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I can see how one can develop, through one's practice, a very high degree of confidence in the truth of emptiness through inferring from the conditioned nature of phenomena, their impermanence, their dependence on a perceiving consciousness, and on the need for memory and intelligence in order to recognize them as existent, but is it possible to ever be 100% certain? Who's to say the Higgs Boson isn't the fundamental, truly existent building block of matter that can never be further reduced, even if quantum physics tells us it's in superposition when not interacting with an observer?

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Enlightenment happen when knowledge is certain (such knowledge is usually called jñāna), so practice is supposed to provide result as 100% certain knowledge, in regard to what is also required to cease defilements and suffering. Knowledge about 'everything in the World' is not included in that. (Maybe Buddha knows all that, though.)

Who's to say the Higgs Boson isn't the fundamental, truly existent building block of matter that can never be further reduced, even if quantum physics tells us it's in superposition when not interacting with an observer?

Higgs Boson is a concept. And, as with any concept, we can invent into concepts any idea whatsoever, with any property we can imagine. What is constructed (and thus empty) in Higgs Boson is it's conceptuality, the way how that knowledge is reached.

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The Buddhist equivalent of the Higgs Boson is Atta Kalapa. Though the practice of Vippassana you will be able to start seeing the arising and passing away of such particles. There is vast emptiness between the particles which we call ourselves. (There may be other doctrines of emptiness.) There particles arise and passes away. (Hence there is some substance through there seam to be energy and matter duality.) These particles are not under our control as we cannot manipulate this process at this lowest level through will hence we cannot associate ourself with such process which we have not mastery or control over and trying to do so out of ignorance result in misery. Since our metal image of our self and any sense of ownership of such rapidly changing cluster of phenomena over which we do not have absolute control would entail that there will be many occasions where there is a gap with our metal image and reality resulting in unsatisfactoriness.

Observation of these phenomena is possible by sharpening your mind. For this you should be passive with respect to the process of observations. But active and ardent in the methodology and practice of observation.

Revisiting the energy and matter duality: Some times phenomena are vibrating and gaseous, sometimes they are like liquid in nature with more cohesion and flowing, sometimes they tend to be solid and less vibrations and even more cohesive, also the presence of heat alters state of phenomena and vibrations.

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