Nearly one-third of law firms have not undertaken a formal information, security and privacy assessment.
95% of corporate counsel believe that cybersecurity breaches are becoming more frequent in their industries.
27% of corporate counsel and 47% of law firms say their companies do not regularly test their cybersecurity programs.
New York, N.Y.—December 16, 2015—ALM Legal Intelligence's inaugural cybersecurity study of law firms and corporate counsel has found legal professionals recognize that cyber-attacks pose an unprecedented danger to their clients and businesses, but struggle to implement adequate solutions to mitigate the threat. In two reports released today during ALM's cyberSecure conference in New York City (http://www.almcybersecure.com), ALM Legal Intelligence discusses the implications of its research findings, outlines information about the changing cybersecurity landscape, and offers best practices and valuable checklists that law firms and corporate counsel can follow to protect against breaches. The reports also include interviews with law firms and corporate counsel discussing challenges facing their respective firms, and the solutions and processes they have adopted to solve them.
In October 2015, ALM Legal Intelligence surveyed law firms in the Am Law 200 and NLJ 350, as well as corporate counsel at companies in a variety of sectors, including technology, industrials and financial services. The majority (80%) of the corporate counsel represent firms with gross revenue of more than $2 billion. The reports, Cybersecurity and Law Firms: Ignorance is Risk and Cybersecurity and Corporate Counsel: Ignorance is Risk, are available online at http://pages.email.alm.com/cybersecure-pressrelease/.
Nearly one-third of law firms have not carried out a formal information, security and privacy assessment.
Approximately one-third of law firms do not hold cyber liability insurance policies.
More than two-thirds of law firms have either already established a cybersecurity practice or have plans to form one.
95% of corporate counsel respondents agree that cyber-attacks are increasing in frequency.
Only 6% of respondents say their companies' cybersecurity teams include board members, and only 3% say outside counsel are represented. This suggests that many corporate cybersecurity teams are limited in scope.
While 68% of corporate counsel respondents indicated their companies have purchased cyber liability insurance, only 49% stated their firms require third parties to carry such insurance.
27% say their firms do not conduct regular cybersecurity tests.


Firstly I must thank the Workers Party of Belgium on behalf of the Communist Party of Malta, for inviting the Party to participate in this seminar.
As a political organization, The Communist Party of Malta, feels that one of the major problems with youth in Malta, is total alienation from political activity. This alienation is systematic and carefully controlled, by the mass media which the big corporations have under their tight control. Again when a youth becomes politically aware and class conscious, through no consequences of their own, they are imbued with negative propaganda the enemies of socialism had seen fit to brainwash them through the education system, and the mass media. With propagandistic speculations, about the mistakes committed under the socialist system, that existed in the USSR and Eastern Europe prior to 1987. Resulting from this, youths in Malta today, are more ready to fight for rights of animals, then for rights of the working classes.
Of course environment and animal rights are important issues as well, but the fight for change and for socialism is equally, and even more important, as only under a Socialist system where maximum profits are not the aims, but the well being of each individual, and the improvement of the quality of life, environment is safeguarded and animal rights are ensured.
Another form of alienation that youths fall victim for, is drug abuse and addiction, along with alcoholism afflict youth in Malta giving a rise to juvenile crime and other social ills that are common in today's society. Brought about, by the Neo Liberal phase, of this post cold war epoch. This can be combated by more awareness of the harmful effects and the promotion of sports and athletics among youths killing two birds with one stone, as this will lessen obesity amongst youths, which brings about coronary diseases in later life.
Employment is one of the major problems that school leavers face. Unemployment is the first stumbling block. In the November 2008 official statistics for those youths unemployed was in the range of 5.8% for males and 4.1% for females. Those gainfully employed find that they also face various problems varying from getting a mismatched job to what they had studied and obtained and obtained a university degree for. Other problems are those of exploitation which is rampant in Malta. Most of the new jobs created, are given under a definite contract whereby a person is employed without the benefits of a regular job, vocational leave and sick leave are not part of the employee entitlement, extra hours are not paid as overtime, and most of the times not paid at all. Jobs are terminated at the whim of the employer, when a worker is not required any longer, he is unceremoniously told not to report to work, always within the limits of what the law specifies. The Main culprit is the government. Another plague is part time employment whereby the worker is not entitled to anything except the pittance the worker receives as pay. A worker is considered to be a part time worker if his working hour week does not exceed 20hrs Mobility of workers within the EU was usurped by the big corporations instead of an unemployed worker seeking a job with the same conditions in another EU country, is being interpreted by the European Court of Justice as the right of mobility of inferior conditions from one country to another.
These problems will grow with the present economic crises that the capitalist world is undergoing. This crises brought about by the neo liberals is deep rooted and will only be defeated the attainment of Socialism where individuals and not markets are free.
Towards this aim is our goal and we should strive harder to make today's youths politically conscious so they will be instrumental in bringing socialism taking example from the experiment that is going in the Southern American Continent. Where Socialism, is triumphing over the U.S. imperialism which in previous decades held sway over the destinies of the countries forming this continent. We should win over support especially from the youths to continue on the same path till Socialism is universal in each an every country of the globe.


text:
Inspiring Business Women In APAC: Betsy Westcott
Betsy Westcott is the Director of Retail Banking at Xinja Bank, an independent Australian digital bank that enables customers to make intuitive, optimised, rapid & better money decisions without the angst.
Looking at your career to date, have you encountered any unnecessary obstacles because of your gender?
Certainly not in the early stages of my career as the gender split amongst entry level roles were basically even - I think the statistic was around 44% female in entry level roles. At that point in my career, I felt very confident that my performance would be rewarded according to merit.
It's a well-documented fact that as role seniority increases the percentage of women who hold those roles decreases. This has certainly been my observation too. In saying that, I have had an exciting career and don't feel that my gender has ever stopped me from progressing or taking on more responsibility.
What I have personally experienced in a handful of environments is that I needed to be extra prepared and thorough with my work, because on face value I was assumed to be less competent than other colleagues, and that was frustrating at times. Sometimes you see that through interactions as well. When you say something but it's not heard until someone else says it, or when you put forth an idea and must have had every scenario mitigated for it to be deemed well thought out. I don't think this is purely due to gender, I think it's a combination of gender, age and my own challenges in overcoming 'imposter syndrome'.
I'm actually grateful for the experience because it's made me more resilient, fostered great habits such as being thorough and diligent, and increased my own confidence in my abilities.
Having worked in different industries/sectors, what have your experience been like in terms of diversity?
My observation of both hospitality and finance is that the level of diversity is increasing. The challenge to have more women represented in senior position remains. The fintech industry is definitely male-dominated, however, companies like Xinja are bucking the trend by deliberately focusing on building diverse teams. It's literally rule number 9 of the Xinja's 10 golden rules.
I think as organisations and society as a whole we have much work to do to enable parents, particularly mothers, to continue to participate in the workforce after starting a family, if they want to. For my cohort of friends and I, the conversation about starting a family circulates around the question of can we afford to, what will it do to my career, how and when could I return to work, how do you juggle it all and so on. The greatest underutilised resource in our economy is mothers in their childbearing years. According to the Grattan Institute, if Australia had the same level of working mothers as Canada, there would be a $20 million boost to our economy. I don't have all the answers but I know that enabling both parents to partake in child rearing activities through better policies, improving the affordability of childcare and making our workplaces more accommodating to family responsibilities would help.
Is there a point in time when you noticed an emphasis on diversity?
I think it happened at once in both my private and professional life, when conversations around gender, relationships, and workplaces arose. That was around 6 years ago, when I really started to notice programmes aiming to sponsor women to get to those leadership positions.
How do you balance between your work and personal life?
I set myself clear priorities each day and stick to them. I focus on output over hours worked. In a lot of workplaces people confuse working long hours with being productive. Presenteeism does not equal productivity. I've learnt to work efficiently during the day, so that I can leave work at a reasonable hour and make sure I get to the gym, have a home cooked meal, see my friends, and check in with my husband, before coming back on the next day and doing it again. To be innovative, creative and happy, you need to be well rested.
Having clear priorities helps me to know what to say 'yes' or 'no' to. This allows me to create the time and space needed to get the important things done. You'll never get everything done so it's important to prioritise getting what matters done.
What do you think might be the problem with some companies' approaches and why is D&I important?
My belief is that organisations should be reflective of the society that they serve. When half of the population is female, why wouldn't your organisation reflect that? Diversity (in all of its forms - gender, age, race, religion, experience) and inclusion is not only the right thing to do but it leads to better business outcomes. Boston Consulting group did a study that found that diverse companies actually produce 19% more revenue due to better risk management and innovation. What this tells us is that diversity is not something to simply be strived for, it's an integral part of a successful revenue generating business.
Are there any initiatives at Xinja that aims to promote diversity and inclusion?
We place a heavy focus on diversity and inclusion here at Xinja. Currently two of the six Xinja board members (including the Chair) are women. Three of the seven Xinja Executive are women. And of the 39 full time employees, 21 are women. This is a great start, the challenge is in maintaining the balance as we scale. We are looking to extend that to other forms of diversity like cultural and sexual orientation.
In terms of practices, we remove names or any other identifiers from CVs that might cause unconscious bias. As an organisation, we also try to set ourselves up to work cross-functionally, to have people from different disciplines and backgrounds giving varying perspectives on how to achieve particular business outcomes. That way, we can work towards creating a robust and energetic environment, making sure that we're validating our assumptions and also getting to the right answers.
Where do you think we are in the journey?
We've come a long way but there is still a lot more to do, especially around unconscious bias in terms of gender and cultural backgrounds. Currently there are societal changes taking place, where we see gender roles at home changing. Having the option to choose is great for everyone, as women are no longer shamed for choosing to work and men are no longer patronised for choosing to take a more active role in parenting.
And what do you think would be next?
Over and above promoting diversity and inclusion, I think organisations need to change their expectations of their staff always being on and available 24/7. This expectation leaves them no time to play or rest, and it's really hurting us as the human race. Personally, I appreciate that getting the balance between work and life takes conscious effort. It's a daily practice for me. As a leader I encourage my team to work smart and efficiently, I don't support presenteeism or working long hours when it's not productive. We work to live and not vice versa.
As the business continues to evolve, do you foresee diversity and inclusion staying as a part of the DNA of the business?
Yes, we are very committed to it. Obviously, there would be more governance and framework as we scale-up, but we are very deliberate in maintaining the practices we started in the beginning, and have been clear about the kind of workplace we want to create – flat hierarchy, lots of diversity in terms of skills, gender, background, and thought. We want a diverse team that's united by a shared 'why'. As in "why" we're all here. It's something that has always united us at Xinja in building a bank that's here to help customers get ahead and do more with their money by understanding it better.
Brett Rose

redpajama_set_name: RedPajamaCommonCrawl


text:
Стара Бања је насеље у Србији у општини Медвеђа у Јабланичком округу. Према попису из 2011. било је 33 становника (према попису из 2002. било је 91 становник).

Демографија
У насељу Стара Бања живи 80 пунолетних становника, а просечна старост становништва износи 43,9 година (42,1 код мушкараца и 46,6 код жена). У насељу има 32 домаћинства, а просечан број чланова по домаћинству је 2,84.

Становништво у овом насељу веома је нехомогено (према попису из 2002. године).

Референце

Спољашње везе

 Мапе, аеродроми и временска ситуација локација (-{Fallingrain}-)
 Гугл сателитска мапа (-{Maplandia}-)

Општина Медвеђа
Насељена места у Јабланичком управном округу
Википројект географија/Насеља у Србији

redpajama_set_name: RedPajamaWikipedia


Here are a few real photographs from the Hubble Telescope. Besides the beauty aspects, the vastness of the universe is mind numbing and sobering. I just put them here as a reminder of creation's immensity and the minuscule dot we represent among so vast a universe. Enjoy, these are all Real photos from NASA's online displays.
In the centre of this image, taken with the NASA/ESA Hubble Space Telescope, is the galaxy cluster SDSS J1038+4849 — and it seems to be smiling. You can make out its two orange eyes and white button nose. In the case of this "happy face", the two eyes are very bright galaxies and the misleading smile lines are actually arcs caused by an effect known as strong gravitational lensing. Galaxy clusters are the most massive structures in the Universe and exert such a powerful gravitational pull that they warp the spacetime around them and act as cosmic lenses which can magnify, distort and bend the light behind them. This phenomenon, crucial to many of Hubble's discoveries, can be explained by Einstein's theory of general relativity. In this special case of gravitational lensing, a ring — known as an Einstein Ring — is produced from this bending of light, a consequence of the exact and symmetrical alignment of the source, lens and observer and resulting in the ring-like structure we see here. Hubble has provided astronomers with the tools to probe these massive galaxies and model their lensing effects, allowing us to peer further into the early Universe than ever before. This object was studied by Hubble's Wide Field and Planetary Camera 2 (WFPC2) and Wide Field Camera 3 (WFC3) as part of a survey of strong lenses. A version of this image was entered into the Hubble's Hidden Treasures image processing competition by contestant Judy Schmidt.


When using the library function PLIB_USART_Transmitter9BitsSend (USART_MODULE_ID index, int8_t data, bool Bit9th) were 9-bit mode to send data, if the parameter data of bit7 bit is 1, even Bit9th value false, but observed on the TX pin timing display bit9 bit is 1, and the receiver indeed receives the address bit is 1. The parameter data corresponding real parameter data type is defined as unsigned char or signed char, the problem still exists; No single step through the program logic problems.
The issue is resolved after the above modifications. Because the chip is not clear assembly instructions, did not see the original library functions compiled assembly code.


Limited edition woven vintage Afghani Hazara wool kilim.
This textile is in a combination of rust, grey, black, brown, yellow and pink. Adjustable/removable leather strap, Leather handle and bottom.
Snap closure & brass hardware.
Strap length - up to 43" x 1.25"
"Afghanistan is one of the three main areas of kilim production along with Anatolia in Turkey and Iran. The majority of peoples were nomads (living in yurts) or settled farmers. Their lives have inspired a wealth of motifs and patterns. Each ethnic group has particular symbols, patterns and colour combinations. They are woven by people who collect the raw materials then spin, dye and weave the wool. Each village or family has distinctive motifs. Using portable looms built from tree branches and wool from their flocks they produce a stunning range of rugs. Traditionally the weaving is the women's domain."
"Girls learn on tiny toy looms. Once competent they join their mothers and grandmothers and kilims are included in their dowries. Kilims are often woven from memory, with children absorbing the patterns. The patterns have nicknames such as mousetail, arrow and comb. The symbolism in the patterns has been passed down through generations. Kilims are often a form of visual communication expressing the hopes for good fortune, fertility and protection. The troubled history of Afghanistan has brought together a great diversity of ethnic groups from the Baluchi to the Uzbek and thus a varied range of designs."
Limited edition alpaca wool weave paired with leather top and strap & burnt orange wool lining.
Fits your camera, wallet, cellphone, makeup, odds and ends. Perfect little bag for a minimal outing or inside your lager bag. H: 7" W: 9" D: 1.75"
*note: each bag varies slightly on pattern.


On 4 April 2019, the results for the third quarter was presented.
Presentations and webcasts can be downloaded and viewed here.
Company information such as articles of association, remuneration policies, general guidelines for incentive schemes, financial calendars and IR policies can be read and downloaded here.
Bang & Olufsen is a global luxury lifestyle brand founded in 1925 in Struer, Denmark by Peter Bang and Svend Olufsen whose devotion and vision remains the foundation for the company.
The rich heritage built around the relentless determination to create products that push the boundaries of audio technology continues to place the company on the forefront of audio innovation. Today, every Bang & Olufsen product is still characterised by the unique combination of beautiful sound, timeless design, and unrivalled craftsmanship.
On 4 April 2019, Bang & Olufsen will present the results for the third quarter of 2018/19.


the measurement of attitudes and preferences likely to affect BUYER BEHAVIOUR. Motivational research is concerned with exploring the underlying reasons why consumers buy products, which can range from functional requirements to psychological needs like status and esteem. There are various techniques which may be employed to explore consumers' psychological needs, including in-depth interviews, psychoanalytical tests and group discussions. The results of motivational research can be used to generate ideas for new products, reposition existing products, and design ADVERTISING COPY to appeal specifically to the motives identified. See MARKETING RESEARCH.
The latter will result in the beginning of the new and most recent phase of L2 motivational research (Dornyei & Ushioda, 2011).
Self-determination theory has come to the forefront of motivational research over the past thirty years and runs contrary to some of the mainstream motivational theories that exist today.
His model was based on a comprehensive integration of social goals and social motivational research.
He refers to Packard in "Why the Edsel Laid an Egg: Motivational Research vs.
Early motivational research was conducted primarily in the workplace, and centered on ways to motivate industrial workers to work harder, faster and better.
In its earlier days, Wendy Gordon comments, the findings of motivational research, as designated by Dichter and his followers, aroused suspicions because of the 'poorly constructed and inadequately controlled' samples from which they were derived.
In The Presidential Papers of 1963, Mailer writes of society: "Our emotions are turned like television dials by men in motivational research.
Motivational research seeks to discover and comprehend what consumers do not fully understand about themselves.
Alarmed by new techniques that convinced people to run out and buy things, he detailed advertising's fascination with the school of consumer analysis known as motivational research.
Walker Smith, managing partner of Yankelovich, said: "Audience measurement, the power of the impression, and motivational research represent the central elements of an integrated service for understanding online commercial opportunities.
TNS combines its specialist sector knowledge with expertise in the areas of new product development, motivational research, brand and advertising research and stakeholder management to bring our clients up-to-the minute, internationally consistent information.


text:
Новая консервативная партия:

Новая консервативная партия (Латвия)
Новая консервативная партия (Япония)
Новая консервативная партия (Великобритания)

Консервативные партии


Our core market health indicators bounced around a bit this month. Perceptions of risk rose a little, measures of the economy fell, and the other categories strengthened. Overall it was an improvement, but our measures of market quality didn't rise enough to change our core portfolio allocations. We're still 80% long in the long/cash portfolios and 90% long 10% short in the hedged portfolio. Below is a chart of the current condition of each health category.
The consolidation warning that was issued for Amazon (AMZN) on 10/10/13 has been cleared. This signal was a huge miss and illustrates two points that I often mention. The first is that trading against the trend will lower your batting average. The second is that the execution of a trade is much different than trade signals. A person who tried to short AMZN on this signal would have got a warning the very next day as the stock moved higher. A week later the stock gapped to new highs. This should have told anyone short the stock that the signal was a miss and consequently it was time to take the loss and wait for another opportunity.
Small cap stocks (IWM) have cleared their warning as of the close today (11/19/13). I'm still seeing weakness in some of our other indicators and the underlying tweets, so I'd wait for a break to new highs before giving the all clear signal.
Below are charts with the bearish intensity scores for the most bearish stocks on Twitter for the week and month ended 11/19/13.


El Paso, Texas – Sun Metro will be required to detour routes 9, 10, 11, 14, 15, 34, 35, 36, 50, and Mesa Brio due to El Paso's Easter Eggstravaganza and Egg Hunt on Saturday, April 15, 2017.
The detours are expected to be in effect from 5:00 a.m. to 7:00 p.m. near San Jacinto Plaza. Sun Metro staff will monitor the affected area to assist passengers and the driver will make courtesy stops along the detoured routes as required.
Buses traveling outbound from the Union Plaza Transit Terminal will turn left onto El Paso, right onto San Antonio, left onto Campbell, right onto Mills continuing to the regular route.
Buses traveling outbound from Fourth Street will turn left onto El Paso, left onto San Antonio, right onto Santa Fe continuing to the regular route.
Buses traveling inbound from Oregon will turn right onto Missouri, left onto Santa Fe continuing to the regular route.
Buses traveling outbound from Fourth will turn left onto Oregon, right onto Paisano, left onto Campbell, left onto Missouri, right onto Oregon, right onto Wyoming, left onto Stanton continuing to the regular route.
Buses traveling inbound from Oregon will turn right onto Missouri, left onto Santa Fe, right into the Downtown Transfer Center.


I was born and raised in St Louis, MO. I graduated from the University of Missouri - Columbia with a degree in Hotel & Restaurant Management, GO Tigers! I started my Raymond career working at the Hampton Inn Columbia, while attending MIZZOU. From there I went on to work at the Hampton Inn Kansas City/Liberty and helped open the Hampton Inn & Suites Oklahoma City/Bricktown and TownePlace Suites Kansas City/Liberty. In my sophomore year of college I met my wife Sara and we got married in June of 2009 and we have 2 children.


text:
PP Vol.9 No.6 , June 2018
Uromedic® Pumpkin Seed Derived Δ7-Sterols, Extract and Oil Inhibit 5α-Reductases and Bind to Androgen Receptor in Vitro
Stefan Heim1, Stephanie Seibt2, Heike Stier2, Margret I Moré2*
1 Omega Pharma Manufacturing GmbH & Co. KG, Benzstr. 25, Herrenberg, Germany.
2 Analyze & Realize GmbH, Department of Consulting and Strategic Innovation, Waldseeweg 6, Berlin, Germany.
Abstract: Dihydrotestosterone (DHT) is implicated in the development of benign prostate hyperplasia (BPH). We investigated if Uromedic? pumpkin (variety of Cucurbita pepo L. convar. citrullinina GREB. var. styriaca GREB) seed soft extract (active ingredients of GRANUFINK? Prosta forte 500 mg), seed oil and isolated Δ7-sterols could inhibit the conversion of [1,2,6,7-3H(N)]-testosterone to DHT by 5α-reductases. Also, we tested competition with [3H]-DHT for binding to the androgen receptor (AR). Pumpkin seed oil and pumpkin seed soft extract were identified as moderately active inhibitors of 5α-R1 and 5α-R2, with almost similar inhibitory capacities (IC50 < 5 mg/ml for 5α-R1 and about IC50 = 6 mg/ml for 5α-R2). The isolated Δ7-sterols were more active inhibitors (IC50 = 0.3 mg/ml for 5α-R1, IC50 = 1.0 mg/ml for 5α-R2). All three test compounds bound to the AR dose-dependently, with strong binding by Δ7-sterols (IC50 = 0.2 mg/ml) and weaker binding by pumpkin seed oil (IC50 = 0.4 mg/ml) and pumpkin seed soft extract (IC50 = 1.1 mg/ml). We propose that inhibition of 5α-reductases and competitive binding to the AR are mechanisms of action, by which the Uromedic? pumpkin seed derived test compounds, most specifically Δ7-sterols, counteract DHT and thereby exert clinically positive effects on the prostate, as well as bladder-strengthening effects.
Keywords: 5-Alpha-Reductases 5α-R1 and 5α-R2, Androgen Receptor, Dihydrotestosterone, Uromedic® Pumpkin Seed Oil and Soft Extract, (Delta-7) Δ7-Sterols
Benign prostate hyperplasia (BPH) is commonly found in men, with a worldwide prevalence of from 20% - 62% in men over 50 years [1] . Affected men suffer from the frequent urge to urinate, especially at night, weakened urinary flow, delayed start of urination, intermittency, urine leaking, incomplete bladder emptying as well as difficult or painful urination. The steroidal androgen dihydrotestosterone (DHT) has been implicated in the development and maintenance of BPH.
A common BPH treatment option is the inhibition of the 5-alpha-reductases, enzymes catalyzing DHT formation from testosterone [2] [3] . There are three 5-alpha-reductase isoenzymes: 5α-R1 is expressed in low levels in the prostate, whereas 5α-R2 is highly expressed there. 5α-R3 appears to have a role in malignant tissues [3] [4] .
5-alpha-reductase―inhibition has previously been shown for saw palmetto (Serenoa repens (Bartr.) Small.) extracts (and for several contained fatty acids) [5] [6] , as well as for Urtica dioica Linn. extract [7] . 5-alpha-reductase―inhibition was also proposed for Cucurbita pepo L. (pumpkin) seed preparations [8] .
A further possibility to reduce the pathologic effects of DHT represents the inhibitory competition with DHT for its binding site at the androgen receptor (AR). The AR is activated by binding either testosterone or the more potent androgen dihydrotestosterone. Upon binding, AR undergoes conformational changes and translocates from the cytoplasm to the nucleus, where it dimerizes and regulates transcription by binding to androgen response elements [9] . The AR has two isoforms, AR-A and AR-B [10] .
Pumpkin (Cucurbita pepo L.) seeds or preparations thereof have long been recognized for their potential of relieving lower urinary tract symptoms related to benign prostatic hyperplasia or to an overactive bladder [11] . The seed soft extract of a special pumpkin breed ("Uromedic® pumpkin", a variety of Cucurbita pepo L. convar. citrullinina GREB. var. styriaca GREB) [12] [13] is rich in Δ7-sterols, which are typical components in pumpkin seeds [14] and seeds of other Cucurbitaceae, as well as in Amaranthaceae [15] . Δ7-sterols were shown to influence the prostate metabolism [16] [17] . Furthermore, they competitively reduced the binding of DHT to human fibroblasts [18] .
Extracts from C. pepo, Prunus Africana (Hook. f.) Kalkman and S. repens displayed antiandrogenic activity in an AR responsive reporter gene assay [19] . However, the molecular effectors appear to vary: in the case of P. africana, N-butylbenzenesulfonamide was characterized as active constituent [19] , whereas in S. repens, certain fatty acids may act by binding―instead―to the alpha-1-adrenergic, muscarinic and 1,4-dihydropyridine receptors, as well as to 5-alpha-reductases [6] . Interestingly, pumpkin seed oil contains high amounts of putatively active fatty acids, i.e. oleic acid and linoleic acid [12] [13] .
The inhibition of the 5α-reductases as well as the inhibitory binding to the AR are two possible mechanisms by which the pumpkin seed derived test compounds―Uromedic® pumpkin seed soft extract, seed oil and isolated Δ7-sterols―could exert their positive effects on the prostate and bladder system, especially in relation to BPH. Thus, we tested inhibition of 5α-reductase and competitive androgen receptor-binding using radioactively labeled ligands.
Experimental procedures were performed by "rent-a-lab Dr. Carsten Tober" in Reutlingen, Germany, between April-September 2016.
2.1. Test Compounds and Materials
Test compounds: 1. Pumpkin seed oil of Uromedic® pumpkin seeds (Material 3000000293, Omega Pharma batch: 511062, vendor/batch: 603827/283484), one of the active substances in "GRANUFINK® Prosta" (Omega Pharma Deutschland GmbH). 2. Δ7-sterols isolated from Uromedic® pumpkin seed oil; 3. Pumpkin seed soft extract (DER 15-25:1) from Uromedic® pumpkin seeds; extraction solvent ethanol 92% (m/m) (Material 3000000299, Omega Pharma batch: 531057, vendor/batch: 600516/15000533); active substance of GRANUFINK® Prosta forte 500 mg (Omega Pharma Deutschland GmbH), supplying approximately 30 mg/day Δ7-sterols [14] (Supplementary Table S1).
The test compounds were dissolved and stored in DMSO (dimethyl sulfoxide) at 4˚C.
Commercial hexane extracted saw palmetto fruit extract (Serenoa repens W. Bartram; DER 7-11:1) served as positive control (5α-reductase―inhibition). Finasteride (C23H36N2O2, 5α-reductase―inhibitor) was used to quantify 5α-reductase inhibition, and DHT to quantify AR binding.
AR (recombinant rat protein, ligand binding domain, code: A15675) was from ThermoFisher Scientific (Braunschweig, Germany). Dihydrotestosterone (DHT) (code: A83809), testosterone (code: T1500) and finasteride (code: F1293) were from Sigma (Taufkirchen, Germany). [3H]-Dihydrotestosterone ([3H]-DHT, code: NET 453), [1,2,6,7-3H(N)]-testosterone, code: NET370) and Ysi Copper His-Tag SPA Beads (code: RPNQ0096) were from PerkinElmer (Rodgau, Germany). Other chemicals were from Sigma or VWR.
2.2. Preparation of Sources of 5α-R1 and 5α-R2
Sprague Dawley rats (Elevage Janvier, Le Genest, Saint Isle, France) were sacrificed by decapitation. Liver was dissected on ice, frozen in liquid nitrogen and stored at −80˚C. For the experiments at pH 7.0 (5α-R1), rat liver microsomes were prepared as described [20] . For the experiments at pH 5.0 (5α-R2), a crude rat liver enzyme preparation was used as described [21] .
2.3. 5α-Reductase Activity Assays
The enzyme reactions were mainly carried out as described [21] . In a total volume of 90 μl radioactive (3H-testosterone; 0.5 μCi) and non-radioactive (9.5 μM) testosterone, 0.5 mM beta-NADPH and liver microsomes/crude liver enzyme preparation were incubated in assay buffer (0.1 M Tris-citrate, pH 5.0 or 7.0) in a shaking water bath at 37˚C for 20 or 60 min. The assay was terminated by the addition of 10 μl 2.8 M NaOH. Educt (3H-testosterone) and products (3H-DHT, 3H-alpha-adiol and other metabolites) were separated by HPLC from each other using an adapted [22] and validated method, and using a Beckman System Gold HPLC (Beckman Instruments, San Ramon, CA, USA) fitted with an Onyx monolitic C18 (Phenomenex Ltd. Deutschland, Aschaffenburg, Germany) reversed phase column (100 × 3 mm). Chromatography was performed isocratically for 15 min at a flow rate of 0.5 ml/min with 0.2% NH4OH in 65% methanol as mobile phase, separating 3H-testosterone and 3H-DHT. Radioactivity in collected fractions was determined in a scintillation counter (WinSpektral, Wallac, Finland). Data typically represent results gained by two experiments performed in duplicate (see results section).
Data evaluation: The inhibition by 10 µM finasteride (3.7254 µg/ml) was considered 100% inhibition, the inhibitory activity of the vehicle/solvent 0% inhibition. The inhibition of the test compounds was calculated relative to that of finasteride. IC50 values were determined by non-linear regression (algorithm "sigmoidal dose-response"; GraphPadPrism, San Diego, USA).
2.4. Competitive AR Binding Assay
The competition of each test compound (or DHT) with [3H]-DHT for binding to the rat recombinant AR was measured by detecting [3H]-DHT. The basic assay conditions were taken from Freyberger and Ahr [23] and adapted to the scintillation proximity assay (SPA) format, in which beads emit light when a radio-labeled molecule is in proximity. Incubation was in assay buffer (50 mM Tris-HCl pH 7.5, 800 mM NaCl2, 10 mg/ml human γ-globulin, 0.05% bovine serum albumine) at room temperature for 90 min. Then Ysi Copper His-Tag SPA beads were added and the incubation continued for another 60 min. The radioactivity-induced light was determined by a microplate reader (Microbeta, Wallac, Finland). For each test compound, two measurement series were done, each in duplicate.
Data evaluation: In order to exclude binding to non-specific sites, incubations using the radioactive ligand [3H]-DHT and unlabeled DHT as the natural ligand of the AR were run simultaneously at different concentrations. Excess unlabeled DHT occupied the high-affinity specific sites and blocked the binding of [3H]-DHT to the AR. As a result, the radio-labeled ligand only bound to the non-specific sites. Such radioactive binding in the presence of excess unlabeled DHT was considered non-specific binding.
The amount of [3H]-DHT bound in the absence of unlabeled DHT was referred to as total binding. Specific binding was calculated as:
Total (radioactive) binding − Non-specific (radioactive) binding = Specific binding
Thus, the data of the reference compound DHT are presented as total bound radioactivity (in counts per minute, cpm). Test compound data are presented as specific radioligand binding to the receptor. The specific inhibition in % was calculated as (% specific radioligand binding mean ? 100) × (−1). IC50 values were determined by non-linear regression (algorithm "sigmoidal dose-response"; Graph Pad Prism, San Diego, USA).
3.1. Rat Liver 5α-Reductase Activity―Assay Validation
Rat liver microsomes were shown to obtain higher levels of 5-alpha-reductase compared to rat prostate microsomes [20] . Therefore, rat liver microsomes were used as source of 5α-R1. For 5α-R2, a crude liver preparation was found to be more active. 5α-R1 exhibits a broad pH optimum (between pH 6.0 - 8.5), whereas 5α-R2 shows a narrow acidic pH optimum (pH 5 - 5.5) [4] . To distinguish 5α-R1 from 5α-R2, the assays for 5α-R1 were performed at pH 7.0, and those for 5α-R2 at pH 5.0 [21] . Experiments at pH 5.0 led to a very low, almost negligible signal from the rat liver microsomal preparation (source of 5α-R1; data not shown).
At pH 7.0 the reference compound finasteride inhibited the activity of 5α-R1 derived from rat liver microsomes with an IC50 of 48 nM (Figure 1). This compares to a published IC50 of 21 nM [20] , demonstrating test system suitability. A commercial hexanic extract of Serenoa repens [5] was able to inhibit 5α-R1 with an IC50 = 4.9 mg/ml and 5α-R2 with an IC50 = 1.8 mg/ml.
Figure 1. Inhibition of 5-alpha-reductase isoform I, derived from rat liver microsomes, at pH 7.0 by finasteride. Data represent the mean inhibition of enzyme activity (%) of one experiment performed in duplicate. An IC50 value of 48 nM was determined for the inhibition by finasteride.
3.2. Inhibitory Effect of the Test Compounds on Microsomal Rat Liver 5α-R1
The inhibitory potential of the test compounds on 5α-R1 was tested using our validated assay at pH 7, favoring 5α-R1 activity. Table 1 shows that pumpkin seed oil (5 mg/ml), pumpkin seed soft extract (5 mg/ml) and Δ7-sterols (0.5 mg/ml) had similar inhibitory capacities, between 70% - 95% compared to 10 µM finasteride. The results for Δ7-sterols showed a dose dependency. The calculated IC50 values are indicated.
3.3. Inhibitory Effect of the Test Compounds on Rat Liver 5α-R2
The inhibitory potential of the test compounds on 5α-R2 was tested using our validated assay at pH 5, favouring 5α-R2 activity. Table 2 shows that pumpkin seed oil (5 mg/ml), pumpkin seed soft extract (5 mg/ml) and Δ7-sterols (0.5 mg/ml) had similar inhibitory capacities, between 25% - 50% compared to 10 µM finasteride. The results for Δ7-sterols showed a dose dependency. The calculated IC50 values are indicated.
Table 1. Inhibition of microsomal rat liver 5α-R1 by the Uromedic® pumpkin-derived test compounds at pH 7.0.
a-c: see Table 2.
Table 2. Inhibition of rat liver 5α-R2 by the Uromedic® pumpkin-derived test compounds at pH 5.0.
a: Inhibition relative to 10 µM (3.7254 µg/ml) finasteride (100% inhibition); activity with vehicle DMSO was considered 0% inhibition. b: Both experiments in duplicate; means of duplicate measurements shown; c: IC50 values: concentration of test compound causing 50% inhibition. d: This value was judged as outlier and not taken into consideration.
3.4. AR Binding―Assay Validation
DHT is the natural ligand of the AR. DHT competed with [3H]-DHT for binding to the AR with an IC50 of 8.5 nM (Figure 2). This is in agreement with an IC50 of 4.2 nM described in literature [23] , demonstrating test system suitability.
3.5. Binding of the Test Compounds to ARs
Overlaid mean specific binding data of pumpkin seed soft extract, pumpkin seed oil and Δ7-sterols are depicted graphically (Figure 3(a) and Figure 3(b)); numeric data is shown in Supplementary Tables S2-S4. All test compounds show typical concentration dependent binding. Strongest specific AR binding was observed for Δ7-sterols (mean IC50 = 0.2 mg/ml, corresponding to 0.48 mmol/l) and weaker binding for pumpkin seed oil (mean IC50 = 0.4 mg/ml) and pumpkin seed soft extract (mean IC50 = 1.1 mg/ml) (Table 3).
Figure 2. Concentration-dependent competition of DHT with [3H]-DHT for binding to rat recombinant AR. An IC50 value of 8.5 nM was determined for the binding of DHT. Data represents the bound radioactivity (cpm).
Figure 3. Competitive binding of the test compounds at the AR. The test compounds pumpkin seed soft extract (p, blue) and pumpkin seed oil (r, red) and Δ7-sterols (n, green) competed with [3H]-DHT for binding to the rat AR within two independent measurements (a and b). Data in each graph represent the mean specific binding ± standard error of the mean (SEM) of duplicate measurements. Calculated IC50-values from each experiment are indicated in Table 3. See Supplementary Tables S2-S4 for numeric data.
a: Calculated using the molecular mass of the main Δ7-sterol within pumpkin seeds: Δ7.25-stigmastadienol − 412 g/mol [14] .
4.1. Inhibition of Human 5-Alpha-Reductases
As previously published, rat liver tissue expresses 5-alpha-reductases. Microsomal liver preparations were used as source for 5α-R1 (isoform I). However, the same was found unsuitable for measurement of isoform II at pH 5.0, which was instead investigated in crude liver preparations. Assay validation was done for both preparations using known enzyme inhibitors. Both pumpkin seed soft extract and oil showed similar inhibitory capacities (both: IC50 < 5 mg/ml for 5α-R1 and IC50 ≈ 6 mg/ml for 5α-R2). The isolated Δ7-sterols (IC50 = 0.3 mg/ml for 5α-R1, IC50 = 1.0 for 5α-R2) were more potent than the pumpkin seed soft extract or oil, most likely since the Δ7-sterols are the main active principle within pumpkin seeds regarding anti-androgenic activity.
4.2. Androgen Receptor Binding
The test compounds inhibited the [3H]-DHT binding to AR in a concentration-dependent manner (Table 3), with IC50 (Δ7-sterols) = 0.2 mg/ml), IC50 (pumpkin seed oil) = 0.4 mg/ml and IC50 (pumpkin seed soft extract) = 1.1 mg/ml. This dose-dependency indicates the capacity of all three test compounds to bind to the AR.
Among the tested substances, the Δ7-sterols had the lowest IC50 and thus bind most potently to the AR.
Chang and Liao classified the antagonistic effects of different cyclic hydrocarbons on the AR [24] . Accordingly, the binding of Δ7-sterols (mean IC50 of 0.48 mmol/l) corresponds to moderately active substances (IC50 range 0.1 - 2 mmol/l). In a published experiment, human cells were pre-incubated with Δ7-sterols and then treated with DHT. In a concentration-dependent manner, a reduced binding of DHT to its binding sites could be demonstrated [18] . This goes along with our findings.
4.3. Extrapolation to the in Vivo Situation
The inhibition of 5-alpha-reductase by Δ7-sterols and their inhibitory binding to AR are plausible due to the similar structure of these compounds compared to DHT [18] [25] . Several studies support that our in vitro observations also take effect in vivo:
Trevisan et al. 2012 found that orally administered Δ7 sterol (alpha-spinasterol) was well absorbed by mice [26] . Pumpkin seed or pumpkin seed oil in the diet of BPH animal models inhibited prostate growth [13] [27] [28] [29] . Effects were observed with only 40 mg pumpkin seed oil/kg body weight [28] . Furthermore, patients taking 90 mg of a Δ7 sterol mixture isolated from Uromedic® pumpkin seeds 3 - 4 days before prostatectomy had a lower DHT content in the operated prostate tissue than control patients [17] . Thus anti-androgen effects seen in our studies presumably take effect also in vivo, while, the safety of pumpkin seed soft extract and pumpkin seed oil has been established by human data [11] [30] [31] [32] . As a next step, the isolated Δ7 sterols (versus seed soft extract and seed oil) could be tested in BPH animal models, and finally in BPH patients.
4.4. Study Limitations
In order to get more reliable IC50 values, more experiments using at least 3 different concentrations of the test compounds (especially in the case of the 5-alpha-reductases), and using more independent measurements should be done. Since all our experiments were done using rat enzymes, potential differences in binding and inhibition to human orthologues cannot be excluded.
In our study, Uromedic® pumpkin seed soft extract (active ingredients of GRANUFINK® Prosta forte 500 mg), pumpkin seed oil and―more effectively―isolated Δ7-sterols inhibit 5α-reductase and competitively bind to the AR in vitro. It is plausible that the Δ7-sterols are the active compounds contained within the pumpkin seed soft extract and oil, regarding these activities. This is supported by the dose-dependency of the observed inhibitory effects, as well as by the lower IC50 values of the Δ7-sterols compared to the seed soft extract or oil. Other constituents, such as fatty acids, may also be involved. Our results are promising for a mechanistic understanding of pumpkin seed-derived preparations, and more specifically Δ7-sterols, regarding anti-androgenic effects and the inhibition of 5α-reductase.
Acknowledgements and Funding
We thank Dr. S. Förster for her valuable contribution on planning the studies. Stefan Heim is employee of Omega Pharma Manufacturing GmbH & Co. KG, who funded the study. Stephanie Seibt, Dr. Heike Stier and Margret Moré, Ph.D. are employees of the consulting company analyze & realize GmbH.
Table S1. Herbal preparations used for the in vitro experiments.
GC-IT-MS, gas chromatography ion trap mass spectrometry (Muller C, Bracher F. Determination by GC-IT/MS of phytosterols in herbal medicinal products for the treatment of lower urinary tract symptoms and food products marketed in Europe. Planta Med 2015; 81: 613 - 620); TLC, thin layer chromatography; GC, gas chromatography.
Table S2. Individual data of the AR binding measurements for pumpkin seed soft extract.
*Data excluded from further analysis, because they obviously represent measurement artifacts with an opposite value as can be expected by the corresponding dose-response-relationship.
Table S3. Individual data of the AR binding measurements for pumpkin seed oil.
Table S4. Individual data of the AR binding measurements for Δ7-sterols.
Cite this paper: Heim, S. , Seibt, S. , Stier, H. and Moré, M. (2018) Uromedic® Pumpkin Seed Derived Δ7-Sterols, Extract and Oil Inhibit 5α-Reductases and Bind to Androgen Receptor in Vitro. Pharmacology & Pharmacy, 9, 193-207. doi: 10.4236/pp.2018.96015.
[1] Yeboah, E.D. (2016) Prevalence of Benign Prostatic Hyperplasia and Prostate Cancer in Africans and Africans in the Diaspora. Journal of the West African College of Surgeons, 6, 1-30.
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[6] Abe, M., Ito, Y., Oyunzul, L., Oki-Fujino, T. and Yamada, S. (2009) Pharmacologically Relevant Receptor Binding Characteristics and 5-alpha-reductase Inhibitory Activity of Free Fatty Acids Contained in Saw Palmetto Extract. Biological and Pharmaceutical Bulletin, 32, 646-650.
https://doi.org/10.1248/bpb.32.646
[7] Nahata, A. (2014) Dixit VK. Evaluation of 5-alpha-reductase Inhibitory Activity of Certain Herbs Useful as Antiandrogens. Andrologia, 46, 592-601.
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[8] Dreikorn, K. and Schonhofer, P.S. (1995) Status of Phytotherapeutic Drugs in Treatment of Benign Prostatic Hyperplasia. Urologe A, 34, 119-129.
[9] Meehan, K.L. and Sadar, M.D. (2003) Androgens and Androgen Receptor in Prostate and Ovarian Malignancies. Frontiers in Bioscience, 8, d780-800.
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[11] EMA Committee on Herbal Medicinal Products (HMPC). Community Herbal Monograph on Cucurbita pepo L., Semen EMA/HMPC/136024/2010.
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[12] Fruhwirth, G. and Hermetter, A. (2007) Seeds and Oil of the Styrian Oil Pumpkin: Components and Biological Activities. European Journal of Lipid Science and Technology, 109, 1128-1140.
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[14] Muller, C. and Bracher, F. (2015) Determination by GC-IT/MS of Phytosterols in Herbal Medicinal Products for the Treatment of Lower Urinary Tract Symptoms and Food Products Marketed in Europe. Planta Medica, 81, 613-620.
[15] Munger, L.H., Jutzi, S., Lampi, A.M. and Nystrom, L. (2015) Comparison of Enzymatic Hydrolysis and Acid Hydrolysis of Sterol Glycosides from Foods Rich in Delta(7)-Sterols. Lipids, 50, 735-748.
[16] Bombardelli, E. and Morazzoni, P. (1997) Cucurbita pepo L. Fitoterapia, 68, 291-302.
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[18] Schilcher, H. and Schneider, H.-J. (1990) Beurteilung von Kürbissamen in fixer Kombination mit weiteren pflanzlichen Wirkstoffen zur Behandlung des Symptomenkomplexes bei BPH. Urologe (B), 30, 62-66.
[19] Schleich, S., Papaioannou, M., Baniahmad, A. and Matusch, R. (2006) Extracts from Pygeum africanum and Other Ethnobotanical Species with Antiandrogenic Activity. Planta Medica, 72, 807-813.
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[20] Iwai, A., Yoshimura, T., Wada, K., Watabe, S., Sakamoto, Y., Ito, E. and Miura, T. (2013) Spectrophotometric Method for the Assay of Steroid 5alpha-Reductase activity of Rat Liver and Prostate Microsomes. Analytical Sciences, 29, 455-459.
https://doi.org/10.2116/analsci.29.455
[21] Pratis, K., O'Donnell, L., Ooi, G.T., McLachlan, R.I. and Robertson, D.M. (2000) Enzyme Assay for 5alpha-Reductase Type 2 Activity in the Presence of 5alpha-Reductase Type 1 Activity in Rat Testis. The Journal of Steroid Biochemistry and Molecular Biology, 75, 75-82.
[22] Yang, H.Z., Miao, Z.R., He, Z.X., Ji, S. and Zeng, F.S. (1988) Separation of Testosterone and Dihydrotestosterone in Semen by High Performance Liquid Chromatography. Journal of Liquid Chromatography, 11, 3253-3259.
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[25] Chang, C. and Liao, S. (1987) Topographic Recognition of Cyclic Hydrocarbons and Related Compounds by Receptors for Androgens, Estrogens and Glucocorticoids. The Journal of Steroid Biochemistry and Molecular Biology, 27, 123-131.
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[26] Trevisan, G., Rossato, M., Walker, C., Klafke, J., Rosa, F., Oliveira, S., et al. (2012) Identification of the Plant Steroid Alpha-Spinasterol as a Novel Transient Receptor Potential Vanilloid 1 Antagonist with Antinociceptive Properties. Journal of Pharmacology and Experimental Therapeutics, 343, 258-269.
[27] Abdel-Rahman, M. (2006) Effects of Pumpkin Seed (Cucurbita pepo L.) Diets on Benign Prostatic Hyperplasia (BPH): Chemical and Morphometric Evaluation in Rats. World Journal of Chemistry, 1, 33-40.
[28] Gossell-Williams, M., Davis, A. and O'Connor, N. (2006) Inhibition of Testosterone-Induced Hyperplasia of the Prostate of Sprague-Dawley Rats by Pumpkin Seed Oil. Journal of Medicinal Food, 9, 284-286.
https://doi.org/10.1089/jmf.2006.9.284
[29] Tsai, Y.S., Tong, Y.C., Cheng, J.T., Lee, C.H., Yang, F.S. and Lee, H.Y. (2006) Pumpkin Seed Oil and Phytosterol-F Can Block Testosterone/Prazosin-Induced Prostate Growth in Rats. Urologia Internationalis, 77, 269-274.
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[30] Bach, D. (2000) Placebokontrollierte Langzeittherapiestudie mit Kürbissamenextrakt bei BPH-bedingten Miktionsbeschwerden. Der Urologe, 40, 437-443.
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[31] Schiebel-Schlosser, G. and Friederich, M. (1998) Kürbissamen in der Phytotherapie der BPH. Zeitschrift für Phytotherapie, 19, 17-76.
[32] Vahlensieck, W., Theurer, C., Pfitzer, E., Patz, B., Banik, N. and Engelmann, U. (2015) Effects of Pumpkin Seed in Men with Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia in the One-Year, Randomized, Placebo-Controlled GRANU Study. Urologia Internationalis, 94, 286-295.


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Ha giocato nella massima serie dei campionati turco, sudcoreano ed iraniano.

Note

Collegamenti esterni


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IV. The reporting of m...
Sam Perlo-Freeman
The United Nations Report on Military Expenditures remains an important source of official data on military expenditure.1 The reporting mechanism, which was introduced in 1981, is managed by the UN Office for Disarmament Affairs (UNODA). Each year the UN Secretary-General invites all member states (currently 193) through a note verbale to report their military expenditure by 30 April for the most recent financial year for which data is available. The original basis for this request is a UN General Assembly resolution adopted in 1980.2 Successive biennial General Assembly resolutions have called for the continued reporting of military expenditure by member states.3
Perlo-Freeman, Sam. "9. Military expenditure." SIPRI Yearbook. SIPRI. Oxford: Oxford University Press. 2016. Web. 20 Jan. 2020. <https://www.sipriyearbook.org/view/9780198737810/sipri-9780198737810-chapter-9-div1-5.xml>.
Perlo-Freeman, S. (2016). 9. Military expenditure. In SIPRI, SIPRI Yearbook 2015: Armaments, Disarmament and International Security. Oxford: Oxford University Press. Retrieved 20 Jan. 2020, from https://www.sipriyearbook.org/view/9780198737810/sipri-9780198737810-chapter-9-div1-5.xml
Perlo-Freeman, Sam. "9. Military expenditure." In SIPRI Yearbook 2015: Armaments, Disarmament and International Security, SIPRI. (Oxford: Oxford University Press, 2016). Retrieved 20 Jan. 2020, from https://www.sipriyearbook.org/view/9780198737810/sipri-9780198737810-chapter-9-div1-5.xml


A sick baby needs lots of love to bounce back to their normal smiles and giggles. Kids can nurture the Sweet Tears Baby doll to help her back to health. First, fill her ""juice"" box with water to feed her. . .oh no! She cries tears that mommy or daddy can wipe away. The Sweet Tears Baby doll has an expressive face and responds to her accessories. Kids can give Sweet Tears Baby doll a check-up with the stethoscope and thermometer. Her nose lights up to let kids know she needs her tissue. Pretend to blow her nose or bandage a pretend boo-boo. Flip the switch in her back to choose who she's speaking to -- she says ""Mommy"" and ""Daddy"" so girls and boys can play out nurturing moments. With 35 plus sounds and phrases in English or Spanish, she can tell kids how she's feeling. . .and that she loves them!


We are now halfway through the month of Elul, and are turning our hearts and minds toward the New Year ahead. As we turn we find blessings and gratitude for the year that is now ending, finding appreciation for the joy and love that we have experienced. And we recognize the pain and challenges that we have encountered, and the hurts we may have caused to others or have brought to our own selves. We make this cheshbon hanefesh, this journey of the soul so that we may meet with clarity and openness all that the New Year brings, with all of our mind, heart and soul.
To dwell in the Sacred Presence all the days of my life.
As I pass through this world.
As we focus our soul's journey at this time of year, what it is that we are seeking? What does it mean for us to dwell in the Sacred Presence? To awaken to the beauty of each moment? Where have we become disconnected, disengaged?
This year is 5779, תשע״ט. The letters that form the number 79 are עט, ayin tet. In Hebrew an eit is a pen, a writing implement with ink. As the new year begins we have the opportunity and challenge to write the answers to these questions in our own personal book of life. In this new year 5779 may we find what we are seeking, may we be awakened to the beauty of each moment. And may we find the path of return, renewal and wholeness as we become conscious of our dwelling in the Sacred Presence.


Price Reduced 3/19/2019!! Beautiful corner lot home in North Lakeland in Winchester Estates. Open floor plan with Kitchen overlooking Living room. The master suite has dual sinks, a garden tub and a walk in shower! This home offers a large privacy fenced in backyard, and a screened in lanai and also features a 2 car garage.
Additional Lease Restrictions Please Contact Hoa For Lease Restrictions.


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Elizabeth McAlister
Professor of Religion
NPR : Fresh Air with Terry Gross
In 1996, Terri Gross invited Elizabeth McAlister to be a guest on Fresh Air to discuss "Rhythms of Rapture," the album of Haitian religious music that McAlister compiled for Smithsonian Folkways. They talked about life in Haiti in 1993 during the coup d'etat against Jean-Bertrand Aristide, about Vodou music, and about getting to know a culture through its music.
"Liza McAlister video on music and the Haiti earthquake"
NPR All Things Considered
"Voodoo Brings Solace to Grieving Haitians"
Interfaith Radio
"Understanding the Haiti Earthquake: A Crisis of Faith and Meaning"
The Takeaway/WNYC Radio
"Haiti's Musical Traditions, Past and Present"
Symposium Podcast: Considering Syncretic Practices, Beliefs, and Religions in the Caribbean
This moderated panel discussion took place at the Museum on October 27, 2007. Scholars and artists included Elizabeth McAlister, John Amira, and Marta Vega discussing the ways belief functions in the daily life of Caribbean peoples within the islands and in New York.
Click Here to Listen to Panel Discussion
Music and the Story of Haiti
From Vodou to Compas to Racine to Rara and Beyond: Haiti became the first black-ruled republic in the Americas in 1804, and music has mirrored, and at times shaped, the twists and turns of Haiti's politics and culture ever since. A primary source of Haitian culture is Dahomey, the birthplace of vodou–the most commonly held world view among Haitian people today. We explore how each of Haiti's rulers has championed his own preferred music. The Duvalier dictators favored compas dance music, and suppressed the most African-identified cultural expressions. When Baby Doc was run out of the country in 1986, African-derived racine, or roots, music exploded. Elizabeth McAlister, professor of religion at Wesleyan University, and community scholar Holly Nicolas, interweave music and history to tell a dynamic, and at times heart-breaking story. Included in the mix we'll hear the sweet sound of troubadour balladeers, as well as the exuberant tones of rara bands, the call and response of a capela kombit songs of work parties, impassioned choral music of evangelical churches, and the sophisticated, improvisational rhythms used in vodou rituals.
An episode of Afropop Worldwide
Produced by public radio's Afropop Worldwide and Elizabeth McAlister. To see a transcript of an interview with Elizabeth McAlister, Click Here.
Abbreviated version (6 minutes): 6-minute Complete program (1 hour): 1-hour
If the embedded players do not work, try clicking these text links for the 6-minute or 1-hour versions.
Modified on: Oct 14th, 2016 Log in
emcalister@wesleyan.edu
Elizabeth McAlister © 2020 All Rights Reserved.
Visit Wesleyan
WESU (radio)
Wesconnect


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South Broadway Library
Discover the Center
Tweets by @sbccABQ
Peter and the Starcatcher http://www.cabq.gov/south-broadway-cultural-center/events/peter-and-the-starcatcher http://www.cabq.gov/@@site-logo/seal-small.png
http://www.cabq.gov/south-broadway-cultural-center/events/peter-and-the-starcatcher
1025 Broadway Blvd SE
Tony-winning Peter and the Starcatcher upends the century-old story of how a miserable orphan comes to be The Boy Who Would Not Grow Up (a.k.a. Peter Pan). From marauding pirates and jungle tyrants to unwilling comrades and unlikely heroes, Peter and the Starcatcher playfully explores the depths of greed and despair... and the bonds of friendship, duty and love.
A young orphan and his mates are shipped off from Victorian England to a distant island ruled by the evil King Zarboff. They know nothing of the mysterious trunk in the captain's cabin, which contains a precious, otherworldly cargo. At sea, the boys are discovered by a precocious young girl named Molly, a Starcatcher-in-training who realizes that the trunk's precious cargo is starstuff, a celestial substance so powerful that it must never fall into the wrong hands. When the ship is taken over by pirates – led by the fearsome Black Stache, a villain determined to claim the trunk and its treasure for his own – the journey quickly becomes a thrilling adventure.
General Admission $15
Chloe Nieto


The restaurant and function areas are situated in one of the largest and oldest formal gardens in Kenya. Huge jacaranda, candelabra cactus,bottle brush and other trees and over 200 species of blooming flower varieties surround the restaurant.The bar which opens out to a lounge, with delicious tamambo cocktails, bar snacks and satellite tv to catch all the sporting events, has become a popular meeting place for many karen residents.
Here are 3 versatile venues that include; grand marquise tent, grogan house and the inside dining room.
Conference package includes:note pads, pens, a flip chart and a 500 ml bottle of water in the morning and the afternoon per person. A 10am and a 4pm coffee/tea break is served with cookies. Lunch is a set menu with a starter, main course and desert, tea and coffee. The bar sits up to 100 pax and can be extended to the outside lawns/gardens. Grogan house includes a partition which has a bar and kitchen. It can sit up to 25 pax for conferences and 70 pax for cocktail parties.
The garden holds a capacity of 70 – 100 pax depending on the weather and shade available. The tent is mainly used for functions, major lunches/festive seasons. It can hold a capacity of 150 pax seated and 200 pax stand up (cocktail parties).


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Q: Website text appearing only on hover I'm facing a strange issue on the text rendering of a website I have developed. When loading the page, some of the text doesn't appear until I hover over it; some not even then.
I am using font-face. If I reload the page, it works fine. If I empty the cache, the problem comes back. Frontend design is developed using bootstrap 2.3.2.

A: Are you using Chrome?
This may be due to a recent Chrome bug:
https://code.google.com/p/chromium/issues/detail?id=336476
Looks like they're working on a fix.
I'm using this as a temporary fix:
$(function() {
    // temporary fix for chrome font bug
    $('*').css('zoom', '1').css('zoom', '');
});

The idea is that it will trigger a redraw of all elements.

A: As said in the bug forum :
https://code.google.com/p/chromium/issues/detail?id=336476
It's related to @font-face
just try to use arial or something instead your @font-face font and this should work.

A: Remove font-face and re try. May be your text color is same color as your background color?
Hover color is different or something? Can you show your code or a link to a site?

redpajama_set_name: RedPajamaStackExchange


My thanks to Net Galley and Hachette Children's Group for the review copy.
I was super excited to receive a Net Galley eARC of this novel, I have followed Paper Fury on her blog and social media for a few years now, and I was really excited to read her novel.
This is a really emotionally charged novel. The author deals with some big, heavy hitting subjects, including physical and emotional abuse, so beware of this.
But, saying this, this novel is incredible, I was so drawn in by the premise, and the novel kept me hooked the whole way through. This is a unique novel, especially in YA, and it stands strong and proud.
The writing style is so beautiful. For a debut novel the author shows an incredible talent for writing beautifully descriptive and lyrical prose. She also writes a moving and emotive novel. Her ability to write and describe the sound of music is quite wonderful to read, and this is a real talent the author has. I cannot wait to read whatever Drews writes next.
I loved the characters in this novel a lot. Beck is an amazing boy who cares for his sister so much, and although he appears to have a very tough shell he is very sensitive and caring. He has so much to deal with in his life yet he is still able to think of others, and consider the effect he and his decisions have on others. The relationship between him and August was so well crafted, and they just seemed so right for each other, and fitted together so well, it was amazing!
Although this book dealt with some pretty hard hitting topics it was also very funny. Beck and August have a lot of witty and sarcastic banter, and Beck's little sister is another source of hilarity. The humour woven throughout the narrative allows this novel to glow; the novel is both sad and happy simultaneously.
The end of this novel did make me cry, but it wasn't just tears of sadness, they were also tears of hope, and I think that's the most important aspect of this novel.


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War Years
Mortehoe
Mortehoe History
Woolacome & Mortehoe
Mortehoe Museum
Woolacombe
Woolacombe History
Mortehoe & Woolacombe Station
Posted on December 8, 2017 by woolacombemortehoevoice
The London and South Western railway line was extended from Barnstaple to Ilfracombe in July 1874, when the Mortehoe railway station was opened. On Tuesday 9th January 1894 the station saw a fire that very nearly destroyed it. The local newspaper reported it the following day: "Yesterday the officials were able to work the signals at Mortehoe Railway Station from the signal-box which was destroyed by fire early on Sunday morning. Karslake, the signalman, left the box quite safe on Saturday night. Mr Loader, the stationmaster, was also there at half past nine, and, as the fire was not discovered until nearly 5 o'clock the next morning it must have been smouldering all night. Fortunately the wind was not in the direction of the station house, or the whole block would have come down."
The railway became a busy line and the orginal single track line was doubled between 1889 and 1891. On the northbound platform, stood the station masters house, waiting room and ticket office. There also stood a small, 20 lever, signal box and the entrance to a small goods yard. On the southbound platform stood a simple shelter. The name of the station was known as Mortehoe until it was changed to Mortehoe & Woolacombe on the 13th May 1902, and Woolacombe was not added until the 5th June 1950. Michael Karslake worked at the station for 40 years, prior to this he worked as a railway porter. When he moved to Mortehoe he and his family lived in the Railway Cottages, Mortehoe. Michael would retire from the station work, after 48 years of service, 40 of which had been spent in Mortehoe "After 40 years service with the London and South Western Railway, which have been spent Morte-Hoe Station, Mr. Michael Karslake has retired, carrying with him the respect and esteem his colleagues and the public generally. Of cheerful and obliging disposition, and ever ready to help in any good cause, religious and social, Mr Karslake will much misted by the community. It is proposed make public presentation appreciation of his services
Mortehoe and Woolacombe Railway station in 1908 appeared in the London and South Western Railway Guides: "Although the railway does not penetrate into this delightful seaside village, the line of the London and South Western Railway, on its way to Ilfracombe, passes through Morte-Hoe, whence a descending road among the hills takes the traveller the famous Woolacombe Sands, which extend round the curve of Morte Bay for a distance of three miles, and constitute one of "the finest in the county. The little creek that runs under to the forbidding headland of Morte Point well known as shell-gathering ground, and many types of sea birds are found the numeroua of Baggy Point. This year Woolacombe will be more attractive to visitors than ever, inasmuch as it now possesses marine drive extending from one end of the sands to the other. Golfers have the use excellent 15-hole course; and during the summer months tennis and cricket" The station was eventually closed to passengers in October 1970. The North Devon Railway company tried to reopen the line in the early 1970s but were unable to raise the asking price. The tracks were removed in 1974, following its closure the station remained derelict until the mid 1980's when it was opened as the theme park 'Once upon a time.' Once upon a time became a railway themed park, where it was enjoyed by many children until its closure in 2005, when it was put up for sale for £800,000. Designed to be 'fun', it was run for a time by the same people who operate nearby Watermouth Castle. The theme park included a number of old train coaches, and railway stock which were used to create displays and interactive attractions. Following it's closure in 2006 the land was approved for a housing development consisting of seven units located where the orginal platforms had been and thirty seven holiday let units. The signal box became a reception area and a shop for the holiday accommodation.
Category: Mortehoe History, Woolacombe History
← Kenneth Vernon Dodgson (1891-1915)
Kelly Moss →
woolacombemortehoevoice.co.uk


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← Capitalist Contortions: How Amazon Survives the State
Editing for Liberty #15: So Long, Friend →
by Nathalie Marcus | July 5, 2012 · 7:56 pm
Editing for Liberty #14: A Whale of an Error
Spot the Error
Insurance companies must compete for clients, while the client must bare the fiscal responsibility of his actions.
Whaling is still as prevalent today as anytime in history, due to the close cultural and religious associations the fish has with various indigenous groups of Ainu, Inuit, and the Basque people of the Bay of Biscay.
Obama seems hell bent on expanding the US welfare state at any cost, and of course no welfare state debate is complete without bringing up the Scandinavian countries as the perfect example of massive statism bringing prosperity.
But mass production, if applied to anything beyond the simplest kind of article, depends not only on division of labor and multiple operations, but also on uniformly accurate, interchangeable parts.
Read on for the solutions!
Naked Fiscal Responsibility
Ah, those pesky homonyms. No, the client in sentence #1 does not need to denude anything, but rather bear the weight of his decisions.
Insurance companies must compete for clients, while the client must bear the fiscal responsibility of his actions.
Whales Are Mammals
Bruce the Shark (from Finding Nemo) and his friends claim (add Aussie accent as you read), "Fish are friends, not food."
Bruce may not eat fish, but he could eat whale (if he dared), because whales aren't fish. They're mammals. Sentence #2 ought to reflect that.
To Hell and Back Again
If you think the error in sentence #3 is that "welfare state debate" should be "welfare-state debate," you've found half of the errors. It turns out that "hell-bent" is hyphenated in the dictionary and should, therefore, appear hyphenated whether it's before or after the noun being modified. So the sentence should read,
Obama seems hell-bent on expanding the US welfare state at any cost, and of course no welfare-state debate is complete without bringing up the Scandinavian countries as the perfect example of massive statism bringing prosperity.
(Admittedly, the Chicago Manual of Style says that such hyphens are "usually unnecessary." See Chicago 7.81.)
Not Only But
This is one of the rules I am always forgetting. When you have what I'll call a "not only but" clause, there is NO comma before the "but" unless there is alsoa a comma before the "not only." Sentence 4 should be,
But mass production, if applied to anything beyond the simplest kind of article, depends not only on division of labor and multiple operations but also on uniformly accurate, interchangeable parts.
Name That Reference
Do you know what painting is behind the flag in this Mises Daily? Look to this Mises Daily for an unveiling.
Just for Fun: UK English
A.Word.A.Day with Anu Garg
Recently I visited London to attend a wedding. The bride had graduated from Oxford, and among the invitees were some of her fellow graduates and a professor. During the long ceremony, we intermittently chatted about London weather, Gordon Brown, Queen Lizzie, and language.
Among other things, we talked about the differences between British and American English. I recalled reading about the inroads American English is making even in the UK, so I decided to carry out an experiment to find to what extent American English had "corrupted" English English.
I told them that sometimes the British write certain numerals (e.g. 1 and 7) differently from how they're written in the US, and asked them to write a short sentence so I could see if there were other differences in the script.
I quickly thought of a sentence for them to write:
"Her favorite flavors were in the gray catalog, she realized."
I said it aloud and the five Oxonians and the Oxford don kindly wrote it down on their napkins (serviettes). I collected the napkins and then told them about the experiment — it had nothing to do with handwriting. In reality, that sentence had five words that could be written with American or British spellings (favorite/favourite, flavor/flavour, gray/grey, catalog/catalogue realize/realise).
Of the six people who participated in the experiment, three spelled (spelt) everything the British way. The other three had one or more words spelled in American English.
Is there something you'd like to contribute or see covered in Editing for Liberty? Post a comment! Cartoons, quips, and contributions to "Spot the Error" and "Name That Reference" are especially welcome.
Filed under Editing for Liberty


text:
Tablets are arranged for a photograph at an Apotik Mahakam pharmacy in Jakarta, Indonesia, on July 11, 2019.
Photographer: Dimas Ardian/Bloomberg
Covid Seen as Tipping Point to Lower Drug Prices, Patent Sharing
By Valerie Bauman and Susan Decker
Governments could mandate licenses for Covid-related drugs
Rare moment to change conversation on drug pricing
The pandemic has exposed weaknesses in the world's health system that patient advocates say can move the needle on years-long arguments over pricing and availability of medicines.
The drug industry says it's undertaken an unprecedented effort to find vaccines and treatments for Covid-19, the respiratory disease caused by the new coronavirus. Researchers are sharing work and pledging to ensure that any treatments are widely available and affordable.
These global efforts give patient advocates new leverage in the debate over drug prices that could continue after the pandemic ebbs.
Much of the conversation so far has centered on compulsory licensing, when a government mandates that a pharmaceutical company other than the one that innovated a drug can produce it—without consent of the patent owner.
There are less drastic ways to share intellectual property, such as patent pools and cross-licensing, and drug companies say those voluntary methods should stave off government patent intervention. Patient advocates are also fans of cross-licensing, which saves companies money on research and in turn helps lower drug prices.
Because of Covid-19, "people will demand that we have more of a say here and around the world," said David Mitchell, president and founder of Patients for Affordable Drugs. "Folks will get a big, highly visible dose of how pharma does business and it will fuel calls for reform."
"People tend to be comfortable with a lot of inequality in a lot of normal situations," said James Love, director of Knowledge Ecology International. "In a pandemic, that reaches a different level. The idea that you would hoard a vaccine seems pretty messed up to people."
Covid-19 could cause the United Nations' Medicines Patent Pool to expand. It negotiates licenses for medicines needed in low- and middle-income countries for things like HIV, Hepatitis C, and tuberculosis.
Governments could also make producing new drugs less expensive by offering cash rewards for certain breakthroughs and expanding research grants, tax credits, and subsidies. That would radically upend the current pharmaceutical business model, which relies on sales of blockbuster drugs to fund years of prior research in developing them.
Pharma companies would get "a very good return for innovating a new drug, and once the R&D is paid for, you allow for open production," said Fred Abbott, a Florida State University professor who has advised the World Health Organization and United Nations on patents and drugs.
The coronavirus's presence in wealthy countries gives that debate more heft. "It's one thing when you discuss it in the abstract over cocktails in Geneva, but it's another thing when people in your country are dying," he said.
Global Effort
The U.S. lags behind other countries that are compelling drugmakers to license their intellectual property for Covid-19 products to other companies.
The countries most likely to invoke their right to a compulsory licenses are "upper middle income" countries, according to Reed Beall, a population health researcher at the University of Calgary. Those are countries that are developed enough to have an established patent system but not quite rich enough to easily afford high prices of places like the U.S. and most of Europe.
Germany, the U.K., and Canada are among the developed nations that have announced they may limit patent rights to ensure any treatments or vaccines are widely available at a low price.
They join slightly less wealthy countries like Chile, Brazil, and Ecuador that often back compulsory licensing. Costa Rica's president is promoting a WHO-based pool of IP rights for technologies to fight Covid-19.
Israel recently invoked an emergency patent suspension clause for the first time, allowing it to import a generic version of Kaletra, an AbbVie Inc. drug that may be able to treat the virus.
Groups like Medecins sans Frontieres have called on countries to do more, including imposing price controls, and have urged companies to promise to not enforce any patents on Covid-related treatments. Some Democrats in Washington want to ban exclusive licenses for government-funded Covid-19 research.
Dodging a 'Blunt Instrument'
Patent lawyers and leaders in the pharmaceutical industry are skeptical that the U.S. will invoke its power to seize pharma companies' patents—even in the midst of a pandemic.
"There's really no signs in the current crisis that any patents have been in the way," said Hans Sauer, deputy general counsel and vice president for intellectual property at BIO, the lobbying group for the biopharmaceutical industry. "There's been a vast mobilization of resources. Pharma and bio companies have never moved as fast and with as much effort as they have now."
Drugmakers, already widely criticized for high drug prices, know they are under pressure to make Covid-19 treatments widely available and affordable, said Randall Kuhn, a professor at the University of California's Fielding School of Public Health.
"If [drugmakers] try to hold back these treatments, you will simply kill the golden goose," Kuhn said. "You would not be able to defend the patent anywhere, and you would threaten the entire patent system."
But if patient advocates push too hard to force the equivalent of open sourcing in medical research, it could discourage drugmakers from investing in new vaccines or treatments, said Stephen Ezell, vice president of global innovation policy at the Information Technology and Innovation Foundation.
"We don't know which [vaccine or treatment] is going to work, so we want to have a lot of people attacking this problem, and we should be providing appropriate incentives," Brian O'Shaughnessy, senior vice president of public policy for the Licensing Executives Society, said.
Compulsory licensing is "a blunt instrument," he said.
Unprecedented Crisis
Covid-19 is an unprecedented situation that could be the tipping point for advocates of lower prices for all pharmaceuticals.
The U.S. is among the most reluctant of countries to promote IP sharing. It's a "well-developed, capitalistic country" in which big businesses "have a huge stake in shaping all of our laws, including our patent law and antitrust law," said Tara Nealey, an IP attorney in Polsinelli's St. Louis office.
In developing nations, "compulsory licensing is not deemed to be a major threat to the underlying order," she said.
The current pandemic is driving a new, broader awareness of the role of patents in drug pricing, said Tahir Amin, co-founder of the Initiative for Medicines, Access & Knowledge. "The realization is that we can't let intellectual property rights slow down any way of dealing with the impacts of Covid."
To contact the reporter on this story: Valerie Bauman in Washington at vbauman@bloomberglaw.com and Susan Decker in Susan Deckerin Washington at sdecker1@bloomberg.net
To contact the editors responsible for this story: Fawn Johnson at fjohnson@bloomberglaw.com; Andrew Childers at achilders@bloomberglaw.com
Valerie Bauman
Susan Decker
Trump Urged to Limit Patent Rights on Ventilators, Treatments
Inoculating the World May Mean Reviving Old Curbs on Patents (3)
pharmaceutical research and development
compulsory patent licensing
pharmaceutical patents
biologics research
drug pricing
funding for medical research


Love how you organized your takeaways! I loved the VBT section, too Best of luck with your new book!
Return to Share your comments.
PaTrisha, I too love virtual book tours and find them to be incredibly effective as a book marketing tool! Can't wait to see how you apply this to your eBook series!
That's a very nice summary. Looks like your plan is perfectly ready ;-) Good luck with your project!
I agree with the comment that visualised a whole host of Visual Book Tours hitting the cyber waves over the next months! What fun! Me too!
I have visions of the majority of the group suddenly becoming involved in this gigantic virtual book tour and the vision is spectacular.
Thank you for a wonderful and concise recap of the 30-day challenge. Your direction for success shows through in your writing and your compassion in the comments and help you have provided throughout the experience.
I look forward to continuing our journey!
I love your summary. You covered it all very well.
Thank you for processing the information and providing you summary of what you learned in the challenge. I completely agree with the multiple income streaming strategies.
Being positive is the key, I could not agree more. If you can turn your negatives into a positive and keep on climbing, you will reach the summit sooner rather than later.


Today's Talk Back Question: If prices were lower, would you install solar panels on your roof?
October 15, 2015 Economy, Energy, Environment, Florida, newsfeed.
Voters saw through a utilities-based solar amendment.
If the prices of installation dropped, would you put solar panels on your roof?


text:
"""
File to keep track of installed extensions. Do not hand-modify.
"""

# The next line will be modified by the extension installer.
installed_extensions = []

# The next line will be modified by the extension installer.
extension_versions = {}

redpajama_set_name: RedPajamaGithub