Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Tukwila, WA United States - Job Description At Boeing, we innovate and collaborate to make the world a better place. From the seabed to outer space, you can contribute to work that matters with a company where diversity, equity and inclusion are shared values. We’re committed to fostering an en... View

Huntington Beach, CA United States - Job Description At Boeing, we innovate and collaborate to make the world a better place. From the seabed to outer space, you can contribute to work that matters with a company where diversity, equity and inclusion are shared values. We’re committed to foster... View

John Hopfield dreamed up the modern neural network while at Caltech. Geoffrey Hinton built on it, creating an AI firm that Google bought for $44 million.

Copyright 2019 NPR. To see more, visit ARI SHAPIRO, HOST: When William Kaelin was a pre-med student, one professor suggested he get a taste for laboratory research. It did not go well. WILLIAM KAELIN: It turns out in hindsight that virtually everything that could have been wrong in a laboratory was wrong in this laboratory. And I remember getting a C-minus, which for a pre-med is like having a wooden stake driven through your heart. SHAPIRO: Safe to say William Kaelin overcame that C-minus just fine. Not only did he make it through medical school and launch a career in research, today it was announced he will be awarded the 2019 Nobel Prize for Physiology or Medicine. NPR science correspondent Richard Harris picks up the story. RICHARD HARRIS, BYLINE: After his disastrous start in the lab, William Kaelin figured he would focus his attention on treating patients. And indeed, he started down that path, settling into a job at the Dana-Farber Cancer Institute in Boston. KAELIN: And it

The CBS Sports basketball analyst remembers the competition.

Are you just getting started?  GO HERE!

Before one approaches seriously the study of metaphysics, magick, the occult, or mysticism, it is appropriate that one prepares oneself on all levels: mentally, emotionally, physically and spiritually.

It is of vital importance that the student be psychologically prepared for the reception of Cosmic truths; for without adequate preparation, without the required purity, the right attitude and the right motive, one simply deludes or sidetracks oneself from all that which is essential in occult study to those phenomena and teachings that are unessential, delusive, and misleading; to phenomena that simply strengthen one's hold in a world of illusion, glamour, pride and ego; aside from this, should one attempt occult work without due preparation one exposes oneself to certain dangers which are far-reaching. Without adequate preparation the student would abuse and misuse occult, spiritual teachings and powers.

The karmic consequences of this abuse may stall or cause stagnation in one's
spiritual evolution for countless incarnations. Basically, religion without the theological dogmas, is an appropriate basis for the study of metaphysics. Students of metaphysics are advised to deepen their religious activities by engaging in personal study of their scriptures or holy book without relying on the usual channels or interpreters for clarification. This is to preserve one's bicameral mind from
external influence and dependency on "authority figures" that may be damaging to the psyche in the long run.

Purity, sincerity, humility, and a selfless motive which seeks to serve one's fellow men are qualities to possess or develop when requesting from, or studying the teachings of a spiritual/ metaphysical teacher, or even when embarking on our own by studying books on the occult. These qualities or virtues are our safeguard. They protect us from negative forces which affect our mental and emotional stability.

One of the keys to preparation is to eliminate the false ego from our thinking and centeredness. Think from the Christ level. Think the thoughts of Jesus, Muhammad-the Prophet, Krishna, Lao Tze, or Buddha. What do you think these avatars and prophets of God think constantly of? They think of God, Truth, Beauty, and Goodness. Therefore we advise each student to do likewise. Thinking abstract thoughts, divine thoughts, spiritual thoughts, and holy thoughts raises the vibrations of the physical, etheric, astral and mental bodies. This facilitates metaphysical and spiritual development so needed by the human race. It improves the quality of humanity.

One of the problems which poses as an obstacle to occult and metaphysical study is that of the crystallized mind. As a preparation, the first step that has to be undertaken by the student of metaphysics and the occult is to temporary put away all previous concepts and beliefs regarding them. There are many false beliefs and superstition concerning the occult perpetuated by ignorant individuals, by psychics of a low caliber, by secular education, and even by religion, that we have to cast all of those beliefs aside and prepare our minds to really think and use our reason and intuition.

Even if we had learnt metaphysics or branches of it previously from genuine teachers, it is still required of us to shelve them aside when we begin our apprenticeship under a new tutor.  Our minds should be open and receptive to the teachings of the higher worlds, but if our minds are closed and crystallized, we fail to register the truths concealed in occult and metaphysical teachings regarding the laws of the cosmos, the higher worlds, the principles of mind and one's psychic nature.

If the teachings of any metaphysical system or teacher (including this writer) contradict your personal notions and feelings and you have trouble accepting them, simply shelve them aside for the time being and consider them again at a later date when you have acquired more experiences and knowledge. Realize, however, that most of the time opinions and beliefs do not reflect Truth. We teach what we personally know or what others personally know. We do not proselytize or impose our words upon others against their will. We are happy to give to others the teachings of the Spiritual Masters should they be receptive and just as happy not to give should they be non-receptive. We can lead a horse to a drinking trough but we are unable to make it drink.

Granted, that information concerning the occult the tyro or neophyte often has to regard as hypothesis, or working theories, but in time the student is given methods for investigating and proving to himself the verities of metaphysical truths and the realities of the higher worlds. We seek knowledge, wisdom, and experience--not mere beliefs. For the student of Nature's mysteries, beliefs will not do. Beliefs are blatant expressions of one's ignorance, for if one knows, why is there a need for beliefs? If one should say that one believes in the existence of something, one
implies in that statement that one does not really know if that something exists.

Belief and knowledge are poles apart. In spiritual and occult training one invokes intense energies, powers and forces emanating from the spiritual worlds. These energies flow into the whole microcosm even down to the physical level. Should the physical body and its force-field vibrate at a very low level because of the presence of
impurities, toxins, and negative forces, the nervous and energy systems of the physical and etheric bodies would explode and rupture during the influx of those higher energies. This is one reason why one embarks upon the Path of Purification prior to engaging in advance occult work.

The Master's Advice
In days gone by, when a student approached a spiritual or occult master for instructions, the master would say "empty your cup." The master illustrates the purpose of this by pouring fresh tea into a cup already filled to the brim with the liquid. The tea would naturally overflow. "Likewise," the master would say, "will the teachings I fill your mind be rejected by all of your previous thoughts and false
beliefs. Therefore, empty your cup." Which means, in other words, "empty your mind of previous ideas and conceptions." Most people are disinclined to accepting new ideas. They dislike change, and yet we must change towards a positive direction if we are to progress. There is a senseless fear and laziness in most people in operating their brain faculties such as using their mind to reason. Our
minds must be open and flexible, yet putting all new ideas to the test where possible before accepting them. We must strive to see the logic and rationality in concepts, if any, that are new to us. In other words, we must think! It would not hurt to be critical in a positive and constructive sense of novel ideas or even religious ideas if we believe that our criticism is valid. Although the mind is limited, it
has its purpose and we should not shirk from using it.

It is an important requirement for the occult student not to form any false ideas concerning himself and lower his self-esteem. He should not limit his mind and divine expression by saying "I can't do this," "I can't do that." One never knows what one can do until one tries. This applies to all branches of learning and study. Often we hear people say "nobody's perfect," and they use this as an excuse not to improve their morality, their character, their minds or even their social standing. If one approaches the study of metaphysics and the occult in this manner, one is bound to fail. Metaphysics is hard work, and those who are not interested in work should leave metaphysics alone. Metaphysical truths awaken a person from self-complacency and the slumber of mortal errors. The student of metaphysics
should be prepared for this and not rebel when it occurs. When you come to the point where you can think of nothing but metaphysics in your everyday activities, you shall succeed in being a metaphysician. Metaphysics has to be incorporated into one's life 24 hours a day.

Studying the occult and metaphysics requires great perseverance, endurance, patience, and fortitude. It even requires a certain degree of intelligence. Note that we do not say education or intellect, for the educated mind and intellect at times can be more of a hindrance than an asset. Unless our mind is receptive and open to modify previous findings or concepts expounded by science or religion which
from the point of view of metaphysics are erroneous, one would simply fail in metaphysical study and the probing of Nature's higher laws. The intellect, as the result of education is simply the building blocks that we accumulate, whereas intelligence is the conscious directive power that builds an edifice out of those blocks. Being educated implies gathering data and information that may or may
not be true or even relevant to one's life. We should seek the sort of knowledge that is applicable to our everyday lives with its countless challenges and problems.

Overcoming human problems is mastership. Intelligence is a necessary attribute to comprehending metaphysical principles. You need not be concerned of any lack of intelligence, however, for metaphysical practices itself raises one's I.Q., E.Q., and S.Q. Some occultists, metaphysicians, and mystics have declared that it is much easier acquiring an academic degree than getting fruitful results from occult study. This is indeed true, for occult study requires unfolding the inner senses to register higher vibrations and the various phenomena of the higher dimensions, and this takes much time and energy for practice and training. The purpose of metaphysical study is to make each and every one torchbearers of Truth. Work for Truth, live in
Truth, promote Truth and it is guaranteed that you will evolve into God's Light.

However, seek no reward. Metaphysical development requires time, patience, perseverance and great concentration--the type of concentration not normally possessed by the average person. This training of psychic and metaphysical faculties may take a whole life time for its perfect functioning and control. We should
not be daunted by this, however. The Master Jesus said, "In patience possess ye your soul," and this each student of metaphysics must be conscientious of. The student must have patience and possess his or her soul and not allow the Dark forces to possess it. In metaphysics we learn to direct our lower self, if we do not do this, negative beings will. It is expedient that the student remove religious and any form of prejudice from his mind and heart.

At times teachers of metaphysics may refer to the text of one religion in preference to another to illustrate or substantiate certain metaphysical concepts. This they do, not because of their personal background and not because of any animosity toward the other religions, but because of convenience sake. We know that the essence of all religions is Truth itself. Metaphysicians, therefore, teach and refer to the Truth in all religions whenever possible.

This brings up another subject to mind:
fanaticism. Fanaticism is not to be tolerated, not in metaphysics, not in religion, not in any human endeavor whatsoever. Fanaticism simply indicates a blind belief in principles and opinions, most of which may be dubious as to their validity. Fanaticism is separatism, narrow-minded and destructive, and should be avoided. It breaks up unity by creating divisions and schisms. It is the very antithesis
of the spiritual precept: "unity in diversity." The motto of the Dark forces will always be "divide and conquer."

Man is a microcosm of the macrocosm. In religious terms, man is a reflection of God, for he/she was made in God's image. Since God is perfect, man likewise, in a spiritual sense, is perfect. Man carries the seeds of perfection within him. He only needs to unfold this divine seed of perfection lying dormant within him. When this is done all things become possible to man. In order to nurture these divine seeds, one must overcome inertia and work with the evolutionary forces of Nature.

The Motive of Study
One of the first few things that a student of metaphysic has to do is to introspect and analyze as to the motive for approaching metaphysical study. Why does one want to study metaphysics, its branches, and its various arts such as magick, mysticism, esotericism, psychometry, dowsing, or telepathy? For what reason? For what motive? Is it simply to gain advantage over another, for power over others? Or
is it simply to acquire name and fame or the riches that it will produce? Approaching metaphysics with such motives would retard one's spiritual growth and is not condoned by any spiritual teacher of worth. A true and noble motive would be to serve God and humanity in spiritualizing this physical world, in manifesting Heaven on Earth, where Truth, Justice, Righteousness, Love, Peace and Goodwill between men prevails. Should your motive be negative, you are advised to transform it
now. Do not deceive yourself as to your motive. Another thing that we must not do, is to steal the secrets of heaven or gain entry into it by force, meaning that we should not force our occult growth by engaging in dubious exercises obtained through sources with no real integrity or authority to transmitting them and hoping for an instant development with their application. Should occult abilities be "instantly" procured, it would not be permanent and would result in adverse effects in most cases. We all know the low quality of plants cultivated in greenhouses as compared to the cultivation done underneath Nature's roof. It is the same with metaphysical growth. Heaven is not willing to release her secrets to the profane, and if by
chance any of us acquire her secrets and apply them without the proper motive and purity, we unknowingly curse ourselves. The scriptures say that God is not mocked. This is a symbolic way of saying that the Law of Karma is operative and no one is able to avoid its influence.

The student should be aware that there are false Gurus in the metaphysical field. Every student should be wary and cautious in accepting what they have to teach, for though what they teach be sweet to the mouth, their effects may be bitter to the stomach. These Gurus have no sense of responsibility, and they control and manipulate the minds of their followers for their own nefarious reasons. They create
a morbid dependency on the part of the student. Without the adequate and correct preparation through the Path of Purification, although one may unfold in a psychic manner, if accepted and trained by a "Guru," one would limit one's psychic
development and stagnate in one's spiritual evolution. The higher occult and mystical abilities requires that one be spiritually developed, and this cannot be attained without the necessary purification of the microcosm.

Spiritual Masters of the occult and metaphysics are wary and watchful of students with impure motives. It is not unusual for Spiritual Masters to reject applicants for study or to put them through certain tests, or to give them some advise and told to return at a later date, perhaps a week, or a year later. Just because a student is anxious to study the occult does not imply that he is ready for it or that he should be accepted by a Spiritual Master or Adept. Acceptance by a Spiritual Master and the
initiations that he has to offer requires sincerity of motive and more besides. The false Guru may perhaps accept such a student for personal reasons--for fame, name, glory or wealth. The true Guru, however, never consider these things as criteria for accepting students, although he may work in  strange ways that sometimes seem amoral or irrational in order to test candidates. An occult axiom
states that, "When the student is ready, the master appears." The advise here is to make oneself ready through proper preparation and not sit and wait and twiddle one's thumbs. The master in this axiom may refer to a spiritual being, one's personal spiritual guide or guardian, or even to a metaphysical school.

It should be known that the metaphysical path is a strenuous one requiring every minute of the day. One does not engage in metaphysics at certain spare moments available. One must make time for the study and practice of metaphysics. Reduce unnecessary socializing and reduce watching TV and movies to a bare minimum; preferable not at all wasting time on them. This may result in some conflict between your friends and relatives as you settle-in to your new metaphysical routine, but
consider this: what is more important, their egoistic and personal gratification and demands or your study of Truth with its eternal worth and its spiritual application in the affairs of men? It is up to you to decide; however, if results are not forthcoming from your practice because of your lack of application, you have no one to blame but yourself. One piece of advice: you may drop-out from metaphysical study but never drop-out from life, for it may be that your real metaphysical teacher and lesson is life itself. Accept whatever life brings and learn from it; otherwise, seek to change it using your God-given creative powers.

The Contemplation of Life and Death
Perhaps one of the things that a novice of metaphysics is told to do at the very outset by a true metaphysical or spiritual teacher is to contemplate the meaning of death and the opportunity that life offers. This dual theme is a healthy, sane, and balanced contemplation that when analyzed individually tends to produce an unhealthy pessimistic or overly hopeful attitude. How does one begin this contemplation? By reflecting on the following: first of all realize that we are all heading toward physical death, This might seem discouraging nevertheless is a true statement that cannot be contradicted. With every second, with every breath that we take we approach closer to our grave. Nature guarantees us nothing in life but our coming demise. This is her promise. We do not know when we will leave the physical body permanently. It may be the next hour, today or tomorrow, but leave it we shall. From these musings questions would arise: "What then is the meaning of life?" What is the purpose of life?" Shall we say as the materialists would say, "let us eat, drink, and be merry, for tomorrow we die"? What sort of a philosophy is that when our query remains unanswered? It would be preferable to say "let us study the purpose and meaning of life for we know not when we will pass away and God's purpose for us here may not be carried-out if we spend our time on frivolous matters." Contemplating further, we will realize one major thing, and that life here is an opportunity. Opportunity for what? An opportunity to grow, to become, and to be.

Heraclitus, the philosopher of ancient Greece said that everything is becoming. This is the Law of Change. From our metaphysical point of view, we understand that he was referring to the Law of Evolution. If we think about it we will realize that we are unable to take anything material with us to the higher worlds when we pass on. We are unable to take along with us our house, our money, our possessions, our titles, etc. What we do take along are things that are immaterial--our knowledge, our memories, our karma, our habits, our character, our spiritual and psychic development, our aspirations and desires. We can see from this that our purpose in this world, in this physical plane is in connection with those immaterial things mentioned above, and if--and metaphysics declare it to be so--evolution
is a law of Nature, a Cosmic law, then our true purpose is to evolve, to improve and to purify those immaterial things. Our greatest opportunity in this world is the correct use of time. Use this gift of God searching for Truth and not wasting it on non-essentials.

Perhaps after being a little pessimistic about reflecting death just awhile ago we may now be cheerful and be optimistic about life and to carry-out the main purpose of physical existence instead of wasting our precious time, energy and resources on immoderate and excessive entertainment: too much watching TV, too much sex, the taking of drugs, and indulgence in other material devices invented and designed by the Dark forces to sidetrack and make us forget our divine heritage, purpose of being and our mission here on Earth. This is the nature of evil: it diverts us from
experiencing our true soul-purpose and need. Anything that distracts us from improving our soul nature, our character, our morals, or acquiring metaphysical knowledge of Cosmic laws and truths, is to be considered as an evil mechanism and an intruder to our microcosmic system. These evil intruders sometimes work in such a subtle manner at times that even disciples of metaphysics are sometimes caught off-guard.

The Pure Life
A metaphysical life entails living a life of purity. Even before approaching a Master for
apprenticeship, a pure, spiritual, constructive life should be lived as best as one is able to. The degree of purity within us can be seen and felt by the Spiritual Masters and Adepts of metaphysics and the occult. They know our spiritual state and status by the colors and the luminosity of our aura, by our facial expression, by the quality of the emanations of our eyes, and by the way we think, speak and act.
By the above we do not imply that one has to be a saint in order to be a worthy student of the occult or metaphysics. What we are saying is that purity is a necessary quality to possess and to develop when one becomes a serious student of the occult. It is an indispensable quality for it prepares our psycho-biological system, our nervous systems to withstand intense energies that we invoke from the
higher worlds through our occult and metaphysical studies. We often hear of people going insane because of their involvement with the occult or metaphysics. This is because of their lack of purity. Their nervous systems were not able to sustain the spiritual vibrations coursing through them. When this occurs, as mentioned before, the nervous system ruptures, certain brain cells and nerve centers are destroyed, and the etheric webs protecting the student from overexposure to impressions of higher frequencies coming from the other dimensions, are shattered. One is then unable to shift focus from one reality to another but is opened to both. This causes too much strain. Insanity is the sad result. Spiritual energy invoked through mystical practices also evokes the undesirable elements lying within us. If these elements are not cleared by a process of purification, they would cause us trouble. This is not to say that metaphysics or the occult is an unsafe study. There is danger in  everything. One simply needs the right information and common sense, and take precautionary measures when delving into any study, especially metaphysics and the occult.

Purification is a multi-level process. It should occur on all levels of the microcosm. For instance, our physical body, our blood-stream, our energy-structures, our emotions, our minds, our aura, and chakras, all need to undergo purification. The Path of Purification is a basic step in any system of occult, metaphysical, and spiritual study. To neglect this essential step is to open-up ourselves to spiritual dangers. Any Guru neglecting the Path of Purification in his or her metaphysical system is a false teacher working against the evolutionary tide and spiritual current. It is not beyond the means of any average person to become pure and holy. The difficulty is that people do not see purity or holiness for what it is. They have many erroneous concepts regarding it. For instance, some of us believe that to be holy one has to seclude oneself from society, be celibate, or wear white robes or
even tattered clothing. They believe that to be holy one must dress oneself in some special way or wear a certain hairstyle or do strange things, or act a little mad. These are all fallacies. We should all  strive for holiness by being what we truly are, and not be what we think ourselves to be. In the name of Light, Life and Love, we appeal to all students to be pure and holy.

A Balanced Approach Towards Metaphysics
In metaphysics or in the occult, the student is requested to take a balanced approach. There are three factors that students have to consider:
1) Knowledge of metaphysical laws, principles, and cosmic truths.
2) Unfoldment of spiritual and psychic senses, faculties, and abilities.
3) Acceleration of one's spiritual development, of one's soul evolution.
The pursuit of these three together in a harmonious way is necessary in
developing a well-rounded attainment. When one is over-emphasized and the
others compromised as to their importance, then trouble results for the
metaphysical student. For instance, too much knowledge without spiritual
abilities and a spiritual development results in a poor instrument, one ineffective
in the service of men, and one filled with pride and vanity. Psychic abilities
without knowledge and a degree of spiritual advancement causes similar
symptoms as the above--pride and vanity, together with a poor understanding of
what one registers through the psychic centers. Though one be "spiritual,"
without metaphysical knowledge and understanding one is often deluded and
misled by psychic forces. One falls into the trap of glamour and illusion.
To be spiritually developed without adequate knowledge and psychic ability results in one's ineffectiveness in serving humanity. We can see from this that the problem facing the metaphysical
student is the correct pursuit and development of those three factors simultaneously. The unfoldment of these three factors causes that Divine Spark (Spirit), the Soul-Flame within us to grow in strength and magnitude. This Spark is threefold. There is a will-power aspect (blue), a love-wisdom aspect (pink) and an intelligence-understanding aspect (yellow). This divine flame, metaphysically, has its location within our physical heart and is about 2 cm in size. It is representative of the Higher Soul within the microcosm which is likewise threefold in nature. Esoteric students of Theosophy, for instance, call these components of the threefold Soul, atma, buddhi, and manas.

Too often metaphysical, occult, or so-called spiritual Gurus teach on the basis of a single approach. This does much harm to the student and to society in the long run, or in the very least, it does no lasting good. Advanced teachers, or true Spiritual Masters would synthesize the above three factors. Their approach as a synthesis of those triune factors, would be practical, instructive, and informative. Let us look again at those three factors. What do we mean by occult and metaphysical knowledge?

By such knowledge we mean of the following :
Knowledge concerning, the origin of Spirit-Man; the origin of human beings; the origin of the solar system; civilizations of unrecorded history; the real history of man; man's purpose of being; the progression and the transmission of the ageless teachings throughout the centuries; the origin of religion; the Mystery Schools; the occult anatomy of man; man's latent powers and faculties; the secret teachings and oral tradition of the prophets; the nature and laws governing the higher worlds and man; the application of Cosmic laws; the hidden laws of this three-dimensional world; the principles of counseling and healing; the nature of man, etc.
Now what do we mean by the unfoldment of psychic and spiritual abilities? What are they? Here are just a few: the ability to register spiritual impulses emanating from the Soul, the Spirit, the Spiritual Hierarchy, one's spiritual group, and Master; telepathy; the ability to direct the elements and forces of Nature; spiritual vision; etheric vision; the ability to function consciously in the higher worlds; the
ability to attune with the Divine Cosmic Mind; the ability to know the past, present and future; the ability to heal body, mind and soul; the power to create; etc.
And lastly, what do we mean by spiritual development? We means expanding one's consciousness; opening up the intuitive channels; the transcendence of the false ego; the expression of one's divinity; oneness with Nature, God and one's fellow men; the purification of one's thoughts, words, and actions; the realization and awareness of one's true identity, and the unfoldment of all spiritual virtues
and attitudes such as sacrifice, renunciation, detachment, steadfastness, endurance, strength, self-control, patience, magnanimity, purity, heroism, truthfulness, generosity, compassion, understanding, love, affection, serenity, faithfulness, altruism, tolerance, reason, devotion, adaptability, sincerity,
joy, discernment between the real and the unreal, service, balance, beauty, harmony, creativity, confidence, perception, reverence, sympathy, punctuality, love, tenderness, gratitude, gentleness, harmlessness, inclusiveness, desirelessness, forgiveness, trust, self-discipline, etc. 

So far we have used the words occult, metaphysics, and spirituality interchangeably. At this time this suits our purpose, but we have to realize that these terms are not synonymous and each have a specific definition of their own. To these terms we may include mysticism, magick, parapsychology, parapsychic science, and esotericism as each having a definite meaning and yet still connected with
metaphysics in general. In the course of one's metaphysical study one would gradually come to realize the fundamental difference. Humility and Fearlessness
So far, we have already dealt at some length with the qualities that the candidate of metaphysical studies has to possess, such as purity and an open mind. Other important qualities are those of humility and fearlessness.

Humility is the quality of acknowledging the greatness of God as expressing throughout Nature. It is the realization that no matter what one attains or what one becomes there is always room for further growth. Thus, one never view oneself as representing a final attainment such as being the smartest kid in school, for one knows that there are still others much more smarter than oneself. There is
always room for improvement. We should not just look down before us, look upwards as well and see that there are others far above us. Reaching one peak allows us to see a higher summit. There is pride in thinking of being wise or in being stupid. There is also pride in thinking of being rich or in being poor. The writer has often heard people lamenting on how poor they are, and they enjoy saying this and proving it. They would take quite a lot of trouble to prove that they are poor and
that none are in as much a need as themselves. This is pride expressing itself, for they fail to see that they possess many of God's precious gifts to them, such as their senses to register impressions, their minds to think, their will to act, and their hands and feet to carry-out their desire; in short, all that is required to manifesting prosperity. Such people are ungrateful beings. In this they show their lack of
humility.

When approaching an Occult Master in an egoistic manner, he would most certainly reprimand us verbally . . . or in silence. Such applicants for the teachings are quickly shown the exit. Demanding to be taught indicates one's unreadiness for occultism and metaphysics. Instead of requesting from the Guru the higher teachings, one should come to realize that one still requires the lower teachings and
disciplines from the many challenges that life has to offer and instruct us. All of these challenges are simply for the purpose of taming the human ego. The ego when unbridled, is an unfit vessel for metaphysical and spiritual teachings. Where the ego strives, there humility dies. Fear is one of the obstacles to metaphysical understanding and awareness. Approaching and advancing on the occult path entails facing many enemies and frightening phenomena, the worst of
these is our own lower self with its many subconscious projections which in occult circles is called the Dweller on the Threshold. If we wish to pursue occult studies, fearlessness is a paramount virtue to possess, for in truth nothing can hurt us unless we give it the power to do so. One of the maxims of the Great White Brotherhood is to know, to dare, to do, and to be silent. Make this maxim a part of
yourself.

In the maxim above the student is advised to be silent. It is disrespectful to the teacher and to the Cosmic to reveal secret and esoteric matters to those unprepared for it. Be ever watchful of your mouth, for as the Master Jesus said: "Do not cast pearls before swines." Silence is a protective quality. It protects the person who keeps silent on sacred matters as well as others who may be inclined to misuse the information. Assume silence when you should be silent and only speak when others are not courageous enough to defend Truth. Silence is golden at the right place and at the right time, and on sacred matters. Students will progress more rapidly should silence be a part of their being. Do not draw attention to yourself. Do not speak of your occult experiences to those unsympathetic to metaphysics, for this would simply provide them with offensive weapons.
In metaphysics too often than not, one may encounter contradictions. These contradictions may just be apparent and not real. Truth is like a cut diamond with its many facets. Keep in mind that what is relatively true is synonymous to being relatively false. However, in cases of contradictions, adopt that which seems more logical to you.

This is an important article and the student is advised to consider it wisely. It is hoped that the student be sincere and apply these teachings that he or she may acquire the virtues that we have referred to. In the days of Atlantis, men misused and abused occult and metaphysical teachings. This was one of the direct reasons why the continent submerged and leaving very few traces as to its geographical
location, its place in the memory of men, or in our history books. Many civilizations ended drastically because of the misuse and exploitation of knowledge for selfish ends. People mistakenly believe that the ends justify the means. This is false. The means determines the end. Let us not repeat our ancient mistakes, as it interrupts the evolutionary process and cause the holy ones to weep.

Find out what it’s all about! Click HERE!

What is metaphysics, and why should we bother studying it? What benefits does it have for humanity? What is its purpose? How will its teachings help advance society? How will it assist our civilization and culture to progress? How will our lives be re-created individually and collectively with the application of metaphysical principles?

Questions abound concerning metaphysics, for people intuitively feel that it may have something precious to offer in terms of facilitating personal growth and self-empowerment. Among those spiritually inclined, it has become a "prime directive" to understanding their lives in terms of metaphysical principles and concepts such as multi-dimensional realities, the Higher Self, love, karma, reincarnation, etheric
energies, psychicism, oneness with all, cosmic beings, the ascension, etc., and some of the causes of this higher thinking and awareness is the thinning of the cosmic veil between dimensions; the increased contact with invisible forces; the influence of intense electromagnetic cosmic energies bombarding upon our planet and solar system at this time; the influx of higher spiritual beings incarnating in the physical realm; the discoveries of many ancient secrets left hidden in monumental structures and time capsules; scientific developments in hyper-space technologies,
and shifts in its paradigms, etc. All of these are occurring on a global  scale, in every nation of this planet, and it is affecting every human being. So it would seem that  humanity is awakening from its long sleep of forgetfulness and ignorance.

The Tree of Life of immortality, enlightenment, and illumination will be found hidden in the seeds of the Tree of metaphysical knowledge--using the word "metaphysics" in its most spiritual, Gnostic sense.

For thousands of years we have sought for truth, and most of the time from  the wrong persons and in the wrong places--what we received were man-made opinions and beliefs which were forced upon our minds to be accepted as the "word of God," or the way that Nature had decreed, and that there is nothing that anyone can do to change it. While in our infancy, physically and spiritually speaking, we accepted everything told to us by organized religion, elders, and
pedagogues as gospel and truth and we based our philosophy of life on the indoctrination imposed upon us and which subsequently formed our false sense of "conscience," and a poor understanding of spiritual values. This caused us great soulful sufferings and torment in succeeding years in our everyday life--an intense sense of shame, guilt, fear, and sin whenever we "violated" any so-called law of God formulated by theology; and it never occurred to us to
question the systems, the mechanisms, and their origins that brought about our morbid condition. This naturally lowered our self-esteem. Conscience is not similar to the concept of the "still, small voice." The latter is the silent voice of the Spirit, whereas conscience in part, is simply the engrams or programs imprinted upon the subconscious mind. Conscience is also partially our memory of the negative consequences of our past actions impinging upon our conscious mind
whenever we are about to act in a negative way resembling that of the past.

But to return from our digression: in past centuries we were told lies by false prophets and the ministers of religions that mediators between God and men were necessary; that theirs was the only way to God; that their race or sect were the chosen one of God; that everything that God would reveal to humanity lies in a single book; that God punishes us for sinning and perhaps in the afterlife casts us into hell; that illness, old-age, and death were a natural part of life; that one no longer receives any new revelation from God, etc. We were told to fear God, to see
everything as separated from us, to believe that we were born in sin, that  the sexual act is shameful, that we were simply mortals subjected to the whims of God for the determination of our fate, that we were inherently bad--and even more--that the world was flat! While at the same time heinous crimes against the Holy Human Spirit were being committed by those very same representatives of religions such as the crimes of persecution, torture, and murder of innocent human beings who simply were more spiritually and psychically inclined or conceived the universe from a different viewpoint--and all these atrocious acts were carried-out in the name of
Religion, Love and God. The Crusades and the Inquisition are dark chapters in the history of man.

One of the points that we wish to put forth here is that since time began  the dark, retrogressive forces have infiltrated or have tried infiltrating every institution that have sought to improve the condition of the soul, and the expression of the human spirit in our mundane lives. They have always opposed and attacked the true representatives of God and steered seekers of truth away from them. Their purpose is to stall human evolution and progression indefinitely, that human beings cringe and cower under their manipulative control, that humans be made into slaves and
automatons answering to their every whim. They work openly and subtly, physically and psychically. They make us believe that we need them--their services and wares--and we are psychologically controlled to be dependent upon them and return to them again and again for their assistance--usually for a large fee or with some loss on our part.

We will not be too specific here, we simply caution our readers to "be wary, be very, very wary!"

Treading the spiritual metaphysical path will assist one to be more discerning as to the understanding of what is True and what is false, what is Real and what is illusory. Generally speaking, a portion of humanity is now more experienced in the ways of men and the world than in bygone days, and they seek for that which will release them from all their mortal limitations and errors, from that Gorgon we  call "the human ego," from concepts that bind one to personal illusions and glamour, and from that state of human mortality.

Many of us are beginning to realize the existence of different dimensions and multifold realities. We seek ways for improving the human condition, for perfecting human expression, and the generation of a new type of Homo sapiens whose intelligence and heart matches those of the immortal gods. Human beings are basically seekers. Some of us thirst for that which we know not what. The
"curiosity instinct" impels every one of us to learn everything we can of  our environment, of ourselves, of the universe, of Nature, and of God. What fascinates and intrigues us most are the phenomena caused by forces and powers that transcends the perceptual capacity of the physical senses and the apprehension of the human mind. Humanity is intensely interested in the Intelligence that shapes human destiny--whether this "Intelligence" be considered as a being, a force, a Universal Mind, an omnipresent energy, or a collective consciousness. People are
seeking explanations to their "inexplicable" experiences in the field of  psychicism and the paranormal. Such occurrences as coincidences or "synchronicity" also baffles the mind as it begs for enlightenment. Those of elderly years wonder what lies for them in the "after-life," as the youthful ones wonder of their place in this world. A questioning being is a thinking being and it denotes, whether consciously realized or not, as a desire to seek, to know, and to be aware of Truth. The curiosity instinct mentioned above could well be the primitive stirrings of the divine will of the highest aspect of Man seeking to be aware of Its essential nature. The teachings of the Ageless Wisdom as taught in metaphysical, esoteric, occult and arcane schools are filled with principles that would help us understand ourselves and our  omniverse.

Humanity as a whole, is jaded and sickened by the constant wars and conflicts; with the materialistic and hedonistic life that do not offer any permanent peace and happiness or solutions to the various problems facing us as we approach a new millenium with its tremendous supernal and mundane challenges. Many seek for a more profound meaning in life, for they see through their mundane activities as a brittle illusory facade presenting itself as reality. We often ask "why am I here?" "why do I exist?" "where will I go from here?" Our present systems of religion, philosophy, and science offer no real solution, consolation, solace or comfort to our hearts and
soul-search, instead they tend to mislead, confine, and circumscribe the soul and mind to a certain area of life; to a limited way of living and thinking; to a sense of separatism; to a dualistic judgmental attitude; to a sense of fear and helplessness; and to a state of external dependency-it especially confines man to a mortal sense of existence--and we say this not from a sense of judgment but from an  observational standpoint. Conversely, metaphysics as a repository of "New-Age" concepts, the Ageless Wisdom, divine energies, power-centers, and angelic and cosmic support, seek to liberate us from self-imposed limitations as it offers answers to questions that troubles the human soul. The soul loves freedom
for freedom is ingrained in the soul. God gave man the liberty to choose,  and this privilege should not be taken away from man by any being for it is a violation of the natural order of things. Freedom may be considered as an instinct for it is to be found in animals as well. No creature enjoys being confined in a cage. Every creature love to be free and to express the genetic joy programmed in its DNA. Nature has granted all creatures their freedom of expression but some
of us would impose our will upon Divine Will by creating cages of man-made laws and regulations that do not reflect the laws of Heaven. Man-made laws may easily be manipulated by the unscrupulous for their own heinous purposes. Crimes may be committed that are "lawful," that goes undisciplined in our courts of judgment. In the laws of our society, the innocents are often made to pay for the crimes of another. Where is the love (religion), and rationality (science), and justice (philosophy) in that?

We are writing intuitively here and our statements may be interpreted and applied in various ways. In fact, statements in our literary works may seem to lack any logical structure or sequence. They may appear to be non sequitur. Logic may appeal to the thinking mind, however it is more than conceptual reasoning that we have to develop. There are higher faculties of the soul that should be cultivated and made used of, such as intuition. The cliché "reading between the lines" may seem irrational to the scientific type and yet it is this particular mode of perception that has to be practiced as a spiritual stimulus to the Soul. There are many scholarly definitions of metaphysics and they are all valid; however, for our purpose, without explaining metaphysics in an overly-academic way, let us say that metaphysics
in its more modern connotation, deals with cosmic laws and principles, with unseen forces and powers influencing ourselves and the circumstances and conditions of our daily lives, and how we may take advantage of those laws and principles by re-directing them so as to improve our holistic lives for the better. Metaphysics teaches us how to harness and apply the cosmic power lying latent within us. In its most profound spiritual aspect metaphysics teaches us the nature of
Reality and how we and Nature relate to it. Metaphysics instructs us how to harmonize ourselves with the Divine Plan of God, and it reveals the true purpose of life.

Metaphysics, therefore, has a dual function: it helps us to improve our lives secularly now in this physical dimension, and it also prepares us for a glorious life in the higher cosmic realms. Actually, as seen from a spiritual perspective, life has no divisions: life is one, as it is continuous. There is no death only a constant change.

The application of certain metaphysical principles assists the acceleration of one's evolution and the quantum leap to a higher level of intelligence and spiritual awareness. We emphasize the word "application," for knowledge of principles or techniques alone is of no value. Knowledge of itself is not power, it is the application of knowledge that empowers one. Spiritually, it is not what we know or the psychic powers that we possess that counts, it is what we are. We know
many people possessing a little knowledge or power feel themselves highly superior to their fellow men. This is arrogance and carries the seeds of peril. The saying that "a little knowledge is a dangerous thing" is literally and evidently true; we can well understand how insufficient knowledge and a disregard for life may result in catastrophes. It was the cause of destruction of previous high-tech civilizations, historically unrecorded, as it is the cause of our present social, political, and ecological unrest.

To understand the above concept of incomplete knowledge, consider for instance the knowledge that we have to construct nuclear weapons--how much do we really know of the impact that it will have upon us and the universe should we choose to detonate one? We may presently believe that the effects of a nuclear blast be localized causing the exploded area to be radioactive for centuries to come. This is an obvious effect, but what about the not-so-obvious rippling, chain- reaction that it would cause in the physical and not-physical universes to the very end of our
galaxy? Basically, arrogance is an inferior attitude masking as superiority.  Inferiority or superiority complexes are both egoic expressions. The human ego often wishes the Self to appear what it is not. Even if we knew a lot, if we have read a thousand books, studied under countless Gurus, have permanent contact with a Cosmic Master, experienced a 1001 delights and terrors, meditate constantly, possess the world, or are powerful in some psychic way, it still does not give us a reason to egoically compare others with ourselves, or to judge them--by seeing others as inferior to us, by labeling them as bad, low, and vile. Many so-called spiritual teachers still do this. They criticize and condemn others without realizing that, spiritually speaking, there is no separation between others and themselves. What we see in others also lies below the conscious threshold within ourselves; what we do to others, we also do to ourselves, what we think of others, we also think of ourselves. What another is doing in the present we may well have done so ourselves in the past or perhaps will do so in the future. There is no need for judgment but a lot of need of mercy, understanding, and tolerance. Essentially, a spiritual being will not indulge in the judgment of dualistic concepts and the relativistic opposites such as good and bad, right and wrong, rich and poor, strong and weak, etc. These things are reconciled or transcended by the mage. St. Paul once said that if we owned the world and all powers and gifts of the spirit but lack
love we were nothing. This is felt by all true spiritual teachers and practitioners.
Metaphysics should not be confused with the paranormal nor with parapsychology. The paranormal and parapsychology are simply aspects of metaphysics--using the term in its broadest sense..In regards to metaphysical experiences we should keep in mind that metaphysics encompasses the two basic divisions of psychicism and mysticism, thaumaturgy and theurgy. Experiences in both fields may be  considered "metaphysical," however, a psychic experience is dissimilar to a
mystical one, and vice versa. One relates to the perception of events occurring in the lower planes or dimensions, the other to spiritual Self-awareness and the expansion of the consciousness encompassing the Whole.

As can be understood from the above, metaphysics has a transcendent value. It caters to both the physical and spiritual aspects of man. Metaphysics begins where traditional psychology leaves off, it goes where dogmatic religion is afraid to go, it extents further than mainstream science is able to reach with its laboratory equipment--although we must admit that many technological advances have been made in this direction, most of which have not yet been made available to
the general public for reasons of censure. The release of such technology would dethrone the powers that seek to enslave the world and the Dark forces are trying very hard to prevent humanity from being empowered.

One of the misconceptions regarding metaphysics is that it is unscientific and based upon superstitious ideas. This is not in our experience. Metaphysics is scientific, rational, empirical and pragmatic, or it could indeed well e "superstitious" depending on one's attitude, beliefs, and manner of approach, or how one would like it to be. This might seem as a paradox and yet it may be reconciled. We liberate our minds or impose limitations upon it by our beliefs and attitudes, and by those limitations we circumscribe our mental and spiritual growth.

Our beliefs and attitudes form our basic interpretation of Reality. If a thing is of value, because of prejudice we will not see it. We will see what we want to see, and refuse to see what we refuse to see. Metaphysics may be approached in various ways. If one has a background in mathematics, one's approach would be mathematical. If one has a psychological background one would naturally approach it from a psychological standpoint. And if one simply believes or disbelieves in
metaphysical principles then the result would be in accordance to that  mental condition. For instance, if we disbelieve that man may go to the moon we would not exert effort to putting him there. If we believe that we are doomed to failure we would never motivate ourselves to work for success. This concept relates to how we form our own personal experiences in life, our own personal reality. Intrinsically, however, personal opinions do not affect the natural laws operating in our universe. We may discount the reality of gravity, for instance, and yet the law still functions in our everyday experience. The same goes with the other natural laws like karma and
reincarnation. Belief or disbelief in them will not affect their existence and operation. Just because these laws are not mentioned by prophets and written about in Holy Scriptures do not nullify their activity. Come to think of it, many scientific natural laws are not mentioned in Holy Writ, does this prove their non-existence?

Though certain aspects of metaphysics may be considered to be speculative, as it deals with the Ultimate Reality, the First Cause, creation, and ontology or the nature of being--what interests us is the application of its principles and direction of Cosmic laws in everyday life. The worth of a science lies in its value, relevancy, and applicability in everyday living. If it is inefficient in aiding humanity to create abundance, peace, health, etc., then it is impractical and worthless. Some people have this kind of misconception concerning metaphysics, they believe that
metaphysics is impractical, too abstract, or that it violates natural law  and hence, religion; however, the opposite is true. Metaphysics and its principles work in  harmony with Cosmic laws and is extremely practical. Applied Metaphysics, as differentiated from Speculative Metaphysics, is wholly practical and essential to daily life. It empowers us with the tools and knowledge necessary to achieve a successful and fulfilled life. Though the art and science of metaphysics is still in its infancy compared to what lies ahead, there is enough teachings, techniques and systems to assist us live a fruitful, productive and creative life in accord with the Divine Will. The more we know and understand, the more wisdom we possess, the more motivated, focused and confident we are--the more chances we have of fulfilling our mission in life.

There is an on-going electromagnetic regeneration occurring in our solar system in our present "time-period." The present interaction and interfacing of energy fields in the part of our galaxy that our solar system is entering are causing the transformation of worlds and all beings connected to them in an evolutionary manner. Electromagnetic energies radiating from power centers in multi-dimensional universes are affecting and transforming everything in its path or
field of influence. These energies induce and impel all beings to rise in  their awareness level. They stimulate Man and Nature to form a new relationship based on trust and healthy cooperation. St Francis of Assisi was a pioneer and a model for us in this regard. This friar considered all beings--trees and animals, included--as his brothers and sisters. The transformations that are currently occurring politically and socially in the world are just a few of the physical effects of the cosmic bombardment of these energy rays. Changes will occur at every level lifting humanity to a new state of being, to a higher level of divine expression. The
transmutational process currently operating is represented by the Water Bearer-the sign of Aquarius, and the Aquarian Age. The water flowing from the vessel represents the energies flowing from the Mental, Buddhic and Atmic realms. These are just some of the higher dimensions operating above the personality level. Collectively, these three dimensions are represented by the pail held by the Water Bearer from whence these energies flow, and the Water Bearer as the Higher Christ Self within each individual.

The New Age or the Aquarian Age can be interpreted as the "second-coming" of Christ, for His sign (Aquarius) shall appear or is appearing in the sky in an astronomical sense; he "appears" in the clouds or energies of the New Age, and every eye shall "see" him—that is, feel his influence. How can we appreciate the value of metaphysics? It takes careful study and analysis with a non-prejudicial mind before a true evaluation can be made of any science or thing. Metaphysics is of
no exception. The problem is that too many people have preconceived the nature of metaphysics without having investigated the matter. Some consider it as the science of Lucifer or other such nonsense. All knowledge is essentially neutral in nature. Nothing is good or bad in itself. We attribute a thing as good or bad, right or wrong from the standpoint of our own moral standards or preference and this is constantly changing in consonance with the level of our spiritual awareness.
Metaphysical teachings help us in various ways. It teaches us the  existence of the many Cosmic laws operating in the universe and how these laws function in the world of beings. If understanding just a simple Cosmic law like karma helps one to correct misconceptions and alleviate our struggles, and relieve certain  psychological pain, can you imagine how the awareness and understanding of a dozen Cosmic laws would help improve the quality and value of one's life? It should be realized that if a person were to cry out in pain to God for an explanation to all of her problems and excruciating experiences, and that if she were confused and at a loss of knowing how to react or respond to certain situations, then it should be known that there are possible errors in that person's philosophy of life, in that person's understanding of the functions and laws of the universe, and the purpose of life, or of the person's personal mission. Since one's philosophy of life is associated with one's cultural and religious beliefs, then those beliefs should be looked into for possible false notions and dogmatic errors that do not reflect the workings of Nature.

True religion brings joy, bliss, understanding and wisdom to the heart, and is scientifically inclined. If it does not do so, and if it simply causes one to believe a thing without offering personal determination of its truth through experience,  knowledge and  understanding then it may be seen as a diversion from the true spiritual path. We state emphatically here that to be religious is not synonymous to being spiritual. A spiritual person may be religious, but a religious person  is not always spiritual. A spiritual person knows whereas a religious person simply possesses faith, which at times may be expressed blindly in the condition called fanaticism.

In metaphysics we develop power, intelligence and wisdom. Wisdom is a blend of knowledge, understanding, and experience directed by the buddhic principle of love--unconditional love. It is thinking with the heart and feeling with the mind. This distinguishes the higher metaphysical development of spirituality from the lower metaphysical unfoldment of psychicism. In a lower metaphysical development we may solely possess psychic ability or power but no wisdom and understanding to use it. We unfold in an unbalanced way. When power exceeds the wisdom to
apply it, the seeds of self-destruction is inherent and might be the  probable outcome. Advanced metaphysicians have all three aspects of divinity in full development or unfolding in a balanced and harmonious way, these three are: the aspects of love/wisdom, power/will, and intelligence/activity. The more Cosmic laws and truths we apprehend with our souls and apply in our every day lives, the more spiritual, divine, and powerful we become. The more we purify ourselves from all the
dross and toxins in our energy-structures, and the more we liberate ourselves from preconceived human mortal limitations, the more we are able to access divine energies and express our divinity, or our divine attributes. We are able to manifest our Christ Self. The term "Christ Self" should be understood as a component within the microcosm, or Man--both visible and invisible, and as the True Self functioning at a certain consciousness level beyond personality functions and expressions. In metaphysics Christ is not conceived as a historical person but rather understood from a mystical and mythical standpoint. Christ is often apprehended as a state of
awareness of man functioning at a spiritual level. This is real power: the  power derived from one's own spiritual knowing, awareness and being. Most of the so-called powers claimed by some psychics are borrowed from disembodied entities and are basically illusory and impermanent. Such temporal and borrowed powers in the end may seek to control and obsess the person using them. This is one reason that one should be aware of the dangers in psychicism before embarking upon its development. It is always safer to first develop true spirituality and
the taming of the false ego. The injunction is to first seek the kingdom  of God that all things shall be added unto us. In metaphysics we come to learn of many teachings of Cosmic laws and principles that aid us to deal with life, to master our lower self and express all that is divine in us. This is true mastery. The word Master does not mean being able to control Nature or others, it is the ability to effectively work in cooperation with Her and with our fellow man in creating harmony, peace,
and abundance in our world, in our shared reality, in our conjoined dream.  Real Masters are those who have mastered the animalistic and humanistic elements of their being and are now expressing their god-hood. Cosmic or Ascended Masters do not generally consider themselves as Masters for they realize that they themselves are in a state of learning.

Such is their humility.

Two NASA telescopes helped an international team of astrophysicists peer far enough back in time to gain new insight on how black holes form.

The scientific feat is also "a breakthrough for practical applications because entangled molecules can be the building blocks for many future applications.” says physicist Lawrence Cheuk.

Hopfield, the Howard A. Prior Professor in the Life Sciences, Emeritus, and professor of molecular biology, emeritus, shares the 2024 Nobel Prize with Toronto's Geoffrey E. Hinton.

As the James Webb Space Telescope delights stargazers with breathtaking images and groundbreaking discoveries, we connected with Princeton astrophysics luminaries Gillian “Jill” Knapp and Neta Bahcall, both contributors to a new book by women astronomers.

Sixty years ago a teenager’s homemade ice cream raised a surprisingly complicated question: Can hot liquids freeze faster than cold ones?

Jerusalemite of the week: India Abraham is a practitioner of medical tattooing who had already helped scores of people before Oct. 7, but her work has taken on even greater significance since then.

Time's arrow may not be as unidirectional as we were led to believe. According to Scientific American, a group of quantum physical researchers at the University of Toronto had observed evidence of what they're calling "negative time"—specifically, of photons exiting a material before they ever entered it, to begin with. — Read the rest

The post Physicists find evidence of "negative time" in photons appeared first on Boing Boing.

Sean R. Collins
Mar 1, 2007; 6:439-450
Research

CJ Fielding
Feb 1, 1995; 36:211-228
Reviews

Phospholipase Cε (PLCε) is activated downstream of G protein–coupled receptors and receptor tyrosine kinases through direct interactions with small GTPases, including Rap1A and Ras. Although Ras has been reported to allosterically activate the lipase, it is not known whether Rap1A has the same ability or what its molecular mechanism might be. Rap1A activates PLCε in response to the stimulation of β-adrenergic receptors, translocating the complex to the perinuclear membrane. Because the C-terminal Ras association (RA2) domain of PLCε was proposed to the primary binding site for Rap1A, we first confirmed using purified proteins that the RA2 domain is indeed essential for activation by Rap1A. However, we also showed that the PLCε pleckstrin homology (PH) domain and first two EF hands (EF1/2) are required for Rap1A activation and identified hydrophobic residues on the surface of the RA2 domain that are also necessary. Small-angle X-ray scattering showed that Rap1A binding induces and stabilizes discrete conformational states in PLCε variants that can be activated by the GTPase. These data, together with the recent structure of a catalytically active fragment of PLCε, provide the first evidence that Rap1A, and by extension Ras, allosterically activate the lipase by promoting and stabilizing interactions between the RA2 domain and the PLCε core.

In animals, the response to chronic hypoxia is mediated by prolyl hydroxylases (PHDs) that regulate the levels of hypoxia-inducible transcription factor α (HIFα). PHD homologues exist in other types of eukaryotes and prokaryotes where they act on non HIF substrates. To gain insight into the factors underlying different PHD substrates and properties, we carried out biochemical and biophysical studies on PHD homologues from the cellular slime mold, Dictyostelium discoideum, and the protozoan parasite, Toxoplasma gondii, both lacking HIF. The respective prolyl-hydroxylases (DdPhyA and TgPhyA) catalyze prolyl-hydroxylation of S-phase kinase-associated protein 1 (Skp1), a reaction enabling adaptation to different dioxygen availability. Assays with full-length Skp1 substrates reveal substantial differences in the kinetic properties of DdPhyA and TgPhyA, both with respect to each other and compared with human PHD2; consistent with cellular studies, TgPhyA is more active at low dioxygen concentrations than DdPhyA. TgSkp1 is a DdPhyA substrate and DdSkp1 is a TgPhyA substrate. No cross-reactivity was detected between DdPhyA/TgPhyA substrates and human PHD2. The human Skp1 E147P variant is a DdPhyA and TgPhyA substrate, suggesting some retention of ancestral interactions. Crystallographic analysis of DdPhyA enables comparisons with homologues from humans, Trichoplax adhaerens, and prokaryotes, informing on differences in mobile elements involved in substrate binding and catalysis. In DdPhyA, two mobile loops that enclose substrates in the PHDs are conserved, but the C-terminal helix of the PHDs is strikingly absent. The combined results support the proposal that PHD homologues have evolved kinetic and structural features suited to their specific sensing roles.

DNA polymerases are today used throughout scientific research, biotechnology, and medicine, in part for their ability to interact with unnatural forms of DNA created by synthetic biologists. Here especially, natural DNA polymerases often do not have the “performance specifications” needed for transformative technologies. This creates a need for science-guided rational (or semi-rational) engineering to identify variants that replicate unnatural base pairs (UBPs), unnatural backbones, tags, or other evolutionarily novel features of unnatural DNA. In this review, we provide a brief overview of the chemistry and properties of replicative DNA polymerases and their evolved variants, focusing on the Klenow fragment of Taq DNA polymerase (Klentaq). We describe comparative structural, enzymatic, and molecular dynamics studies of WT and Klentaq variants, complexed with natural or noncanonical substrates. Combining these methods provides insight into how specific amino acid substitutions distant from the active site in a Klentaq DNA polymerase variant (ZP Klentaq) contribute to its ability to replicate UBPs with improved efficiency compared with Klentaq. This approach can therefore serve to guide any future rational engineering of replicative DNA polymerases.

Rhodopsin is a canonical class A photosensitive G protein–coupled receptor (GPCR), yet relatively few pharmaceutical agents targeting this visual receptor have been identified, in part due to the unique characteristics of its light-sensitive, covalently bound retinal ligands. Rhodopsin becomes activated when light isomerizes 11-cis-retinal into an agonist, all-trans-retinal (ATR), which enables the receptor to activate its G protein. We have previously demonstrated that, despite being covalently bound, ATR can display properties of equilibrium binding, yet how this is accomplished is unknown. Here, we describe a new approach for both identifying compounds that can activate and attenuate rhodopsin and testing the hypothesis that opsin binds retinal in equilibrium. Our method uses opsin-based fluorescent sensors, which directly report the formation of active receptor conformations by detecting the binding of G protein or arrestin fragments that have been fused onto the receptor's C terminus. We show that these biosensors can be used to monitor equilibrium binding of the agonist, ATR, as well as the noncovalent binding of β-ionone, an antagonist for G protein activation. Finally, we use these novel biosensors to observe ATR release from an activated, unlabeled receptor and its subsequent transfer to the sensor in real time. Taken together, these data support the retinal equilibrium binding hypothesis. The approach we describe should prove directly translatable to other GPCRs, providing a new tool for ligand discovery and mutant characterization.

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme and transcriptional coactivator and is critical for tumor metabolism. In cancer cells, native tetrameric PKM2 is phosphorylated or acetylated, which initiates a switch to a dimeric/monomeric form that translocates into the nucleus, causing oncogene transcription. However, it is not known how these post-translational modifications (PTMs) disrupt the oligomeric state of PKM2. We explored this question via crystallographic and biophysical analyses of PKM2 mutants containing residues that mimic phosphorylation and acetylation. We find that the PTMs elicit major structural reorganization of the fructose 1,6-bisphosphate (FBP), an allosteric activator, binding site, impacting the interaction with FBP and causing a disruption in oligomerization. To gain insight into how these modifications might cause unique outcomes in cancer cells, we examined the impact of increasing the intracellular pH (pHi) from ∼7.1 (in normal cells) to ∼7.5 (in cancer cells). Biochemical studies of WT PKM2 (wtPKM2) and the two mimetic variants demonstrated that the activity decreases as the pH is increased from 7.0 to 8.0, and wtPKM2 is optimally active and amenable to FBP-mediated allosteric regulation at pHi 7.5. However, the PTM mimetics exist as a mixture of tetramer and dimer, indicating that physiologically dimeric fraction is important and might be necessary for the modified PKM2 to translocate into the nucleus. Thus, our findings provide insight into how PTMs and pH regulate PKM2 and offer a broader understanding of its intricate allosteric regulation mechanism by phosphorylation or acetylation.

Defining discontinuous antigenic epitopes remains a substantial challenge, as exemplified by the case of lipid transfer polyproteins, which are common pollen allergens. Hydrogen/deuterium exchange monitored by NMR can be used to map epitopes onto folded protein surfaces, but only if the complex rapidly dissociates. Modifying the standard NMR-exchange measurement to detect substoichiometric complexes overcomes this time scale limitation and provides new insights into recognition of lipid transfer polyprotein by antibodies. In the future, this new and exciting development should see broad application to a range of tight macromolecular interactions.

RNA-protein interfaces control key replication events during the HIV-1 life cycle. The viral trans-activator of transcription (Tat) protein uses an archetypal arginine-rich motif (ARM) to recruit the host positive transcription elongation factor b (pTEFb) complex onto the viral trans-activation response (TAR) RNA, leading to activation of HIV transcription. Efforts to block this interaction have stimulated production of biologics designed to disrupt this essential RNA-protein interface. Here, we present four co-crystal structures of lab-evolved TAR-binding proteins (TBPs) in complex with HIV-1 TAR. Our results reveal that high-affinity binding requires a distinct sequence and spacing of arginines within a specific β2-β3 hairpin loop that arose during selection. Although loops with as many as five arginines were analyzed, only three arginines could bind simultaneously with major-groove guanines. Amino acids that promote backbone interactions within the β2-β3 loop were also observed to be important for high-affinity interactions. Based on structural and affinity analyses, we designed two cyclic peptide mimics of the TAR-binding β2-β3 loop sequences present in two high-affinity TBPs (KD values of 4.2 ± 0.3 and 3.0 ± 0.3 nm). Our efforts yielded low-molecular weight compounds that bind TAR with low micromolar affinity (KD values ranging from 3.6 to 22 μm). Significantly, one cyclic compound within this series blocked binding of the Tat-ARM peptide to TAR in solution assays, whereas its linear counterpart did not. Overall, this work provides insight into protein-mediated TAR recognition and lays the ground for the development of cyclic peptide inhibitors of a vital HIV-1 RNA-protein interaction.

Cation diffusion facilitator (CDF) proteins are a conserved family of divalent transition metal cation transporters. CDF proteins are usually composed of two domains: the transmembrane domain, in which the metal cations are transported through, and a regulatory cytoplasmic C-terminal domain (CTD). Each CDF protein transports either one specific metal or multiple metals from the cytoplasm, and it is not known whether the CTD takes an active regulatory role in metal recognition and discrimination during cation transport. Here, the model CDF protein MamM, an iron transporter from magnetotactic bacteria, was used to probe the role of the CTD in metal recognition and selectivity. Using a combination of biophysical and structural approaches, the binding of different metals to MamM CTD was characterized. Results reveal that different metals bind distinctively to MamM CTD in terms of their binding sites, thermodynamics, and binding-dependent conformations, both in crystal form and in solution, which suggests a varying level of functional discrimination between CDF domains. Furthermore, these results provide the first direct evidence that CDF CTDs play a role in metal selectivity. We demonstrate that MamM's CTD can discriminate against Mn2+, supporting its postulated role in preventing magnetite formation poisoning in magnetotactic bacteria via Mn2+ incorporation.

Intrinsically disordered protein domains often have multiple binding partners. It is plausible that the strength of pairing with specific partners evolves from an initial low affinity to a higher affinity. However, little is known about the molecular changes in the binding mechanism that would facilitate such a transition. We previously showed that the interaction between two intrinsically disordered domains, NCBD and CID, likely emerged in an ancestral deuterostome organism as a low-affinity interaction that subsequently evolved into a higher-affinity interaction before the radiation of modern vertebrate groups. Here we map native contacts in the transition states of the low-affinity ancestral and high-affinity human NCBD/CID interactions. We show that the coupled binding and folding mechanism is overall similar but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex and more heterogeneous transient interactions, including electrostatic pairings, and an increased disorder for the human complex. Adaptation to new binding partners may be facilitated by this ability to exploit multiple alternative transient interactions while retaining the overall binding and folding pathway.

Systemic antibody light chains (AL) amyloidosis is characterized by deposition of amyloid fibrils derived from a particular antibody light chain. Cardiac involvement is a major risk factor for mortality. Using MAS solid-state NMR, we studied the fibril structure of a recombinant light chain fragment corresponding to the fibril protein from patient FOR005, together with fibrils formed by protein sequence variants that are derived from the closest germline (GL) sequence. Both analyzed fibril structures were seeded with ex-vivo amyloid fibrils purified from the explanted heart of this patient. We find that residues 11-42 and 69-102 adopt β-sheet conformation in patient protein fibrils. We identify arginine-49 as a key residue that forms a salt bridge to aspartate-25 in the patient protein fibril structure. In the germline sequence, this residue is replaced by a glycine. Fibrils from the GL protein and from the patient protein harboring the single point mutation R49G can be both heterologously seeded using patient ex-vivo fibrils. Seeded R49G fibrils show an increased heterogeneity in the C-terminal residues 80-102, which is reflected by the disappearance of all resonances of these residues. By contrast, residues 11-42 and 69-77, which are visible in the MAS solid-state NMR spectra, show 13Cα chemical shifts that are highly like patient fibrils. The mutation R49G thus induces a conformational heterogeneity at the C terminus in the fibril state, whereas the overall fibril topology is retained. These findings imply that patient mutations in FOR005 can stabilize the fibril structure.

Replication protein A (RPA) is a eukaryotic ssDNA-binding protein and contains three subunits: RPA70, RPA32, and RPA14. Phosphorylation of the N-terminal region of the RPA32 subunit plays an essential role in DNA metabolism in processes such as replication and damage response. Phosphorylated RPA32 (pRPA32) binds to RPA70 and possibly regulates the transient RPA70-Bloom syndrome helicase (BLM) interaction to inhibit DNA resection. However, the structural details and determinants of the phosphorylated RPA32–RPA70 interaction are still unknown. In this study, we provide molecular details of the interaction between RPA70 and a mimic of phosphorylated RPA32 (pmRPA32) using fluorescence polarization and NMR analysis. We show that the N-terminal domain of RPA70 (RPA70N) specifically participates in pmRPA32 binding, whereas the unphosphorylated RPA32 does not bind to RPA70N. Our NMR data revealed that RPA70N binds pmRPA32 using a basic cleft region. We also show that at least 6 negatively charged residues of pmRPA32 are required for RPA70N binding. By introducing alanine mutations into hydrophobic positions of pmRPA32, we found potential points of contact between RPA70N and the N-terminal half of pmRPA32. We used this information to guide docking simulations that suggest the orientation of pmRPA32 in complex with RPA70N. Our study demonstrates detailed features of the domain-domain interaction between RPA70 and RPA32 upon phosphorylation. This result provides insight into how phosphorylation tunes transient bindings between RPA and its partners in DNA resection.

The recent structural elucidation of ex vivo Drosophila Orb2 fibrils revealed a novel amyloid formed by interdigitated Gln and His residue side chains belonging to the prion-like domain. However, atomic-level details on the conformational transitions associated with memory consolidation remain unknown. Here, we have characterized the nascent conformation and dynamics of the prion-like domain (PLD) of Orb2A using a nonconventional liquid-state NMR spectroscopy strategy based on 13C detection to afford an essentially complete set of 13Cα, 13Cβ, 1Hα, and backbone 13CO and 15N assignments. At pH 4, where His residues are protonated, the PLD is disordered and flexible, except for a partially populated α-helix spanning residues 55–60, and binds RNA oligos, but not divalent cations. At pH 7, in contrast, His residues are predominantly neutral, and the Q/H segments adopt minor populations of helical structure, show decreased mobility and start to self-associate. At pH 7, the His residues do not bind RNA or Ca2+, but do bind Zn2+, which promotes further association. These findings represent a remarkable case of structural plasticity, based on which an updated model for Orb2A functional amyloidogenesis is suggested.

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (Cltc), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of Cltc, similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency. Using atomic force microscopy (AFM), we demonstrate that mESCs lacking Cltc display higher Young's modulus, indicative of greater cellular stiffness, compared with WT mESCs. The increase in stiffness was accompanied by the presence of actin stress fibers and accumulation of the inactive, phosphorylated, actin-binding protein cofilin. Treatment of Cltc knockdown mESCs with actin polymerization inhibitors resulted in a decrease in the Young's modulus to values similar to those obtained with WT mESCs. However, a rescue in the expression profile of pluripotency factors was not obtained. Additionally, whereas WT mouse embryonic fibroblasts could be reprogrammed to a state of pluripotency, this was inhibited in the absence of Cltc. This indicates that the presence of active CME is essential for the pluripotency of embryonic stem cells. Additionally, whereas physical properties may serve as a simple readout of the cellular state, they may not always faithfully recapitulate the underlying molecular fate.

Transient receptor potential vanilloid 1 (TRPV1) channel is a multimodal receptor that is responsible for nociceptive, thermal, and mechanical sensations. However, which biomolecular partners specifically interact with TRPV1 remains to be elucidated. Here, we used cDNA library screening of genes from mouse dorsal root ganglia combined with patch-clamp electrophysiology to identify the voltage-gated potassium channel auxiliary subunit Kvβ1 physically interacting with TRPV1 channel and regulating its function. The interaction was validated in situ using endogenous dorsal root ganglia neurons, as well as a recombinant expression model in HEK 293T cells. The presence of Kvβ1 enhanced the expression stability of TRPV1 channels on the plasma membrane and the nociceptive current density. Surprisingly, Kvβ1 interaction also shifted the temperature threshold for TRPV1 thermal activation. Using site-specific mapping, we further revealed that Kvβ1 interacted with the membrane-distal domain and membrane-proximal domain of TRPV1 to regulate its membrane expression and temperature-activation threshold, respectively. Our data therefore suggest that Kvβ1 is a key element in the TRPV1 signaling complex and exerts dual regulatory effects in a site-specific manner.

The kinesin-3 family contains the fastest and most processive motors of the three neuronal transport kinesin families, yet the sequence of states and rates of kinetic transitions that comprise the chemomechanical cycle and give rise to their unique properties are poorly understood. We used stopped-flow fluorescence spectroscopy and single-molecule motility assays to delineate the chemomechanical cycle of the kinesin-3, KIF1A. Our bacterially expressed KIF1A construct, dimerized via a kinesin-1 coiled-coil, exhibits fast velocity and superprocessivity behavior similar to WT KIF1A. We established that the KIF1A forward step is triggered by hydrolysis of ATP and not by ATP binding, meaning that KIF1A follows the same chemomechanical cycle as established for kinesin-1 and -2. The ATP-triggered half-site release rate of KIF1A was similar to the stepping rate, indicating that during stepping, rear-head detachment is an order of magnitude faster than in kinesin-1 and kinesin-2. Thus, KIF1A spends the majority of its hydrolysis cycle in a one-head-bound state. Both the ADP off-rate and the ATP on-rate at physiological ATP concentration were fast, eliminating these steps as possible rate-limiting transitions. Based on the measured run length and the relatively slow off-rate in ADP, we conclude that attachment of the tethered head is the rate-limiting transition in the KIF1A stepping cycle. Thus, KIF1A's activity can be explained by a fast rear-head detachment rate, a rate-limiting step of tethered-head attachment that follows ATP hydrolysis, and a relatively strong electrostatic interaction with the microtubule in the weakly bound post-hydrolysis state.

Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is, therefore, crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Ceramide (Cer) emerges as a common mediator of inflammation and death of neuronal and retinal pigment epithelium cells in animal models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. Sphingosine-1-phosphate (S1P) has opposite roles, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide-1-phosphate may also contribute to uveitis. Notably, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), preserves neuronal viability and retinal function. These findings underscore the relevance of alterations in the sphingolipid metabolic network in the etiology of multiple retinopathies and highlight the potential of modulating their metabolism for the design of novel therapeutic approaches.

The dominant role of CaV2 voltage-gated calcium channels for driving neurotransmitter release is broadly conserved. Given the overlapping functional properties of CaV2 and CaV1 channels, and less so CaV3 channels, it is unclear why there have not been major shifts toward dependence on other CaV channels for synaptic transmission. Here, we provide a structural and functional profile of the CaV2 channel cloned from the early-diverging animal Trichoplax adhaerens, which lacks a nervous system but possesses single gene homologues for CaV1–CaV3 channels. Remarkably, the highly divergent channel possesses similar features as human CaV2.1 and other CaV2 channels, including high voltage–activated currents that are larger in external Ba2+ than in Ca2+; voltage-dependent kinetics of activation, inactivation, and deactivation; and bimodal recovery from inactivation. Altogether, the functional profile of Trichoplax CaV2 suggests that the core features of presynaptic CaV2 channels were established early during animal evolution, after CaV1 and CaV2 channels emerged via proposed gene duplication from an ancestral CaV1/2 type channel. The Trichoplax channel was relatively insensitive to mammalian CaV2 channel blockers ω-agatoxin-IVA and ω-conotoxin-GVIA and to metal cation blockers Cd2+ and Ni2+. Also absent was the capacity for voltage-dependent G-protein inhibition by co-expressed Trichoplax Gβγ subunits, which nevertheless inhibited the human CaV2.1 channel, suggesting that this modulatory capacity evolved via changes in channel sequence/structure, and not G proteins. Last, the Trichoplax channel was immunolocalized in cells that express an endomorphin-like peptide implicated in cell signaling and locomotive behavior and other likely secretory cells, suggesting contributions to regulated exocytosis.

Electrospray ionization is today the most widely used ionization technique in chemical and bio-chemical analysis. Interfaced with a mass spectrometer it allows to investigate the molecular composition of liquid samples. With electrospray a large variety of chemical substances can be ionized. There is no limitation in mass which enables even the investigation of large non-covalent protein complexes. Its high ionization efficiency profoundly changed bio-molecular sciences because proteins can be identified and quantified on trace amounts in a high throughput fashion. This review article focusses mainly on the exploration of the underlying ionization mechanism. Some ionization characteristics are discussed which are related to this mechanism. Typical spectra of peptides, proteins and non-covalent complexes are shown and the quantitative character of spectra is highlighted. Finally the possibilities and limitations in measuring the association constant of bivalent non-covalent complexes are described.

Physicists have developed a deep understanding of the fundamental laws of nature through careful observations, experiments, and precise measurements. However, what if artificial intelligence (AI) could uncover governing laws of […]

The post Archetype AI’s Newton Model Masters Physics From Raw Data appeared first on HPCwire.

PITTSBURGH, Feb. 22, 2024 — Ansys and Intel Foundry have collaborated to provide multiphysics signoff solutions for Intel’s innovative 2.5D chip assembly technology, which uses EMIB technology to connect the […]

The post Ansys, Intel Foundry Collaborate on Multiphysics Analysis Solution for EMIB 2.5D Assembly Tech appeared first on HPCwire.

PITTSBURGH, June 19, 2024 — Ansys today announced that it is adopting NVIDIA Omniverse application programming interfaces (APIs) to offer 3D-IC designers valuable insights from Ansys’ physics solver results through […]

The post Ansys Enables 3D Multiphysics Visualization of Next-Gen 3D-IC Designs with NVIDIA Omniverse appeared first on HPCwire.

Bradley Voytek
Sep 23, 2015; 35:13257-13265
BehavioralSystemsCognitive

In demanding listening situations, a listener's motivational state may affect their cognitive investment. Here, we aim to delineate how domain-specific sensory processing, domain-general neural alpha power, and pupil size as a proxy for cognitive investment encode influences of motivational state under demanding listening. Participants (male and female) performed an auditory gap-detection task while the pupil size and the magnetoencephalogram were simultaneously recorded. Task demand and a listener's motivational state were orthogonally manipulated through changes in gap duration and monetary-reward prospect, respectively. Whereas task difficulty impaired performance, reward prospect enhanced it. The pupil size reliably indicated the modulatory impact of an individual's motivational state. At the neural level, the motivational state did not affect auditory sensory processing directly but impacted attentional postprocessing of an auditory event as reflected in the late evoked-response field and alpha-power change. Both pregap pupil dilation and higher parietal alpha power predicted better performance at the single-trial level. The current data support a framework wherein the motivational state acts as an attentional top–down neural means of postprocessing the auditory input in challenging listening situations.

Key event-related potentials (ERPs) of perceptual decision-making such as centroparietal positivity (CPP) elucidate how evidence is accumulated toward a given choice. Furthermore, this accumulation can be impacted by visual target selection signals such as the N2 contralateral (N2c). How these underlying neural mechanisms of perceptual decision-making are influenced by the spatial congruence of distractors relative to target stimuli remains unclear. Here, we used electroencephalography (EEG) in humans of both sexes to investigate the effect of distractor spatial congruency (same vs different hemifield relative to targets) on perceptual decision-making. We confirmed that responses for perceptual decisions were slower for spatially incongruent versus congruent distractors of high salience. Similarly, markers of target selection (N2c peak amplitude) and evidence accumulation (CPP slope) were found to be lower when distractors were spatially incongruent versus congruent. To evaluate the effects of congruency further, we applied drift diffusion modeling to participant responses, which showed that larger amplitudes of both ERPs were correlated with shorter nondecision times when considering the effect of congruency. The modeling also suggested that congruency's effect on behavior occurred prior to and during evidence accumulation when considering the effects of the N2c peak and CPP slope. These findings point to spatially incongruent distractors, relative to congruent distractors, influencing decisions as early as the initial sensory processing phase and then continuing to exert an effect as evidence is accumulated throughout the decision-making process. Overall, our findings highlight how key electrophysiological signals of perceptual decision-making are influenced by the spatial congruence of target and distractor.

Use #physnobel on Twitter to submit your questions. The 2014 Nobel Prize in Physics will be announced on Tuesday, October 7. Join guests Charles Day of Physics Today, Andrew Grant of Science News, Jennifer Ouellette of Cocktail Party Physics and Amanda Yoho of Starts With A Bang! as they discuss predictions for possible winners. Who are the best contenders, and who are the potential "dark horse" candidates? Which major physics finds of this year might stand a shot at a win in the future? Victoria Jaggard and Helen Thompson of Smithsonian.com will be your hosts for the event. Tune in on October 2, and submit your questions on Twitter. Charles Day is the Online Editor for Physics Today magazine. Follow him on Twitter @CSRDay Andrew Grant is the physics reporter for Science News magazine. Follow him on Twitter @sci_grant Jennifer Ouellette is a science writer and blogger at Cocktail Party Physics. Follow her on Twitter @JenLucPiquant Amanda Yoho is a graduate student in theoretical and computational cosmology at Case Western Reserve University and a blogger at Starts With A Bang! Follow her on Twitter @mandaYoho Victoria Jaggard is the science editor for Smithsonian.com. Follow her on Twitter @vmjaggard99 Helen Thompson is a science reporter for Smithsonian.com. Follow her on Twitter @wwrfd

The act of dive bombing during World War II was a death defying trial of skill and nerve. You aimed your plane down, four miles above the ocean and plummeted at speeds of up to 275 miles per hour