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datasheet, pdf, data sheet, datasheet, data sheet, pdf, National Semiconductor, Data Selectors/Multiplexers. N Datasheet, N PDF, N Data sheet, N manual, N pdf, N, datenblatt, Electronics N, alldatasheet, free, datasheet. Datasheet search engine for Electronic Components and Semiconductors. N data sheet, alldatasheet, free, databook. N parts, chips, ic.
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High and Low refer to the voltages not the logical values, ie. Optoelectronic devices for recording or transmission of images. Similar considerations apply for field effect phototransisitors and photothyristors, since these also come into the category of junction photodetectors with internal amplification.
The newly produced electrons then arrive in the N-region and the holes in the P-region. The proportional radiance q is a relative value.
Similarly, the absolute differential sensitivity sj is obtained from equation 9. With LED's giving a green light output, the spectral distribution can be assessed superficially by subjective colour comparison.
The relative spectral sensitivity s A m re i is determined by the equation 9.
Datasheet pdf – Data Selectors/Multiplexers – National Semiconductor
By excitation processes, e. If the momentum values are calculated, both of a moving charge carrier and of a light quantum in the wavelength range which is of interest, it is found, that the momentum of the light quantum is negligibly small in comparison with that of the charge carrier, so that in practice, only the changes of momentum of the charge carriers need to be taken into account, even though light quanta are involved in the process.
Such a radiation quantum, also called a photon, corresponds to a certain amount of energy, dependent on the frequency of the radiation, which has a minimum value for any given frequency. I am pleased to say I finally understand the concepts.
By means of special design measures, it is possible to build semiconductor lasers from GaAs of GaAlAs with a small aluminium concentration. Tne particle darasheet is hardly any smaller than the wavelength. With further increase in the applied voltage, an arc discharge is datahseet obtained with very heavy currents, while the voltage on the electrodes collapses to a fairly low value. Cd ; Gold-doped germanium-silicon alloy Ge-Si: Sorry for all the stupid questions!!!
The spectral radiation distribution S A X of the standard light A has been stated in the wavelength range from nm to nm in a table in DatasehetPart 7. I have connected the two inputs, A and B. The following calculations now only relate to the photometric datsheet equivalent K X of the photopic sensitivity V X of the eye.
For this, Figure 9. With the single atom, the electrons adopt exactly defined, discrete energy states. The retina of the human eye consists of about 1 rod-shaped visual cells and 7.
Flash discharge tubes in photography In amateur flash units, xenon flash lamps or tubes are used as a flash radiation source. The candela, abbreviated cd, applies as the light unit for photopic vision.
Therefore it is advantageous to work with the radiant emittance M ei. So-called "dead zones" on the device surface, which are caused by surface recombination of diffusion atoms, prevent a higher quantum yield and higher sensitivities.
In future developments in this field, the so-called II-VI compounds should also have a certain part to play. 74151h invisible UV radiation excites the coating of flurescent material, which is wash-coated onto the interior wall of the glass tube, to fluorescent radiation.
Multisim and Ultiboard
The photometric inverse square law is obtained: On impact with a dynode auxiliary anodea photo- electron produces several secondary electrons. From the previous formula, the proportional radiation qi up to the wavelength Xi and the proportional radiation q2 up 741151n the wavelength X2 can be determined. Read my gating paper for all the combinations. Irradiance measurements of Planck radiation are carried out exactly with wide- band radiant power meters.
N – S – IC Chips – Kynix Semiconductor
If the input values X Z and X N are related to the absolute photopic sensitivity K X of 74115n eye, then the modified form of equation 5. The cavity emerges through an aperture, while its character as black radiation does not change. Potentiometer Questions Started by norbss Yesterday at Is produced by the deformation of certain crystals.
Provided there is no risk of confusion with other spectral units, the designation "spectral density of a radiation-distribution unit" can be shortened to "spectral unit". Thus, for the attenuation in a layer thickness dx, one can insert: The distance r should always be greater than the photometric limiting distance see Section 3.
It will show what the function of the component and what each pin does.
With the exception of the xenon tube, discharge tubes produce a discrete line dataheet. The photodetectors with internal photoeffect include photoelectromagnetic dattasheet, photoconductors and barrier-layer photodetectors.
Diffuse reflection occurs at rough reflecting surfaces. The receiver converts the incident radiant energy into a DC signal which is processed further and evaluated in DC amplifiers. Corresponding to the above conversion, the irradiance can be determined more simply by measuring the illuminance with an accurately calibrated Luxmeter. Wafer geometries will be described in Section The calculation of the radiation function SX is stated in Section 4.
I'm exhausted, and a newb…
The difference between the photon energy and the escape energy is taken up by the electron as kinetic energy. In these it is immaterial, which radiation unit is taken into account.
In this case, the base current I]j is the variable. Selective radiators are mostly luminescence emitters.
The limiting frequency lies between 10 kHz and kHz, depending on the type. The spectral sensitivity of a phototransistor also depends on the DC current gain B see Section 9. From this graph, the radiation function SX can also be seen from the datzsheet of the desired wavelength X and the maximum wavelength X max of the black body.


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March 12th, 2017
Today I met a strange woman, she was walking down the road, at the hottest hours of the day (40 degrees to be precise) and asked me for lift. I gave her lift and in return, she thanked me so much that she blessed me saying "I wish you have a great day today". I […]
By: Priyanka Yadav
In Blogging


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In this episode, Steve moderates the YouTube Group Chat panel of Matt and Chris. This episode aired live July 15, 2019. This raw audio only version of what can be found on our YouTube channel does not include any edits.
To celebrate our 200th YouTube subscriber, the Sixth Scale Scavengers are giving away a 3A Bumblebee figure.


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Hi, Alan Stratton, from As Wood Turns (www.AsWood Turns.com) I've been doing these videos now for six years. It seems like I should know everything […] Read More
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AmazonBasics Zippered Storage Bag with Window
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|Oracle FAQ
|Your Portal to the Oracle Knowledge Grid
Home -> Community -> Mailing Lists -> Oracle-L -> RE: how to find INDEX CORRUPTION ???
analyze table MSG_HISTORY validate structure cascade;
If there is a problem with the table or any indexes, you should receive an error message. Rebuild that object.
Validating the structure of the table locks it up so don't do this while anyone is using the table especially if it's a large table with a lot of indexes.
Jerry Whittle
NCI Information Systems Inc.
> -----Original Message-----
> From: Prem Khanna J [SMTP:jprem_at_kssnet.co.jp]
> Guys,
> I faced this error in an instsance of 8.1.6/win2k.
> Errors in file E:\ORACLE\ADMIN\ORA816\UDUMP\ORA00696.TRC:
> ORA-00600: Internal Error :[13013],[5001],[22211],[134225362],[15],[134225362],
> [1],[]
> but this morning i dropped an existing index ( on 3 columns together ).
> and created a bitmap index on FROMMEMNO ( a column in MSG_HISTORY table ).
> when i delete a row from MSG_HISTORY table now , i get this ORA 600 error.
> if i drop the index , DELETE works fine .
> if i create a index , it results in ORA 600.
> metalink says that it might be because of ondex corruption.
> how do i find index corruption ?
> does it mean that even a new index on this particular column will be a corrupted
> index ?
> Help me guys.
> Jp.
-- Please see the official ORACLE-L FAQ: http://www.orafaq.net -- Author: Whittle Jerome Contr NCI INET: Jerome.Whittle_at_scott.af.mil Fat City Network Services -- 858-538-5051 http://www.fatcity.com San Diego, California -- Mailing list and web hosting services --------------------------------------------------------------------- To REMOVE yourself from this mailing list, send an E-Mail message to: ListGuru_at_fatcity.com (note EXACT spelling of 'ListGuru') and in the message BODY, include a line containing: UNSUB ORACLE-L (or the name of mailing list you want to be removed from). You may also send the HELP command for other information (like subscribing).Received on Wed Apr 02 2003 - 08:28:54 CST
Original text of this message


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Writer: Jamie Gorenberg
Director: Glen Winter
(Spoilers ahead)
If you enjoyed the previous episode of Titans, then this week's Aqualad is something you've been waiting for. The show continues to lean more into the light heartedness, while still incorporating it's darker origins. The more I watch this show and the more news that drops about The CW's Arrowverse crossover this year, the more I'm hoping to see Brenton Thwaites announced as part being part of it.
Like last week, this episode puts most (read all) of the focus on the original incarnation of the team. We see Dick and Dawn in a relationship, Hank all kinds of mellow, Donna acting like a Mean Girl, and introduced to Aqualad himself, Garth. Dick is also the Robin most would expect from the Titans team; a happy non-brooding leader. There's also an odd Deathstroke montage that doesn't seem to do the character much justice.
The first scene of the OG Titans team in Aqualad shows this young team, 5 years in the past, taking on some street level thugs—which makes sense; a young team shouldn't be taking on Batman level villains this early in their career (despite some having some training from Justice League members). A majority of the episode focuses on Garth and Donna's relationship, or lack thereof. This accomplishes two things—what happened to Aqualad and why Donna was so hostile to Dick about reforming the Titans last week. It's unclear if their battle with Dr. Light is the Titans first big baddie; but even if it isn't, it seems to go a bit too easy for the team.
While Titans has seemed like it's been improving dramatically in Season 2, Aqualad takes a tiny step backwards. I really loved the backstory to the OG Titans, but something was off. I'm not sure if it was the writing or the performances, but it seemed more 90210 than usual. I'm also overly confused over the Hank, Dawn, and Dick triangle—I thought Season 1 established Hank and Dawn being a couple before joining the Titans; yet by the time they get to Titan Tower, Dick and Dawn are a couple? Once again, some 90210 bullshit that I don't need in my superhero shows (which doesn't mean I don't like drama in them).
My other big complaint is that at the end, and I'll write this as best as I can without a major spoiler, it's seems very uncharacteristic for Deathstroke to give up when there are loose ends no longer in view. Why wouldn't he walk around the corner to make sure no one was still there (knowing that he missed at least 1 target)? There was a whole montage establishing how good this guy was!
I think it bears mentioning that in an episode titled Aqualad, I don't think we got enough time with him to really get to know him. Again, with out any major spoilers, I'm not sure how this made me care for him? It made me understand, and maybe even care more for, Donna more; but I feel like it needed more love for Garth.
Going forward, I'd like to see more episodes like this: focusing on the original team and what drove them disband the team. I just need tighter writing and a little less teen drama (especially when the characters are all in their early 20s). That being said, Titans runs the risk of having too much story to tell for Titans 2.0 if those characters aren't intermingled within the story. I don't think there's much to worry about quite yet, but there's a lot to get to only 9 episodes left.
Aqualad was mixed bag. It's what I wanted—an entire episode focusing on the original Titans team—but lacked some quality either in the writing or performances for this episode to really sit with me in a meaningful way. I think there could have been a more effective way to tell this story with a Donna-centric episode, set in the present with those sweet Berlanti style flashbacks. The best parts of this episode were the ones focusing on Donna and Garth as it were, however it was nice to see what the entire OG team was up to 5 years ago.
Score: 8/10
Images courtesy of DC Entertainment
Enjoyed this review? Check out more from the author below! Interested in writing your own reviews for your favorite shows? Contact us today!
Kevin M. Gallagher, Jr
Kev is the host of the podcast, Everything is Awesome and is the co-host of The Zombcast. He is the former host of the podcasts Happy Hour with Steel Tip, Creepcast, Happy Hour, 30 Minute Outsider, The Muff Squad, That's Entertainment, 215th Entertainment Presents: Sounds of Philly, Academic Nerds, and OuaT: The Unofficial Once Upon a Time Podcast.
Kev also writes for Dark Knight News and is working on a science fiction series.
Most of all, Kev is a dad to two wonderful children.
Latest posts by Kevin M. Gallagher, Jr (see all)
- Capstone Games Announces RIDE THE RAILS - January 2, 2020
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Three-phase asynchronous motors are widely used, but by the long-running, various fault occurs, determine the cause of the fault in a timely manner and dealt with accordingly, is to prevent the failure to expand, to ensure the normal operation of the equipment is an important work.
Energized motor can not rotate, but no abnormal sound, no smell and smoke.
1. ① Power of the cause of the malfunction has not rotary joints passed (at least two phases did not pass); the ② blows a fuse (fuse at least two phases); ③ overcurrent relays tune too small; ④ control equipment wiring error.
2. Troubleshooting ① Check the power circuit switches, fuses, junction boxes at whether there is a breakpoint repair; (2) Check the fuse type, fuse reason, a new fuse; ③ adjust the relay setting in conjunction with the motor; the ④ corrections wiring.
Energized motor does not turn, then the fuse
1. The cause of the fault (1) one phase power, or given an opposite connection trunk circle; the ② stator winding phase short circuit; ③ stator winding ground; ④ the stator windings wiring error; the ⑤ fuse cross section is too small; ⑤ power cord short circuit or ground.
2. Troubleshooting ① check whether there is a phase not Gehao knife, power supply circuit has a phase wire; to eliminate reverse fault; (2) detect short-circuit point, be repaired; ③ eliminate ground; ④ mistakenly identified then be corrected; ⑤ replacement The fuse; ③ eliminate the grounding point.


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Model: WSE3472
Weight ca. 0,90g
Pendant. Enamel. Silver 0,925. Dimensions 8x10 mm. Lenght 16,3 mm.
Out of stock!
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text: Weird day...2 up, 30min tempo, 2 down. wasn't sure how the run would go, but legs felt good and springy. Felt kind of winded during the tempo, so figured I was off pace and just tried to hang on. Turned out I was doing all right though. A little under on pace, so that's comforting. Rolling after


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Fun Faces Stress Ball
Kids love to get their hands on this unique fidget toys. These unique balls feature funny faces and a mane of hair made of yarn. You can easily manipulate the shape of the ball due it's clay-like texture. For ages 5+. Each sold separately.
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The Best Place To Buy And Sell Exhibition Trucks And Trailers, Stands, Display Panels, Lecterns, Av Equipment
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DescriptionSecond Hand Selfie pod stand
Never been used - however some scuffs form storage
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Holds an Ipad Pro
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My name is Eric, and I'm currently a postdoc at the Museum of Vertebrate Zoology at UC Berkeley. After college, I decided to abandon my ambition of becoming a dentist and moved to the Galapagos Islands. I spent several months working at hotels and teaching English, but then I got an opportunity (which I was remarkably unqualified for) to work on a deserted island studying a colony of Nazca boobies. Since that experience, I haven't looked back. I love what I do, and I also love spending time with my family, friends, and fishing.
Follow the links below if you wanna learn more about me and my research.
Media attention
Media coverage for Plasticity reveals hidden resistance to extinction from climate change in the global hotspot of salamander diversity (Riddell et al. 2018, Science Advances).


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Life doesn't wait for you to show up for it. No matter how happy or unhappy you are, how patient or impatient, how conscious or unconscious, it will continue with or without you. But that doesn't leave you powerless. 'Cause you can either undergo it all or act according to…Leave a Comment
Category: Self-awareness
Sometimes when you dance, your heart skips a beat or two… You get lost in the music, carried away by your partner, and your movement together becomes like ice to water and water to gas. Fluid, transforming, and…2 Comments
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Frequent self-inquiry and reflection can form a great starting point to make progress in any area of your life. But are you asking yourself the right questions? Regardless of what it is we seek to improve, we always start by identifying a current situation as less than optimal and then…Leave a Comment


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|Product Detail
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|20.4 Gms Approx
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Member Since:
Jan 10, 2011
Goal Type:
Local Elite
Running Accomplishments:
Some day I will not be able to do this...today is not that day!
Started Running (6/1/10) @ 50 Yrs Old
5 Miles:
Short-Term Running Goals:
Upcoming Races:
Long-Term Running Goals:
Married, two kids Kirby 24 (Baylor University, Married not a a Runner), Callie 27 (TCU University, Married and Runner).
My main sport is Team Roping, I've been doing that all my life.
I started running in the spring of 2010.
I Just Run
Favorite Blogs:
Couldn't resist the nice weather this morning. I was all packed to go to the gym but then felt how nice it was outside and opted to stay home and run.
I have a little concern this morning with my left foot (not my right that I've had surgery on), this morning when I was simply putting on my shoe if felt as if something stung me on my foot right at the same spot where my right foot began hurting. As I rub on that spot there seems to be a little tinder spot there....Oh I hope I'm not getting the same hammer foot condition on my left foot now! :-(
Just an easy low effort run this morning.
That's my kind of run...with a low HR.


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Did this ever happen to you? You catch your pet looking irresistibly cute so you grab your camera and snap a picture. When you view it, suddenly instead of looking cute they look like they're possessed by some demon. Their eyes are glowing white or some other unnatural color.
Don't panic and call an exorcist, just launch Photoshop Elements to easily fix white eyes. Follow this tutorial to restore your pet's eyes and their cuteness.
Open an image of an animal with white-eye. In the Layers palette drag the background layer onto the Create A New Layer icon. That way we will fix white eyes on a separate layer.
The photo below is of our dog Lydia. Lydia is the sweetest golden retriever ever and you can see she loves her creature comforts. But with that white eye glowing it's hard to imagine how lovable she is.


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Current Satellite News
January 18th, 2016
Satellite Number Five For India's Navigation System To Storm Space On January 20
ISRO said navigation payload will transmit navigation service signals to the users, and will be operating in L5-band and S-band.
Orion Spacecraft Support @ NASA's Stennis Space Center Is All Fired Up
Earlier this fall, Stennis engineers completed a series of tests on a subscale diffuser system.
The Dream Chaser Cargo System From Sierra Nevada Corp. Will Be Heading To The ISS
SNC is the owner and prime operator of the reusable Dream Chaser spacecraft, which has been in development for over 10 years.
Airbus Group Ventures West To Silicon Valley
Airbus Group Establishes VC Fund + Innovation Center in Silicon Valley
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An Additive Attitude @ Orbital ATK Proves To Be Successful
The combustor, produced through an additive manufacturing process known as powder bed fusion (PBF), was subjected to a variety of high-temperature hypersonic flight conditions over the course of 20 days.
ESA's ExoMars 2018 Mission Brings Thales Alenia Space-UK Into The Project
Thales Alenia Space-UK will be responsible for the Reaction Control Subsystem (RCS) in the Carrier Module, performing the design and engineering activities.
FSM Telecommunications Extends Their Partnership With ABS For The Federated States Of Micronesia
FSMTC has contracted additional capacity to provide connectivity to its neighboring islands in the Micronesia states.
Sencore Introduces Their Next Generation Of Portable RF Analysis
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Moving On Up... LeoSat Names van der Breggen As New CCC
Van der Breggen has more than 20 years of experience in the telecom and satellite industries.


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Prevod reči: površan
Smer prevoda: srpski > engleski
površan [ pridev ]
artificial [ pridev ]
ETYM Latin artificialis, from artificium: cf. French artificiel. Related to Artifice.
Artificially formal; SYN. contrived, stilted.
Contrived by art rather than nature; SYN. unreal.
Not arising from natural growth or characterized by vital processes.
cursory [ pridev ]
ETYM Latin cursorius, from cursor. Related to Cursor.
Characterized by haste; hastily or superficially performed; slight; superficial; careless.
Quick; superficial.
flighty [ pridev ]
Absent-mindedly irresponsible; SYN. head-in-the-clouds, scatterbrained.
Irresponsibly frivolous; SYN. flyaway.
frivolous [ pridev ]
ETYM Latin frivolus; prob. akin to friare to rub, crumble, Eng. friable: cf. French frivole.
Not serious in content or attitude or behavior.
nodding [ pridev ]
Bending downward or forward; pendulous, drooping
Slight, superficial
outward [ pridev ]
Relating to physical reality rather than with thoughts or the mind
partness [ imenica ]
perfunctory [ pridev ]
ETYM Latin perfunctorius, from perfunctus dispatched, p. p. of perfungi to discharge, dispatch; per (see Per) + fungi to perform.
Done merely to get rid of a duty; performed mechanically and as a thing of rote; done in a careless and superficial manner.
Hence: Mechanical; indifferent; listless; careless.
Related to Function.
Mechanical, routine, cursory.
shallow [ pridev ]
Lacking depth of intellect or knowledge; concerned only with what is obvious
Lacking physical depth; having little spatial extension; downward ); or inward from an outer surface ); or backward ); or outward from a center.
Not deep or strong; not affecting one deeply
sketchy [ pridev ]
Giving only major points; lacking completeness; SYN. unelaborated.
superficial [ pridev ]
ETYM Latin superficialis: cf. French superficiel. Related to Superficies.
Being or affecting or concerned with a surface; not deep or penetrating emotionally or intellectually.
Of little substance or significance; SYN. trivial.
Relating to a surface.
touch and go [ pridev ]
Slightly dangerous.
trivial [ pridev ]
ETYM Latin trivialis, properly, that is in, or belongs to, the crossroads or public streets.
Concerned with trivialities.


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Become a CPA > Public accounting in New Zealand > How to build an accounting practice from the ground up
Tony Kaye
There's a strong element of pride in Saurav Wadhwa's voice as he recounts how he went about setting up his independent public practice in Auckland five years ago.
From a standing start in 2013, with no clients and working out of a front room in his then rented family home, Wadhwa's business, IBBZ Accounting, has evolved into an award-winning, multi-disciplined public practice that delivers tax and accounting solutions to hundreds of clients around New Zealand and overseas.
His journey towards setting up his own public practice started well before he officially opened his doors for business, and that's one of the most valuable lessons Wadhwa has for anyone wanting to go it alone: Before one can start properly building up a practice, it's essential to have strong foundations.
That includes having the ambition, passion and dedication to start up and run a business in the first place.
"I think the key part would be that you need to put your heart and mind into it, like really believe in it," Wadhwa says. "Once you're 100 per cent focused on this part, then things are much easier."
He adds that it's also important to plan ahead, and to have everything in place for your practice before opening for business. First impressions count. Beyond the registration of a business name, that includes organising the basics such as creating a business logo and cards, and building a professional website. Don't open for business until the foundations are ready.
New to public practice or interested in starting a practice in NZ? Gain valuable insights, network with like-minded peers, and ask questions at our no-obligation complimentary sessions.
Provide your details
Wadhwa says a very useful early step was to utilise the training and development resources available through CPA Australia.
He attended a two-day conference on running an accounting practice, which also afforded him the opportunity to meet representatives from other practices and learn from them.
"It's good to have role models, to witness the industry trends, and in the back of my mind I knew that this was where I wanted to end up in five to 10 years."
Wadhwa says that it's very easy to spend money when starting up a practice, but the trick is to only spend on essentials until there is enough business income to justify the cost.
"Don't blow up on your budget and keep your overheads low. That's what I followed."
That included saving on business rent by working from his home and avoiding buying equipment until such time as not having it would be detrimental to business growth.
"For example, we needed an EFTPOS machine terminal for the office, but that costs about A$100 to A$250 a month. But when I had to turn a few people away because we didn't have a terminal, I then saw the need.
"Now multiple payments come through EFTPOS, so we don't have to chase clients for payments."
Wadhwa says he has had a dedicated budget for advertising right from the beginning, and that has really paid off in terms of bringing in new business leads.
"Advertising brings in money and business … you have to pay to get leads coming in."
While it may be a financial stretch at the beginning, Wadhwa says his philosophy is to buy assets rather than borrow to have them.
Having worked from home at the start, his first major step was to buy a building when he had enough money saved up.
"Rent can kill any new business, but when you have the ownership of a building you can give yourself a loan from the business profits. So, even today, I believe in having ownership.
"I know some accountants might not agree with me, but all ownership – motor vehicles, printers, the phone system, anything – it's all owned outright."
Wadhwa now has five accountants working for him, providing a range of specialised tax and accounting services for businesses, individuals, trusts and not-for-profit organisations.
He says having a vision for your practice is an essential ingredient for growth, and central to this is setting the core values that the practice and all its staff will adhere to when servicing clients.
"As far as starting up your own business, it's a great way of really putting your own stamp on how you want to run the business," he notes.
"Our values include open communication and honesty with our clients. We also believe in helping our clients, and sometimes we do work for a lower rate or sometimes for free."
Rather than trying to compete with other firms on price, Wadhwa says innovation is more important because this enables the practice to open up new revenue streams where there is little or no competition.
He gives the example of IBBZ creating an online portal that enables anyone searching for tax advisory information in New Zealand to access a library of articles. Doing so has created a strong sales funnel for his business, which he estimates generates an extra NZ$3000 a week in revenue.
"About 2000 people come there every week from all over the world, the majority from New Zealand. Some then contact us for tax advisory information if they have any questions, and that's how we get business. This is something where we're not trying to compete with anyone. Create, don't compete."
If you are new to public practice or interested in starting a practice in NZ, these no-obligation complimentary information sessions will provide you with valuable insights as well as the opportunity to ask questions and network with like-minded peers.
By submitting this form, you acknowledge that you have read the Privacy Policy and Statement and consent to your personal information being collected, held, used and disclosed in the way and for the purposes stated there.
Copyright 1997-2020 CPA Australia Ltd


text:
Cancer is one of the leading causes of unnatural death globally, and is considered a major public health problem (Siegel et al., 2016; Wang et al., 2016). Cancer therapy is based primarily on the association of surgical resection of tumors with radiotherapy, immunotherapy and/or chemotherapy (Kakde et al., 2011; Baskar et al., 2012). However, many cancers still present modest responses to clinical protocols, limiting the indication and efficacy of treatment of both primary tumors and metastases (Costa-Lotufo et al., 2010). The efficacy of cancer drugs is often limited by their insolubility and instability, the low rate at which the tissue absorbs them, and drug resistance of the tumor (Akindele et al., 2015). In addition, many antineoplastic agents have high rates of adverse reactions and toxicity (Prakrash et al., 2013).
All these drawbacks presently associated with available chemotherapeutic agents provide the impetus for the search of newer, more efficacious, and better tolerated drugs. In order to achieve more effective and safer results, pharmacological studies with substances extracted from plants as well as synthetic derivatives from these natural compounds have been intensified (Chorawala et al., 2012; Newman and Cragg, 2016). Medicinal plants have been a valuable source of successful therapeutic agents, the production of chemically diversified secondary metabolites are optimized to exert biological functions (Atanasov et al., 2015). Natural products are a major source of effective drugs for cancer treatment and often inspire the development of new potential agents (Newman and Cragg, 2012).
The Asteraceae family has many species with ethnopharmacological applications, including anti-inflammatory, antiseptic, and anti-tumor properties. Phytochemical studies of Asteraceae species report the presence of triterpenes, sesquiterpene lactones, lignans, flavonoids, and caffeoylquinic acid derivatives (Costa et al., 2015).
In South America, the species Solidago chilensis Meyen, Asteraceae, is known as arnica-brasileira, arnica-do-campo, erva-lanceta, and espiga-de-ouro (Lorenzi and Matos, 2002). The aerial parts of the plant are commonly used for their diuretic potential, analgesic abilities, anti-inflammatory, anti-rheumatic and healing effects, as well as for the treatment of burns (Lorenzi and Matos, 2002; Assini et al., 2013).
Chemical studies have shown that the ethanolic extract of the aerial parts of S. chilensis contains flavonoids (quercitrin, quercetin and rutin), diterpenes (solidagenone), along with, α-epinasterylglycopyranoside, caffeic acids, chlorogenic, clerodanic, β-farnesene, α-amirin, and other derivatives of solidagolactol (Torres et al., 1987; Schmeda-Hirshmann, 1988; Torres et al., 1989). Solidagenone is the major chemical compound of the dichloromethane extract of plant inflorescences, and quality parameters was proposed by high performance liquid chromatography (Valverde-Soares et al., 2009).
Preclinical studies have shown that the aqueous extract of the inflorescence had wound-healing (Facury-Neto et al., 2004) and gastroprotective effects (Rodríguez et al., 2005; Bucciarelli et al., 2010). The hydroalcoholic extract of the aerial parts have been shown to have anti-inflammatory effects (Tamura et al., 2009; Silva et al., 2010), and was recently found to have hypolipidemic (Roman Junior et al., 2015) and hypoglycemic activities (Schneider et al., 2015). However, there are no reports evaluating the antiproliferative effects of the plant.
The present study aimed to produce extracts of different polarities from S. chilensis, isolate their chemical constituents, and evaluate their antitumor effects in vitro.
Materials and methods
Solvents and chemicals
All solvents and reagents used were of analytical grade, and distilled and deionized water was used. The other solvents used were methanol, ethanol, acetonitrile, ethyl acetate, dichloromethane, chloroform and acetic acid (Vetec®, Rio de Janeiro, Brazil). Quercitrin and solidagenone was obtained from Sigma-Aldrich®, St. Louis, MO, USA. Chromatographic analysis was performed using HPLC with a Varian® Pro-Star chromatograph with an automatic injector (20 µl handle), ternary pump gradient, UV/Vis detector, and Kromasil® ODS column (5 mm) C-18 reverse phase (250 × 4.5 mm). HRMS were run in a QSTAR XL Q-TOF (Applied Biosystems) using electrospray ionization (ESI) with an Agilent 1100 HPLC. The NMR (1H and 13C) experiments were performed on a Bruker Avance 400 (400 and 100 MHz, respectively) spectrometer with the substances diluted in CDCl3 and CD3OD. The 1H and 13C NMR chemical shifts were expressed in ppm (δ) using TMS (0.00 ppm) as an internal reference and the coupling constants (J) in Hz.
Plant material
The aerial parts of Solidago chilensis Meyen, Asteraceae, were collected in Chapecó (SC), Brazil (26°59′31.03″ S and 52°41′17.89″ O), in February of 2016. The plant material was identified by Osmar dos Santos Ribas, curator of the Municipal Botanical Museum of Curitiba (PR), where a voucher specimen was deposited (MBM #356792).
Production of extracts
The aerial parts were reduced to small fragments and subjected to drying (25 °C), protected from direct light and humidity. The dehydrated plant species were ground in a knife mill (Ciemlab®, CE430) and sieved to select particles of 425 µm (35 Tyler/Mesh).
Aliquots of dry milled S. chilensis aerial parts (10 g) were extracted succecively with dichloromethane (200 ml) and ethanol (70%, 200 ml) by maceration during 5 days. After filtration, the solvents were eliminated under reduced pressure using a rotary evaporator and the resulting dichloromethane (DES) and hydroalcoholic (HES) extracts from S. chilensis were lyophilized, weighed, and stored in a freezer at − 20 °C.
HPLC analysis of extracts from Solidago chilensis
Chromatographic analysis by HPLC of the HES was carried out using Kromasil® ODS column (5 µm), RP-18 reverse phase (250 × 4.5 mm) at a temperature of 24 ± 2 °C. Two solvent systems was used: H2O:AcOH (40:1 v/v; solvent A) and CH3CN (solvent B) at a flow rate of 1 ml/min. The gradient used was 86% A for 15 min, 65% A for 30 min, and 100% B for 2 min. Detection was performed at 360 nm, and the results were compared with an authentic external standard, followed by UV/Vis spectrometry (Apáti et al., 2006).
HPLC analysis of the DES was performed using Kromasil® ODS column (5 µm), RP-18 reverse phase (250 × 4.5 mm) at a temperature of 25 ± 2 °C. As mobile phase was used an isocratic solvent system consisting of H2O (30%; solvent A) and MeOH (70%; solvent B) for 15 min, with a flow rate of 1 ml/min. Detection was performed at 220 nm, and the results were compared withan authentic external standard (solidagenone), followed by UV/Vis spectrometry (Valverde-Soares et al., 2009).
Chemical isolation
An aliquot of HES (20 g) was diluted with water (200 ml) followed by mechanical agitation (20 min). Subsequently, the resulting solution was transferred to a separating funnel and submitted to liquid/liquid partition successively with hexane and EtOAc (ten times per solvent, 500 ml each). After solvent evaporation, an aliquot (2 g) of the EtOAc fraction was dissolved in CHCl3 (minimal amount) and submitted to liquid column chromatography using silica gel (0.063–0.200 mm; Merck®, Darmstadt, Germany) as the stationary phase and eluents CHCl3 and EtOH (80:20 v/v) in increasing polarity up to 80% EtOH (v/v) as mobile phase. The eight subfractions obtained were similarly pooled by using thin layer chromatography (TLC) with EtOAc:MeOH:H2O (100:13.5:10 v/v) as the mobile phase and analyzed using a UV/Vis spectrometer at 366 nm and revealed with H2SO4 (10% in methanol) followed by heating at 110 °C (10 min). Subfraction 6 (0.06 g) was observed as a spot by the TLC analysis, yielding the compound 1.
A sample of DES (3 g) was dissolved in a sufficient quantity of hexane and subjected to liquid column chromatography using silica gel (Merck®, Darmstadt, Germany) as the stationary phase and a solution of hexane and EtOAc (90:10 v/v) in increasing polarity to 90% (v/v) of EtOAc for elution. Ten subfractions were obtained, which were pooled by means of TLC using hexane:EtOAc (80:20 v/v) as the mobile phase with further analysis in a UV/Vis spectrometer at 366 nm, and revealed with H2SO4 (10% in methanol) followed by heating at 110 °C (10 min). The subfraction 9 (0.04 g) showed only spot yielding the compound 2.
Antiproliferative assay
The antiproliferative effects of HES, DES, and compounds 1 and 2 were investigated using the protocol described by Monks et al. (1991). The assays were performed using a panel with five human cancer cell lines [glioblastoma (U-251), breast (MCF-7), kidney (786-0), non-small cell lung (NCI-H460) and prostate (PC-3) cells] kindly provided by Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, MA, USA. Stock and experimental cultures were grown in 5 ml of complete medium [RPMI-1640 supplemented with 5% fetal bovine serum and 1% penicillin:streptomycin mixture (1000 U/ml:1000 mg/ml)]. Stock solutions each sample (5 mg) were prepared in DMSO (50 µl) followed by successive dilutions in complete medium affording final concentrations of 0.25, 2.5, 25, and 250 µg/ml. Doxorubicin was used as a positive control at final concentrations of 0.025, 0.25, 2.5, and 25 µg/ml. Cells in 96-well plates (100 µl cells/well, cell densities: 3–7 × 104 cells/ml) were incubated with each of the four concentrations of the sample solution or doxorubicin (100 µl/well) in triplicate, for 48 h at 37 °C and 5% CO2. Before (T0 plates) and after (T1 plates) sample addition, the cells were fixed with 50% trichloroacetic acid (50 µl/well) and stained with sulforhodamine B (50 µl/well) to quantitate cell proliferation using the reading at 540 nm. The TGI (sample concentration that resulted in total cellular growth inhibition) values were determined through non-linear regression applied to a sigmoidal curve using Origin 8.0 software (OriginLab Corporation).
Calculation of molecular properties
The molecular properties were calculated on basis of simple molecular descriptors used by "Lipinski's rule of five" (Lipinski, 2004), to estimate the oral bioavailable. The five properties consist of molecular weight (u), hydrogen donor; acceptors, Log P, and total polar surface area (PSA; Â2) which were calculated using the online chemoinformatics tool molinspiration (2018).
HPLC analysis
The HES chromatogram (360 nm) showed great similarity with the quercitrin standard (RT = 9.82 min), indicating that this compound may be the major constituent of the extract. The DES chromatogram (220 nm) revealed that solidagenone (RT = 4.23 min) was the constituent present in greater concentration (Fig. 1).
Chemical compounds of S. chilensis
By chromatographic fractionation, compounds 1 and 2 were isolated from HES and DES, respectively. These compounds were identified by comparison of their experimental spectra (1H NMR, 13C NMR and ESI-MS) with those previously described: quercitrin (1) (Tiberti et al., 2007;Correia et al., 2008) and solidagenone (2) (Rodríguez et al., 2005).
Quercetin-3-O-rhamnoside (quercitrin; 1): This compound was obtained as a yellow crystalline powder, with a melting point of 183–185 °C (water): C21H20O11; ESI-MS: 449.0 [M+H]+; 1H NMR (400 MHz, CD3OD, δ, ppm): 0.94 (3H, d; J = 6.1 Hz; 6″-H), 3.35 (1H, dd; J = 9.4: 9.4 Hz; 4″-H), 3.43 (1H, dq; J = 9.4: 6.1 Hz; 5″-H), 4.23 (1H, dd; J = 3.4: 1.5 Hz; 2″-H), 4.76 (1H, dd; J = 9.4: 3.4 Hz; 3″-H), 5.35 (1H, d; J = 1.5 Hz; 1″-H), 6.20 (1H, d; J = 2.1 Hz, 6-H), 6.37 (1H, d; J = 2.1 Hz, 8-H), 6.91 (1H, d; J = 8.3 Hz; 5′-H), 7.31 (1H, dd; J = 8.3: 2.1 Hz; 6′-H), 7.34 (1H, d, J = 2.1 Hz; 2′-H); 13C NMR (100 MHz, CD3OD, δ, ppm): 17.8 (C-6″-CH3), 72.0 (C-2″), 72.2 (C-3″), 72.2 (C-4″), 73.4 (C-5″), 94.9 (C-8), 100.0 (C-6), 103.7 (C-1″), 106.4 (C-10), 116.5 (C-5′), 117.1 (C-2′), 123.0 (C-6′), 123.1 (C-1′), 136.4 (C-3), 146.5 (C-3′), 150.0 (C-2), 158.7 (C-9), 159.4 (C-4′), 163.4 (C-5), 166.0 (C-7), 179.8 (C-4).
(4R,4aS)-4-[2-(furan-3-yl)ethyl]-4-hydroxy-3,4a,8,8-tetramethyl-1,4,4a,5,6,7,8,8a-octahydronaphthalen-1-one (solidagenone; 2): This compound was obtained as a colorless crystal, with a melting point of 132–134 °C (water): C20H28O3; HRMS-ESI: [M+H]+ for C20H29O3: 317.2111; found: 317.2106 m/z ESI-MS: 317.2111 [M+H]+; 1H NMR (400 MHz, CDCl3, δ, ppm): 1.00 (3H, s, 20-H), 1.15 (3H, s, 19-H), 1.19 (3H, s, 18-H), 1.36–1.16 (2H, m; 3-H), 1.59–1.53 (2H, m; 2-H), 1.78–1.58 (2H, m; 1-H), 2.02 (3H, d; J = 1.5 Hz, 17-H), 2.05–1.90 (2H, m; 11-H), 2.67–2.65 (2H, m; 12-H), 2.71 (1H, s; 5-H), 5.71 (1H, q; J = 1.5 Hz; 7-H), 6.30 (1H, dd; J = 1.8; 0.9 Hz; 14-H), 7.26 (1H, dd; J = 1.5; 0.9 Hz; 16-H), 7.37 (1H, dd; J = 1.8; 1.5 Hz; 15-H); 13C NMR (100 MHz, CDCl3, δ, ppm): 17.9 (C-2), 18.4 (C-20), 20.1 (C-17), 21.4 (C-12), 21.7 (C-18), 31.7 (C-1), 32.3 (C-4), 33.4 (C-11), 33.8 (C-19), 42.7 (C-3), 46.5 (C-10), 55.8 (C-5), 76.7 (C-9), 110.8 (C-14), 125.1 (C-13), 129.3 (C-7), 138.7 (C-16), 143.8 (C-15), 155.7 (C-8), 200.2 (C-6).
Antiproliferative effects of the extracts and the isolated compounds of Solidago chilensis
Both DES and HES inhibited cell proliferation with slightly different profile (Fig. 2). DES was more effective than HES in total growth inhibition, been U-251 cells the most sensitive (TGI = 33.24 µg/ml) (Table 1).
|Cell lines
Human tumor cell lines: glioblastoma (U-251), breast (MCF-7), 786-O (kidney), non-small cells (NCI-H460), prostate (PC-3), TGI, total growth inhibition (µg/ml) after 48 h-exposition.
aEffective concentration higher than the highest tested concentration (250 µg/ml).
Besides, quercitrin (1), isolated from HES, was inactive (TGI > 250 µg/ml) while solidagenone (2), isolated from DES, showed a promisor antiproliferative activity inhibiting totally cell proliferation of U-251, MCF-7, 786-0, NCI-H460, and PC-3 cell lines at concentrations of 5.38 to 12.53 µg/ml (Fig. 3, Table 1).
Molecular properties of solidagenone
The molecular properties study was performed on basis of "Lipinski's rule of five" using the Molinspiration server. This same bioinformatics tool was used to obtain the bioactivity score. The results it is evident that solidagenone show quality binding energy values and also follow the Lipinski's Rule of Five (number of violations = 0). The bioactivity scores evidenced the predisposition of solidagenone to interact with nuclear receptors and enzymatic inhibitors (0.54 and 0.31, respectively) (Table 2).
|Property molecular
|Bioactivity score
|Molecular mass (u)
|GPCR ligand
|- 0.03
|Partition coefficient (log P)
|Ion channel modulator
|Polar surface area (Â2)
|Kinase inhibitor
|- 0.76
|Number of hydrogen acceptors
|Nuclear receptor ligand
|Donor hydrogen atoms
|Protease inhibitor
|- 0.15
|Enzime inhibitor
Natural products obtained from animals, microorganisms and plants present great potential for the development of novel therapeutic agents (Hassig et al., 2014). These products are considered important sources of anticancer substances. It is estimated that 60% of all chemotherapeutic drugs are obtained, either directly or indirectly, from natural products (Newman and Cragg, 2016).
In this study, we prepared extracts from S. chilensis aerial parts with high and low polarity (HES and DES, respectively) identifying quercitrin (1) and solidagenone (2) from HES and DES, respectively. These results corroborated previous studies of S. chilensis roots, inflorescences and aerial parts (Torres et al., 1987; Schmeda-Hirshmann, 1988; Torres et al., 1989; Valverde-Soares et al., 2009; Roman Junior et al., 2015).
The flavonoids and diterpenes present in several medicinal species arouse considerable interest and may have chemopreventive and chemotherapeutic effects. Their mechanisms of action include deactivation of carcinogens, anti-proliferative effects, cellular division inhibition, induction of cell death and differentiation, angiogenesis inhibition, antioxidant effects, reversal of multidrug resistance, or a combination of these mechanisms (Huang et al., 2012; Raffa et al., 2017).
According to Fouche et al. (2008), in the in vitro antiproliferative screening proposed by the National Cancer Institute (NCI) guidelines, extracts that showed TGI values equal or below to 50 µg/ml are promisor candidates. Using this criterium, in our study the HES was inactive while DES showed promisor antiproliferative effect against glioma cell line. This probably occurs due to increased lipophilic chemical constituents present in lower polarity extracts that results in higher affinity of these molecules to cellular membranes (Lee and Houghton, 2005).
There are a few descriptions of the antiproliferative effects of Solidago genus. The S. microglossa DC.leaves infusions was able induct to cytostatic effects, at 14 mg/ml, in the mitotic index method with Allium cepa (Bagatini et al., 2009). More, S. virgaurea L. rhizomes extract showed antitumor effect related to the presence of triterpenic saponins (Plohmann et al., 1997), while the diterpenes 6β-angeloyloxykolavenic acid and 6β-tigloyloxyolavenic acid, isolated from S. canadensis L. inflorescences, displayed cytotoxic activity against breast, cervix, leukemia, colon, and hepatoma tumor cell lines (Wu et al., 2008).
Unlike the results obtained by Cincin et al. (2014), who described the effects of 50 µM quercitrin against the NSCLC line (non-small cell lung cancer), we found that quercitrin did not inhibited any tumor cell line. In contrast, solidagenone isolated from the DES revealed very promissor TGI values specially against MCF-7 (breast), 786-0 (kidney) and PC-3 (prostate) cell lines (TGI < 6.25 µg/ml), that can be considered as potent antiproliferative activity according to Fouche et al. (2008), besides moderate cytostatic effect against U-251 and NCI-H460 cell lines (TGI = 8.21 and 12.53 µg/ml, respectively).
The "Rule of Five" proposed by Lipinski (2004) describes five theoretical parameters that molecules must possess in order to satisfy the pharmacokinetic aspects necessary to maximize the chance of success to become prototypes of new drugs. The molecular mass must be ≤500 atomic mass units (u), the partition coefficient (log P) must be ≤5, the polar surface area (PSA) should be ≤140 Â2, number of hydrogen acceptors ≤ 10, and the molecule must also have a maximum of five donor hydrogen atoms. In this context, solidagenone has been found to satisfy all five theoretical parameters required to be a promisor drug candidate (314.94 u, log P = 4.22, 5.44 Â2, 3 acceptors of hydrogen, one atom donor of hydrogen).
Moreover, using chemo-informatics tools (http://www.molinspiration.com) to evaluate probable affinity of a molecule for a given biological receptor (site of action), it was possible to observe the predisposition of solidagenone to interact with nuclear receptors and enzyme inhibitors (bioactivity score: 0.54 and 0.31, respectively). This interaction may in part help us understand the potent antitumoral activity of this compound and to propose further mechanistical studies.
Finnaly, the intraperitoneal LD50 of solidagenone has been described as higher than 600 mg/kg suggesting a "not harmful" molecule (Rodríguez et al., 2002).
The interest in natural products is increasing, especially those derived from plants, due to the increasingly high number of cancer cases worldwide (Rates, 2001; Jemal et al., 2009). In order to look for new sources of therapeutic anticancer agents, many plant extracts and active principles have been studied in in vitro and in vivo cancer models, and the correlation of both studies became one of the key steps for the success of this type of research (Newman and Cragg, 2012; Marchetti et al., 2012). In this study, was observed strong effect antiproliferative in vitro to the solidagenone and the results make this molecule promising for antitumor activity assays in vivo.
The dichloromethane extract from the aerial parts of S. chilensis (DES) has a promisor antiproliferative effects in vitro. The major constituent of DES, the diterpene solidagenone showed a potent antiproliferative effect against human breast, kidney and prostate tumor cell lines. Solidagenone meets the theoretical physico-chemical criteria for bioavailability of drugs and the observed biological effects were probably related to the interaction of the molecule with nuclear receptors and as an enzymatic inhibitor.


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Link to this page: https://secure.socialistparty.org.uk/issue/844/20110
From The Socialist newspaper, 18 February 2015
Workers' pay down £2,500... Bosses' pay up £700,000
Fight for decent pay, jobs and benefits
James Kerr
Feeling the pinch? Cutting back on spending? Wondering how you'll make it to the end of the month? You're not alone. Workers everywhere are struggling with stagnating wages and rising prices.
A recent TUC report confirmed what we're experiencing on a daily basis when it outlined that workers are £2,500 a year worse off since the start of the Con-Dem government. That's an 8.4% fall in five years!
Government attacks on working class people are absolutely unrelenting. Cameron recently pledged to cut housing benefit for 18 to 21 year olds if the Tories win the next election.
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Contrast that with what's happening in Britain's boardrooms, where fat cats have seen their pay soar by 26% - £700,000 - in a year.
Big winner
Who is singled out as a big winner in the report? None other than Stuart Gulliver, chief executive of HSBC, the bank implicated in a massive tax avoidance scandal. It makes Cameron's 2009 "we're all in this together" refrain seem like a really sick joke.
It's clear that it's one rule for them and another for us. The enormous pay gap graphically highlights the staggering and growing inequality under capitalism. Working people pay the price for the contradictions of a broken system.
What's the alternative? All of the establishment parties are keen to bang the drum for the super-rich, squabbling for the crown of 'most pro-business'. It is clear that, whoever wins the general election, we'll need to fight for decent pay, jobs and benefits you can live on.
The trade unions need to channel the anger that exists into a massive campaign for decent pay, including making the demand for a £10 an hour minimum wage a reality. We also need to build the Trade Unionist and Socialist Coalition (see page 5) as an important step towards a mass working class party.
Ultimately we have to fight for socialist policies to ensure that the wealth is taken out of the hands of the super-rich 1% and used to benefit the lives of the mass of people.
Why not click here to join the Socialist Party, or click here to donate to the Socialist Party.
In The Socialist 18 February 2015:
Socialist Party news and analysis
Workers' pay down £2,500... Bosses' pay up £700,000
How the super-rich get away with it
Socialist Party congress
Preparing the forces to fight capitalist austerity
International socialist news and analysis
Greece: If the Troika does not back down?
"Dogs of war" unleashed against water tax movement
Trade Unionist and Socialist Coalition
"Vote for hope and an alternative"
"I want to tell the truth about the crime of austerity"
Socialist Party election appeal
Socialist Party workplace news
Lewisham: striking against 'academisation'
London bus strike suspended - prepare for more action
Protest wins reinstatement of Crossrail worker
Fighting for a £10 minimum wage
Socialist Party reports and campaigns
Fighting racism with Solidarity Street
Labour council to deal 'savage blow' to Coventry
May Day greetings with the Socialist
Socialist Party comments and reviews
Decades of disastrous and bloody interventions
Shallow look at racist far right
Individual registration excludes voters...
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