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TrakCar – Drivers’ Peace of Mind
– As you’ve probably lost count of the times you’ve asked yourself “where have I parked my car?”, TrakCar has been unleashed to the iOS market to record your parking location with your iPhone or Apple Watch.
Developed by GeniusApp Technologies and completely compatible with the Apple Watch, TrakCar is the only app on the market that records the location of your car automatically, removing the need for expensive accessories or fiddling around. Utilising state-of-the-art, patent pending artificial intelligent technology, the intuitive TrakCar just needs to be turned on and will seamlessly work its magic without any effort needed.
TrakCar is truly automatic. Simply select the app, let it work in the background and, when the time comes, you can check your iPhone and TrakCar will let you know exactly where you have parked, meaning no embarrassing searches for your vehicle ever again! And, what’s more, TrakCar lets you see new parking events for free and offers an in-app upgrade to see past events.
Privacy is of the utmost importance to TrakCar’s developers, that’s why, after storing your parking location, the app will never send data to anyone. Simple, effective fully automatic, TrakCar’s is now fully integrated with the Apple Watch to ensure complete flexibility and peace of mind.
Excited about his creation, GeniusApp Technologies’ chief scientist said: “No other App can do it! We basically have no competition! All other "find your car" apps require you to press a button when you park. TrakCar does it all by itself!”
TrakCar is available to download for free from the Apple iTunes Store and is compatible with devices running iOS 7.1 or later.
Facebook - www.facebook.com/TrakCar.io
Twitter - www.twitter.com/TrakCarAppContinue reading
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Remember: Knowledge is Power.Continue reading
Adapted from http://www.nih.gov/
Researchers have shown that magnetic resonance imaging (MRI) can detect the earliest signs of breast cancer recurrence and fast-growing tumors. Their approach detects micrometastases, breakaway tumor cells with the potential to develop into dangerous secondary breast cancer tumors elsewhere in the body. The approach may offer an improved way to detect early recurrence of breast cancer in women and men. The work was completed at Case Western Reserve University (CWRU), Cleveland and was funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the National Institutes of Health.
“MRI has a wide array of diagnostic applications and shows promise in breast cancer detection and treatment monitoring,” said Richard Conroy, Ph.D., director of NIBIB Division of Applied Science and Technology. “The technique used by researchers in this study enables very early detection of metastatic spread, which would allow adaptation of treatment more quickly and hopefully lead to better outcomes in the future.”
The study, published online in the Aug. 12, 2015, issue of Nature Communications, was led by Zheng-Rong Lu, Ph.D., CWRU M. Frank Rudy and Margaret Domiter Rudy Professor of biomedical engineering and an expert in molecular imaging for cancer and other diseases.
“We showed with this technique that we can detect very tiny tumors of just a few hundred cells,” Lu said, adding that the study pushed imaging boundaries, revealing smaller cancers than can be detected with current clinical imaging modalities. “Our imaging technology has the potential to differentiate aggressive tumors from low-risk tumors. These are two things that potentially can make a big impact on clinical practice and also management of cancer.”
One-third of patients diagnosed with breast cancer eventually develop metastases in distant organs, with an increased risk of death. Breast cancer has a high rate of metastasis to bone, lung, liver, lymph nodes, and the brain. Since small, early-stage cancers are the most responsive to drug treatments, screening is an important aspect of follow-up care for breast cancer patients, and early detection is critical in tailoring appropriate and effective therapeutic interventions. While multiple imaging techniques, including MRI, are currently used in breast cancer detection and clinical management, they are neither able to detect specific cancer types or early cancer growth.
The earliest signs of cancer spread are called micrometastases. As the name implies, they are often too small to be detected with standard screening. Dr. Lu’s team used a biochemical approach combined with MRI to detect molecular changes that signal micrometastases. To detect micrometastases, Lu and his team used MRI imaging — which uses a magnetic field and radio waves to produce images – and combined it with a special chemical contrast solution.
The contrast solution that the team developed contains a short piece of protein, or peptide, tagged with a minuscule magnet. They chose the peptide — a chain of just five amino acids — for its inclination to bind to protein matrix structures around cancer cells, called fibrin-fibronectin complexes. More importantly, the fibronectin part of the complex is expressed during a cell’s transition to cancer and plays a role in cell growth, migration and differentiation. Fibronectin is associated with high-risk breast cancer with poor prognosis.
The researchers collected images depicting metastases where breast cancer had spread beyond the original tumors. Metal molecules within the contrast solution are magnetized during the MRI process and enhance the image wherever the molecules of solution bind with the targeted protein.
“The primary tumor sends signals to distant tissue and organs to prepare the soil for metastasis,” Lu said. “By also binding with the magnetically tagged peptide, the biomarker is enhanced, generating enough signal for MRI detection of small, high-risk cancer and micrometastases.”
The researchers tested the approach in mice into which they had introduced breast cancer cells. After a two-week waiting period, the researchers injected the contrast solution and performed MRI. The MRI imaging detected metastatic tumors, including micrometastases, in lung, liver, lymph node, adrenal gland, bone, and brains of the mice.
Analysis of images showed that the contrast used by the research team bound almost exclusively to the fibrin-fibronectin complexes, producing a strong and prolonged image enhancement of micrometastases and tumors compared with normal tissue. Using a microscopic imaging approach, called cryo-imaging, and MRI, the researchers verified that the MRI technique could detect micrometastases, even observing bone micrometastases that were less than 0.5mm — the diameter of a very fine pencil lead.
Prior to their study with this contrast agent, Lu’s team had conducted studies to determine its clearance from the body after the imaging, which is essential for safe clinical use. Their testing showed that the agent is readily cleared from the body and has a low level of retention in tissues. Therefore, they expect it will be safe if ultimately developed for clinical use.
“The recurrence rates of some forms of breast cancer and the consequence of metastatic cancer make these efforts urgent and important,” said Lu, adding that his research team also hopes to advance the approach for prostate cancer detection. “We think this targeted approach holds great promise for earlier imaging of high-risk cancers in the clinic. It could also become useful as a non-invasive way to assess breast cancer treatment progress.”
The team plans to complete safety testing of the imaging agent during the next three years. They will then pursue human trials with this approach.
This work was supported in part by NIH grants EB00489.
About the National Institute of Biomedical Imaging and Bioengineering: NIBIB’s mission is to improve health by leading the development and accelerating the application of biomedical technologies. The Institute is committed to integrating the physical and engineering sciences with the life sciences to advance basic research and medical care. NIBIB supports emerging technology research and development within its internal laboratories and through grants, collaborations, and training. More information is available at the NIBIB website: http://www.nibib.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
NIH...Turning Discovery Into Health®
Molecular MRI of Breast Cancer Micrometastases
Zhou Z, Qutaish M, Han Z, Schur RM, Liu Y, Wilson DL, Lu ZR. Nat Comms. 2015 Aug 12. [Epub]
Science is more than just benchwork – even the most exciting results need to be communicated effectively. That’s why scientific illustrations are often appealing: they provide information in lieu of a block of text.
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Plagiarism has far reaching consequences. These consequences are financial, emotional and traumatic. There have been innumerable examples of students, writers, lawyers and scientists who once believed that it was OK to copy but it was too late by the time they could undo the damages. A similar story was recently seen in the press when a famous South Korean artist Shin Kung-sook was implicated for plagiarized content in her short story ‘Legend’ published over 10 years ago. Shin had won the prestigious Man Asian literary prize in 2011. Leading newspapers blaming her of stealing another writer’s words have now tainted her fame. Her publisher has withdrawn this collection from the market.
There are many reasons why someone is tempted to copy that range from innocent to intentional. Students may be pressured in delivering quality content that is beyond their capability. Added to this, the increased competition makes it difficult for one to think clearly between right and wrong. Corporate executives may need to meet deadlines to deliver their works and find obtaining someone else’s content as the easiest way out.
People commonly claim lack of knowing as the commonest reason once they are caught. Even if you forget this to be an obvious slander, there is no escaping the fact that you are impossible to be saved by this fact.
The reason that Plagiarism is harder today than ever is due to the development of amazing tools that are able to pick up Plagiarism in a matter of seconds. The best tool we have found is Unplag.com. Unplag is not just one of the highest quality plagiarism detectors but also one that has features that are non-existent in other tools. To begin with, Unplag has an engine that checks against 16 billion pages that are found on google, bing and their own database. Unplag has an official partnership with Google and Bing that helps them analyze the deep sea of Internet content. To add to this, unplag gives results in a matter of seconds. Unplag creators have built this engine keeping the user in their mind. You can continue to work on whatever you are doing while unplag runs in the background. They have made sure that your information is safe and secure with a 128-bit encryption. Unplag will soon replace the opposite of plagiarism. Don’t make it late to be plagued by plagiarism. Unplag it at unplag.com
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Ever wondered why so many relationships fade away in oblivion? For decades, psychologists have struggled to understand the science behind keeping the spark alive in a relationship. The answer to reviving your romance is not that simple. The fact is that humans need ideas that are not a part of our daily lives. We need a constant reminder of rejuvenating our romance.
People believe that long-term relationships are bound to end one day. They blame it on age, work, stress and other factors beyond their control. Surprisingly, given the right spark in a relationship – none of these factors can dampen the spirit of romance.
There has been extensive research on this topic and well known psychologists and institute have published their research that gives us an insight into this problem. Some of these famous names include Harvey and Omarzu, the Gottman institute and the attachment research.
A few important points that have come out of these researches include
Keeping a focus on these facts, finally there is a solution to help you have a more fulfilling and sensual relationship.
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HSV or Herpes Simplex Virus, the etiological agent for Herpes has been a complexity for doctors and scientists for decades. Finally, cure for Herpes has been discovered in the most amazing place of all – nature. As seen on
Herpessecrets, there is a natural safe and effective remedy available that not only cures your Herpes but also provides fast symptom relief and stops further outbreaks.
The main cause of Herpes that causes genital ulcer diseases is a sexually transmitted virus known as the Herpes simplex virus type 2 (HSV-2). This virus also increases your susceptibility to HIV-1. The only options available to these patients are antiviral medications but limited success has been seen with these. Till date there is no cure available and even vaccines are at a premature stage of development.
Increasing evidence from research has shown that people affected with Herpes go through brief shedding episodes even when they have no symptoms. This alarming finding sheds light on the high transmission rates seen.
HSV virus enters the body thought inoculation through the mucosal surface as well as through skin cracks. The most common cause of this is by sexual transmission. Once inside the body, this virus starts replicating and destroying tissues resulting in its cytopathic effect. HSV virus escapes immunity by entering the sensory root ganglia and climbs the peripheral sensory nerves. The reason for its recurrence is reactivation of this virus from latently infected sacral nerve root ganglia.
Clinically Herpes presents as a first episode and subsequently recurrent outbreaks. This commonly starts in the genitals where HSV 1 or 2 has been shown to have similar severity and result in painful genital or extra-genital lesions. Besides the commonly known genital infection, HSV is known to cause other complications including Meningits, Pharygitis, as well as autonomic nervous system sacral radiculopathy. Also headaches and photophobia has been seen in patients infected with HSV.
HSV is transmitted both during outbreaks as well as during asymptomatic periods though viral shedding. Although common in both sexes, asymptomatic shedding is seen more in women. Transmission also occurs from a mother to a child through the vaginal passage delivery.
The established way of diagnosing HSV is through cell culture with HSV-1 and 2 typing. Monoclonal antibodies directed towards type specific antigens are used to subtype this virus. Newer developments include DNA detection tests as well as PCR of HSV.
Although so much is known about this virus, there is an absolute lack of treatments available. Current options available are Acyclovir, famciclovir,penciclovir and intravenous foscarnet. None of these drugs have been shown to cure Herpes and only cause (if at all) a brief, symptomatic relief.
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Television and movies are moving online more than ever before. According to Adobe, online viewership has increased over 146% in the last year itself. Viewers want to break free of getting stuck with their TV sets and mobile technology makes it possible to do that.
More movies and episodic content is available online and has seen a growth much higher than watching sports online. With so much content showing up on the Internet there was a dire need of a platform that could make it easier to know when your shows come online.
Finally there is one service that consolidates and tracks these shows called Marmo TV. Marmo TV was conceived by enthusiasts who loved watching shows online but could not find a way to know when their favorite programs were available. The result was a fantastic product called Marmo TV. Currently the Marmo TV group can be seen at their facebook page www.facebook.com/marmotv as well as on twitter at @Marmo_TV
With the ease of access using different devices like computers, laptops, tablets and mobile phones, users expectations are rising. Content providers and distributors are doing their best to catch up with fulfilling these expectations. Marmo TV is a growing service that is already seen as indispensable by their users. The beauty of this service is that it is a one-stop-shop to know when and where the programs you are waiting for become online.
Marmo TV goes beyond just a regular set of shows. They are growing not just because they love what they do but they are doing it for their users. Users are able to post requests for what they are seeking for and Marmo TV is the first to find for them as soon as those shows are Internet-aired.
Marmo TV is a platform that will soon be seen as necessary not just by the vast number of users but also by the entire showbiz industry.
The media and entertainment industry are making strides into the digital world - Marmo TV is the guide to when that happens.Continue reading
Our skin has the ability to absorb LED light and use it as a source of energy to stimulate cellular regeneration. LED light therapy, first researched by NASA for use in the U.S. Space Program, can reverse and control the visible signs of aging and help you look years younger without harsh chemical treatments or invasive surgical procedures. Tightening of skin, disappearing blemishes, smoothing of wrinkles and rough spots, softening of redness, and shrinking of pore size can be achieved with this natural light treatment.
Cells in the skin absorb wavelengths between 590 and 950 nanometers. Our cells convert this light energy into “fuel” that is used to increase cellular metabolism. Research by the National Aeronautics and Space Administration (NASA) has shown that light therapy increases cellular growth up to 200%.
While the NASA study focused on healing injuries, the effect of light therapy on skin is exactly the same. The increased cellular activity stimulates formation of new collagen and elastin — the building blocks of healthy skin. This is what makes red light therapy so effective in removing scars and general skin rejuvenating.
Yellow/Amber Light Therapy:
Amber light therapy can be referred to as yellow or orange light therapy. It encompasses the range of wavelengths from 570 nm to 600 nm.
Amber light has quite a shallow skin penetration but is effective in the treatment of skin issues involving redness, such as spider veins. Though it is not typically used for tissue healing or collagen/elastin production, where it excels is in the treatment of problems such as sun damage. It is often considered to be an ideal therapy for sensitive skin, as its therapy is calming and soothing.
Amber light therapy is frequently recommended as a drug free alternative treatment for skin redness and flushing, irritation, rosacea, UV radiation damage, and reducing the appearance of the tiny blood vessels on the nose and face. It helps to flush waste from the skin, boost lymphatic flow, and increase cellular growth.
Red Light Therapy:
Visible red light is capable of penetrating the skin to a depth of about 8 to 10 mm. Once absorbed, the light energy is converted to cellular energy, stimulating the body’s natural processes on a cellular level:
All of these things work together to produce many benefits for you in the areas of anti-aging, the healing of wounds and injuries, and the relief of pain, as we’ll see below. But no matter what the application, red and infrared light therapy share the same benefits overall.
Blue Light Therapy
Blue light is right next to UV light on the electromagnetic spectrum, and science has found that it retains some of the antibacterial properties of UV light, but without the risks associated with UV overexposure. Blue light was found to kill acne bacteria, and was FDA approved for that purpose around 2002.
Green Light Therapy:
Green light therapy typically falls in the wavelength range of 515 nm to 520 nm and is most frequently used for skin treatments and anti-aging therapies, such as an LED photofacial.
The rejuvenating benefits of green light therapy can help to improve pigmentation issues that have come from causes such as sun damage. This treatment can help to fade the appearance of freckles, as well as age spots, sun spots, reddish and brown patches, and liver spots. Other forms of hyper pigmentation and melanin problems that are caused by age can also be lightened through the use of light in these wavelengths.
Green light affects the melanocytes (the cells that produce the melanin, which is the pigmentation in the bottom layer of the epidermis), reducing its production. Over time, spots simply fade away for a younger looking, rejuvenated, and more even complexion.
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M. Mooney, ministry practitioner
Executive Elders Gregory Roberson and Michael Mooney are scheduled to hold lectures during a ministerial conference being held at the Freewater Institute of Pastoral Ministry in Kogi State, Nigeria. The provost, Brother Freewater Issah is a member of the National Association of Christian Ministers, and the Bible college holds a spiritual alliance with the NACM. Some 45 graduates are scheduled to receive ordination by the laying on of hands and ministerial licensing into during this event. Elders Roberson and Mooney are humbled by the privilege to partake in this ceremony, while representing the NACM internationally. With these things in mind, the following cultural analysis has been conducted for report.
Purpose of Report
The purpose of this report is to establish background information in preparation for a missions trip to Nigeria. The objective of the trip is to conduct a ministerial leadership workshop designed to equip emerging native pastors to effectively lead others in the 21st century. Herein, the cultural differences and similarities between American and Nigerian perspectives of leadership are considered. This report is written to prepare the traveling ministers with the knowledge necessary to position themselves appropriately within the culture; thereby, increasing the probability of successful communications, and interpersonal relations.
How this Information May Assist Future Missions
Missionaries from US cultures are often sent to Nigeria to establish new churches, and or to offer training to Nigerian pastors already overseeing established churches. The information herein may be utilized to increase the effectiveness of Kingdom objectives during their expedition.
Expectations for Leadership Acceptance
Leadership training is likely to be well received by Nigerians within the concept of its definition and scope. That is defining leadership as a process toward fellow persuasion within the domains of generating inspiration, developing and casting vision, modeling leadership behavior, and providing regular encouragement accompanied with feedback. However, there are striking contrasts between American and Nigerian perceptions of power distances between authority, and appreciation for individuality. For these reasons, special attention may be necessary when communicating leadership principles which emphasize originality, innovation, challenges to traditions, and prioritization of organizational goals above communal well being.
Leadership is a process by which initiators persuade members toward organizational objectives, visions and goals (Weathersby, 1999). In other words, “leadership is a process whereby an individual influences a group of individuals to achieve a common goal” (Northouse, p. 3, 2010). Kouzes and Posner (2002, 1987) describe leadership as something which occurs through modeling, inspiring, challenging, enabling, and encouraging constitutes. This approach to visionary leadership has been more specifically defined within the quantifiable behaviors of:
1. Challenging traditional process,
2. Inspiring a Shared Vision,
3. Inspiring others to take positive action,
4. Modeling the “way” of leadership, and
5. Encouraging the heats of those around us
Following these five attributes, research by Zagorsek, Jaklic, and Stough (2004) found little differences between American and Nigerian approaches to leadership when samples were taken from MBA students in both countries. The utility of this finding is that there may be a reasonable level of acceptance for charismatic approaches to leadership. Although, it still should be anticipated that there will be differences regarding cultural attitudes in areas such as power distance, individuality, and gender roles. In order to maintain mutual understanding, Americans should maintain a respect for those holding traditional mindsets toward gender and political power. Americans should be sensitive to varying opinions and careful not to assume that such cultural element are somehow wrong or discriminatory –in light of their US afforded freedoms. Further, they should not attempt to undermine these dynamics while expecting to maintain welcomed communications.
Geert Hofstede offers a systematic approach to cultural analysis which has become a standard in global relations. His method seeks to view cultures through the lenses of five categories:
1. Power Distance (PDI),
2. Individualism (IDV),
3. Masculinity (MAS),
4. Uncertainty Avoidance (UAI) and
5. Long Term Orientation (LTO) (Northouse, 2010).
According to the Hofstede Centre (2013), the cultural dimensions between Nigeria and the US are as follows: PDI 80/40, IDV 30/91, MAS 60/62, and UAI 55/46, LTO 16/29. Each score is an assigned number out of 100. These numbers are generally interpreted as existing in one of two categories: high or low. A score is high when it is above 50, and low when below 50. Comparisons and contrasts between two cultures are generally considered as being either similar or not similar. Below are the results between Nigerians and North Americans.
Nigerian & American Power Distance: Not similar
Power Distance (PDI) describes the levels of social tolerance toward the gaps that exist between authorities and subordinates –in other words the lack of social equality. Nigeria holds a high score at 80 vs. the US position of 40. The implications are that Nigerians are much more accepting of social classes, and much more accepting of autocratic authority which clearly defines objectives (Hofstede, 2012).
Nigerian & American Individualism: Not similar
Individualism (IDV) considers societal preferences for communal solidarity. Nigeria holds a low score in this category at 30 vs. the US at 91. The implications are that Nigeria is a collectivist country, holding high regard for community, group membership, shared responsibility, and loyalty that at times supersedes rationality. Even in matters of organizational promotions of leadership, decisions may be most influenced by family connections or group membership –as opposed to qualifications (Hofstede, 2012). This position stands in contrast to the self-promoted society of the US. Yet, there are many biblical similarities with the Nigerian concept of community, and their culture may be a good model for how church members should prefer one another.
Nigerian & American Masculinity: Similar
Masculinity (MAS) describes the extent to which a society is competitive, results driven, and achievement oriented, as opposed to femininity, which describes success in terms of overall quality of life. Nigeria scores a 62 in this category, which is very similar to the US holding a 60. Therefore, the implications are that both cultures are predominately masculine, while maintaining an appreciation for femininity (Hofstede, 2012).
Nigerian & American Uncertainty Avoidance: Not Similar
Uncertainty Avoidance (UAI) determines the extent to which a society is comfortable with undefined leadership roles, and how anxiety relates to unpredictable events (Jones, & Alony, 2007). In other words, it is projected that people with high scores in this area are inclined to seek situations where circumstances are predictable. Nigeria scores a 55 in this area, and the US a 46. The implications are that Nigerians are prone to hold strict codes of behavior, prone to structure, highly regard punctuality, and value security as a great priority (Hofstede, 2012).
Nigerian & American Long Term Orientation: Similar
Long Term Orientation (LTO) is descriptive of a society’s view of the future in terms of something hopeful, innovative, and in need of preparation –as opposed to the short term orientation which holds high regard for tradition, enjoys quick results, and less likely to save for future endeavors. Nigeria holds a score of 16 in this domain vs. the US which is a 29. The implications are that Nigerians and Americans are typically interested in quick results and are often motivated to keep up with the social wealth of their neighbors (Hofstede, 2012).
From this analysis it may be concluded that Nigerians and Americans hold similar attitudes in areas of ambition, competition, results orientation, and achievement. Ministers of the gospel may uses these as points by which to establish rapport and mutual understanding during times of general communication, formal training sessions, and selection of content for illustrations.
Further, there is a shared interest in “quick fixes” and avoiding the pain of delayed gratification. This information may be a useful launching pad by which ministers may point out their perusal weaknesses and lack of patience; thereby also developing opportunities to gain rapport while teaching from scripture.
Nevertheless, Nigerians and Americans hold different perspectives regarding social equality, individuality, and the willingness to take risks. Therefore, careful attention should be given to these areas in order to enjoy the potential associated with effective communication. Additionally, Americans may have a few things to learn from Nigerians in the virtues of their selfless contributions as members of greater communities.
Hofstede, G. (2013). Geert Hofstede cultural dimensions: Greece. Retrieved June 1, 2013, from http://geert-hofstede.com/nigeria.html
Hugo Zagorsek, Marko Jaklic, & Stanley J. Stough. (2004). Comparing leadership practices between the united states, nigeria, and slovenia: Does culture matter? Cross Cultural Management: An International Journal, 11(2), 16-34. doi:10.1108/13527600410797774
Jones, M., & Alony, I. (2007, January). The Cultural Impact of Information Systems -- Through the Eyes of Hofstede -- A Critical Journey. Issues in Informing Science & Information Technology, 4(13), 407.
Kouzes, J., Posner, B. 2002. The Leadership Challenge. Jossey-Bass Publishing.
Kouzes, J.M. & Posner, B.Z. (1987) The Leadership Challenge: How to Get Extraordinary Things Done in Organizations. San Francisco: Jossey-Bass.
Northouse, P. G. (2010). Leadership: Theory and Practice (5th ed.). Thousand Oaks, CA: Sage Publications. ISBN: 978-1-4129-7488-2.
Weathersby, G. (1999). Leadership vs. Management. Management Review, 88(3), 5.
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Years before they show any other signs of disease, pancreatic cancer patients have very high levels of certain amino acids in their bloodstream, according to a new study from MIT, Dana-Farber Cancer Institute, and the Broad Institute.
This finding, which suggests that muscle tissue is broken down in the disease’s earliest stages, could offer new insights into developing early diagnostics for pancreatic cancer, which kills about 40,000 Americans every year and is usually not caught until it is too late to treat.
The study, which appears today in the journal Nature Medicine, is based on an analysis of blood samples from 1,500 people participating in long-term health studies. The researchers compared samples from people who were eventually diagnosed with pancreatic cancer and samples from those who were not. The findings were dramatic: People with a surge in amino acids known as branched chain amino acids were far more likely to be diagnosed with pancreatic cancer within one to 10 years.
“Pancreatic cancer, even at its very earliest stages, causes breakdown of body protein and deregulated metabolism. What that means for the tumor, and what that means for the health of the patient — those are long-term questions still to be answered,” says Matthew Vander Heiden, an associate professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and one of the paper’s senior authors.
The paper’s other senior author is Brian Wolpin, an assistant professor of medical oncology at Dana-Farber. Wolpin, a clinical epidemiologist, assembled the patient sample from several large public-health studies. All patients had their blood drawn when they began participating in the studies and subsequently filled out annual health questionnaires.
Working with researchers at the Broad Institute, the team analyzed blood samples for more than 100 different metabolites — molecules, such as proteins and sugars, produced as the byproducts of metabolic processes.
“What we found was that this really interesting signature fell out as predicting pancreatic cancer diagnosis, which was elevation in these three branched chain amino acids: leucine, isoleucine, and valine,” Vander Heiden says. These are among the 20 amino acids — the building blocks for proteins — normally found in the human body.
Some of the patients in the study were diagnosed with pancreatic cancer just one year after their blood samples were taken, while others were diagnosed two, five, or even 10 years later.
“We found that higher levels of branched chain amino acids were present in people who went on to develop pancreatic cancer compared to those who did not develop the disease,” Wolpin says. “These findings led us to hypothesize that the increase in branched chain amino acids is due to the presence of an early pancreatic tumor.”
Early protein breakdown
Vander Heiden’s lab tested this hypothesis by studying mice that are genetically programmed to develop pancreatic cancer. “Using those mouse models, we found that we could perfectly recapitulate these exact metabolic changes during the earliest stages of cancer,” Vander Heiden says. “What happens is, as people or mice develop pancreatic cancer, at the very earliest stages, it causes the body to enter this altered metabolic state where it starts breaking down protein in distant tissues.”
“This is a finding of fundamental importance in the biology of pancreatic cancer,” says David Tuveson, a professor at the Cancer Center at Cold Spring Harbor Laboratory who was not involved in the work. “It really opens a window of possibility for labs to try to determine the mechanism of this metabolic breakdown.”
The researchers are now investigating why this protein breakdown, which has not been seen in other types of cancer, occurs in the early stages of pancreatic cancer. They suspect that pancreatic tumors may be trying to feed their own appetite for amino acids that they need to build cancerous cells. The researchers are also exploring possible links between this early protein breakdown and the wasting disease known as cachexia, which often occurs in the late stages of pancreatic cancer.
Also to be answered is the question of whether this signature could be used for early detection. The findings need to be validated with more data, and it may be difficult to develop a reliable diagnostic based on this signature alone, Vander Heiden says. However, he believes that studying this metabolic dysfunction further may reveal additional markers, such as misregulated hormones, that could be combined to generate a more accurate test.Continue reading
Since the start of the military conflicts in Iraq and Afghanistan, more than 300,000 soldiers have returned to the United States with traumatic brain injury (TBI) caused by exposure to bomb blasts — and in particular, exposure to improvised explosive devices, or IEDs. Symptoms of traumatic brain injury can range from the mild, such as lingering headaches and nausea, to more severe impairments in memory and cognition.
Since 2007, the U.S. Department of Defense has recognized the critical importance and complexity of this problem, and has made significant investments in traumatic brain injury research. Nevertheless, there remain many gaps in scientists’ understanding of the effects of blasts on the human brain; most new knowledge has come from experiments with animals.
Now MIT researchers have developed a scaling law that predicts a human’s risk of brain injury, based on previous studies of blasts’ effects on animal brains. The method may help the military develop more protective helmets, as well as aid clinicians in diagnosing traumatic brain injury — often referred to as the “invisible wounds” of battle.
“We’re really focusing on mild traumatic brain injury, where we know the least, but the problem is the largest,” says Raul Radovitzky, a professor of aeronautics and astronautics and associate director of the MIT Institute for Soldier Nanotechnologies (ISN). “It often remains undetected. And there’s wide consensus that this is clearly a big issue.”
While previous scaling laws predicted that humans’ brains would be more resilient to blasts than animals’, Radovitzky’s team found the opposite: that in fact, humans are much more vulnerable, as they have thinner skulls to protect much larger brains.
A group of ISN researchers led by Aurélie Jean, a postdoc in Radovitzky’s group, developed simulations of human, pig, and rat heads, and exposed each to blasts of different intensities. Their simulations predicted the effects of the blasts’ shockwaves as they propagated through the skulls and brains of each species. Based on the resulting differences in intracranial pressure, the team developed an equation, or scaling law, to estimate the risk of brain injury for each species.
“The great thing about doing this on the computer is that it allows you to reduce and possibly eventually eliminate animal experiments,” Radovitzky says.
The MIT team and co-author James Q. Zheng, chief scientist at the U.S. Army’s soldier protection and individual equipment program, detail their results this week in the Proceedings of the National Academy of Sciences.
Air (through the) head
A blast wave is the shockwave, or wall of compressed air, that rushes outward from the epicenter of an explosion. Aside from the physical fallout of shrapnel and other chemical elements, the blast wave alone can cause severe injuries to the lungs and brain. In the brain, a shockwave can slam through soft tissue, with potentially devastating effects.
In 2010, Radovitzky’s group, working in concert with the Defense and Veterans Brain Injury Center, a part of the U.S. military health system, developed a highly sophisticated, image-based computational model of the human head that illustrates the ways in which pressurized air moves through its soft tissues. With this model, the researchers showed how the energy from a blast wave can easily reach the brain through openings such as the eyes and sinuses — and also how covering the face with a mask can prevent such injuries. Since then, the team has developed similar models for pigs and rats, capturing the mechanical response of brain tissue to shockwaves.
In their current work, the researchers calculated the vulnerability of each species to brain injury by establishing a mathematical relationship between properties of the skull, brain, and surrounding flesh, and the propagation of incoming shockwaves. The group considered each brain structure’s volume, density, and celerity — how fast stress waves propagate through a tissue. They then simulated the brain’s response to blasts of different intensities.
“What the simulation allows you to do is take what happens outside, which is the same across species, and look at how strong was the effect of the blast inside the brain,” Jean says.
In general, they found that an animal’s skull and other fleshy structures act as a shield, blunting the effects of a blast wave: The thicker these structures are, the less vulnerable an animal is to injury. Compared with the more prominent skulls of rats and pigs, a human’s thinner skull increases the risk for traumatic brain injury.
Shifting the problem
This finding runs counter to previous theories, which held that an animal’s vulnerability to blasts depends on its overall mass, but which ignored the role of protective physical structures. According to these theories, humans, being more massive than pigs or rats, would be better protected against blast waves.
Radovitzky says this reasoning stems from studies of “blast lung” — blast-induced injuries such as tearing, hemorrhaging, and swelling of the lungs, where it was found that mass matters: The larger an animal is, the more resilient it may be to lung damage. Informed by such studies, the military has since developed bulletproof vests that have dramatically decreased the number of blast-induced lung injuries in recent years.
“There have essentially been no reported cases of blast lung in the last 10 years in Iraq or Afghanistan,” Radovitzky notes. “Now we’ve shifted that problem to traumatic brain injury.”
In collaboration with Army colleagues, Radovitzky and his group are performing basic research to help the Army develop helmets that better protect soldiers. To this end, the team is extending the simulation approach they used for blast to other types of threats.
His group is also collaborating with audiologists at Massachusetts General Hospital, where victims of the Boston Marathon bombing are being treated for ruptured eardrums.
“They have an exact map of where each victim was, relative to the blast,” Radovitzky says. “In principle, we could simulate the event, find out the level of exposure of each of those victims, put it in our scaling law, and we could estimate their risk of developing a traumatic brain injury that may not be detected in an MRI.”
Joe Rosen, a professor of surgery at Dartmouth Medical School, sees the group’s scaling law as a promising window into identifying a long-sought mechanism for blast-induced traumatic brain injury.
“Eighty percent of the injuries coming off the battlefield are blast-induced, and mild TBIs may not have any evidence of injury, but they end up the rest of their lives impaired,” says Rosen, who was not involved in the research. “Maybe we can realize they’re getting doses of these blasts, and that a cumulative dose is what causes [TBI], and before that point, we can pull them off the field. I think this work will be important, because it puts a stake in the ground so we can start making some progress.”Continue reading
Bacillus anthracis bacteria have very efficient machinery for injecting toxic proteins into cells, leading to the potentially deadly infection known as anthrax. A team of MIT researchers has now hijacked that delivery system for a different purpose: administering cancer drugs.
“Anthrax toxin is a professional at delivering large enzymes into cells,” says Bradley Pentelute, the Pfizer-Laubauch Career Development Assistant Professor of Chemistry at MIT. “We wondered if we could render anthrax toxin nontoxic, and use it as a platform to deliver antibody drugs into cells.”
In a paper appearing in the journal ChemBioChem, Pentelute and colleagues showed that they could use this disarmed version of the anthrax toxin to deliver two proteins known as antibody mimics, which can kill cancer cells by disrupting specific proteins inside the cells. This is the first demonstration of effective delivery of antibody mimics into cells, which could allow researchers to develop new drugs for cancer and many other diseases, says Pentelute, the senior author of the paper.
Hitching a ride
Antibodies — natural proteins the body produces to bind to foreign invaders — are a rapidly growing area of pharmaceutical development. Inspired by natural protein interactions, scientists have designed new antibodies that can disrupt proteins such as the HER2 receptor, found on the surfaces of some cancer cells. The resulting drug, Herceptin, has been successfully used to treat breast tumors that overexpress the HER2 receptor.
Several antibody drugs have been developed to target other receptors found on cancer-cell surfaces. However, the potential usefulness of this approach has been limited by the fact that it is very difficult to get proteins inside cells. This means that many potential targets have been “undruggable,” Pentelute says.
“Crossing the cell membrane is really challenging,” he says. “One of the major bottlenecks in biotechnology is that there really doesn’t exist a universal technology to deliver antibodies into cells.”
For inspiration to solve this problem, Pentelute and his colleagues turned to nature. Scientists have been working for decades to understand how anthrax toxins get into cells; recently researchers have started exploring the possibility of mimicking this system to deliver small protein molecules as vaccines.
The anthrax toxin has three major components. One is a protein called protective antigen (PA), which binds to receptors called TEM8 and CMG2 that are found on most mammalian cells. Once PA attaches to the cell, it forms a docking site for two anthrax proteins called lethal factor (LF) and edema factor (EF). These proteins are pumped into the cell through a narrow pore and disrupt cellular processes, often resulting in the cell’s death.
However, this system can be made harmless by removing the sections of the LF and EF proteins that are responsible for their toxic activities, leaving behind the sections that allow the proteins to penetrate cells. The MIT team then replaced the toxic regions with antibody mimics, allowing these cargo proteins to catch a ride into cells through the PA channel.
‘A prominent advance’
The antibody mimics are based on protein scaffolds that are smaller than antibodies but still maintain structural diversity and can be designed to target different proteins inside a cell. In this study, the researchers successfully targeted several proteins, including Bcr-Abl, which causes chronic myeloid leukemia; cancer cells in which that protein was disrupted underwent programmed cell suicide. The researchers also successfully blocked hRaf-1, a protein that is overactive in many cancers.
“This work represents a prominent advance in the drug-delivery field,” says Jennifer Cochran, an associate professor of bioengineering at Stanford University. “Given the efficient protein delivery Pentelute and colleagues achieved with this technology compared to a traditional cell-penetrating peptide, studies to translate these findings to in vivo disease models will be highly anticipated.”
The MIT team is now testing this approach to treat tumors in mice and is also working on ways to deliver the antibodies to specific types of cells.Continue reading