed little to the axonal calcium elevation during nAChR activation. During repetitive stimulations, the compound action potential in neonatal mouse optic nerves underwent a gradual reduction in amplitude that could be partially prevented by d-tubocurarine, suggesting an activity-dependent release of acetylcholine that activates axonal AChRs. We conclude that mammalian optic nerve axons express nAChRs and suggest that these receptors are activated in an activity-dependent fashion during optic nerve development to modulate axon excitability and biology.
Recent studies have demonstrated that mammalian axons express at least three molecular pathways for mediating calcium influx: voltage-gated calcium channels (Callewaert et al. 1996; Fern et al. 1995; Jackson et al. 2001; Lev-Ram and Grinvald 1987; Sun and Chiu 1999), reverse operation of Na/Ca exchangers under ischemic conditions (Stys et al. 1995), and the calcium permeable vanilloid receptor TRPV1 (Fischer et al. 2003). Axonal calcium influx can trigger diverse cellular processes, including stimulating axonal transport, modulation of excitability, long-term changes in intracellular biochemistry, and excitotoxicity under pathological conditions (Breuer et al. 1992; Callewaert et al. 1996; Stys et al. 1995; Sun and Chiu 1999; Verbny et al. 2002). In this study, we describe a third pathway for mediating calcium influx into mammalian axons of the optic nerves: ligand-gated neurotransmitter receptors. Two mechanisms by which neurotransmitter receptor activation mediates calcium influx are considered. The first mechanism is that axonal receptor activation causes a membrane depolarization, which indirectly promotes calcium influx through activation of voltage-gated calcium channels. Indirect calcium entry is possible in mammalian optic nerve axons since they are known to express GABAA receptors (Sakatani et al. 1992), whose activation will depolarize axonal membrane and activate calcium channels. The focus of this paper is on the second mode of calcium entry occurring directly via calcium permeable axonal neurotransmitter receptors.
The possibility that axons express receptors that directly mediate calcium influx was first suggested in earlier studies (Armett and Ritchie 1961) that demonstrated that acetylcholine exerts a depolarizing action on nonmyelinated vagus nerves in rabbits. Subsequently, it has been established that one subtype of acetylcholine receptor, the nicotinic acetylcholine receptor (nAChR), is a ligand-gated, calcium permeable ion channel well documented to be present in both pre- and postsynaptic membranes. A recent calcium imaging study (Edwards and Cline 1999) directly investigated the possibility for nAChR-mediated calcium influx in nonsynaptic regions by focusing on nicotine-induced calcium signaling in axon arbors of the developing frog optic tectum. Intriguingly, Edwards and Cline (1999) observed nAChR-mediated calcium influx in nonsynaptic regions that correlates with sites of axonal branching. Since local rise in calcium may trigger actin/cytoskeletal assembly (Bentley and O'Connor 1994; Lankford et al. 1996), Edwards and Cline (1999) hypothesized that nAChR-mediated calcium influx regulates branching in growing retinal axons. Histological evidence previously demonstrated that AChRs containing beta 2 subunits are present in the retinal ganglion cells and transported along the optic nerve, presumably destined for insertion in the nerve terminals (Swanson et al. 1987). However, an important question is whether nAChR is actually inserted along the entire axon and plays a role in axon biology.
We set out to address this issue by using mouse and rat optic nerves excised between the eyes and optic chiasm, which are completely devoid of synaptic elements, branching, and growth cones. Using a method developed in our laboratory for selectively loading calcium indicators into the axons (Verbny et al. 2002), we examined if nAChR-mediated calcium signaling can be detected in these axons, and if so, how it relates to axonal excitability. Our results suggest that nAChRs are present in optic nerve axons. Furthermore, we characterized the antagonist profile of nAChRs, examined the relationship between nAChR expression and myelination, and provided evidence for activity-dependent release of acetylcholine in the neonatal mammalian optic nerves.
Selective axonal staining
In this paper, we used an in vitro method developed by Verbny et al. (2002) to selectively stain axons with calcium indicators. This in vitro method involved locally applying a high concentration of the cell-impermeant form of Oregon Green BAPTA-1 to the cut end of an excised optic nerve through a tight suction pipette and allowed approximately 3 h for the dyes to load into the axonal cylinders. We used Oregon Green BAPTA-1 conjugated to the high molecular weight (MW) dextran (MW =10,000) to exclude movement of dyes through glial gap junctions and to allow better retention in axons (Verbny et al. 2002).
Most of the experiments were performed on mice (about 120 mice), with a small number of experiments performed on rats (6 rats) when the length of the optic nerve became an issue. Each animal was killed, and optic nerves were taken out for study. In the rat optic nerve, the mean diameter of the axons remains about 0.2 μm for the first postnatal week and increases rapidly to about 1 μm in adults (>P28 days after birth), when the axons are fully myelinated (Foster et al. 1982). No morphometric data exist for the mouse optic nerves, and the developmental profile for the axon diameters is assumed to be similar to rats. Briefly, optic nerves excised between the eye and the chiasm were obtained from P1-P30 mice and laid down on the bottom of a perfusion chamber. The distal end of the nerve trunk was loosely drawn into a stimulating pipette, and the proximal end was drawn tightly into a recording pipette. The nerves were allowed to stabilize for 60 min before dye loading began. For dye loading, the normal saline solution in the recording pipette (the one with the cut end of the nerve tightly drawn in) was replaced either with a high-K (140 mM) or a high-Na (140 mM), low-calcium (0 calcium with or without 1 mM EGTA) solution containing 4-5 μl of the cell impermeant form of calcium indicators. The axons were stained by diffusion of the dyes from the cut end into the axonal cylinders. In our earlier studies, we used 1 mM EGTA in the loading pipette because we reasoned that this may prevent the cut ends of the axons from resealing, thereby facilitate dye loading into the axon cylinders. In latter studies, we found that robust axonal staining was also achieved without EGTA, and we routinely omitted EGTA in the loading pipette. The nicotine-induced calcium responses were not affected by the presence or absence of EGTA in the loading pipette. A standard loading time of 3 h was allowed before experiments began. We typically performed calcium imaging at a site approximately 500-1,000 μm away from the dyeloading pipette. The dyes were allowed to remain in the loading pipette (also serve as the recording pipette) during the entire experiment. Calcium levels were not reported in absolute levels, but as ΔF/F0, where F0 is the baseline fluorescence signal before drug application.
Confocal fluorescence imaging of axonal calcium
Calcium images were viewed with a 40× (Olympus) objective lens on a Noran Odyssey confocal system (Madison, WI). For calcium indicators, we used the cell-impermeant, high-affinity Oregon Green 488 BAPTA-1 (Kd = 170 nM; MW = 1,114) conjugated to the high MW dextran (MW = 10,000; Molecular Probes). The reason for using the dextran-conjugated dye is that dextran cannot pass through gap junctions (Eckert et al. 1999), thus excluding contribution from glial signals resulting from transfer of dyes from glial cells at the site of loading to the site of optical recording via gap junctions (Verbny et al. 2002). As argued in Verbny et al. (2002), the absence of an adenosine-evoked calcium response, a hallmark for glial cells, demonstrates that selective staining of axons has been achieved with this method. All dyes were used at a concentration of 5 mM in the loading pipette; the actual axonal dye concentration at optical recording site was estimated in our previous study (Verbny et al. 2002) to be approximately 1.3% of the dye concentration at the loading pipette, which would be about 65 μM. Experiments were performed with the Noran Odyssey System, with the dyes excited by an argon laser at 488 nm and confocal fluorescence signals collected through a 500-nm long-pass emission filter. In most studies, the average fluorescence signal from the whole field (approximately 10,000 μm2 area) was collected on-line at near video rate (30 Hz) and stored for off-line analysis. In other studies, images were captured of individual or groups of axons for image analysis of calcium changes. Image acquisition and on-line calculations were controlled through the Metamorph software (Universal Imaging). Experiments were done at room temperature (20-22°C).
Compound action potentials (CAPs) were evoked by a 125% supramaximal stimulus applied via the suction electrode to the cut end and recorded from a second suction electrode at the other cut end. The amplitude of the CAP data was analyzed using Pclamp 6.0 software (Axon Instruments). Compound axonal resting potentials were measured in neonatal rat optic nerve using the grease gap technique as previously described (Stys et al. 1995). Briefly, optic nerves were excised and inserted into a silastic tube filled with petroleum jelly, spanning two compartments. One was perfused with Ringer solution and test compounds, and the other was perfused with isotonic K solution where NaCl was replaced with KCl. A stable steady-state potential develops across the two wells that is a reliable fraction of the true axonal resting potential of the inserted fiber bundle. Typical absolute potentials recorded from P7 rat nerves were in the range of -25 to -35 mV.
Solution and drugs
The optic nerves were normally bathed in a Ringer solution containing (in mM) 129 NaCl, 3 KCl, 1.2 NaH2PO4, 2.4 CaCl2, 1.3 MgSO4, 3 HEPES, 20 NaHCO3, and 10 glucose. All solutions were rigorously oxygenated with 95% O2-5% CO2. Calcium-free solutions were prepared by replacing Ca2+ with Mg2+ to keep the external divalent cation concentration constant and by adding EGTA (1 mM); pH was adjusted to 7.4 with NaOH or HCl as necessary.
All compounds were from Sigma. The handling of the chemicals and animals was approved by the Biological Safety and Animal Research Committee at the University of Wisconsin, Madison.
Selective staining of axons
Representative axonal stains in this study are shown in Fig. 1 for neonatal (Fig. 1B, left) and adult (Fig, 1, C and D, right) optic nerves. In most cases, a large number of axons were stained. Most stained axons do not stay in the same focal plane, making it difficult to follow a single axon for its entire length along the optic nerve. Figure 1D shows example of an occasional stained axon that resided in the same focal plane for ≤200 μm within the field of view. We also verified axonal staining by an in vivo method in which we injected Oregon-Green-Dextran into the vitreous space of the eye of an adult mouse in vivo and allowed 24 h for the dyes to be taken up by the ganglion cells and transported down the axons, killed the animal, and mounted the optic nerve for image analysis. Single axons stained by this in vivo injection method (Fig. 1E) have morphology that is identical to that stained by the in vitro suction pipette method. In general, the staining method using suction pipette produces large populations of dye-loaded axons for analysis compared with the in vivo injection that only produces occasional stained axons. The pattern of axonal staining can be compared with the staining obtained by injecting the cell-permeant form of the dye into the nerve trunk (Fig. 1A), which also labeled glial cells (Kriegler and Chiu 1993). Since we are primarily interested in the axonal response to nicotine in this work, our analysis is based only the axonal staining pattern exemplified by Fig. 1, B-D. Since the in vitro loading method was developed for the mouse optic nerves, most of the experiments were performed in the mouse optic nerves. However, where necessary when nerve size becomes a technical issue, the larger rat optic nerves were used.
nAChR-mediated axonal calcium influx in mouse optic nerves
Figure 2 shows pseudo-color image of a single axon from a P8 optic nerve before (Fig. 2A) and about 40 s after (Fig. 2B) bath application of 50 μM nicotine. Figure 2, C and D, shows the same images recomputed as ΔF/F0 on a pixel-by-pixel basis, a procedure that normalizes for differences in the resting signal due to differences in dye loading and to changes in focus as the axon slightly goes in and out of the focal plane. Nicotine induces calcium elevation throughout the axon (Fig. 2, B and D). The goal of this paper is to characterize this nicotine response. In all the subsequent experiments, we captured the population fluorescence from the entire field of view without discerning individual axons to achieve a much faster time resolution (population signal sampled every 30-50 ms) than image analysis. A typical population response induced by nicotine is seen in Fig. 3A. Since this population response is the subject of our analysis, it is important to rule out certain possible artifacts associated with the usage of a nonratiometic dye such as Oregon Green BAPTA-1. One possible artifact is that the increase in the fluorescence is related to volume changes in the axons, rather than an increase in free calcium concentration, following nicotine application. To test for this possibility, we loaded axons with Oregon-Green conjugated to dextran but lacking BAPTA-1, rendering the dye insensitive to calcium. If the increase in fluorescence in Oregon-Green-BAPTA-1 is related to volume changes in the axons, then we should see the same fluorescence increase when the nonBAPTA dye is used. This, however, was not the case (Fig. 3). We thus concluded that the fluorescence increase is related to an increase in axonal free calcium concentration.
Next we examined the nature of the axonal calcium elevation induced by nicotine. We selectively stained large axon populations in mouse optic nerves at various stages of myelination and simultaneously measured CAPs and axonal calcium signals. Figure 4A shows a single CAP (top) and the associated axonal calcium influx (bottom). The action potential is approximately 4 ms long (as measured from the half-width of the positive deflection), while the calcium transient is much longer, being approximately 10-20 s. Our previous study (Sun and Chiu 1999) showed that this calcium transient is due to calcium influx with partial contribution from N-type calcium channels. To unambiguously demonstrate direct calcium influx mediated by neurotransmitter receptors (i.e., nAChR), we first needed to eliminate calcium influx through voltage-gated ion channels, achieved by adding the wide spectrum calcium channel blocker Cd2+ (50 μM) to the bath solution. The efficacy of calcium channel block was verified by the abolishment of the calcium transient (Fig. 4B, bottom) evoked by a single action potential (Fig. 4B, top). Next, TTX was added to block Na channels since they are slightly calcium permeable; the efficacy of the Na channel block was verified by a complete block of the action potentials (Fig. 4C). Having blocked voltage-gated ion channels that might contribute to calcium influx, we observed that bath application of nicotine (50 μM) produced a large increase in the axonal calcium level (Fig. 4D). To verify that this calcium response is receptor mediated, we applied various nAChR antagonists including d-tubocurarine (curare), mecamylamine, and α-BTX (Fig. 5A). In these experiments, the nerve was first treated with a 100-s exposure to 50 μM nicotine to elicit an axonal calcium response, which was followed by 40-60 min of antagonist application before the same concentration of nicotine was applied for a second time. Curare markedly (20 μM) reduced the second response by 87% relative to the first response (Fig. 5, A and B) in neonatal nerves. The nicotine-induced calcium response is much smaller in adult nerves, but the response is still inhibited by curare (Fig. 5D). In control experiments, no reduction in the second nicotine response was seen if curare was absent in the 40- to 60-min intervening period between the first and second nicotine applications, showing that the reduction in the second nicotine response in curare was not due to receptor desensitization. Similarly, the nicotinic receptor antagonist mecamylamine (10 μM) inhibited the nicotine response (Fig. 5, A and E) in neonatal nerves. In contrast, α-BTX (100 nM, 60-min application) is without effect on the nicotinic response (Fig. 5, A and D). Since α-BTX has a MW of 8,000, which is considerably larger than the MW of 681 for curare, the possibility existed that α-BTX may not be gaining access to the receptors due to restricted diffusion in the extracellular space. To test this possibility, we tested accessibility of another high MW toxin, α-DTX (MW = 7,054) in P7 optic nerves. Since DTX blocks delayed rectifying K channels in optic nerves and prolongs the action potential (Devaux et al. 2002), toxin accessibility can be determined from the broadening of the action potential after the K channels are blocked. We found that α-DTX produced a dramatic prolongation of the action potential that reached a steady state at approximately 15 min after toxin application (data not shown), proving that axonal receptors are accessible to toxins with MWs comparable to α-BTX.
From the antagonist profile (Fig. 5A), the nicotine receptors in neonatal mouse optic nerves are certainly not pure α7 subtype, since a pure α7 homomer would be very sensitive to α-BTX. Endogenous nAChRs could be hetero-multimers of various subunits, including the β subunit. To further assess the subunit composition in the neonatal mouse optic nerves, we examined the agonist profile of the axonal calcium response. Since β subunits have been suggested to determine nAChR sensitivity to cytisine (Luetje and Patrick 1991), we examined the sensitivity of the calcium response to cytisine, a nicotinic agonist. Figure 6A shows that when tested at two concentrations (1 and 10 μM), the rank order of potency for various agonists is (most potent first) cytisine > nicotine >> acetylcholine. Since it has been suggested that the β4 subunit confers cytisine sensitivity and β2 subunit confers cytisine insensitivity, our results are consistent with the presence of β4 subunits in the neonatal mouse optic nerves. However, the precise subunit composition of functional AChRs in the optic nerves remains open. Finally, the nicotinic response was abolished when nicotine was applied in a calcium-free bath solution, demonstrating that the bulk of the nicotinic response was due to calcium influx (to be discussed in Fig. 9).
Kainate and ATP
Glial cells are known to contain neuroactive substances (Martin 1992), and it is possible that nicotine stimulates glial cells to release these substances, which diffuse to axons to induce a calcium response. We examined two likely candidates released from glial cells, glutamate and ATP. For glutamate, we used the analog kainate known to activate calcium permeable channels. For ATP analogs, we used both BzATP and ATP. Figure 6B shows that none of these neuroactive substances, when examined in their respective effective concentrations, evoked axonal calcium responses that approached that seen with 50 μM nicotine. Hence, the simplest explanation for the nicotine-induced calcium response is that it results from direct activation of nAChR on axons.
Effects of nicotine on the CAP
In addition to evoking axonal calcium influx, nicotine also causes an abrupt reduction of the CAP in the neonatal mouse optic nerves. Figure 7A shows that, during a maintained nicotine application at 50 μM, the action potential amplitude first undergoes a transient depression and then recovers to a sustained, depressed level. This depression is dose dependent, with the half-maximal inhibition of the action potential occurring at approximately 2-5 μM nicotine. Figure 7B shows representative CAP traces before and at 2 and 10 min during nicotine application. The transient nature of the depression presumably reflects receptor desensitization. The transient depression of the action potential was largely prevented when nicotine was applied to nerves pretreated with curare (Fig. 8A). The nature of the sustained depression of the action potential by nicotine in the presence of curare is unclear; it could be due to a nonspecific action of nicotine in the mouse optic nerves. The inhibitory effect of nicotine (50 μM) on the action potential was also prevented by mecamylamine (Alkondon and Albuquerque 1993) at 10 μM (Fig. 8D). In comparison, methyllycaconitine (MLA) at 5 μM was only partially effective (Fig. 8B). In contrast, dihydro-β-erythroidine (DHβE) was completely ineffective between 40 nM and 20 μM (Alkondon and Albuquerque 1993; Rogers et al. 2001). As will be mentioned in the discussion, this antagonist profile provides strong argument against glial nAChRs mediating the inhibitory effects on the action potentials.
The reduction of action potentials suggests that nicotine depresses axonal excitability. What is the mechanism by which nicotine depresses axonal excitability? There are at least two possibilities. First, the nicotinic receptor is permeable also to Na and K, and activation of nonspecific cationic permeability on axons would lead to membrane shunting, thereby reducing the amplitude of the action potential. Second, the axonal calcium influx induced by nicotine could cause a change in membrane conductance that could block excitability (e.g., either by activating a calcium-activated K conductance or by inhibiting voltage-gated Na conductance). To sort out these two possibilities, we performed simultaneous measurement of action potentials (Fig. 9, top) and axonal calcium signals (Fig. 9, bottom) with or without calcium present in the bath solutions. In calcium-free Ringer solutions, we replaced calcium with magnesium to maintain a constant extracellular divalent cation concentration to avoid changes in surface charge effects and added 1 mM EGTA. Figure 9 (left column) shows that, with calcium present in the Ringer solution, a brief application of nicotine causes a transient depression of the action potential and a corresponding transient rise in axonal calcium; the two effects are mirror images of each other. Each action potential (generated at 1/min) evoked a calcium spike (arrow) resulting from calcium influx mediated partly through N-type calcium channels (Sun and Chiu 1999). We then applied calcium-free Ringer solutions. This caused a slight reduction in the CAP (data not shown). However, when nicotine was added, there was a similar reduction in the action potential, but without any parallel increase in the axonal calcium (Fig. 9, middle). This shows that the nicotine-induced calcium response is due to calcium influx. Furthermore, the calcium influx is not responsible for reducing the action potential. The effect is fully reversible on re-introducing calcium in the Ringer solution (Fig. 9, right). Taken together, these results show that nicotine mediates at least two independent events on the optic nerve axons: induction of axonal calcium elevation (via calcium-permeable nAChR channels) and inhibition of axonal excitability (via membrane shunting due to the nonspecific cationic permeability of the nAChR channels).
Since external calcium has been shown to potentiate the nAChR response in various tissues (Liu and Berg 1999), we performed a more detailed analysis on possible calcium dependence of the effect of nicotine on action potentials using long nicotine exposure (Fig. 10). It has been shown that, in the absence of extracellular calcium, Na influx through the nAChRs under physiological conditions is significantly reduced (Liu and Berg 1999). If the axonal nAChRs are similarly regulated, we should expect less action potential reduction in calcium-free Ringer solution in response to nicotine. Figure 10, A and C, shows that this is not the case; indeed, external calcium actually lessens the inhibitory effect of nicotine (Fig. 10C). Furthermore, the rate of desensitization (reflected by the return of the action potential amplitude to the normal, prenicotine level) is not affected by calcium (Fig. 10B). Thus axonal nAChRs appear not to be regulated by extracellular calcium.
nAChR elevates axonal [Ca2+]i without using voltage-gated calcium channels
How much of the nicotine-induced calcium influx is attributed to calcium influx via voltage-gated calcium channels? Calcium channels might contribute to calcium entry if nAChR activation causes a membrane depolarization. In certain mammalian neurons, nAChRs elevate [Ca2+]i primarily by promoting calcium influx through calcium channels; the calcium influx component directly through nAChR is very small (Barrantes et al. 1995). Is the neuronal model applicable to axons? To address this issue, we performed the experiment shown in Fig. 11A. We first depolarized the axons with a 12-mM K Ringer solution, which elevated [Ca2+]i due presumably to activation of voltage-gated calcium channels (Fig. 11A, bottom). This membrane depolarization was associated with a significant depression of the action potentials as shown (Fig. 11A, top). The nerve was washed for 10 min and followed by nicotine (50 μM) application. This depresses the action potential to a similar level as the K-solution (Fig. 11A, top), suggesting equivalent membrane depolarization and comparable activation of calcium channels in both cases. However, the observed [Ca2+]i elevation in nicotine is approximately 10 times larger than that observed in the K-depolarization (Fig. 11A, bottom), suggesting negligible contribution of voltage-gated calcium channels to the nicotine-induced calcium response.
One uncertainty of this study is that the reduction in action potential in nicotine may be due to membrane shunting rather than depolarization. We therefore directly measured membrane potential using a grease gap during nicotine application. Since neonatal mouse optic nerves are too small to be mounted in the gap, we switched to the larger rat neonatal nerves (also at P7) for this purpose. We first verified that P7 rat optic nerves displayed a nicotine-evoked axonal calcium response similar to that seen in P7 mice (data not shown). Interestingly, when P7 rat optic nerves were mounted in the grease gap, no membrane depolarization was observed when nicotine was bath applied (Fig. 11B, n = 4). In contrast, GABA (1 mM) did cause a membrane depolarization as expected (Sakatani et al. 1992), demonstrating that our technique can detect neurotransmitter-mediated depolarization. Figure 11C shows that 1 mM GABA depressed the action potential to a larger degree than 50 μM nicotine. It is possible that the depolarization in nAChR is small and escaped our detection. Alternatively, the shunting produced by the increase in Na and K permeability due to nAChR activation is not sufficient to override the resting conductance to significantly depolarize the membrane. From the studies in Fig. 11, we conclude that the elevation in axonal [Ca2+]i evoked by nAChR activation is not accompanied by significant membrane depolarization and that contributions from voltage-gated calcium channels are negligible. In most of the experiments in this paper, nicotine was applied without calcium channel blockers.
Calcium-induced calcium release
To examine if calcium-induced calcium release (CICR) contributes to the axonal calcium elevation induced by nicotine, we blocked microsomal calcium pumps with bath application of thapsigargin (2 μM) for 30 min (Sharma and Vijayaraghavan 2001). At the end of the application, the CAP was not affected. We did no see any significant effect of thapsigargin on the nicotine (50 μM)-evoked calcium response (data not shown, n = 2). These preliminary studies therefore suggested that CICR is not important in the nAChR-mediated axonal calcium elevation.
Relationship between nAChR expression and myelinogenesis
Mammalian optic nerves express GABAA receptors whose expression is downregulated with myelin maturation (Sakatani et al. 1992). We therefore examined whether there is a similar decline of nicotine response in mouse optic nerves during development. Figure 12B shows a decline of the inhibitory effect of nicotine on the CAPs during myelinogenesis. During the premyelinated stage (P1-P3), nicotine exerts a strong inhibition on the action potential, reducing it by approximately 90%. As myelin is gradually formed, nicotine becomes progressively less effective in reducing action potentials, so that by P15, the inhibitory effect of nicotine on the action potential is barely noticeable. In parallel, calcium imaging reveals a downregulation of the nicotine-induced calcium response during development (Fig. 12A). An interesting question is whether the nicotinic response is expressed in dysmyelinated axons. We therefore examined the CNS dysmyelinating mutant mice Jimpy. At P17, a developmental time point in normal mouse optic nerves when the nicotine-induced calcium response is reduced to approximately 10%, we still detected significant nicotine-mediated calcium response, at approximately 50%, in the dysmyelinating mutant. Dysmyelinating axons therefore express nAChRs in the absence of normal myelin.
Activity-dependent release of acetylcholine
We next examined if axonal nAChRs are activated during normal nerve activity. If acetylcholine is released during nerve activity and activates axonal nAChRs, there should be a reduction of the CAP (Fig. 7). Furthermore, any inhibitory effect of nAChR activation on the action potential should be potentiated if the action of acetylcholine is prolonged with neostigmine (a blocker of the enzyme acetylcholinesterase that normally degrades extracellular acetylcholine) or attenuated if the nAChRs are blocked by curare. We used this rationale to design the experiment in Fig. 13. In the control (normal Ringer solution), we applied a tetanus (2 min, 5 Hz) and measured the amplitude of the CAPs during the tetanus. The action potential shows a gradual decline during the tetanus (Fig. 13A, control). There are several traditional factors that might contribute to this action potential decline, including potassium accumulation and ion channel inactivation. However, a new factor we are interested in is whether nAChR activation might contribute to this decline. To test this idea, we applied neostigmine (0.2 μM) to the contralateral optic nerve from the same animal to prolong the action of any released acetylcholine. In these studies, both optic nerves were dissected from the same mouse and equilibrated for 1 h in oxygenated Ringer solution before studies began. Each nerve (control or drug treated) was subjected to only one tetanus. Neostigmine has no effect on the shape and amplitude of a single compound action potential (data not shown). However, neostigmine significantly deepened the inhibition of the action potential during a tetanus (Fig. 13, A and C). This neostigmine-sensitive component of the action potential decline is eliminated when curare (20 μM) was co-applied to block nAChRs (Fig. 13, B and C). Interestingly, neostigmine still deepened the action potential inhibition during the tetanus when calcium was omitted from the bath, suggesting that activity-dependent acetylcholine release is calcium independent (Fig. 13C). These experiments suggest that acetylcholine is released during nerve activity, targets axonal nAChRs, and causes a progressive shunting of the membrane potential and depression of excitability during high-frequency stimulation.
Significance of this study
Despite the extensive work already done on acetylcholine signaling in the visual pathways (Brocher et al. 1992; Butt et al. 2000; Edwards and Cline 1999; Imamura and Kasamatsu 1989; Nobili and Sannita 1997; Reed et al. 2002; Swanson et al. 1987), little is known regarding nAChR expression on the axon proper of the retinal ganglion cells. Here, we utilize a method developed in our laboratory to selectively stain axon populations with calcium indicators, allowing us to observe directly nicotine-mediated calcium influx in axons, examine receptor antagonist profile, correlate calcium signaling with nerve excitability, and assess the functionality of nicotine receptors in the mammalian optic nerves. By cutting the ganglion cell bodies and the presynaptic terminals, nAChR expression on the axon proper is studied in complete isolation from any synaptic elements.
Expression of nAChRs on axons
Several pieces of evidence suggest that nAChRs are present on axons of neonatal optic nerves. First, nicotine application induced an axonal calcium influx that is blocked by nAChR blockers α-tubocurarine and mecamylamine. Interestingly, the nAChR is insensitive to 100 nM of α-BTX, suggesting that the axonal nAChR is not a pure α7 subtype. The antagonist profile of axonal nAChR is consistent with patch-clamp studies demonstrating that nAChRs on the soma of mammalian retinal ganglion cells are sensitive to α-tubocurarine but insensitive to α-BTX (Lipton et al. 1987). Hence, the same nAChR subtype appears to be distributed on both the soma and the axon. Second, bath application of nicotine causes an abrupt reduction in the action potential, consistent with a direct shunting effect of nAChRs on axons. The restoration of action potentials during a sustained nicotine application (Figs. 7 and 8) is consistent with the known desensitization of these ligand-gated ion channels. Third, an indirect effect of nAChR activation on glial cells is rendered unlikely, as described in Indirect effects of nAChR activation on glial cells.
Indirect effects of nAChR activation on glial cells
It is possible that axonal calcium influx is mediated by activation of nAChRs on glial cells. Recent studies have established the presence of nAChRs on astrocytes (Sharma and Vijayaraghavan 2001; Teaktong et al. 2003). However, the astrocytic nAChRs are of the α7 subtype and are sensitive to α-BTX (Sharma and Vijayaraghavan 2001). O-2A progenitor cells cultured from P7 corpus callosum also express nAChRs (Rogers et al. 2001). However, nAChRs in O2A cells are blocked by the α4/β2 antagonist DHβE at 10 nM (Rogers et al. 2001), which contrasts with the DHβE insensitivity in our study at ≤20 μM (Fig. 8C). Release of a diffusible substance from glial cell is a possibility. One candidate might be potassium ions released by glia, which cause axonal depolarization, calcium channel activation, and axonal calcium influx. However, we cannot mimic the large axonal calcium influx seen in nicotine by K depolarization (Fig. 11). Other possible candidates for a diffusible substance from glial cells include glutamate and ATP. However, analogs of these substances did not elicit a comparable calcium response seen in nicotine (Fig. 6B). Thus the simplest explanation for the axonal calcium response and the abrupt reduction in action potential, both blockable by d-tubocurarine and mecamylamine, is that they result from nAChRs directly present on axons.
Does calcium influx through nAChRs account for all the calcium elevation?
Even though nAChR is calcium permeable, this receptor elevates [Ca2+]i by different means in different cell types. In hippocampal neurons, the nAChR elevates [Ca2+]i primarily by promoting calcium influx through voltage-gated calcium channels; calcium influx directly through nAChRs contributes little to the neuronal [Ca2+]i elevation (Barrantes et al. 1995). In astrocytes, nAChR elevates [Ca2+]i primarily by CICR (Sharma and Vijayaraghavan 2001). In this study, the axonal [Ca2+]i elevation triggered by nAChR activation has virtually no contribution from voltage-gated calcium channels since nAChR activation is not accompanied by detectable membrane depolarization (Fig. 11B). Why does activation of the cation nonselective nAChR pore not lead to membrane depolarization? One possibility is that the calcium influx through the nAChR pore might activate a calcium-activated K conductance that counteracts the depolarizing action of nAChR activation. Even without membrane depolarization, nAChR activation evidently leads to significant membrane shunting via conductance increase to impact excitability. With regard to the role of CICR in nAChR-induced calcium response, we did not detect significant effect of thapsigargin on the response. A smaller contribution from internal Ca stores triggered by nAChRs, possibly very localized at the subaxolemmal region (and therefore difficult to detect with confocal microscopy) with significant effects on excitability, cannot be ruled, given the recent demonstration of CICR mechanisms in CNS axons in ischemic conditions (Ouardouz et al. 2003).
Functions of axonal nAChR
We propose that axonal nAChRs have various functions during development, including modulation of axonal transport, axonal elongation, and modulation of axonal excitability.
axonal elongation and guidance. In the developing retina, nAChR-mediated spontaneous activity may be important in neurite extension and guidance during development (Feller et al. 1996; Lipton et al. 1988). nAChR-mediated axonal calcium elevation might alter the dynamics of actin/cytoskeletal assembly (Bentley and O'Connor 1994; Lankford et al. 1996) and modulate axonal elongation during development. The source for acetylcholine might be the glial cells, because the acetylcholine synthesizing enzyme (ChAT) has been demonstrated in cultured astrocytes (Wessler et al. 1997) and in oligodendrocytes in situ (Lan et al. 1996).
regulation of axonal transport. Axonal transport of proteins is crucial to long-term maintenance of the structure and excitability of axons, and the calcium ion is an important modulator of axonal transport (Breuer and Atkinson 1988a,b; Chan et al. 1980; Kanje et al. 1982; Worth and Ochs 1982). In the cat peroneal nerve, axonal transport was inhibited in a calcium-free bath solution (Chan et al. 1980). Calcium channel blockers, such as dihydropyridines and d-600 (Breuer and Atkinson 1988b; Kanje et al. 1982), cadmium, and nickel (Bartlett et al. 1999) have been shown to modulate axonal transport under various normal and pathological conditions. Collectively, voltage-gated calcium channels present on optic nerve axons (Brown et al. 2001a,b; Fern et al. 1995; Sun and Chiu 1999), as well as calcium-permeable nAChRs described in this study, may be involved in regulation of axonal transport in optic nerves during development.
modulation of excitability. We found that low-frequency stimulation at 5 Hz, which is well within the range of spontaneous activity of 10-30 Hz in a developing retina (Masland 1977; Meister et al. 1991), is sufficient to induce acetylcholine release (Fig. 13). Glial cells are the likely source of acetylcholine since they contain choline acetyltransferase (Lan et al. 1996; Wessler et al. 1997). Activation of nAChRs might modulate excitability by depressing action potential propagation.
Pathological implications: nAChR expression in demyelinated nerves
In addition to normal nerves, we found that nAChR is expressed in dysmyelinated axons from the mutant Jimpy mice (Fig. 12A). The expression of nAChR in demyelinated axons is particularly interesting for several reasons. First, given that acetylcholine is known to have a role in developmental plasticity, the existence of nAChR on demyelinated axons is functionally important in axon biology during and following demyelination. Second, an upregulation of axonal nAChR expression, as suggested by Fig. 12A, may be relevant to calcium-mediated toxicity. Glial cells or inflammatory cells near sites of nerve lesions may provide an abnormal source of acetylcholine in pathological conditions. Furthermore, axonal degeneration is a major factor in the pathology of multiple sclerosis (Trapp et al. 1998), and an important issue is whether expression of nAChRs on demyelinated axons might contribute to excitotoxic calcium elevation. Molecular pathways that mediate calcium influx into demyelinated axons include voltage-gated calcium channels, Na/Ca exchangers, and receptor-mediated calcium influx (nAChRs). These molecular pathways for calcium influx may be dysregulated in pathology, possibility contributing to calcium-mediated axonal damage in demyelinating diseases. An example is the recent finding that axonal N-type calcium channels appear to be upregulated in lesion sites in CNS white matter from patients with multiple sclerosis (Kornek et al. 2001), leading the authors to suggest a possible link between axonal damage and excessive calcium channel expression. Likewise, a possible linkage between axonal nAChR expression and axonal pathology in demyelinating diseases is an interesting area for further investigation.
Work in S. Y. Chiu's laboratory is supported by Grants RO1-23375 from the National Institutes of Health (NIH) and RG-3247-A-6 from the National Multiple Sclerosis Society underwritten by the Estate of Norman Cohn. P. K. Stys is supported by a Career Investigator Award from the Heart and Stroke Foundation of Ontario and in part by NIH Grant R01 NS-40087-01.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2004 by the American Physiological Society

domain: chemistry


A chalkboard in the main entrance of Parisian institution Palais de Tokyo certainly didn’t go unnoticed with French graffiti artists Lek and Sowat. During few months and without authorisation both artists have invited writers to perform and create ephemeral art using chalk and water. The installation “Tracés Directs” has been secretly filmed and will be shown during la Nuit Blanche on 5 October at O’Connells.
Participating Artists: Philippe Baudelocque, Wxyz, Alëxone, Smo, L’Outsider, Sowat, Babs, Skki, Jay one, Tcheko, Apôtre, Kan, Seb174, Sambre, Nassyo, Popay, Spé, Fléo, Lek, Dem189, Swiz and Jacques Villeglé (in order of appearance).
The film will be screened at O’Connells , 142 rue Oberkampf 75011 Paris
Tracés Directs on 5 October from 19:00
Pics by Butterfly and Sowat
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21.11.2013 · Jack London's Writing Style and Narrative Themes By: Francis Maglaqui Survival The man ate four raw chicks to try to survive. He ate them …
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06.02.2017 · A detailed discussion of the writing styles running throughout White Fang White Fang including including point of view, structure, setting, language, and
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How chic. How Charlie Rose. Current TV’s “Full Court Press” radio program went dark this morning as Pepco killed power for the entire building where Bill Press‘s studio is housed in Washington’s Eastern Market neighborhood.
Pepco says “a feeder” went out. Press was forced to do half his show in the dark.
All in all, Press saw the glass half full. “Hey, we lost the lights, but we kept doing the radio show in the dark,” he said. “Thank goodness for iPhone flashlights!”
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Hyundai Genesis review
The Genesis is packed with hi-tech kit and is decent quality, but it won't worry its German rivals
The Genesis has been Hyundai’s flagship model since its debut in 2008, but it’s never been available in Europe or the UK. However, that’s all set to change as the all-new second-generation car arrives.
There’s only one version, which is powered by a 3.8-litre V6 engine paired with an eight-speed automatic, with Hyundai saying they will sell just a handful of cars each year. The lack of diesel powertrain means the appeal of the Genesis will be limited in the UK.
But if a big V6-powered petrol luxo-barge is the kind of thing you're after and you value comfort and refinement over a sporty drive, then the Genesis could well surprise you. It's spacious and absolutely loaded with kit, which all go some way to compensate for what initially looks like a steep £48,000 price.
Engines, performance and drive
Hyundai has clearly worked hard on the Genesis’ refinement, as it’s a quiet place to be a lot of the time. The 3.8-litre V6 is whisper-hushed at idle and only becomes intrusive when worked hard, while there’s also very little wind and road noise.
The standard air-suspension also does a fair job of soaking up bumps, floating over rough surfaces that would cause some rivals such as the Lexus GS to fidget. However, hit a ridge or a pothole, and an uncomfortable thump is sent shuddering through the cabin. This soft suspension set-up also has an impact on the Genesis’ handling.
Even with the dampers in their stiffest setting – drivers can choose between Sport and Normal – the Hyundai rolls through corners, while body movement isn’t that tightly controlled. It also has a confidence-sapping tendency to roll into oversteer under high cornering loads.
The electronically assisted steering doesn’t boost confidence, either; although it’s direct, it lacks feedback. Plus, it suffers from a sticky and imprecise action in the straight ahead position, which forces the driver to make lots of small corrections to keep the car in your chosen lane on motorways. As a result, the Genesis isn’t as relaxing over long distances as you’d expect.
The 3.8-litre V6 also feels out of place in a luxury executive saloon. The petrol unit is refined enough, but it lacks the effortless low-speed response you’d expect in this type of car.
Below 4,500rpm, acceleration is a little sluggish and isn’t helped by the slightly clunky and occasionally hesitant eight-speed auto box. However, work the powerplant hard, and the Genesis performs strongly. The sporty, snarling soundtrack is slightly at odds with the car’s executive image, but it's a sprightly performer when you put your foot down from a standstill.
MPG, CO2 and Running Costs
Spending £47,995 on a car is a lot, let alone for a Hyundai with no track record in such an image-obsessed class. And while the Genesis feels better built and more upmarket than any of the brand’s other models, it’s not special enough to justify such a hefty price tag. Plus, it’s pretty expensive to run.
CO2 emissions of 261g/km result in large Benefit in Kind bills for business users, while private buyers have to cough up £500 annually for tax. The 3.8-litre engine is also very thirsty.
While our experts haven’t yet calculated residual figures for the Genesis, it’s unlikely to perform well. On the plus side, the car comes with a free five-year servicing package.
Interior, design and technology
If imitation really is the sincerest form of flattery, then Germany’s big three will have been paid a great compliment by the styling of the Genesis. For instance, the Hyundai’s front grille and headlamps can be seen as a mish-mash of Mercedes S-Class and Audi, and the rakish profile is pure Audi A7. While it’s not the most imaginative design, the Genesis is handsome and well proportioned, plus it’s long and wide, so it looks quite imposing.
The copycat theme continues inside, where you’ll find a dashboard that bears more than a passing resemblance to the BMW 5 Series’. There’s also a centrally mounted infotainment screen and white-ringed dials, plus an almost identical centre console layout. Still, there are one or two flourishes that help the Hyundai stand out, including the neat, metal-finish starter button and the classy analogue clock.
The quality is good, too. It can’t quite match the best executive cars for upmarket appeal, but the Genesis’ fit and finish is the best yet for any Hyundai. The plastics are all soft touch, the wood trim has a deep gloss finish and the stitching on the leather is neat and consistent.
There’s plenty of kit, including soft-close doors, a reclining rear seat with footrest, a head-up display and a surround-view parking camera system. There’s also a powerful, 14-speaker Lexicon stereo set-up, a panoramic glass roof and heated and ventilated seats front and rear. In fact, it comes so well equipped that there are no optional extras.
It’s not perfect, though. While the cabin is well finished by Hyundai’s standards, there are too many buttons and switches carried over from the brand’s more humble models.
Practicality, comfort and boot space
The Genesis is a big car – at nearly five metres long, it rivals luxury limousines’ dimensions. As a result, it feels slightly more spacious than its main rivals, with rear seat passengers getting more leg and shoulder room.
The rear bench has a 60:40 powered reclining function, while passengers sitting on the left can remotely operate the front passenger seat to create even more legroom.
The only negative is that the standard panoramic glass roof eats into headroom, so even those under six foot tall will be brushing the roof lining.
The Hyundai has a powered tailgate, which opens to reveal a 493-litre boot; yet there’s no split/fold arrangement or a ski-hatch for longer items. Storage in the cabin is good, with a large cubby between the front seats, a useful glovebox and numerous cup-holders.
Reliability and Safety
Hyundai can’t match the like of Lexus for a strong reputation for reliability and quality, but the brand finished our Driver Power 2014 satisfaction survey in a respectable 18th place. Plus, the Genesis represents a big step forward in terms of fit and finish, which helps create a strong impression of durability. And while much of the Hyundai’s underpinnings are new to UK buyers, they’ve been tried and tested in other models across the globe.
One area that shouldn’t be a cause for concern is safety. The Genesis comes packed with features, including seven airbags, stability control, blind spot monitoring, adaptive cruise control and lane keep assist – although the latter intervenes quite aggressively, which can be unnerving.


GA.MA Italy Professional IQ Hairdryer, Rosé
Rapid speed & energy-saving performance
Out of StockNo longer in production.
The GA.MA Italy Professional IQ Hairdryer has a new, innovative design in an elegant rosé colour. t is compact and light with an ergonomic design for fast drying performance compared to standard hairdryers. The sensor regulates the temperature to prevent and protect both the hair and the hairdryer from overheating.
- Oxy Active Technology: Get shiny, elastic hair and a deep-cleansed scalp thanks to the emission of active oxygen with an anti-bacterial function.
- Venturi Effect: The air outlet has been designed to multiply the airflow dispensed by the motor. The extra airflow is produced via a vacuum effect without using extra power.
- Auto-diagnosis System: The IQ hairdryer is equipped with a new auto-diagnosis system that detects any operating problems.
- Auto Clean: Innovative technology that rotates the turbine in reverse to deep-clean the filter.
- Innovative Microfilter: Prevents even the tiniest of particles from entering the motor to promote hair cleanliness and extend motor durability. It is designed to prevent the hair from getting caught in the exterior coil of the hairdryer.
- 3-speed settings
- 3 temperature settings
- cool shot
- ultra-light, 294 g
- power: 2000 W
- voltage: 220-240V
- long-life motor
- 3 m cable
- 2-year warranty (from the date of purchase)
Scope of delivery:
- 1 IQ Hairdryer
- 1 Diffuser
- 2 Nozzles


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This hilarious comedy gave MacMurray a chance to show his comedic chops as Peter, a radio personality who is told he's just inherited two million dollars by a gold-digging secretary.
Did You Know?
Fred MacMurray's return to Santa Monica's Ocean House for a scene in what was being filmed under the working title of "The Golden Goose" brought back a sharp memory, according to the "In Hollywood" column by Erskine Johnson, distributed by NEA. His last visit there was in 1929 - as a saxophone player in an orchestra hired by Marion Davies for a big movie party. (The San Bernardino Daily Sun, San Bernardino, California, Thursday 22 March 1951, Volume LVII, Number 174, page 6.) See more
After Christie says "Follow that car" to the cab driver, his jaw moves, seemingly in response...but there's no line audible. See more
Written by Quirino Mendoza See more


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Everyone knows spirits can be found anywhere, and Sussex County in New Jersey is no exception. My book, Sussex County Hauntings and Other Strange Phenomena: Part ll is a continuation of a compilation of paranormal stories experienced by local residents and my Lady Ghostbuster Team. The strange phenomena chapters were added to affix those categories that didn’t necessarily fit into the ghostly topic but were interesting and relevant enough to want to write about them.
I’ve always been sensitive to some extent. I’ve been able to see things before they happen, connect with deceased loved ones and sense hauntings in buildings. For as long as I can remember, I’ve been fascinated by the paranormal and because of this was inspired to write a book about my own personal paranormal experiences and those of others around me. Sussex County Hauntings and Other Strange Phenomena is the first book in this series. The third in the series is due out this coming winter and I branched out to a surrounding county with Warren County Hauntings and Other Strange Phenomena due out this summer.
Social media has enabled me to connect with individuals from the county willing enough to allow me to interview them about their haunting tale. In most cases, my Lady Ghostbuster Team has been able to initiate paranormal investigations of the buildings in the stories and uncover our own evidence.
Today, the paranormal is widely accepted whereas twenty or thirty years ago not so much. Back then, anyone who spoke about it was considered crazy. Because this is no longer the case, I wanted to target the audience who have experienced things themselves and those who just love a good scare. My main objective has been to make those who’ve had their own experiences aware they’re not crazy, and they’re not alone. In addition, I would hope that readers of my book will find comfort in this knowledge. I wanted to give those readers looking for a good fright exactly what they came looking for. Lastly, Sussex County is so rich in history, I wanted to be able to share the history behind the locations and buildings and sites I write about so that my reader feels and understands a little more about its background.
When I wrote the first book, I never imagined the magnitude of acceptance and response to my social media posts on the subject. I never anticipated the number of books that would come out of the series and how much further I would branch out. I also plan on writing books for Pike County, Morris County, Passaic County and Orange County. The stories from readers continue to pour in. Who knows what county I will add in next!
I didn’t start out writing non-fiction paranormal. In fact, my first book, Dream a Little Dream, released in 2015, is a supernatural love story that takes place in Sussex County. I was in the midst of writing my second fictional supernatural love story when the idea for the hauntings series took over my mindset. I couldn’t let it go. I put the love story temporarily aside and began writing the hauntings series which has since consumed me. I’m happy to report, though, now that Warren County Hauntings is with the editor, I’ve resumed writing the supernatural love story and am hoping to complete it before the year’s end.
Although I began writing in the seventh grade, I stopped writing to raise my children and didn’t pick up the pen again until 2014. If there’s one thing I wish to leave you with here in the Authors’ Lounge, it’s the knowledge that it’s never too late. If I was able to become a published author at the age of 50, anyone can. It’s important to never give up on your dreams. Anything is possible.
If you are interested in looking through the photo galleries I’ve set up with all pictures documenting the sites and investigations, as well as video footage from the same, along with my feature on Paranormal Caught On Camera and all my other interviews, please feel free to visit www.AuthorEleanorWagner.com. I am on various social media platforms and would love for you to follow along with me. You can find me on Facebook at Eleanor Wagner Author. I’m on Instagram as AuthorEleanorWagner. On LinkedIn, I’m Eleanor Wagner. Visit me on Tumblr as AuthorEleanorWagner and lastly, on MeWe as Eleanor Wagner, Author. Reach out and message me. I love to hear from aspiring writers and help them on their journey in any way I can.

domain: literature


During our test review, we got 145,408 AnTuTu score for Galaxy A50.
Yes, Galaxy A50 does support FM radio.
Yes, Galaxy A50 has an in-display fingerprint sensor.
Yes, Samsung Galaxy A50 does have fast charging support. It comes with 15W fast charger in the box. It takes about 30 minutes only to charge the mobile from 0% to 30%.
Yes, Samsung Galaxy A50 does have a 3.5 mm headphone jack.


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The City Council will hold off on the planned construction of a new $4 million City Hall until it has some assurance that is what residents really want.
The council decided Tuesday to hold a town meeting May 29 to find out how residents feel about the construction plans and the proposed renovation of the current City Hall building.The council, which doesn't have enough money to do both without raising taxes, made an informal decision earlier this month to go forward with City Hall construction, then hold a bond election Aug. 5 to finance renovation of the old building and other projects.
"The council wants to feel they've really communicated well with the citizens before deciding what to do," City Manager David Campbell said.
The May 29 meeting will be held at the National Guard Armory, 12953 S. Minuteman Dr., beginning at 7 p.m.
Residents will be asked, among other things, how much money they want to spend to convert the current City Hall into a cultural center. The cost would range from $1.5 million to more than $3 million, depending on the scope of the work.
The new City Hall is to be constructed on a nine-acre parcel at 12100 South and 300 East.

domain: news


What is a monad? — In functional programming, monads are a way to build computer programs by joining simple components in predictable and robust ways. A monad is a structure that represents computations defined as sequences of steps: a type with a monad structure defines what it means to chain operations together, or nest functions of that type. This allows the programmer to build pipelines that process data in a series of steps (i.e. a series of actions applied to the data), in which each action is decorated with additional processing rules provided by the monad. A monad is defined by a return operator that creates values, and a bind operator used to link the actions in the pipeline.


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Montel joins Dr. Oz for a controversial debate. What if you received a devastating diagnosis that forced you to live in chronic, crippling pain for the rest of your days? Should you have the right to end your own life?
President Obama issued a statement Saturday "unconditionally" condemning the fatal shooting of two New York City police officers. "Two brave men won't be going home to their loved ones tonight ...," he said.

domain: sociology


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Gorgeous hand-knotted Turkish Hereke Silk rug, silk on silk, vegetable dyes, 800,000 to 900,000 knots/m², very clean no need cleaning, it has been hanged on a wall for years, collector's item. please look at the pictures.
• Collector's item.
• Item number: 2854
• exported from Turkey before jan. 2015
• Knot density is 800,000 to 900,000 knots/m²
• Country of Origin: Turkey
• Size: approx 108 cm X 69 cm (excluding fringes)
• Pile: 100% Silk
• Chain: Silk
• Condition: very good condition
• Quality: Very high quality super fine
• Processing: Guaranteed Handmade
With certificate of authenticity
The most famous pure silk carpets in the world are produced in the small town of Hereke, east of Istanbul. Due to the unbelievably thin nature of the silk fiber being used, weavers tie exceptionally high number of knots, thus creating more detailed, magnificent carpets. It is also not uncommon for metallic threads to be woven into the pile which only can be done by expert weavers. The sheer beauty and unbelievably strong raw material of these rugs, enables them to be used both on the floor or as a wall hanging. Hereke rugs are to last generations and is not only a rug but truly a work of art.
- 108 cm
- 69 cm
- Seda sobre seda
- País de origen
- Período de fabricación
- Finales del siglo XX
- En muy buenas condiciones
- Alfombra limpiada profesionalmente

domain: artistic


FORCE-SENSING RESISTOR (FSR)
This FSR (Force Sensing Resistor) will vary its resistance depending on how much pressure is being applied to the sensing area. A 2.54 mm male pinheader is provided making it easy to use on bread boards.
- sensor type: single point
- shape of sensitive area: round
- diameter of sensitive area: 10 mm (+/- 1 mm )
- total lenght: 39 mm
- sensor thickness: 0.2 mm
- material: polyester
- range: 100 g to 1 kg
- terminal: male pinheader step 2.54 mm
- principle: piezoresistive
- service life: > 500.000 times
- operating temperature: -25°C to 90°C
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All registered trademarks and trade names are properties of their respective owners and are used only for the clarification of the compatibility of our products with the products of the different manufacturers.
Due to constant product improvements the actual product appearance might differ from the shown images. Product images are for illustrative purposes only.


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Fresh from the success of Appatlo Okadundevadu, actor Nara Rohith is upbeat about his upcoming releases in 2017. Last year, Nara Rohith had seven releases. Continuing the pace, Rohith will be seen in nearly 4, 5 films this year.
Nara Rohith’s immediate film, Kathalo Rajakumari, has completed its shooting except for a song and a fight sequence, which will be wrapped up in five days. Kathalo Rajakumari is a romantic entertainer and it is being directed by debutant Mahesh and produced by Venkat Srinivas.
- Star hero opens about his rift with brother
- Jaya Janaki Nayaka’s impressive first-week collections
- Taapsee raises the heat in her next
- Poll : Which among these films are you excited to watch this weekend?
- Chiru 151 gets an official title?
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Photo Assistant : Masayo Matsuda
This is the new project I am working on. I have photographed about 50 different people who attend weekly London party called ' Slave To Fashion ' created by Graham Rebak and hosted by Daniel Lismore at Beach Blanket Babylon in Shoreditch
"SLAVE TO FASHION is an evening of Style & Couture celebrating Eccentricity, Crazy Costumes, Youth and Beauty! Its an evening where East London Edge collides with Parisian Couture and is for everyone in the fashion industry, Designers, Stylists, Models, Make up artists, Journalists, Jaded models, Bored Billionaires, Bust Bankers, Acid Queens, Rent boys, Gays, Straights, Bi's, Trannies, Club kids and anyone in the fashion world who thinks they have done something lately and acts cool!!"


Photo Credit: MZE Architects
If things weren’t already hot at the Region of Niagara HQ over last week’s ejection of a reporter and unlawful seizure of his equipment, local MPP’s of all parties have turned the oven to broil by taking their concerns to Municipal Affairs Minister, Bill Mauro.
PHOTO CREDIT: WELLAND TRIBUNE
Hot on the heels of Ed Smith’s win over the NPCA in the courts, Welland NDP MPP Cindy Forster and St. Catharines Liberal MPP Jim Bradley have been bringing forth citizen’s concerns on the floor of the legislature.
You can read the full text of their comments here: http://www.iheartradio.ca/610cktb/news/local/two-local-mpp-s-continue-to-raise-niagara-issues-of-concern-at-queens-park-1.3487822
The Auditor General says the pending audit of the NPCA should be finished by summer. More details are available at: http://www.iheartradio.ca/610cktb/news/local/auditor-general-says-audit-of-npca-should-be-out-by-the-summer-1.3487825


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So thanks to the amazing scripts and samples I was able to iterate over 1.5 million streetview type images with cityscapes and mapillary to produce panoptic segmented images. Absolutely amazing.
My question is… now what? I don’t even know what to search for. Somehow, from these georeferenced images, i need to extract features. such as x y coordinates (using depth estimate and angle, and source location from EXIF data) of the identified segments.
At a minimum, i would at least like to identify “picture contains xy and z classes” in some type of attribute file.
But i can’t even seem to get the search terms right? Can someone point me in the right direction?

domain: geography


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The first season of the Kim Kardashian-produced Lifetime beauty reality competition series Glam Masters wrapped on Wednesday, April 28, and California-based cosmetologist Argenis Pinal took home the top honors — and the chance to collaborate with Kim herself on a new KKW Beauty launch! On Wednesday, it was revealed that the new product — KKW x Argenis Creme Color Sticks — will debut at BeautyCon in NYC on Saturday, April 21, and on the KKW Beauty website on Monday, April 23.
The Creme Color Sticks, which is a just a fancy way of saying eyeshadow pencil, will be available in five highly pigmented shades that can be built and blended with ease. In an Instagram video released by KKW Beauty, Pinal applies the deep burgundy hue to Kardashian’s lids to complete a moody monochrome look that perfectly complemented the beauty mogul’s glossy oxblood lip.
A classic matte black (which will be great for smoking out any look), shimmering gold, bright teal and sparkly bronze complete the color options. In the video, Pinal explains how “buildable” the shades are, while KKW remarks that the formula is “so creamy and smooth.”
While Kim initially launched KKW beauty with mostly complexion products (think creamy concealers, contour kits and highlighter sticks), she has recently expanded into color. She launched the KKW x Mario collection with her longtime makeup artist — and Glam Masters judge — Mario Dedivanovic earlier this month. The four-piece lineup included a 10-pan eyeshadow palette, nude lipstick and two lip glosses sold out almost immediately but will be restocked on Friday, April 20.
Given all the buzz around Glam Masters and Pinal’s impressive 330,000 followers on Instagram, we have a feeling the Creme Color Stick launch is going to be just as major!
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Institutionalising Armed Intervention Will Have Grave Consequences
The summit of the Organisation for Security and Cooperation in Europe (OSCE) in November 1999 was the latest one to adopt a charter legitimising armed intervention by member states. It gives participating states, led by the US imperialists, more possibilities to intervene not just in conflicts between states, but within states as well. In his September 20 1999 address to the UN General Assembly, the UN Secretary General Kofi Annan spoke of forceful and armed "humanitarian" intervention with Security Council mandate as a "developing international norm". The US President Clinton had gone a step further and asserted the right of "groups of nations" to bypass even the UN when they wished to militarily intervene in "areas of interest", anywhere in the world, ostensibly to prevent wholesale killings and displacement of peoples and "terrorism".
Earlier this year, the North Atlantic Treaty Organisation (NATO) summit in Washington which was held at the height of the NATO bombing of Yugoslavia had drawn up the "New Strategic Concept". This sought to give NATO the right to intervene not only in Europe and the "North Atlantic" region, but anywhere in the world where it felt its interests were affected. Armed intervention under any pretext is thus being legitimised and even institutionalised as an international norm by the US and other imperialists, and this is bound to have grave consequences for all the peoples of the world.
The OSCE summit was held against the backdrop of Russian military action in Chechnya. After the collapse of the Soviet Union, the peoples in many of the former Soviet Republics have been fighting for sovereignty. Currently, this is happening in Chechnya and Dagistan, where popular forces refuse to recognise the Russian Federation and have declared independence. The Russian Federation has termed those who are asserting their national rights as "terrorists", and has resorted to bombings and massacres in Chechnya and Dagistan. In this context, the new charter adopted by the OSCE meeting envisions a new role for it in "easing tensions before they explode into war", including the possibility of intervening militarily. The document envisions rapid-response teams that could be deployed quickly to in such cases. Far from easing tensions, this kind of action is bound to further complicate the situation and widen the scope of armed conflict in the region.
In South East Asia, massacres by the Indonesian forces in August this year paved the way for armed intervention. A multinational interventionist force is already in place in East Timor, allegedly to defend "human rights" and the sovereignty of East Timor. It was US imperialism, in the first place, which was the biggest military and economic supporter of the Indonesian regime which carried out wholesale massacres of the people in East Timor and the rest of Indonesia. These massacres were justified in the Cold War period as "defence of the free world". US imperialism sought to make Indonesia its fortress against the spread of communism in South East Asia. US imperialism wanted control of East Timor also since the sea route to its north formed an easy and strategically vital connection for US nuclear submarines between the US military bases of Guam in the Pacific and Diego Garcia in the Indian Ocean. The present armed intervention, part of the imperialist plan to retain and increase control in Asia, is being carried out under the slogan of "defence of human rights".
The OSCE conference also sought to adopt new limits on the size of conventional armaments in Europe. It is very clear that this too was done at the behest of the US, which wants to check other powers which might pose a challenge to its supremacy. On its own part, the US has unveiled plans to build a $20 billion "national missile defense system" This has made its European allies join Russia and China in questioning why the United States needs to do so. The utter hypocrisy of the US imperialists is seen from the fact that it is even actively considering withdrawing from the 1972 Anti-Ballistic Missile Treaty if necessary to field the system. Under that treaty, Russia and the United States are restricted to deploying one limited ballistic missile system to defend a small area of their countries. The administration now is negotiating with Russia to alter the treaty to allow for the construction of a missile system to protect the entire country from a limited attack by a state with an "emerging missile threat". This has increased the possibility of a renewed arms race, which in turn will pose a greater threat to peace all over.
Freedom loving people all over the world, as well as states which desire peace, must firmly oppose and condemn the dastardly plans of the imperialists to legitimise and institutionalise armed intervention, as also the US plans to renew the arms race. The utter hypocrisy and total lack of principles shown by the imperialists led by the US in international relations is not only a threat to the peace and sovereignty of the peoples, it is indeed a threat to their very existence.