SHIVARATRI

Introduction

This falls on the 13th (or 14th) day of the dark half of Phalgun (February-March). The name means "the night of Shiva". The ceremonies take place chiefly at night. This is a festival observed in honour of Lord Shiva. Shiva was married to Parvati on this day.

People observe a strict fast on this day. Some devotees do not even take a drop of water. They keep vigil all night. The Shiva Lingam is worshipped throughout the night by washing it every three hours with milk, curd, honey, rose water, etc., whilst the chanting of the Mantra Om Namah Shivaya continues. Offerings of bael leaves are made to the Lingam. Bael leaves are very sacred as, it is said, Lakshmi resides in them.

Hymns in praise of Lord Shiva, such as the Shiva Mahimna Stotra of Pushpadanta or Ravana's Shiva Tandava Stotra are sung with great fervour and devotion. People repeat the Panchakshara Mantra, Om Namah Shivaya. He who utters the Names of Shiva during Shivaratri, with perfect devotion and concentration, is freed from all sins. He reaches the abode of Shiva and lives there happily. He is liberated from the wheel of births and deaths. Many pilgrims flock to the places where there are Shiva temples.

The Story of King Chitrabhanu

In the Shanti Parva of the Mahabharata, Bhishma, whilst resting on the bed of arrows and discoursing on Dharma, refers to the observance of Maha Shivaratri by King Chitrabhanu. The story goes as follows.

Once upon a time King Chitrabhanu of the Ikshvaku dynasty, who ruled over the whole of Jambudvipa, was observing a fast with his wife, it being the day of Maha Shivaratri. The sage Ashtavakra came on a visit to the court of the king.

The sage asked, "O king! why are you observing a fast today?"

King Chitrabhanu explained why. He had the gift of remembering the incidents of his previous birth.

The king said to the sage: "In my past birth I was a hunter in Varanasi. My name was Suswara. My livelihood was to kill and sell birds and animals. One day I was roaming the forests in search of animals. I was overtaken by the darkness of night. Unable to return home, I climbed a tree for shelter. It happened to be a bael tree. I had shot a deer that day but I had no time to take it home. I bundled it up and tied it to a branch on the tree. As I was tormented by hunger and thirst, I kept awake throughout the night. I shed profuse tears when I thought of my poor wife and children who were starving and anxiously awaiting my return. To pass away the time that night I engaged myself in plucking the bael leaves and dropping them down onto the ground.

"The day dawned. I returned home and sold the deer. I bought some food for myself and for my family. I was about to break my fast when a stranger came to me, begging for food. I served him first and then took my food.

"At the time of death, I saw two messengers of Lord Shiva. They were sent down to conduct my soul to the abode of Lord Shiva. I learnt then for the first time of the great merit I had earned by the unconscious worship of Lord Shiva during the night of Shivaratri. They told me that there was a Lingam at the bottom of the tree. The leaves I dropped fell on the Lingam. My tears which I had shed out of pure sorrow for my family fell onto the Lingam and washed it. And I had fasted all day and all night. Thus did I unconsciously worship the Lord.

"I lived in the abode of the Lord and enjoyed divine bliss for long ages. I am now reborn as Chitrabhanu."

Spiritual Significance of the Ritual

The Scriptures record the following dialogue between Sastri and Atmanathan, giving the inner meaning of the above story.

Sastri: It is an allegory. The wild animals that the hunter fought with are lust, anger, greed, infatuation, jealousy and hatred. The jungle is the fourfold mind, consisting of the subconscious mind, the intellect, the ego and the conscious mind. It is in the mind that these "wild animals" roam about freely. They must be killed. Our hunter was pursuing them because he was a Yogi. If you want to be a real Yogi you have to conquer these evil tendencies. Do you remember the name of the hunter in the story?

Atmanathan: Yes, he was called Suswara.

Sastri: That's right. It means "melodious". The hunter had a pleasant melodious voice. If a person practices Yama and Niyama and is ever conquering his evil tendencies, he will develop certain external marks of a Yogi. The first marks are lightness of the body, health, steadiness, clearness of countenance and a pleasant voice. This stage has been spoken of in detail in the Swetaswatara Upanishad. The hunter or the Yogi had for many years practised Yoga and had reached the first stage. So he is given the name Suswara. Do you remember where he was born?

Atmanathan: Yes, his birthplace is Varanasi.

Sastri: Now, the Yogis call the Ajna Chakra by the name Varanasi. This is the point midway between the eyebrows. It is regarded as the meeting place of the three nerve currents (Nadis), namely, the Ida, Pingala and the Sushumna. An aspirant is instructed to concentrate on that point. That helps him to conquer his desires and evil qualities like anger and so on. It is there that he gets a vision of the Divine Light within.

Atmanathan: Very interesting! But how do you explain his climbing up the bael tree and all the other details of the worship?

Sastri: Have you ever seen a bael leaf?

Atmanathan: It has three leaves on one stalk.

Sastri: True. The tree represents the spinal column. The leaves are threefold. They represent the Ida, Pingala and Sushumna Nadis, which are the regions for the activity of the moon, the sun and fire respectively, or which may be thought of as the three eyes of Shiva. The climbing of the tree is meant to represent the ascension of the Kundalini Shakti, the serpentine power, from the lowest nerve centre called the Muladhara to the Ajna Chakra. That is the work of the Yogi.

Atmanathan: Yes, I have heard of the Kundalini and the various psychic centres in the body. Please go on further; I am very interested to know more.

Sastri: Good. The Yogi was in the waking state when he began his meditation. He bundled up the birds and the animals he had slain and, tying them on a branch of the tree, he rested there. That means he had fully conquered his thoughts and rendered them inactive. He had gone through the steps of Yama, Niyama, Pratyahara, etc. On the tree he was practising concentration and meditation. When he felt sleepy, it means that he was about to lose consciousness and go into deep sleep. So he determined to keep awake.

Atmanathan: That is now clear to me; you certainly do explain it very well. But why did he weep for his wife and children?

Sastri: His wife and children are none other than the world. One who seeks the Grace of God must become an embodiment of love. He must have an all-embracing sympathy. His shedding of tears is symbolical of his universal love. In Yoga also, one cannot have illumination without Divine Grace. Without practising universal love, one cannot win that Grace. One must perceive one's own Self everywhere. The preliminary stage is to identify one's own mind with the minds of all created beings. That is fellow-feeling or sympathy. Then one must rise above the limitations of the mind and merge it in the Self. That happens only in the stage of Samadhi, not earlier.

Atmanathan: Why did he pluck and drop the bael leaves?

Sastri: That is mentioned in the story only to show that he had no extraneous thoughts. He was not even conscious of what he was doing. All his activity was confined to the three Nadis. The leaves, I have said before, represent the three Nadis. He was in fact in the second state, namely, the dream state, before he passed into the deep sleep state.

Atmanathan: He kept vigil the whole night, it is said.

Sastri: Yes, that means that he passed through the deep sleep state successfully. The dawning of day symbolises the entrance into the Fourth state called Turiya or superconsciousness.

Atmanathan: It is said that he came down and saw the Lingam. What does that mean?

Sastri: That means that in the Turiya state he saw the Shiva Lingam or the mark of Shiva in the form of the inner lights. In other words, he had the vision of the Lord. That was an indication to him that he would realise the supreme, eternal abode of Lord Shiva in course of time.

Atmanathan: So it appears from what you say that the sight of the lights is not the final stage?

Sastri: Oh no! That is only one step, albeit a difficult one. Now think of how the story continues. He goes home and feeds a stranger. A stranger is one whom you have not seen before. The stranger is no other than the hunter himself, transformed into a new person. The food was the likes and dislikes which he had killed the previous night. But he did not consume the whole of it. A little still remained. That was why he had to be reborn as King Chitrabhanu. Going to the world of Shiva (Salokya) is not enough to prevent this. There are other stages besides Salokya. These are Samipya, Sarupya and finally Sayujya. Have you not heard of Jaya and Vijaya returning from Vaikunta?

Atmanathan: Yes, I have understood now.

Lord Shiva's Assuarance

When creation had been completed, Shiva and Parvati went out to live on the top of Mount Kailas. Parvati asked, "O venerable Lord! which of the many rituals observed in Thy honour doth please Thee most?"

The Lord replied, "The 14th night of the new moon, in the dark fortnight during the month of Phalgun, is my most favourite day. It is known as Shivaratri. My devotees give me greater happiness by mere fasting than by ceremonial baths and offerings of flowers, sweets and incense.

"The devotee observes strict spiritual discipline in the day and worships Me in four different forms during each of the four successive three-hour periods of the night. The offering of a few bael leaves is more precious to Me than the precious jewels and flowers. My devotee should bathe Me in milk at the first period, in curd at the second, in clarified butter at the third, and in honey at the fourth and last. Next morning, he should feed the Brahmins first and, after performing the prescribed ceremonies, he can break his fast. O Parvati! there is no ritual which can compare with this simple routine in sanctity."

Parvati was deeply impressed by the speech of Loid Shiva. She repeated it to Her friends who in their turn passed it on to the ruling princes on earth. Thus was the sanctity of Shivaratri broadcast all over the world.

The two great natural forces that afflict man are Rajas (the quality of passionate activity) and Tamas (that of inertia). The Shivaratri Vrata aims at the perfect control of these two. The entire day is spent at the Feet of the Lord. Continuous worship of the Lord necessitates the devotee's constant presence in the place of worship. Motion is controlled. Evils like lust, anger, and jealousy, born of Rajas are ignored and subdued. The devotee observes vigil throughout the night and thus conquers Tamas also. Constant vigilance is imposed on the mind. Every three hours a round of worship of the Shiva Lingam is conducted. Shivaratri is a perfect Vrata.

The formal worship consists of bathing the Lord. Lord Shiva is considered to be the Form of Light (which the Shiva Lingam represents). He is burning with the fire of austerity. He is therefore best propitiated with cool bathing. While bathing the Lingam the devotee prays: "O Lord! I will bathe Thee with water, milk, etc. Do Thou kindly bathe me with the milk of wisdom. Do Thou kindly wash me of all my sins, so that the fire of worldliness which is scorching me may be put out once for all, so that I may be one with Thee-the One alone without a second."

At the Sivananda Ashram, Rishikesh, the Shivaratri festival is celebrated in the following manner.

1. All spiritual aspirants fast the whole day, many of them without taking even a single drop of water.
2. A grand havan is performed for the peace and welfare of all.
3. The whole day is spent in doing the Japa of Om Namah Shivaya and in meditation upon the Lord.
4. At night all assemble in the temple and chant Om Namah Shivaya the whole night.
5. During the four quarters of the night the Shiva Lingam is worshipped with intense devotion.
6. Sannyas Diksha is also given on this day to sincere seekers on the path.

Legends of Mahashivratri

There are various interesting legends related to the festival of Maha Shivaratri. According to one of the most popular legends, Shivaratri marks the wedding day of Lord Shiva and Parvati. Some believe that it was on the auspicious night of Shivaratri that Lord Shiva performed the 'Tandava', the dance of the primal creation, preservation and destruction. Another popular Shivratri legend stated in Linga Purana states that it was on Shivaratri that Lord Shiva manifested himself in the form of a Linga. Hence the day is considered to be extremely auspicious by Shiva devotees and they celebrate it as Mahashivaratri - the grand night of Shiva.

Traditions and Customs of Shivaratri

Various traditions and customs related to Shivaratri Festival are dutifully followed by the worshippers of Lord Shiva. Devotees observe strict fast in honor of Shiva, though many go on a diet of fruits and milk some do not consume even a drop of water. Devotees strongly believe that sincere worship of Lord Shiva on the auspicious day of Shivaratri, absolves a person of sins and liberates him from the cycle of birth and death. Shivaratri is considered especially auspicious for women. While married women pray for the well being of their husbands unmarried women pray for a husband like Lord Shiva, who is regarded as the ideal husband.

To mark the Shivratri festival, devotees wake up early and take a ritual bath, preferably in river Ganga. After wearing fresh new clothes devotees visit the nearest Shiva temple to give ritual bath to the Shiva Lingum with milk, honey, water etc.

On Shivaratri, worship of Lord Shiva continues all through the day and night. Every three hours priests perform ritual pooja of Shivalingam by bathing it with milk, yoghurt, honey, ghee, sugar and water amidst the chanting of “Om Namah Shivaya’ and ringing of temple bells. Nightlong vigil or jaagran is also observed in Shiva temples where large number of devotees spend the night singing hymns and devotional songs in praise of Lord Shiva. It is only on the following morning that devotee break their fast by partaking prasad offered to the deity.

When do we celebrate Mahashivaratri
Auspicious festival of Mahashivaratri falls on the 13th or the 14th night of the new moon during Krishna Paksha in the Hindu month of Phalgun. The Sanskrit term, Krishna Paksha means the period of waning moon or the dark fortnight and Phalguna corresponds to the month of February - March in English Calendar. Shivaratri Festival is celebrated on a moonless night.

According to Hindu mythology, Shivaratri or 'Shiva's Great Night' symbolizes the wedding day of Lord Shiva and Parvati. Many however, believe, Shivaratri is the night when Lord Shiva performed the Tandava Nritya - the dance of primordial creation, preservation and destruction. Celebrating the festival in a customary manner, devotees give a ritual bath to the Lingam with the panchagavya - milk, sour milk, urine, butter and dung. Celebrations of Shivaratri Festival mainly take place at night. Devotees of Lord Shiva throng Shiva temples across the country and spend ‘the Night of Lord Shiva’ by chanting verses and hymns in praise of the Lord. The festival holds special meaning for the ladies. They pray to Goddess Parvati also called 'Gaura', the giver of 'suhag' for good husbands, marital bliss and a long and prosperous married life.

Shivaratri Rituals
Devotees of Lord Shiva observe the Shivaratri Festival by following the prescribed rituals with sincerity and devotion. All through the day, devotees abstain from eating food and break their fast only the next morning, after the nightlong worship. Ritual baths of Shivalinga in the numerous Shiva temples by Shiva worshiper, mainly women, is another significant feature of Shivratri customs and traditions. Devotees strongly believe that ritual worship of Lord Shiva on the auspicious day of Shivaratri absolves them of past sins and they are blessed with Moksha.

Rituals Observed on a Shivaratri Morning
As a tradition devotees wake up early in the morning of the Mahashivratri day and take a ritual sunrise bath, preferably in the holy waters of river Ganga. They also offer prayers to the Sun God, Vishnu and Shiva as a part of a purification rite observed on all-important Hindu festivals. After wearing fresh new clothes devotees visit the nearest Shiva Temple to give the customary bath to the Shivalinga.

On a Shivratri day, Shiva temples are thronged by devotees, mainly women, who come to perform the traditional Shivalinga pooja and seek blessings from the god. At times there is so much rush in the temples that devotees have to wait for their turn to observe pooja. At their turn for worship, devotees circumambulate the Shivalinga, three or seven times, and then pour water over it. Some also pour milk. Sounds of bell and shouts of ‘Shankarji ki Jai’ or (Hail Shiva) reverberate in the temple premises.

Ritual Bath of Shivalinga

Following the rituals prescribed in the Shiva Purana, every three hours, Shivalingam is given a special bath with milk, yoghurt, honey, sandalwood paste and rose water. Puja, meditation and chanting of ‘Om Namah Shivaya’ accompany the ritual bath. Following the bath, vermilion paste is applied on the linga. Traditionally, leaves of a forest tree Aegle marmelos (bilwa, maredu, wood apple) are used for Shiva puja. Thereafter, Bilwa leaves, which have to be a stalk with three leaves, is kept on top of the Shivalinga. Ber or jujube fruit is a special offering to the god on this day. Beetle leaves are also offered by some. Some also offer bilwa leaves in the belief that the Goddess Lakshmi resides in them. Others believe it is offered for its cooling effects on the hot-tempered deity. Many devotees also decorate the linga with flowers and garlands and offer incense sticks and fruit.



Significance of Puja Items

• According to the Shiva Purana, there is a special significance of the six essential puja items used in the Shiva worship.
• Bathing of Shivalinga with water, milk and honey and wood apple or bel leaves added to it, represents purification of the soul.
• The vermilion paste applied on the linga after the ritual bath represents virtue.
• Offering of fruits symbolizes longevity and gratification of desires.
• Burning of incense sticks yields wealth.
• The lighting of the lamp symbolizes attainment of knowledge.
• Offering of betel leaves marks satisfaction with worldly pleasures.
• All-Night Shiva Worship
  
  
  
  
  
  
  
  
  
  
  
  
  

  Shivaratri Foods and Recipes

  Mahashivaratri is celebrated on Chaturdashi of Falgun Krishna Paksha. Shivaratri is a day of joy and celebration for the devotees of lord Shiva. It is said that once goddess Parvati worshipped lord Shiva with full devotion. Pleased by this lord Shiva said that whoever will observe the fast of Mahashivarati and perform his Puja with full faith, all wishes of that person will get fulfilled. From that day the Mahatmya of Shivaratri fasting was spread in the world.

  
  

  Lord Shiva was married to Devi Parvati on the day of Mahashivaratri. Hence the significance of Shivaratri increases. A person who worship God Shiva and Mata Parvati, on this day, gets the blessing and grace of lord. Jagaran is performed in the night. Shiva Katha and Bhajans are organised.

  
  

  Shivarati Fast

  People observe the fast of Shivaratri according to their faith and capability. Some do fasting without having food and water on the day and night of Shivaratri. Whereas, some people observe fast for the full day and have fruits at night. And, some have sweet food at night. Similar to the fasting manner, the food eaten on this day also varies from person to person.

  
  

  Mahashivarati in Punjab and Sindh Provinces

  In Punjab and Sindh, lord Shiva is made to have a make up on the night of Shivaratri. He is offered Halwa of Kuttu, gram and fruits. People observing fast, eat this Prasaad together with their family members. Worshippers perform Jagran at night by signing Bhajans and Kirtin of lord Shiva. On this night, fruit chat is also eaten.

  
  

  Shivaratri in Uttar Pradesh and Uttaranchal

  Kashi Vishwanath Mahadev temple is situated in Varanasi of Uttar Pradesh. After the partition of Uttar Pradesh, Uttaranchal came into existence. Before this, Kedarnath Mahadev was also located in Uttar Pradesh. On the occasion of Shivaratri, worshippers perform Jalabhishek and Dugdhabhishek in Shiva temple of Uttar Pradesh and Uttranchal. Lord Shiva is offered Dhatura and its fruits. Many people who observe this fast, they eat fruits. Kheer of Sabudana, bannana and apples are eaten. Even Ramdana and Halwa of Kattu is also taken.

  
  

  Shivarati in Jharkhand and Bihar

  People of Bihar and Jharkhand are the followers of Baba Bholenath. They are truly devoted for Baba Baidyanth. With full faith and devotion, people observe the fast of lord Shiva. Some people keep the Akhand fast (24 hours fasting) without having water or food, on the occasion of Mahashivaratri. Mamy worshipers, perform Shiva Puja at night and eat fruits. They also have Kheer made of Makhane and Sabudana. There are some people, who fast for the whole day and eat sweet food at night which include Chuda and curd. Even, Malpua and Kheer is eaten on this day.

  
  
  

Nanoparticles May Enhance Cancer Therapy

In the new study by Rice University and MD Anderson, mice with dual subcutaneous tumors – the left one EGFR-negative, the right one EGFR-positive – were treated with the new Cet/PTX/PEG-HCC mixture, a carbon nanoparticle-based chemotherapeutic drug tuned to target EGFR-positive tumors. Treatment over 30 days proved highly effective in killing the right-side tumors, underscoring the efficacy of the targeted approach. (Credit: E. Loïc Samuel/Rice University)                                  ScienceDaily (Feb. 16, 2012) — A mixture of current drugs and carbon nanoparticles shows potential to enhance treatment for head-and-neck cancers, especially when combined with radiation therapy, according to new research by Rice University and the University of Texas MD Anderson Cancer Center.

A paper on the research was published this month in the American Chemical Society journal ACS Nano.The work blazes a path for further research into therapy customized to the needs of individual patients. The therapy uses carbon nanoparticles to encapsulate chemotherapeutic drugs and sequester them until they are delivered to the cancer cells they are meant to kill.

The new strategy by Rice chemist James Tour and Jeffrey Myers, a professor of head-and-neck surgery at MD Anderson, combines paclitaxel (PTX) and Cetuximab (Cet) with hydrophilic carbon clusters functionalized with polyethylene glycol, known as PEG-HCC.

Cetuximab, the targeting agent, is a humanized monoclonal antibody that binds exclusively to the epidermal growth factor receptor (EGFR), a cell-surface receptor overexpressed by 90 percent of head-and-neck squamous cell cancers. Paclitaxel, an active agent in chemotherapy, is used to treat lung, ovarian, breast and head-and-neck cancers. In combination, they have the ability to target and attack cancerous cells.

Because paclitaxel is hydrophobic -- it won't mix with water -- the substances are generally combined with Cremophor EL, a castor oil-based carrier that allows the compound marketed as Taxol to be delivered intravenously to patients.

Tour, Myers and their associates have found a simple way to mix PTX and Cetuximab with carbon clusters that adsorb the active ingredients. The new compound is water-soluble and is more effective at targeting tumors than Taxol while avoiding the toxic effects of paclitaxel and Cremophor on adjacent healthy cells, they wrote.

"It's very common to administer cortical steroids to limit the allergic response to Cremophor EL," said Tour, Rice's T.T. and W.F. Chao Chair in Chemistry as well as a professor of mechanical engineering and materials science and of computer science.

Tour said the Cet/PTX/PEG-HCC elements combine easily. "We show in the paper that when we take paclitaxel up in our hydrophilic carbon clusters, we can deliver these just as well as commercial Taxol.

"But you can never break into a market with something that's just as good as what's already out there. You have to be substantially better. The beauty of what we're doing is that we can potentially use a much smaller amount of the drug for chemotherapy. Just eliminating the Cremophor is a real advantage," he said.

Tour noted a recently approved chemotherapy drug that combines paclitaxel with albumin nanoparticles, Abraxane, also shows promise. "That works well, but it still only has about 10 percent of the market after six or seven years of use," he said.

Myers, the Hubert L. and Olive Stringer Distinguished Professor in Cancer Research at MD Anderson, said combining Cet/PTX/PEG-HCC and radiation therapy in tests on mice showed a significant boost in killing tumors. "Our hypothesis is that PTX, the chemotherapy drug, sensitizes the cancer cells to the effects of radiation and the Cetuximab/PEG-HCC increases the delivery of PTX to the cancer cells," he said.

Unlike Cremophor, Tour said, the enhanced carbon clusters are nontoxic. Biodistribution and toxicity studies showed the "large majority" of PEG-HCCs are excreted through the kidneys, while trace amounts in the livers and spleens of mice tested showed no damage to the organs.

The strategy sprang from conversations between Tour and Rice chemist and Nobel laureate Richard Smalley, who died of leukemia in 2005. "I was sitting with Rick at MD Anderson while he was being treated, and we got to talking about using carbon particles for delivery as carbon-based carriers.

"But we had nothing specific," Tour said. "I started to work on this without funding, and shortly after Rick's passing in October 2005, I met with Jeff Myers."

"I wanted to establish a multidisciplinary program to study nanoparticle-based therapeutics for cancer in general, and more specifically, head-and-neck cancer," Myers said. "At the time, Dr. Garth Powis (professor and chair of the Department of Experimental Therapeutics at MD Anderson) directed me to Dr. Mauro Ferrari (now president of The Methodist Hospital Research Institute and an adjunct professor of bioengineering at Rice), who ultimately put me in touch with Dr. Tour.

"His enthusiasm for science and willingness to further explore the potential of carbon nanoparticles to treat cancer patients was apparent right away, and we launched a collaborative effort that has been quite productive," he said.

Myers is pleased with what the team has accomplished so far. "This collaborative work has 'proved the principle' that carbon nanoparticles can be used to non-covalently link a chemotherapeutic drug with a targeting antibody that can deliver the drug specifically to a cancer cell," he said. "This principle could be used to deliver other drugs to other types of cells through specific targeting of cell surface receptors as a method of increasing the therapeutic ratio.

"Though I am not an expert in these other areas, this could potentially have applications in infectious diseases, neurologic disorders and cardiovascular illnesses," he said.

Tour sees potential for clinical uses of PEG-HCCs for brain cancer and traumatic brain injuries as well as chemotherapy, but acknowledged the introduction of such drugs for human use is a long way off. "To get a drug through all the different phases, including trials, typically takes 12 to 14 years and about $1.25 billion," he said. "That can sometimes be expedited through experimental trials with patients who have no other options, but it's still a long and expensive haul."

Still, he said the new work is a strong step in the right direction. "This paper is the highlight of six years of research," he said. "It all came together. This is the crescendo, right here."

The paper's lead authors are Daisuke Sano, a former postdoctoral fellow at MD Anderson, now at Yokohama City University Graduate School of Medicine in Japan, and Jacob Berlin, a researcher in Tour's Rice lab and now a professor at City of Hope Hospital, Duarte, Calif. Co-authors are Rice alumnus Tam Pham and graduate student Daniela Marcano; and Ge Zhou, an assistant professor in the Department of Head and Neck Surgery, David Valdecanas, laboratory coordinator in experimental radiation oncology, and Luka Milas, a professor of experimental radiation oncology, all at MD Anderson.

The research was supported by The Alliance for NanoHealth through a Department of Defense subcontract from the University of Texas Health Science Center at Houston; the Mission Connect Mild Traumatic Brain Injury Consortium, also funded by the Department of Defense; the Nanoscale Science and Engineering Initiative of the National Science Foundation; the MD Anderson Cancer Center PANTHEON Program; a National Institutes of Health Cancer Center Support Grant; and an MD Anderson Cancer Center Support Grant.

Video Games Lead to New Paths to Treat Cancer, Other Diseases

Computer science and physics professor Samuel Cho (center) works with his students, graduate student Tyson Lipscomb (left) and senior Anqi Zou ('12). (Credit: Image courtesy of Wake Forest University)                                                      Science Daily — The cure for cancer comes down to this: video games.

"If it wasn't for gamers who kept buying these GPUs, the prices wouldn't have dropped, and we couldn't have used them for science," Cho says.In a research lab at Wake Forest University, biophysicist and computer scientist Samuel Cho uses graphics processing units (GPUs), the technology that makes videogame images so realistic, to simulate the inner workings of human cells.

Now he can see exactly how the cells live, divide and die.

And that, Cho says, opens up possibilities for new targets for tumor-killing drugs.

Cho's most recent computer simulation, of a critical RNA molecule that is a component of the human telomerase enzyme, for the first time shows hidden states in the folding and unfolding of this molecule, giving scientists a far more accurate view of how it functions. The results of his research appear in the Journal of the American Chemical Society. Cho worked with colleagues from the University of Maryland and Zhejiang University in China for this study.

The human telomerase enzyme is found only in cancerous cells. It adds tiny molecules called telomeres to the ends of DNA strands when cells divide -- essentially preventing cells from dying.

"The cell keeps reproducing over and over, and that's the very definition of cancer," Cho says. "By knowing how telomerase folds and functions, we provide a new area for researching cancer treatments."

A new drug would stop the human telomerase enzyme from adding onto the DNA, so the tumor cell dies.

Cho, an assistant professor of physics and computer science, has turned his attention to videogaming technology and the bacterial ribosome -- a molecular system 200 times larger than the human telomerase enzyme RNA molecule. His research group has begun to use graphics cards called GPUs to perform these cell simulations, which is much faster than using standard computing.

"We have hijacked this technology to perform simulations very, very quickly on much larger biomolecular systems," Cho says.

Without the GPUs, Cho estimated it would have taken him more than 40 years to program that simulation.

Now, it will take him a few months.

New Drug Target Found for Lung Cancer

These images show the development of cancer (dark purple) in the mouse lung, initiated by lentiviral vector. A few cancerous cells (top image) proliferate over time into a full-blown tumor (bottom image). (Credit: Image courtesy Yifeng Xia, Salk Institute for Biological Studies)

Science Daily — Drugs targeting an enzyme involved in inflammation might offer a new avenue for treating certain lung cancers, according to a new study by scientists at the Salk Institute for Biological Studies.

The scientists discovered that blocking the activity of the enzyme IKK2, which helps activate the body's inflammation response, slowed the growth of tumors in mice with lung cancer and increased their lifespan.

The findings, reported February 12 inNature Cell Biology, suggest that drugs that hinder the ability of the enzyme to command cellular activity might prove effective as lung cancer therapies.

"Lung cancer is one of most lethal cancers and prognosis for patients is often poor, with only about 15 percent surviving more than 5 years," says Inder Verma, Salk's American Cancer Society Professor of Molecular Biology and lead author of the paper. "We developed a new method of initiating lung cancer in mice, which has properties associated with human lung cancer, and used this model to identify the role of this enzyme in cancer proliferation. We believe that this research could one day lead to therapies that improve the outlook for lung cancer patients."

Scientists have long known that there is a link between cancer and inflammation, the body's first line of defense against infection. Some of the same biochemical players that protect the body by controlling the inflammation response of cells can also be hijacked by genetic mutations involved in the development of cancer.

To better understand how these normally helpful components of the immune system are put to nefarious tasks in cancer cells, Verma and his colleagues developed a new method of inducing non-small-cell lung cancer in mice. This type accounts for as much as 80 percent of all lung cancer cases.

The researchers used a modified virus to insert genetic mutations into cells lining the mice's lungs, causing the animals to develop tumors. This laid the groundwork for studies on the molecular causes of this specific cancer type that would be impossible in humans.

They then turned their attention to a protein complex, NF-KB, that initiates the inflammation response to infection by orchestrating a cell's genetic activity. Malfunctioning regulation of NF-KB has been linked to various types of cancer, including lung cancer, but due to its many functions in the cell, drugs that directly target NF-KB would likely cause severe side effects.

To get around this limitation, the Salk researchers focused on IKK2, an enzyme that spurs NF-KB's activity in response to stress. When they blocked IKK2 activity in the mice with lung cancer, the mice had smaller tumors and lived longer, suggesting that the enzyme is necessary for NF-KB to stimulate tumor growth.

"Now that we understand IKK2 is required for NF-KB to promote tumor growth, we hope to find ways to target its activity with drugs," says Yifeng Xia, a postdoctoral researcher in Verma's lab and first author on the paper. "Systemically and chronically blocking IKK2 activity is too toxic to be used in chemotherapy, but we might be able to target another molecule in the signaling pathway by which IKK2 regulates tumor growth."

The researchers also showed that Timp-1, a gene involved in regulating cell growth, carries orders from NF-KB to tell lung cancer cells to proliferate. When they suppressed the expression of the gene, the mice with lung cancer had smaller tumors and survived longer.

"The next step is to develop antibodies or other types of drugs that can neutralize Timp-1 to abolish its pro-proliferation role in lung cancer," says Xia.

The Salk scientists now hope to develop a mouse model of small cell lung cancer, a more aggressive form of the disease that's been linked to smoking. They will then test whether the potential drug targets they discovered in this study would be relevant for this more deadly cancer.

The other authors on the paper were Reuben J. Shaw, a professor in Salk's Molecular and Cell Biology Laboratory; Salk postdoctoral researcher, Narayana Yeddula, and pathologist, Mathias Leblanc; Eugene Ke, of University of California, San Diego; and Yonghui Zhang and Eric Oldfield, of the University of Illinois at Urbana-Champaign.

The study was funded by the Ellison Medical Foundation, H.N. and Frances C. Berger Foundation, Ipsen/Biomeasure, Sanofi Aventis, Leducq Foundation, National Institutes of Health, Merieux Foundation, Prostate Cancer Foundation and the U.S. Department of Defense.

New Ability to Regrow Blood Vessels Holds Promise for Treatment of Heart Disease

Hindlimb ischemia was created in rats and treatments were delivered over seven days with an osmotic pump. The laser doppler imaging above shows the rat's hind limb prior to treatment (on the left) and with increased blood flow (image on the right) just seven days after treatment. (Credit: Image courtesy of University of Texas at Austin)

Science Daily — University of Texas at Austin researchers have demonstrated a new and more effective method for regrowing blood vessels in the heart and limbs -- a research advancement that could have major implications for how we treat heart disease, the leading cause of death in the Western world.

The treatment method developed by Cockrell School of Engineering Assistant Professor Aaron Baker could allow doctors to bypass surgery and instead repair damaged blood vessels simply by injecting a lipid-incased substance into a patient. Once inside the body, the substance stimulates cell growth and spurs the growth of new blood vessels from pre-existing ones.

Aaron Baker is an assistant professor in the Department of Biomedical Engineering.

The method has been tested successfully on rats, and findings of the study were published recently in the Proceedings of the National Academy of Sciences.

"Others have tried using growth factors to stimulate vessel growth in clinical trials and have not been successful," said Baker, a faculty member in the school's Department of Biomedical Engineering. "We think that a major reason for this is that previous methods assumed that the diseased tissues retained the ability to respond to a growth stimulus. Our method basically delivers extra components that can restore growth factor responsiveness to the tissue of patients with long-standing clinical disease."

The ability to regrow blood vessels could prove crucial to treating chronic myocardial ischemia disease, which affects up to 27 million patients in the U.S. and leads to a reduction of blood flow in the heart and lower limbs -- ultimately causing organ dysfunction and failure.

Central ischemia, which affects the heart, occurs when the coronary vessels that feed blood to the heart become blocked or narrow because of a buildup of fatty deposits called plaques. Such plaques are typically the result of a prolonged unhealthy diet or smoking, and factors such as age, high blood pressure and diabetes increase the risks of the disease, Baker said.

Doctors have typically treated ischemia by physically opening the closed artery with a stent or surgically rerouting blood flow to the poorly perfused tissue. Both methods have limitations, however, and are not effective long-term.

The new method introduced by Baker and his research team builds on a promising revascularization approach that, up until now, has shown limited efficacy in clinical trials for treating human disease.

The method combines a growth factor -- a substance capable of stimulating cellular growth, proliferation and cellular differentiation, as well as healing wounds -- known as fibroblast growth factor 2 (FGF-2) with a lipid-embedded receptor to enhance its activity.

A challenge for scientists and engineers, however, has been getting FGF-2 to bind with cell receptors -- the very molecules often found on the surface of the cell that receive chemical signals and direct activity in the cell from outside sources.

To overcome this, Baker's method embeds the growth factors in synthetic lipid-based nanoparticles containing a coreceptor known as syndecan-4. The nanoparticles containing co-receptors that, when delivered with the growth factor, enable improved cell binding so that the growth factor can direct the targeted cell to divide, proliferate and form new cells for tissue regrowth.

The incased substance was injected into rats with hindlimb ischemia and stimulated a complete recovery from the ischemia in just seven days.

"We hope this research will increase our understanding of how tissues become resistant to revascularization therapies and may lead to more effective treatments for this widespread and debilitating disease," said Baker, who was recognized last year with the National Institutes of Health Director's New Innovator Award.

Low-Carbon Technologies 'No Quick-Fix': May Not Lessen Global Warming Until Late This Century

Science Daily—New research suggests that a drastic switch to low-carbon-emitting technologies, such as wind and hydroelectric power, may not reduce global warming until the latter part of this century.

The study, published February 16, in IOP Publishing's journalEnvironmental Research Letters, claims that the rapid deployment of low-greenhouse-gas-emitting technologies (LGEs) will initially increase emissions as they will require a large amount of energy to construct and install. Furthermore, it states that technologies that offer only modest reductions in greenhouse gases, such as using natural gas and perhaps carbon capture and storage, cannot substantially reduce climate risk in the next 100 years.

These cumulative emissions will remain in the atmosphere for extended periods due to the long lifetime of CO₂, meaning that global mean surface temperatures will increase to a level greater than if we continued to use conventional coal-fired plants.

Delaying the rollout of the technologies is not an option however; the risks of environmental harm will be much greater in the second half of the century and beyond if we continue to rely on coal-based technologies.

The researchers, from Intellectual Ventures and the Carnegie Institution, Stanford, arrived at their conclusions through a set of simple mathematical models that calculated the effect of switching energy technologies on the concentration of greenhouse gases, radiative forcing ( the balance between absorbed and radiated energy from the sun) and global mean temperature.

Coal-based power plants were used as the basis for comparison because they generate the most greenhouse gases per unit of electricity produced -- replacing plants of this kind will have the greatest benefits on the climate.

These power plants were compared to wind power, nuclear power, hydroelectric power, carbon capture and storage, and natural gas. Solar photovoltaics (harnessing the sun for electricity) and solar thermal (harnessing the sun for heat) were also compared.

"Achieving substantial reductions in temperatures relative to the coal-based system will take the better part of a century, and will depend on rapid and massive deployment of some mix of conservation, wind, solar, and nuclear, and possibly carbon capture and storage," the researchers write.

Gecko Feet Inspire Amazing Glue That Can Hold 700 Pounds On Smooth Wall

Science Daily — For years, biologists have been amazed by the power of gecko feet, which let these 5-ounce lizards produce an adhesive force roughly equivalent to carrying nine pounds up a wall without slipping. Now, a team of polymer scientists and a biologist at the University of Massachusetts Amherst have discovered exactly how the gecko does it, leading them to invent "Geckskin," a device that can hold 700 pounds on a smooth wall.

Doctoral candidate Michael Bartlett in Alfred Crosby's polymer science and engineering lab at UMass Amherst is the lead author of their article describing the discovery in the current online issue of Advanced Materials. The group includes biologist Duncan Irschick, a functional morphologist who has studied the gecko's climbing and clinging abilities for over 20 years. Geckos are equally at home on vertical, slanted, even backward-tilting surfaces.

"Amazingly, gecko feet can be applied and disengaged with ease, and with no sticky residue remaining on the surface," Irschick says. These properties, high-capacity, reversibility and dry adhesion offer a tantalizing possibility for synthetic materials that can easily attach and detach heavy everyday objects such as televisions or computers to walls, as well as medical and industrial applications, among others, he and Crosby say.

This combination of properties at these scales has never been achieved before, the authors point out. Crosby says, "Our Geckskin device is about 16 inches square, about the size of an index card, and can hold a maximum force of about 700 pounds while adhering to a smooth surface such as glass."

Beyond its impressive sticking ability, the device can be released with negligible effort and reused many times with no loss of effectiveness. For example, it can be used to stick a 42-inch television to a wall, released with a gentle tug and restuck to another surface as many times as needed, leaving no residue.

Previous efforts to synthesize the tremendous adhesive power of gecko feet and pads were based on the qualities of microscopic hairs on their toes called setae, but efforts to translate them to larger scales were unsuccessful, in part because the complexity of the entire gecko foot was not taken into account. As Irschick explains, a gecko's foot has several interacting elements, including tendons, bones and skin, that work together to produce easily reversible adhesion.

Now he, Bartlett, Crosby and the rest of the UMass Amherst team have unlocked the simple yet elegant secret of how it's done, to create a device that can handle excessively large weights. Geckskin and its supporting theory demonstrate that setae are not required for gecko-like performance, Crosby points out. "It's a concept that has not been considered in other design strategies and one that may open up new research avenues in gecko-like adhesion in the future."

The key innovation by Bartlett and colleagues was to create an integrated adhesive with a soft pad woven into a stiff fabric, which allows the pad to "drape" over a surface to maximize contact. Further, as in natural gecko feet, the skin is woven into a synthetic "tendon," yielding a design that plays a key role in maintaining stiffness and rotational freedom, the researchers explain.

Importantly, the Geckskin's adhesive pad uses simple everyday materials such as polydimethylsiloxane (PDMS), which holds promise for developing an inexpensive, strong and durable dry adhesive.

The UMass Amherst researchers are continuing to improve their Geckskin design by drawing on lessons from the evolution of gecko feet, which show remarkable variation in anatomy. "Our design for Geckskin shows the true integrative power of evolution for inspiring synthetic design that can ultimately aid humans in many ways," says Irschick.

The work was supported by the U.S. Defense Advanced Research Projects Agency (DARPA) through a subcontract to Draper Laboratories, plus UMass Amherst research funds.

A Wirelessly Controlled Pharmacy Dispenses Drugs From Within Your Abdomen

Future pharmacies will be inside our bodies

By Rebecca Boyle

Implantable Chip The chip is about the size of an average flash memory stick. Courtesy of MicroCHIPS Inc.

In the future, implantable computerized dispensaries will replace trips to the pharmacy or doctor’s office, automatically leaching drugs into the blood from medical devices embedded in our bodies. These small wireless chips promise to reduce pain and inconvenience, and they’ll ensure that patients get exactly the amount of drugs they need, all at the push of a button.

In a new study involving women with osteoporosis, a wirelessly controlled implantable microchip successfully delivered a daily drug regimen, working just as well, if not better, than a daily injection. It could be an elegant solution for countless people on long-term prescription medicines, researchers say. Patients won’t have to remember to take their medicine, and doctors will be able to adjust doses with a simple phone call or computer command.

Pharmacies-on-a-chip could someday dispense a whole suite of drugs, at pre-programmed doses and at specific times, said Robert Langer, the Institute Professor at the David H. Koch Institute for Integrative Cancer Research at MIT, who is a co-author on the study.

“It really depends on how potent the drugs are,” he said. “There are a number of drugs for things like multiple sclerosis, cancer, and some vaccines that would be potent enough.”

Langer and fellow MIT professor Michael Cima developed an early version of an implantable drug-delivery chip in the late 1990s. They co-founded a company called MicroCHIPS Inc., which administered the study being published today in Science Translational Medicine. The team decided to work with osteoporosis patients because the disease, and the drug used to treat it, presented a series of special opportunities, Langer said. A widely used drug called teriparatide can reverse bone loss in people with severe osteoporosis, but it requires a daily injection to work properly. This means up to 75 percent of patients give up on the therapy, Langer said. It’s also a very potent drug that requires microgram doses, making it an ideal candidate for a long-term dispensary implant.

Getting the chips to work well required some tinkering on the part of the company, including the addition of a hermetic seal and drug-release system that can work in living tissue. The chip contains a cluster of tiny wells, about the size of a pinprick, which store the drug. Each well is sealed with an ultrathin layer of platinum and titanium, Langer said. At programmed times or at the patient’s command, an external radio-frequency device sends a signal to the chip, which applies a voltage to the metal film, melting it and releasing the drug. The wells melt one at a time.

“It’s like blowing a fuse, the way we’ve got it set,” Langer said. He said the amount of metal is near nanoscale levels and is not toxic.

The team also had to ensure the chips were secure and could not be hacked. The chips communicate via a special frequency called the Medical Implant Communications Service band, approved by both the FCC and the FDA. A bidirectional communications link between the chip and a receiver enables the upload of implant status information, including confirmation of dose delivery and battery life. A patient or doctor would then enter a special code to administer or change the dose, Langer said.

The research team recruited seven women in Denmark who had severe osteoporosis and surgically implanted the chips into their abdomens in January 2011. The chips stored 20 doses of the drug. The patients had the implants for a year, and they proved extremely popular, Langer said. “They didn’t think about the fact that they had it, since they didn’t have to have injections,” he said.

Ultimately, the device delivered dosages comparable to daily injections, and there were no negative side effects. There was no skipping the shot if a patient didn’t feel like visiting the doctor — complying with a prescription is of key importance, said Cima, the David H. Koch Professor of Engineering at MIT. “This avoids the compliance issue completely, and points to a future where you have fully automated drug regimens,” he said.

The study points out one interesting phenomenon that will inform future research and development on these types of implants. When you implant a device into a person’s body, the body forms a fibrous, collagen-based membrane that surrounds the foreign device. This can affect how well drugs can move from the device and into the body, which in turn affects dosage requirements and pharmaceutical potency. One of the aims of this study was to examine the effects of that collagen membrane, and the researchers found it did not have any deleterious effects on the drug.

Now that these chips have been proven to work, Langer and the others want to test them with other drugs and for longer dosage periods, he said. Because the well caps melt one at a time, the chips could be used to deliver different types of drugs, even those that would normally interact with each other if taken in shot or pill form, he said. The team wants to build a version with 365 doses to see how well it works.

It could even be used as a long-term sensing device, he said, an interesting possibility of its own. Medical sensing implants can degrade once they’re in the body, so implants that could check for things like blood sugar or cancer antibodies can lose their effectiveness. But a chip with multiple sensors can work a lot longer — once a sensor is befouled, simply melt another well and expose a fresh one, Langer said.

The ultimate goal is to create a chip that could combine sensing and drug delivery — an implantable diagnostic machine that can deliver its own therapy.

“Someday it would be great to combine everything, but that will obviously take longer,” Langer said.

First Drug Delivery Microchip:  Courtesy of MicroCHIPS Inc.