Ex nihilo

From Wikipedia, the free encyclopedia

Tree of Life by Eli Content at the Joods Historisch Museum. The Tree of Life, or Etz haChayim (עץ החיים) in Hebrew, is a mystical symbol used in the Kabbalah of esoteric Judaism to describe the path to HaShem and the manner in which He created the world ex nihilo (out of nothing).

 

Look up ex nihilo in Wiktionary, the free dictionary.

Ex nihilo is a Latin phrase meaning "out of nothing". It often appears in conjunction with the concept of creation, as in creatio ex nihilo, meaning "creation out of nothing", chiefly in philosophical or theological contexts, but it also occurs in other fields.

In theology, the common phrase creatio ex nihilo (lit. "creation out of nothing"), contrasts with creatio ex materia (creation out of some pre-existent, eternal matter) and creatio ex deo (creation out of the being of God). Creatio continua is the ongoing divine creation.

The phrase ex nihilo also appears in the classical philosophical formulation ex nihilo nihil fit, which means "out of nothing comes nothing".

When used outside of religious or metaphysical contexts, ex nihilo also refers to something coming from nothing. For example, in a conversation, one might call a topic "ex nihilo" if it bears no relation to the previous topic of discussion.

History

Ancient Near Eastern mythologies and classical creation myths in Greek mythology envisioned the creation of the world as resulting from the actions of a god or gods upon already-existing primeval matter, known as chaos.^[1]

An early conflation of Greek philosophy with the narratives in the Hebrew Bible came from Philo of Alexandria (d. AD 50), writing in the context of Hellenistic Judaism. Philo equated the Hebrew creator-deity Yahweh with Aristotle's primum movens (First Cause)^[2][3] in an attempt to prove that the Jews had held monotheistic views even before the Greeks.^{[citation needed]} However, this was still within the context of creation from pre-existing materials (i.e., "moving" or "changing" a material substratum.)

The classical tradition of creation from chaos first came under question in Hellenistic philosophy (on a priori grounds), which developed the idea that the primum movens must have created the world out of nothing.^{[citation needed]}

Theologians debate whether the Bible itself teaches creation ex nihilo. Traditional interpreters^[4] argue on grammatical and syntactical grounds that this is the meaning of Genesis 1:1, which is commonly rendered: "In the beginning God created the heavens and the earth." They find further support for this view in New Testament passages such as Hebrews 11:3—"By faith we understand that the universe was created by the word of God, so that what is seen was not made out of things that are visible" and Revelation 4:11, "For you [God] created all things, and by your will they existed and were created." However, other interpreters^[5] understand creation ex nihilo as a second-century theological development. According to this view, church fathers opposed notions appearing in pre-Christian creation myths and in Gnosticism—notions of creation by a demiurge out of a primordial state of matter (known in religious studies as chaos after the Greek term used by Hesiod in his Theogony).^[6] Jewish thinkers took up the idea,^[7] which became important to Judaism, to ongoing strands in the Christian tradition, and—as a corollary—to Islam.

The first sentence of the Greek version of Genesis in the Septuagint starts with the words: ἐν ἀρχῇ ἐποίησεν, translatable as "in the beginning he made".^[8]

A verse of 2 Maccabees (a book written in Koine Greek in the same sphere of Hellenized Judaism of Alexandria, but predating Philo by about a century) expresses the following: "I beseech thee, my son, look upon the heaven and the earth, and all that is therein, and consider that God made them of things that were not; and so was mankind made likewise." (2 Maccabees 7:28, KJV). While those who believe in ex nihilo point to God creating "things that were not", those who reject creation out of nothing point out that the context mentions the creation of man, who was "made from the dust" and not from absolutely "nothing". Many ancient texts tend to have similar issues, and those on each side tend to interpret the text according to their understanding.

Max Weber summarizes a sociological view of the overall development and corollaries of the theological idea:

[...] As otherworldly expectations become increasingly important, the problem of the basic relationship of god to the world and the problem of the world's imperfections press into the foreground of thought; this happens the more life here on earth comes to be regarded as a merely provisional form of existence when compared to that beyond, the more the world comes to be viewed as something created by god ex nihilo, and therefore subject to decline, the more god himself is conceived as a subject to transcendental goals and values, and the more a person's behavior in this world becomes oriented to his fate in the next. [...]^[9]

Supporting arguments

Logical

A major argument for creatio ex nihilo, the first cause argument, states in summary:^{[citation needed]}

1. everything that begins to exist has a cause
2. the universe began to exist
3. therefore, the universe must have a cause

An expansion of the first cause argument is the Kalam cosmological argument, which also requires creatio ex nihilo:^{[citation needed]}

1. Everything that begins to exist has a cause
2. The universe began to exist
3. Therefore, the universe has a cause.
4. If the universe has a cause, then an uncaused, personal creator of the universe exists, who without the universe is beginningless, changeless, immaterial, timeless, spaceless, and infinitely powerful.
5. Therefore, an uncaused, personal creator of the universe exists, who without the universe is beginningless, changeless, immaterial, timeless, spaceless, and infinitely powerful.

Another argument for ex nihilo creation comes from Claude Nowell's Summum philosophy that states before anything existed, nothing existed, and if nothing existed, then it must have been possible for nothing to be. If it is possible for nothing to be (the argument goes), then it must be possible for everything to be.^[10]

Ancient Greek

Some scholars^[which?] have argued that Plethon viewed Plato as positing ex nihilo creation in his Timaeus.

Eric Voegelin detects in Hesiod's chaos a creatio ex nihilo.^[11]

The School of Chartres understood the creation account in Plato's Timaeus to refer to creatio ex nihilo.^[12]

In Jewish philosophy

In The Book of the Articles of Faith and Doctrines of Dogma (Kitāb al-Amānāt wa l-Iʿtiqādāt, Emunoth ve-Deoth, completed 933) written by Saadia Gaon (c. 882−942) the metaphysical problems of the creation of the world and the unity of the Creator are discussed. In this book, Saadia Gaon gives four proofs for the doctrine of the creation of the world ex nihilo (yesh me-ayin).
To harmonize the biblical statement of the creation ex nihilo with the doctrine of the primordial elements, the Sefer Yetzirah assumes a double creation, one ideal and the other real.^[13]

In introducing Sefer Yetzirah's theory of creation Saadia Gaon makes a distinction between the Biblical account of creation ex nihilo, in which no process of creation is described, and matter formed by speech as described in Sefer Yetzirah. The cosmogony of Sefer Yetzirah is even omitted from the discussion of creation in his magnum opus Emunoth ve-Deoth.

Islamic

Early Islamic philosophy, as well as key Muslim schools of thought, have argued a wide array of views, the basis always being that the creator was an eternal being who was outside of the creation (i.e., any materially based entities within all of creation), and was not a part of creation. Several schools of thought stemming from the first cause argument, and a great deal of philosophical works from Muslim scholars such as Al-Ghazali, came from the following verses in the Qur'an. The following quotations come from Muhammad Asad's translation, The Message of The Qur'an:

• 52:35: "Were they created by nothing? Or were they themselves the creators?"
• 2:117: "The Originator is He of the heavens and the earth: and when He wills a thing to be, He but says unto it, 'Be'—and it is."
• 19:67: "But does man not bear in mind that We have created him aforetime while at one point they were nothing?"
• 21:30: "ARE, THEN, they who are bent on denying the truth not aware that the heavens and the earth were [once] one single entity, which We (formal singular) then parted asunder? – and [that] We made out of water every living thing? Will they not, then, [begin to] believe?"
• 21:56: "He answered: 'Nay, but your [true] Sustainer is the Sustainer of the heavens and the earth—He who has brought them into being: and I am one of those who bear witness to this [truth]!'"
• 35:1: "ALL PRAISE is due to God, Originator of the heavens and the earth, who causes the angels to be (His) message-bearers, endowed with wings, two, or three, or four. He adds to His creation whatever He Wills: for, verily, God, is most competent over all things."
• 51:47: "It is We (formal singular) who have built the heaven with (Our creative) power; and, verily, it is We who are steadily expanding it."

Christian

Biblical scholars and theologians within the Christian tradition such as Augustine (354–430),^[14] John Calvin (1509–1564),^[15] John Wesley (1703–1791),^[16] and Matthew Henry (1662–1714)^[17] cite Genesis 1:1 in support of the idea of Divine creation out of nothing.

Some of the early Christian Church Fathers with a Platonic background argued that the act of creation itself involved pre-existent matter, but made that matter in turn to have been created out of nothing.^[18]

Hindu

The RigVeda quotes "If in the beginning there was neither Being nor Non-Being, neither air nor sky, what was there? Who or what oversaw it? What was it when there was no darkness, light, life, or death? We can only say that there was the One, that which breathed of itself deep in the void, that which was heat and became desire and the germ of spirit," which is suggestive of the fact that Ex nihilo creator was always there and he is not controlled by time or by any previous creation.^[19]

Modern physical

A widely supported hypothesis in modern physics is the zero-energy universe which states that the total amount of energy in the universe is exactly zero. It has been argued that this is the only kind of universe that could come from nothing.^[20] Such a universe would have to be flat in shape, a state which does not contradict current observations that the universe is flat with a 0.5% margin of error.

The paper "Spontaneous creation of the Universe Ex Nihilo" provides a model for a way the Universe could have been created from pure 'nothing' in information terms.^[23]

Opposing arguments

Logical

The "first cause" argument was rooted in ancient Greek philosophy and based on observation in physics. Originally, it was understood^{[by whom?]} in the context of creation from chaos. The observed phenomenon seen in reality is that nothing moves by itself. In other words, motion is not self-caused; thus, the Classic Greek thinkers argued that the cosmos must have had a "prime mover" primum movens. However, this scientific observation of motion does not logically extend to the idea of existence, and therefore does not necessarily indicate creation from absolutely nothing.

In theology, ex nihilo creation states that there was a beginning to one's existence, and anything that exists has a beginning. This idea of a required beginning appears to contradict the proposed creator who existed without a beginning. In other words, people are considered to be contingent beings, and their existence depends upon a non-contingent being. However, if non-contingency is possible, then there is no basis for arguing that contingency is required for existence, nor can it be logically concluded that the number of non-contingent beings or non-contingent things is limited to one single substance or one single Being.

David Ray Griffin expressed his thoughts on this as follows:

"No special philosophical problems are raised by this view: If it is intelligible to hold that the existence of God requires no explanation, since something must exist necessarily and "of itself," then it is not unintelligible to hold that that which exists necessarily is God and a realm of non-divine actualities."^[24]

Christian

Bruce K. Waltke wrote an extensive Biblical study of creation theology in which he argues for creation from chaos rather than from nothing - based on the Hebrew Torah and the New Testament texts. The Western Conservative Baptist Seminary published this work in 1974 and again in 1981.^[25] On a historical basis, many^[quantify] scholars agree that the doctrine of creatio ex nihilo was not the original intent of the Biblical authors, but instead a change in the interpretation of the texts that began to evolve in the mid-second century AD in the atmosphere of Hellenistic philosophy.^[26][27] The idea solidified around 200 AD in arguments and in response to the Gnostics, Stoics, and Middle Platonists.^[28]

Thomas Jay Oord, a Christian philosopher and theologian, argues that Christians should abandon the doctrine of creation ex nihilo. Oord points to the work of biblical scholars such as Jon D. Levenson, who points out that the doctrine of creatio ex nihilo does not appear in Genesis. Oord speculates that God created our particular universe billions of years ago from primordial chaos. This chaos, however, did not predate God, for God would have created the chaotic elements as well.^{[29][page needed]} Oord suggests that God can create all things without creating from absolute nothingness.^[30]

Oord offers nine objections to creatio ex nihilo:^[31]

1. Theoretical problem: One cannot conceive absolute nothingness.
2. Biblical problem: Scripture – in Genesis, 2 Peter, and elsewhere – suggests creation from something (water, deep, chaos, etc.), not creation from absolutely nothing.
3. Historical problem: The Gnostics Basilides and Valentinus first proposed creatio ex nihilo on the basis of assuming the inherently evil nature of creation, and in the belief that God does not act in history. Early Christian theologians adopted the idea to affirm the kind of absolute divine power that many Christians now reject.
4. Empirical problem: We have no evidence that our universe originally came into being from absolutely nothing.
5. Creation-at-an-instant problem: We have no evidence in the history of the Universe after the big bang that entities can emerge instantaneously from absolute nothingness. As the earliest philosophers noted, out of nothing comes nothing (ex nihilo, nihil fit).
6. Solitary power problem: Creatio ex nihilo assumes that a powerful God once acted alone. But power, as a social concept, only becomes meaningful in relation to others.
7. Errant revelation problem: The God with the capacity to create something from absolutely nothing would apparently have the power to guarantee an unambiguous and inerrant message of salvation (for example: inerrant Bible). An unambiguously clear and inerrant divine revelation does not exist.
8. Problem of Evil: If God once had the power to create from absolutely nothing, God essentially retains that power. But a God of love with this capacity appears culpable for failing to prevent evil.
9. Empire Problem: The kind of divine power implied in creatio ex nihilo supports a theology of empire, based upon unilateral force and control of others.

Process theologians argue that humans have always related a God to some "world" or another. They^[32] also claim that rejecting creatio ex nihilo provides the opportunity to affirm that God has everlastingly created and related with some realm of non-divine actualities or another (compare continuous creation). According to this alternative God-world theory, no non-divine thing exists without the creative activity of God, and nothing can terminate God's necessary existence.

Some non-trinitarian Christian churches do not teach the ex nihilo doctrine:

• The Church of Jesus Christ of Latter-day Saints (LDS) teaches that Jehovah (whom they identify as the heavenly form of Jesus Christ), under the direction of God the Father, organized this world and others like it out of eternal, pre-existing materials.^[33][34] The first modern (non-biblical) prophet of the religion, Joseph Smith, explained the LDS view as follows: "Now, the word create does not mean to create out of nothing; it means to organize... God had materials to organize the world out of chaos... The pure principles of element are principles which can never be destroyed; they may be organized and reorganized, but not destroyed. They had no beginning and can have no end"^[35] Debate continues on the issue of creation Ex Nihilo versus creation Ex Materia between evangelical authors Paul Copan and William Lane Craig^[36] and LDS/Mormon apologist Blake Ostler.^[37]
• Jehovah's Witnesses teach that God used the energy he possesses to create the Universe based on their interpretation of Isaiah 40:26.^[38] They believe this harmonizes with the scientific idea of the relationship between matter and energy. They distinguish Jehovah from Jesus Christ, teaching that before he created the physical universe, Jehovah created Jesus and that Michael is the heavenly form of Jesus.

Hindu

The Vedanta schools of Hinduism reject the concept of creation ex nihilo for several reasons, for example:

1. both types of revelatory texts (śruti^[39] and smṛti) designate matter as eternal although completely dependent on God—the Absolute Truth (param satyam)
2. believers then have to attribute all the evil ingrained in material life to God, making Him partial and arbitrary,^[40] which does not logically accord with His nature

The Bhagavad Gita (BG) states the eternality of matter and its transformability clearly and succinctly: "Material nature and the living entities should be understood to be beginningless. Their transformations and the modes of matter are products of material nature."^[41] The opening words of Krishna in BG 2.12-13 also imply this, as do the doctrines referred to in BG 16.8 as explained by the commentator Vadiraja Tirtha.^[42]

Most philosophical schools in Hinduism maintain that material creation started with some minute particle (or seed) which had to be co-eternal or a part of ultimate reality (Brahman). This minute starting point is also the point into which all creation contracts at the end of each cycle. This concept varies between various traditions, such as the Vishishtadvaita tradition (which asserts that the Universe forms a part of God, created from some aspect of His divinity) and Tamil Shaiva Siddhanta traditions (which state that the minute initial particle (shuddha Maya) has always existed and was never created).

Linguistic and textual

Scholars have suggested alternative translations from the Biblical Hebrew for the concept often rendered as "created" in English-language versions of Genesis 1. Van Volde, for example, suggests that the Genesis account tells of the "separation" of existing material rather than of creation ex nihilo.^[43]

Note that ordinary language may lack a concise definitive native expression for "creation ex nihilo" - hence the need for the technical Latinate phrase itself. The English-language word "create" itself comes from the Latin creare (to make, bring forth, produce, beget), with a root cognate with crescere (to arise, to grow) and allied to the English word crescent (originally meaning "growing").

DNA-binding protein

From Wikipedia, the free encyclopedia

 

Cro protein complex with DNA

 

Interaction of DNA (orange) with histones (blue). These proteins' basic amino acids bind to the acidic phosphate groups on DNA.

 

The lambda repressor helix-turn-helix transcription factor bound to its DNA target^[1]

 

The restriction enzyme EcoRV (green) in a complex with its substrate DNA^[2]

DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that identify a base pair. However, there are some known minor groove DNA-binding ligands such as netropsin, distamycin, Hoechst 33258, pentamidine, DAPI and others.

Examples

DNA-binding proteins include transcription factors which modulate the process of transcription, various polymerases, nucleases which cleave DNA molecules, and histones which are involved in chromosome packaging and transcription in the cell nucleus. DNA-binding proteins can incorporate such domains as the zinc finger, the helix-turn-helix, and the leucine zipper (among many others) that facilitate binding to nucleic acid. There are also more unusual examples such as transcription activator like effectors.

Non-specific DNA-protein interactions

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes, this structure involves DNA binding to a complex of small basic proteins called histones. In prokaryotes, multiple types of proteins are involved.^[8][9] The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are therefore largely independent of the base sequence.^[10]  Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation.^[11] These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription.^[12] Other non-specific DNA-binding proteins in chromatin include the high-mobility group (HMG) proteins, which bind to bent or distorted DNA.^[13] Biophysical studies show that these architectural HMG proteins bind, bend and loop DNA to perform its biological functions.^[14][15] These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that form chromosomes.^[16]

Proteins that specifically bind single-stranded DNA

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair.^[17] These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

Binding to specific DNA sequences

In contrast, other proteins have evolved to bind to specific DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one specific set of DNA sequences and activates or inhibits the transcription of genes that have these sequences near their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.^[18] Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This alters the accessibility of the DNA template to the polymerase.^[19]

These DNA targets can occur throughout an organism's genome. Thus, changes in the activity of one type of transcription factor can affect thousands of genes.^[20] Thus, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to read the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.^[21] Mathematical descriptions of protein-DNA binding taking into account sequence-specificity, and competitive and cooperative binding of proteins of different types are usually performed with the help of the lattice models.^[22] Computational methods to identify the DNA binding sequence specificity have been proposed to make a good use of the abundant sequence data in the post-genomic era.^[23]

Protein–DNA interactions

Protein–DNA interactions occur when a protein binds a molecule of DNA, often to regulate the biological function of DNA, usually the expression of a gene. Among the proteins that bind to DNA are transcription factors that activate or repress gene expression by binding to DNA motifs and histones that form part of the structure of DNA and bind to it less specifically. Also proteins that repair DNA such as uracil-DNA glycosylase interact closely with it.

In general, proteins bind to DNA in the major groove; however, there are exceptions.^[24] Protein–DNA interaction are of mainly two types, either specific interaction, or non-specific interaction. Recent single-molecule experiments showed that DNA binding proteins undergo of rapid rebinding in order to bind in correct orientation for recognizing the target site.^[25]

Design

Designing DNA-binding proteins that have a specified DNA-binding site has been an important goal for biotechnology. Zinc finger proteins have been designed to bind to specific DNA sequences and this is the basis of zinc finger nucleases. Recently transcription activator-like effector nucleases (TALENs) have been created which are based on natural proteins secreted by Xanthomonas bacteria via their type III secretion system when they infect various plant species.^[26]

Detection methods

There are many in vitro and in vivo techniques which are useful in detecting DNA-Protein Interactions. The following lists some methods currently in use:^[27]

• Electrophoretic mobility shift assay is a widespread technique to identify protein–DNA interactions.
• DNase footprinting assay can be used to identify the specific site of binding of a protein to DNA.
• Chromatin immunoprecipitation is used to identify the sequence of the DNA fragments which bind to a known transcription factor. This technique when combined with high throughput sequencing is known as ChIP-Seq and when combined with microarrays it is known as ChIP-chip.
• Yeast One-hybrid System (Y1H) is used to identify which protein binds to a particular DNA fragment.
• Bacterial one-hybrid system (B1H) is used to identify which protein binds to a particular DNA fragment.
• Structure determination using X-ray crystallography has been used to give a highly detailed atomic view of protein–DNA interactions.

Manipulating the interactions

The protein–DNA interactions can be modulated using stimuli like ionic strength of the buffer, macromolecular crowding,^[28] temperature, pH and electric field. This can lead to reversible dissociation/association of the protein–DNA complex.

Wearable sensors can alert you when you are getting sick, Stanford study shows

January 18, 2017
Original link: http://www.kurzweilai.net/wearable-sensors-can-alert-you-when-you-are-getting-sick-stanford-study-showwearable-sensors-can-alert-you-when-you-are-getting-sick-stanford-study-shows

Current versions of three of the devices used for heart-rate and peripheral capillary oxygen saturation measurements in the study (credits left to right: Scanadu, iHealth, and Masimo)

Fitness monitors and other wearable biosensors can tell when your heart rate, activity, skin temperature, and other measures are abnormal, suggesting possible illness, including the onset of infection, inflammation, and even insulin resistance, according to a study by researchers at the Stanford University School of Medicine.

The team collected nearly 2 billion measurements from 60 people, including continuous data from each participant’s wearable biosensor devices* and periodic data from laboratory tests of their blood chemistry, gene expression, and other measures, and related this data to a range of normal (baseline) values for each person in the study compared to when they were ill.**

Participants wore between one and seven commercially available activity monitors and other monitors that collected more than 250,000 measurements a day. The team collected data on weight; heart rate; oxygen in the blood; skin temperature; activity, including sleep, steps, walking, biking and running; calories expended; acceleration; and even exposure to gamma rays and X-rays.

There were three participant groups: Participant #1 wore seven portable devices for large segments of this study; 43 individuals wore Intel’s Basis to measure activity (steps), heart rate, sleep, and skin temperature, with data securely uploaded to the cloud; and 16 individuals wore either iHealth or Masimo finger devices for sensing heart rate and SpO2 (peripheral capillary oxygen saturation).

Identifying health problems in advance

Wearable devices used by participant 1 (credit: Xiao Li/PLOS Biology)

The study, led by Michael Snyder, PhD, professor and chair of genetics, and senior author of the study, was published online Jan. 12 in open-access PLOS Biology. It demonstrated that, given a baseline range of values for each person, it is possible to monitor deviations from normal and associate those deviations with environmental conditions, illness, or other factors that affect health. Distinctive patterns of deviation from normal seem to correlate with particular health problems. Algorithms designed to pick up on these patterns of change could potentially contribute to clinical diagnostics and research.

The results of the current study raise the possibility of identifying inflammatory disease in individuals who may not even know they are getting sick.

For example, in several participants, higher-than-normal readings for heart rate and skin temperature correlated with increased levels of C reactive protein in blood tests. C reactive protein is an immune system marker for inflammation and often indicative of infection, autoimmune diseases, developing cardiovascular disease or even cancer. Snyder’s own data revealed four separate bouts of illness and inflammation, including a Lyme disease infection and another that he was unaware of until he saw his sensor data and an increased level of C reactive protein.

The wearable devices could also help distinguish participants with insulin resistance, a precursor for Type 2 diabetes. Of 20 participants who received glucose tests, 12 were insulin-resistant. The team designed and tested an algorithm combining participants’ daily steps, daytime heart rate and the difference between daytime and nighttime heart rate. The algorithm was able to process the data from just these few simple measures to predict which individuals in the study were likely to be insulin-resistant.

The study also revealed that declines in blood-oxygen levels during airplane flights were correlated with fatigue. Fortunately, the study showed that people tend to adapt on long flights; oxygen levels in their blood go back up, and they generally feel less fatigued as the hours go by.

The future of wearable devices: monitoring human health continuously

During a visit to the doctor, patients normally have their blood pressure and body temperature measured, but such data is typically collected only every year or two and often ignored unless the results are outside of normal range for entire populations. But biomedical researchers envisage a future in which human health is monitored continuously.

“We have more sensors on our cars than we have on human beings,” said Snyder. In the future, he said, he expects the situation will be reversed and people will have more sensors than cars do. Already, consumers have purchased millions of wearable devices, including more than 50 million smart watches and 20 million other fitness monitors. Most monitors are used to track activity, but they could easily be adjusted to more directly track health measures, Snyder said.

The work is an example of Stanford Medicine’s focus on “precision health,” whose goal is to anticipate and prevent disease in the healthy and to precisely diagnose and treat disease in the ill. With a precision health approach, every person could know his or her normal baseline for dozens of measures. Automatic data analysis could spot patterns of outlier data points and flag the onset of ill health, providing an opportunity for intervention, prevention or cure.

Researcher Elizabeth Colbert, of the Veterans Affairs Palo Alto Health Care System, is also a co-author. This research was funded by the National Institutes of Health, a gift from Bert and Candace Forbes, and Stanford’s Department of Genetics.

* “After evaluating more than 400 available wearable devices at the beginning of the study, we selected [seven] for participants to use. The criteria for selection [were] (1) ability to access the raw data from the manufacturer, (2) cost, (3) overlap in measurement of at least one component with another device to assist in reproducibility, and (4) ease of use, reasonable accuracy, and had a direct interface for raw data. These devices collectively measure (a) three physiological parameters, including heart rate, peripheral capillary oxygen saturation, and skin temperature, (b) six activity-related parameters, including sleep, steps, walking, biking, running, calories, and acceleration forces caused by movement, (c) weight, and (d) total gamma and X-ray radiation exposure.” — PLOS Biology paper authors

** “In this work, we investigate the use of portable devices to (1) easily and accurately record physiological measurements in individuals in real time (or at high frequency), (2) quantify daily patterns and reveal interesting physiological responses to different circadian cycles and environmental conditions, (3) identify personalized baseline norms and differences among individuals, (4) detect differences in health states among individuals (e.g., people with diabetes versus people without diabetes), and (5) detect inflammatory responses and assist in medical diagnosis at the early phase of disease development, thereby potentially impacting medical care.” — PLOS Biology paper authors

---

Abstract of Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information

A new wave of portable biosensors allows frequent measurement of health-related physiology. We investigated the use of these devices to monitor human physiological changes during various activities and their role in managing health and diagnosing and analyzing disease. By recording over 250,000 daily measurements for up to 43 individuals, we found personalized circadian differences in physiological parameters, replicating previous physiological findings. Interestingly, we found striking changes in particular environments, such as airline flights (decreased peripheral capillary oxygen saturation [SpO2] and increased radiation exposure). These events are associated with physiological macro-phenotypes such as fatigue, providing a strong association between reduced pressure/oxygen and fatigue on high-altitude flights. Importantly, we combined biosensor information with frequent medical measurements and made two important observations: First, wearable devices were useful in identification of early signs of Lyme disease and inflammatory responses; we used this information to develop a personalized, activity-based normalization framework to identify abnormal physiological signals from longitudinal data for facile disease detection. Second, wearables distinguish physiological differences between insulin-sensitive and -resistant individuals. Overall, these results indicate that portable biosensors provide useful information for monitoring personal activities and physiology and are likely to play an important role in managing health and enabling affordable health care access to groups traditionally limited by socioeconomic class or remote geography.

References:

• Xiao Li, Jessilyn Dunn, Denis Salins, Gao Zhou, Wenyu Zhou, Sophia Miryam Schüssler-Fiorenza Rose, Dalia Perelman, Elizabeth Colbert, Ryan Runge, Shannon Rego, Ria Sonecha, Somalee Datta, Tracey McLaughlin, Michael P. Snyder. Digital Health: Tracking Physiomes and Activity Using Wearable Biosensors Reveals Useful Health-Related Information. PLOS Biology, 2017; 15 (1): e2001402 DOI: 10.1371/journal.pbio.2001402 (open access)

Ligand (biochemistry)

From Wikipedia, the free encyclopedia

Myoglobin (blue) with its ligand heme (orange) bound. Based on PDB: 1MBO​

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure. The instance of binding occurs over an infinitesimal range of time and space, so the rate constant is usually a very small number.

Binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and Van der Waals forces. The association of docking is actually reversible through dissociation. Measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. In contrast to the definition of ligand in metalorganic and inorganic chemistry, in biochemistry it is ambiguous whether the ligand generally binds at a metal site, as is the case in hemoglobin. In general, the interpretation of ligand is contextual with regards to what sort of binding has been observed. The etymology stems from ligare, which means 'to bind'.

Ligand binding to a receptor protein alters the conformation by affecting the three-dimensional shape orientation. The conformation of a receptor protein composes the functional state. Ligands include substrates, inhibitors, activators, and neurotransmitters. The rate of binding is called affinity, and this measurement typifies a tendency or strength of the effect. Binding affinity is actualized not only by host-guest interactions, but also by solvent effects that can play a dominant, steric role which drives non-covalent binding in solution.^[3] The solvent provides a chemical environment for the ligand and receptor to adapt, and thus accept or reject each other as partners.

Radioligands are radioisotope labeled compounds used in vivo as tracers in PET studies and for in vitro binding studies.

Receptor/ligand binding affinity

The interaction of most ligands with their binding sites can be characterized in terms of a binding affinity. In general, high-affinity ligand binding results from greater intermolecular force between the ligand and its receptor while low-affinity ligand binding involves less intermolecular force between the ligand and its receptor. In general, high-affinity binding results in a higher degree of occupancy for the ligand at its receptor binding site than is the case for low-affinity binding; the residence time (lifetime of the receptor-ligand complex) does not correlate. High-affinity binding of ligands to receptors is often physiologically important when some of the binding energy can be used to cause a conformational change in the receptor, resulting in altered behavior of an associated ion channel or enzyme.

Two agonists with similar binding affinity

A ligand that can bind to a receptor, alter the function of the receptor, and trigger a physiological response is called an agonist for that receptor. Agonist binding to a receptor can be characterized both in terms of how much physiological response can be triggered and in terms of the concentration of the agonist that is required to produce the physiological response. High-affinity ligand binding implies that a relatively low concentration of a ligand is adequate to maximally occupy a ligand-binding site and trigger a physiological response. The lower the K_i concentration is, the more likely there will be a chemical reaction between the pending ion and the receptive antigen. Low-affinity binding (high K_i level) implies that a relatively high concentration of a ligand is required before the binding site is maximally occupied and the maximum physiological response to the ligand is achieved. In the example shown to the right, two different ligands bind to the same receptor binding site. Only one of the agonists shown can maximally stimulate the receptor and, thus, can be defined as a full agonist. An agonist that can only partially activate the physiological response is called a partial agonist. In this example, the concentration at which the full agonist (red curve) can half-maximally activate the receptor is about 5 x 10⁻⁹ Molar (nM = nanomolar). Ligands that bind to a receptor but fail to activate the physiological response are receptor antagonists.

Two ligands with different receptor binding affinity.

In the example shown to the left, ligand-binding curves are shown for two ligands with different binding affinities. Ligand binding is often characterized in terms of the concentration of ligand at which half of the receptor binding sites are occupied, known as the IC₅₀, which is related to but different from the dissociation constant. The ligand illustrated by the red curve has a higher binding affinity and smaller K_d than the ligand illustrated by the green curve. If these two ligands were present at the same time, more of the higher-affinity ligand would be bound to the available receptor binding sites. This is how carbon monoxide can compete with oxygen in binding to hemoglobin, resulting in carbon monoxide poisoning.

Binding affinity is most commonly determined using a radiolabeled ligand, known as a tagged ligand. Homologous competitive binding experiments involve binding competition between a tagged ligand and an untagged ligand.^[4] Real-time based methods, which are often label-free, such as surface plasmon resonance, dual polarization interferometry and Multi-Parametric Surface Plasmon Resonance (MP-SPR) can not only quantify the affinity from concentration based assays; but also from the kinetics of association and dissociation, and in the later cases, the conformational change induced upon binding. MP-SPR also enables measurements in high saline dissociation buffers thanks to a unique optical setup. Microscale Thermophoresis (MST), an immobilization-free method^[5] was developed. This method allows the determination of the binding affinity without any limitation to the ligand's molecular weight.^[6]

For the use of statistical mechanics in a quantitative study of the ligand-receptor binding affinity, see the comprehensive article^[7] on the configurational partition function.

Drug potency and binding affinity

Binding affinity data alone does not determine the overall potency of a drug. Potency is a result of the complex interplay of both the binding affinity and the ligand efficacy. Ligand efficacy refers to the ability of the ligand to produce a biological response upon binding to the target receptor and the quantitative magnitude of this response. This response may be as an agonist, antagonist, or inverse agonist, depending on the physiological response produced.^[8]

Selective and non-selective

Selective ligands have a tendency to bind to very limited kinds of receptor, whereas non-selective ligands bind to several types of receptors. This plays an important role in pharmacology, where drugs that are non-selective tend to have more adverse effects, because they bind to several other receptors in addition to the one generating the desired effect.

Bivalent ligand

Bivalent ligands consist of two drug-like molecules (pharmacophores or ligands) connected by an inert linker. There are various kinds of bivalent ligands and are often classified based on what the pharmacophores target. Homobivalent ligands target two of the same receptor types. Heterobivalent ligands target two different receptor types.^[9] Bitopic ligands target an orthosteric binding sites and allosteric binding sites on the same receptor.^[10]

In scientific research, bivalent ligands have been used to study receptor dimers and to investigate their properties. This class of ligands was pioneered by Philip S. Portoghese and coworkers while studying the opioid receptor system.^[11][12][13] Bivalent ligands were also reported early on by Micheal Conn and coworkers for the gonadotropin-releasing hormone receptor.^[14][15] Since these early reports, there have been many bivalent ligands reported for various GPCR systems including cannabinoid,^[16] serotonin,^[17][18] oxytocin,^[19] and melanocortin receptor systems,^[20][21][22] and for GPCR-LIC systems (D2 and nACh receptors).^[9]

Bivalent ligands usually tend to be larger than their monovalent counterparts, and therefore, not ‘drug-like.’ (See Lipinski’s rule of five.) Many believe this limits their applicability in clinical settings.^[23][24] In spite of these beliefs, there have been many ligands that have reported successful pre-clinical animal studies.^{[21][22][19][25][26][27]} Given that some bivalent ligands can have many advantages compared to their monovalent counterparts (such as tissue selectivity, increased binding affinity, and increased potency or efficacy), bivalents may offer some clinical advantages as well.

Privileged scaffold

A privileged scaffold^[28] is a molecular framework or chemical moiety that is statistically recurrent among known drugs or among a specific array of biologically active compounds. These privileged elements^[29] can be used as a basis for designing new active biological compounds or compound libraries.

Methods used to study binding

Main methods to study protein–ligand interactions are principal hydrodynamic and calorimetric techniques, and principal spectroscopic and structural methods such as

• Fourier transform spectroscopy
• Raman spectroscopy
• Fluorescence spectroscopy
• Circular dichroism
• Nuclear magnetic resonance
• Mass spectrometry
• Atomic force microscope
• Paramagnetic probes
• Dual polarisation interferometry
• Multi-parametric surface plasmon resonance

Other techniques include: fluorescence intensity, bimolecular fluorescence complementation, FRET (fluorescent resonance energy transfer) / FRET quenching surface plasmon resonance, bio-layer interferometry, Coimmunopreciptation indirect ELISA, equilibrium dialysis, gel electrophoresis, far western blot, fluorescence polarization anisotropy, electron paramagnetic resonance, microscale thermophoresis

The dramatically increased computing power of supercomputers and personal computers has made it possible to study protein–ligand interactions also by means of computational chemistry. For example, a worldwide grid of well over a million ordinary PCs was harnessed for cancer research in the project grid.org, which ended in April 2007. Grid.org has been succeeded by similar projects such as World Community Grid, Human Proteome Folding Project, Compute Against Cancer and Folding@Home.

Microbiologists make big leap in developing ‘green’ electronics

January 20, 2017
Original link:  http://www.kurzweilai.net/microbiologists-developing-microbial-nanowires-for-green-electronics

An artist’s rendition of Geobacter expressing electrically conductive nanowires. Microbiologists at UMass Amherst have discovered a new type of natural wire produced by bacteria that could greatly accelerate the development of sustainable “green” conducting materials for the electronics industry. (credit: UMass Amherst)

UMass Amherst research finds microbe yields better electronic material.

Microbiologists at the University of Massachusetts Amherst report that they have discovered a new type of microbial nanowire produced by bacteria that could greatly accelerate the development of sustainable “green” conducting materials for the electronics industry.

The study by Derek Lovley and colleagues appears this week in an open-access paper in mBio, the American Society of Microbiology’s premier journal.

A bacterium known as Geobacter sulfurreducens uses the protein filaments naturally to make electrical connections with other microbes or minerals.

As Lovley explains, “Microbial nanowires are a revolutionary electronic material with substantial advantages over man-made materials. Chemically synthesizing nanowires in the lab requires toxic chemicals, high temperatures and/or expensive metals. The energy requirements are enormous. By contrast, natural microbial nanowires can be mass-produced at room temperature from inexpensive renewable feedstocks in bioreactors with much lower energy inputs. And the final product is free of toxic components.”

Confocal scanning laser micrographs of G. sulfurreducens anode biofilms harvested on day 10. Bar, 25 µm. (credit: Yang Tan et al./mBio)

The Microbial nanowires offer an unprecedented potential for developing novel electronic devices and sensors for diverse applications with a new environmentally friendly technology, Lovely says. “This is an important advance in microbial nanowire technology. The approach we outline in this paper demonstrates a rapid method for prospecting in nature to find better electronic materials.”

When his lab began looking at the protein filaments of other Geobacter species, they were surprised to find a wide range in conductivities. For example, one species recovered from uranium-contaminated soil produced poorly conductive filaments. However, another species, Geobacter metallireducens produced nanowires 5,000 times more conductive than the G. sulfurreducens wires. Lovley recalls, “I isolated metallireducens from mud in the Potomac River 30 years ago, and every couple of years it gives us a new surprise.”

In their new study supported by the U.S. Office of Naval Research, they did not study the G. metallireducens strain directly. Instead, they took the gene for the protein that assembles into microbial nanowires from it and inserted this into G. sulfurreducens. The result is a genetically modified G. sulfurreducens that expresses the G. metallireducens protein, making nanowires much more conductive than G. sulfurreducens would naturally produce.

Further, Lovley says, “We have found that G. sulfurreducens will express filament genes from many different types of bacteria. This makes it simple to produce a diversity of filaments in the same microorganism and to study their properties under similar conditions.”

The high conductivity of the G. metallireducens nanowires suggests that they may be an attractive material for the construction of conductive materials, electronic devices ,and sensors for medical or environmental applications. The authors say discovering more about the mechanisms of nanowire conductivity “provides important insight into how we might make even better wires with genes that we design ourselves.”

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Abstract of Expressing the Geobacter metallireducens PilA in Geobacter sulfurreducens Yields Pili with Exceptional Conductivity

The electrically conductive pili (e-pili) of Geobacter sulfurreducens serve as a model for a novel strategy for long-range extracellular electron transfer. e-pili are also a new class of bioelectronic materials. However, the only other Geobacter pili previously studied, which were from G. uraniireducens, were poorly conductive. In order to obtain more information on the range of pili conductivities in Geobacter species, the pili of G. metallireducens were investigated. Heterologously expressing the PilA gene of G. metallireducens in G. sulfurreducens yielded a G. sulfurreducens strain, designated strain MP, that produced abundant pili. Strain MP exhibited phenotypes consistent with the presence of e-pili, such as high rates of Fe(III) oxide reduction and high current densities on graphite anodes. Individual pili prepared at physiologically relevant pH 7 had conductivities of 277 ± 18.9 S/cm (mean ± standard deviation), which is 5,000-fold higher than the conductivity of G. sulfurreducens pili at pH 7 and nearly 1 million-fold higher than the conductivity of G. uraniireducens pili at the same pH. A potential explanation for the higher conductivity of the G. metallireducens pili is their greater density of aromatic amino acids, which are known to be important components in electron transport along the length of the pilus. The G. metallireducens pili represent the most highly conductive pili found to date and suggest strategies for designing synthetic pili with even higher conductivities.

References:

• Tan Y, Adhikari RY, Malvankar NS, Ward JE, Woodard TL, Nevin KP, Lovley DR. 2017. Expressing the Geobacter metallireducens PilA in Geobacter sulfurreducens yields pili with exceptional conductivity. mBio 8:e02203-16. DOI: 10.1128/mBio.02203-16 (open access)

Making Hydrochloric Acid from Household Ingredients (reposted)

I used to do this when I was young.  I’m uncertain now:  could it not be considered a terroristic threat?  The times, they are a changing!  Anyway, into the science.

Hydrochloric (HCl) acid is simply a solution of the gas HCl (hydrogen chloride) in water.  The basic acid-forming reaction is:

HCl + H₂O ® Cl^- + H₃O⁺

H₃O⁺ ↔ H⁺ + H₂O

The main acidic species can be considered either H₃O⁺  or H⁺ , although the latter is usually used as it is clearer and more consistent.  In almost (but not all) all water based acids, this is the actual acidic species, whatever the starting acid (nitric, sulfuric, acetic, etc.) is.

There are a number of industrial and lab process to make HCl acid, usually from other strong mineral acids.  Another way, however, is to generate HCl gas directly and dissolve it in water (it is highly soluble, almost as much as ammonia).  The household method uses this approach.  Questions:  how do you make HCl gas, and how to you get it into the water?

Warning, Warning!  HCl gas is very irritating and corrosive, so you have to set up some kind of protection for your lungs and throat and eyes before generating it!

At a young age, I loved to tinker with chemicals (perhaps not a good idea when I look back on it, but I was usually reasonably careful), both those I found in the house and those I got in chemistry sets.  And I loved to read chemistry books and ponder what might happen if you mixed such and such with so and so and heated them or dissolved them in water.  Amazingly, I still have all my body parts and they all work well, which might be something of a wonder.

In this case I noticed something.  It seemed as though if you mixed ordinary table salt and baking soda and heated them strongly, you might get the following reaction:

NaCl + NaHCO₃ ® HCl­ + Na₂CO₃

In which the two reactants swapped the hydrogen and chlorine,  Further, since HCl was a gas, it would escape the reaction mixture (the upward arrow) and constantly drive the reaction to the right.

Of course I had to try it.  Now, if I’d had a balance, I’d weigh out 5.85 grams of salt and 8.8 grams of baking soda.  This is one tength of a mole of each product, thus an equal number of molecules of each, perfect for the 1:1 reaction.  It would have yielded 3.85 grams of gaseous HCl ( and 9.4 grams of Na₂CO₃) .  The two weight combinations on either side of the arrow equal, as they should.  I did not have a balance however, and so used a teaspoon or tablespoon of both reactions – good enough.

Now here comes the part where you shouldn’t have done what I did.  I would mix both reactants in an Kimex glass laboratory grade Ehrlenmeyer flask (the triangular shaped one), place the flask on one of our electric stoves, and (at least have the sense to) gradually heat the flask until the stove temperature was at or near high.  I know that gaseous HCl was irritating and corrosive, so I would carefully smell for any gasses coming through the top of the flask.  Sure enough, I found myself tearing and coughing pretty soon, and I knew my hypothesis was a triumph.  The question now was, how to deliver the gas into (preferably cold) water?

You’ve already noticed that household ingredients aren’t quite enough, you also need some laboratory equipment, mostly glassware.  I had such from my chemistry sets:  Ehrlenmeyer flasks, beakers, corks/rubber stoppers that fitted the flask and had a hole large enough for the glass tubing, the tubing, and an alcohol burner I could use to bend the tubing from the top of the Ehrlenmeyer over to the beaker (more than a ninety degree angle) – not as easy as it might sound for glass work requires some practice and experience.  (You can no doubt still get these things, though I don’t know if you’ll attract unwanted attention doing so).

Let’s assume you have a desktop balance for weighing chemicals, though don’t ask me how much they cost; anyway, you don’t need a highly priced one.  Now, if you weigh amount of reactants in the flask as described above, you should generate 0.1 mole (8.8 grams) of HCl gas when you heat it strongly.  After pouring the reactants into the flask, next, assemble the apparatus. The stopper should fit tightly inside the Ehrlenmeyer, the bent glass tube pass through the stopper (not too far, though, just enough to pick up any gasses and deliver them!), and the other end of the tube should reach the bottom of the beaker, which should hold about 100 milliliters (~ 1/10 of a quart, or half a pint or so – use a graduated cylinder if you can) of cold water.  Now strongly heat the mixture in the flask.  What you’ll observe is curious.  First, a stream of bubbles will emerge from the beaker end of the tube, rising and escaping into the air.  Don’t be alarmed; this is just the heated air being forced from the flask through the tube.  What happens next is the main show.  The bubbles stop, and the gas level in the beaker stays pretty much flush with the water.  What is happening here is that HCl gas is now being generated rapidly and, being highly soluble in water, immediately dissolves when it hits it, leaving no more bubbles.  Your HCl acid is starting to form!

You should keep this reaction/process going until you observe the following.  As the reactants are consumed, the HCl is produced in smaller and smaller quantities; and, again because it is so soluble in water, begins to suck liquid up the tube from the beaker.  At this point you should stop the reaction (turn off the heat and move the flask off the stove, remove the flask + stopper + tube from the beaker, etc.).  You DO NOT want water pouring back through the tube into the Ehrlenmeyer under strong heat – I never tried this, but I assume the water will flash into steam, at least cracking if not exploding the Ehrlenmeyer, thereby releasing a lot of acid and HCl gas into the atmosphere, any probably other nasties I haven’t thought about.  All in all, don’t let this happen!

Let it all cool down for a while, before disassembling everything and thoroughly washing out everything but the beaker and its contents (use lots of water, on your hands too).  Now, if the reaction has gone to completion (though remember, some HCl is lost), I figure the concentration to be 0.1 mole HCl gas dissolving into 0.1 liter water, giving around a 1.0 molar (M) solution.  This is a fairly potent concentration (if you get it on yourself, wash thoroughly with water).  It’s more than enough to dissolve aluminum and tin foil, magnesiumzinc, probably lead and iron and some other metals, giving off streams of bubbles of hydrogen gas as it does so (this is also potentially hazardous, and hydrogen gas is highly flammable).  Remember mixing vinegar (a dilute solution of  acetic acid, CH₃CH₂COOH) with baking soda and watching it fizz up?

CH₃CH₂COOH + NaHCO₃ ® Na⁺ + CH₃CH₂COO^- + H₂O + CO₂

The CO₂, or carbon dioxide, is the gas that fizzes up, just as from a can of beer or soda.  If you substitute the weak and highly diluted acid vinegar with fairly concentrated hydrochloric acid, the reaction ought to be considerably stronger:

HCl + NaHCO₃ ® Na⁺ + Cl^- + H₂O + CO₂

Not that I remember trying this.  Oh, one more thing; I’m pretty sure that you can make the acid highly concentrated (though I don’t recommend this, however, as it is VERY HAZARDOUS at very high concentrations), simply by upping the amount of reactants.  Multiply the reactants by five or ten (you may have to run the reaction several times, or find a large enough Ehrlenmeyer flask), and you should get five-ten molar acid.  Again, something you really shouldn’t play around with, unless you know how to do so safely).