Magic angle spinning (MAS) NMR methods provide a means of obtaining high resolution structural data on rhodopsin and its photoin termediates. Current work has focused on the structure of the retinal chromophore and its interactions with surrounding protein charges. The recent development of MAS NMR methods for measuring internuclear distances with a resolution of ∼0.2 will complement diffraction methods for addressing key mechanistic questions.

The solution structures of several small proteins have recently been determined from high‐resolution nuclear magnetic resonance data. The principal features of the methods available to do this are outlined here, together with the advantages, limitations and future prospects of the technique.

Crucial to the establishment of a scientific discipline is a body of knowledge organized around a set of instruments, interpretive techniques, and regimes of training in their application. In this paper, we trace the involvement of scientists and engineers at Varian Associates in the development of nuclear magnetic resonance spectrometers from the first demonstrations of the NMR phenomenon in 1946 to the definitive takeoff of NMR as a chemical discipline by the mid-1960s. We examine the role of (...) Varian scientists in constructing several models of NMR instruments for research scientists in the 1950s and the Varian efforts to influence the adoption of NMR as a standard tool for chemical analysis through Varian-supported publications, participation in scientific meetings, collaborations with academic chemists, workshops, and postdoctoral fellowships. Special attention is devoted to the development of the Varian A-60, the first commercial NMR instrument intended for the broadly trained chemist rather than a custom-built tool for the research specialist. Drawing on an examination of the use-rate of NMR instruments in chemical literature, the assessment of NMR in the chemical review literature by practitioners, and indicators of the establishment of a suitable funding environment for the growth of physics-based scientific instrumentation in the post-Sputnik era, we argue that the establishment of NMR as a discipline coincided with the adoption of the A-60 in the mid-1960s. During the period of our study, Varian Associates was a primary military contractor. This paper is intended to contribute to recent interest in the relation of military fundingto scientific enterprise during the Cold War and to the larger question of university-industry interactions in the growth of knowledge. (shrink)

From the nineteen sixties onwards a branch of philosophy of science has come to development, called history-oriented philosophy of science. This development constitutes a reaction on the then prevailing logical empiricist conception of scientific knowledge. The latter was increasingly seen as suffering from insurmountable internal problems, like e. g. the problems with the particular "observational-theoretical distinction" on which it drew. In addition the logical empiricists' general approach was increasingly criticized for two external shortcomings. Firstly, the examples of scientific knowledge that (...) the logical empiricists were focusing on were con sidered as too simplistic to be informative on the nature of real life science. Secondly, it was felt that the attention of these philosophers of science was restricted to the static aspects of scientific knowledge, while neglecting its developmental aspects. History-oriented philosophy of science has taken up the challenge implicit in the latter two criticisms, i. e. to develop accounts of science that would be more adequate for understanding the development 1 of real life science. One of the more successful products of this branch of philosophy of science is Lakatos's theory of scientific development, sometimes called the "methodology of scientific research programmes". This theory conceives science as consisting of so called research program mes developing in time, and competing with each other over the issue which one generates the best explan~tions of the phenomena that they address. (shrink)

Investigation of the origin and function of three magnets from I. I. Rabi's laboratory at Columbia University leads to a closer inquiry into the early history of molecular beam evaluations of the angular momenta and magnetic moments of atomic nuclei than has been undertaken heretofore. The resulting insights into the background and the course of Rabi's research programme would probably not have occurred without the orientation enforced by these artifacts.

NMR (nuclear magnetic resonance) may be useful for determining the structure of retinal and its environment in rhodopsin, but not for determining the complete protein structure. Aggregation and low yield of fragments of rhodopsin may make them difficult to study by NMR. A long-term multidisciplinary attack on rhodopsin structure is required.

From the height of his ninety years of experience, Robert G. Shulman is not just a veteran of World War II, but a world-class biophysicist with a distinguished research career spanning the California Institute of Technology, Bell Labs, and Yale University. A forerunner in the use of nuclear magnetic resonance, Shulman contributed to the study of biochemical processes, founded the Yale Magnetic Resonance Research Center, and shepherded functional Magnetic Resonance Imaging (fMRI) as a (...) dominant tool of cognitive neuroscience. Together with Gregory McCarthy et al., Shulman authored several of the earliest fMRI studies, including the first to explicitly manipulate cognitive processes (McCarthy, Blamire, Rothman, Gruetter, & Shulman, 1993; Shulman, Blamire, Rothman, & McCarthy, 1993). As such, his ideas concerning conscious research piqued our curiosity. We read Brain Imaging: What It Can (and Cannot) Tell Us About Consciousness with anticipation.Shulman comes full circle with his book on brain imaging: although his career spanned meaningful collaborations with behavioural scientists and interactions with researchers from preclinical and clinical fields, he retreats to the comfort of the biophysical sciences. Two prominent, but related, hesitations give us pause regarding his retreat. First, he claims that a behaviourist approach to brain imaging is reasonable and pragmatic for the science of consciousness. Second, he rebuffs subjective and phenomenal forms of evidence. In... (shrink)

Nuclear spin qubits have the longest coherence times in the solid state, but their quantum readout and initialization is a great challenge. We present a theory for the interaction of an electric current with the nuclear spins of donor impurities in semiconductors. The theory yields a sensitivity criterion for quantum detection of nuclear spin states using electrically detected magnetic resonance, as well as an all-electrical method for fast nuclear spin qubit initialization.

This book gives an overview for practitioners and students of quantum physics and information science. It provides ready access to essential information on quantum information processing and communication, such as definitions, protocols and algorithms. Quantum information science is rarely found in clear and concise form. This book brings together this information from its various sources. It allows researchers and students in a range of areas including physics, photonics, solid-state electronics, nuclear magnetic resonance and information technology, in their (...) applied and theoretical branches, to have this vital material directly at hand. (shrink)

Early practitioners of the social studies of science turned their attention away from questions of institutionalisation, which had tended to emphasize macrolevel explanations, and attended instead to microstudies of laboratory practice. The author is interested in re-investigating certain aspects of institution formation, notably the formation of scientific, medical, and engineering disciplines. He emphasises the manner in which science as cultural practice is imbricated with other forms of social, political, and even aesthetic practices. The author considers the following topics: the organic (...) physics of 1847; the innovative research program of Carl Ludwig as a model for institutionalising science-based medicine, optics, painting, and ideology in Germany, 1845-95; the Haber-Bosch synthesis of ammonia; and the introduction of nuclear magnetic resonance instrumentation into the practice of organic chemistry. (shrink)

This book reflects on the significant and highly original scientific contributions of Hans Primas. A professor of chemistry at ETH Zurich from 1962 to 1995, Primas continued his research activities until his death in 2014. Over these 50 years and more, he worked on the foundations of nuclear magnetic resonance spectroscopy, contributed to a number of significant issues in theoretical chemistry, helped to clarify central topics in quantum theory and the philosophy of physics, suggested innovative ways of (...) addressing interlevel relations in the philosophy of science, and introduced cutting-edge approaches in the flourishing young field of scientific studies of consciousness. His work in these areas of research and its continuing impact is described by noted experts, colleagues, and collaborators of Primas. All authors contextualize their contributions to facilitate the mutual dialog between these fields. (shrink)

The paper illustrates how organic chemists dramatically altered their practices in the middle part of the twentieth century through the adoption of analytical instrumentation — such as ultraviolet and infrared absorption spectroscopy and nuclear magnetic resonance spectroscopy — through which the difficult process of structure determination for small molecules became routine. Changes in practice were manifested in two ways: in the use of these instruments in the development of ‘rule-based’ theories; and in an increased focus on synthesis, (...) at the expense of chemical analysis. These rule-based theories took the form of generalizations relating structure to chemical and physical properties, as measured by instrumentation. This ‘Instrumental Revolution’ in organic chemistry was two-fold: encompassing an embrace of new tools that provided unprecedented access to structures, and a new way of thinking about molecules and their reactivity in terms of shape and structure. These practices suggest the possibility of a change in the ontological status of chemical structures, brought about by the regular use of instruments. The career of Robert Burns Woodward provides the central historical examples for the paper. Woodward was an organic chemist at Harvard from 1937 until the time of his death. In 1965, he won the Nobel Prize in Chemistry. (shrink)

In the 1940s and 1950s, nuclear magnetic resonance , one of the most important analytical techniques in chemistry, grew to maturity in the intermediate research field of chemical physics. Chemists and physicists adapted the new technology to the experimental culture of molecular spectroscopy which was based on a pragmatic experimental style. In molecular spectroscopy, the purpose of experiments was the establishment of methods that suited both the physicists' quest for precision and theoretical model building and the chemists' (...) longing for empirical data and understanding of structural formulae and reaction courses. In this process, an experimental style emerged that can be characterized as reliance on self‐built instrumentation, theoretical foundation in quantum mechanics, and proof of utility in the solution of structural and dynamical questions. This article focuses on the early development of NMR at Harvard University, with particular emphasis on the contributions of the first chemist working in the field of NMR, Herbert S. Gutowsky. (shrink)

In a number of membrane-bound viruses, ion channels are formed by integral membrane proteins. These channel proteins include M2 from influenza A, NB from influenza B, and, possibly, Vpu from HIV-1. M2 is important in facilitating uncoating of the influenza A viral genome and is the target of amantadine, an anti-influenza drug. The biological roles of NB and Vpu are less certain. In all cases, the protein contains a single transmembrane α-helix close to its N-terminus. Channels can be formed by (...) homo-oligomerization of these proteins, yielding bundles of transmembrane helices that span the membrane and surround a central ion-permeable pore. Molecular modeling may be used to integrate and interpret available experimental data concerning the structure of such transmembrane pores. This has proved successful for the M2 channel domain, where two independently derived models are in agreement with one another, and with solid-state nuclear magnetic resonance (NMR) data. Simulations based on channel models may yield insights into possible ion conduction and selectivity mechanisms. BioEssays 20:992–1000, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Julian Schwinger was one of the leading theoretical physicists of the twentieth century. His contributions are as important, and as pervasive, as those of Richard Feynman, with whom he shared the 1965 Nobel Prize for Physics. Yet, while Feynman is universally recognized as a cultural icon, Schwinger is little known even to many within the physics community. In his youth, Julian Schwinger was a nuclear physicist, turning to classical electrodynamics after World War II. In the years after the war, (...) he was the first to renormalize quantum electrodynamics. Subsequently, he presented the most complete formulation of quantum field theory and laid the foundations for the electroweak synthesis of Glashow, Weinberg, and Salam, and he made fundamental contributions to the theory of nuclear magnetic resonance, to many-body theory, and to quantum optics. He developed a unique approach to quantum mechanics, measurement algebra, and a general quantum action principle. His discoveries include 'Feynman's' parameters and 'Glauber's' coherent states; in later years he also developed an alternative to operator field theory which he called Source Theory, reflecting his profound phenomenological bent. His late work on the Thomas-Fermi model of atoms and on the Casimir effect continues to be an inspiration to a new generation of physicists. This biography describes the many strands of his research life, while tracing the personal life of this private and gentle genius. (shrink)

Here we review concepts related to an ensemble description of G-protein-coupled receptors. The ensemble is characterized by both inactive and active states, whose equilibrium populations and exchange rates depend sensitively on ligand, environment, and allosteric factors. This review focuses on the adenosine A2 receptor, a prototypical class A GPCR. 19F Nuclear Magnetic Resonance studies show that apo A2AR is characterized by a broad ensemble of conformers, spanning inactive to active states, and resembling states defined earlier for rhodopsin. (...) In keeping with ideas associated with a conformational selection mechanism, addition of agonist serves to allosterically restrict the overall degrees of freedom at the G protein binding interface and bias both states and functional dynamics to facilitate G protein binding and subsequent activation. While the ligand does not necessarily “induce” activation, it does bias sampling of states, increase the cooperativity of the activation process and thus, the lifetimes of functional activation intermediates, while restricting conformational dynamics to that needed for activation. GPCRs represent a ubiquitous class of transmembrane receptors, responsible for cell signaling and cell homeostasis. Their activation gives rise to conformational changes that allow the receptor to engage downstream partners. Activation can be thought of in terms of a free energy landscape associated with distinct conformers, responsible for the process. Here, the action of ligands is seen to alter this landscape by enabling transitions between key intermediates. (shrink)

In a number of membrane-bound viruses, ion channels are formed by integral membrane proteins. These channel proteins include M2 from influenza A, NB from influenza B, and, possibly, Vpu from HIV-1. M2 is important in facilitating uncoating of the influenza A viral genome and is the target of amantadine, an anti-influenza drug. The biological roles of NB and Vpu are less certain. In all cases, the protein contains a single transmembrane α-helix close to its N-terminus. Channels can be formed by (...) homo-oligomerization of these proteins, yielding bundles of transmembrane helices that span the membrane and surround a central ion-permeable pore. Molecular modeling may be used to integrate and interpret available experimental data concerning the structure of such transmembrane pores. This has proved successful for the M2 channel domain, where two independently derived models are in agreement with one another, and with solid-state nuclear magnetic resonance (NMR) data. Simulations based on channel models may yield insights into possible ion conduction and selectivity mechanisms. BioEssays 20:992–1000, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

Alternate View Column AV-112 Keywords: quantum mechanics entangled states computer computing 7 qubits prime number factoring Schor algorithm NMR nuclear magnetic resonance fast parallel decryption coherence wave-function collapse many-worlds transactional interpretation Published in the June-2002 issue of Analog Science Fiction & Fact Magazine ; This column was written and submitted 12/19/2001 and is copyrighted ©2001 by John G. Cramer.

Quantum theory is highly successful in explaining properties of classes of systems: e.g. chemistry --- molecular binding energies optics --- frequency-dependent susceptibilities superconductivity --- energy gaps nuclear magnetic resonance --- chemical shifts particle physics --- scattering cross-sections cosmology --- helium abundance but many questions arise: What does quantum theory tell us about the nature of reality? Is quantum theory universally valid? Can quantum theory describe individual events? Can quantum theory be applied consistently at the macroscopic level? Is (...) an algorithmic treatment of measurement theory possible? Is it possible to provide an interpretation of quantum theory which is compatible with special relativity/ general relativity/ quantum field theory/ this week's theory of everything? (shrink)

We clarify different definitions of the density matrix by proposing the use of different names, the full density matrix for a single-closed quantum system, the compressed density matrix for the averaged single molecule state from an ensemble of molecules, and the reduced density matrix for a part of an entangled quantum system, respectively. We show that ensembles with the same compressed density matrix can be physically distinguished by observing fluctuations of various observables. This is in contrast to a general belief (...) that ensembles with the same compressed density matrix are identical. Explicit expression for the fluctuation of an observable in a specified ensemble is given. We have discussed the nature of nuclear magnetic resonance quantum computing. We show that the conclusion that there is no quantum entanglement in the current nuclear magnetic resonance quantum computing experiment is based on the unjustified belief that ensembles having the same compressed density matrix are identical physically. Related issues in quantum communication are also discussed. (shrink)

The paper illustrates how organic chemists dramatically altered their practices in the middle part of the twentieth century through the adoption of analytical instrumentation - such as ultraviolet and infrared absorption spectroscopy and nuclear magnetic resonance spectroscopy - through which the difficult process of structure determination for small molecules became routine. Changes in practice were manifested in two ways: in the use of these instruments in the development of 'rule-based' theories; and in an increased focus on synthesis, (...) at the expense of chemical analysis. These rule-based theories took the form of generalizations relating structure to chemical and physical properties, as measured by instrumentation. This 'Instrumental Revolution' in organic chemistry was two-fold: encompassing an embrace of new tools that provided unprecedented access to structures, and a new way of thinking about molecules and their reactivity in terms of shape and structure. These practices suggest the possibility of a change in the ontological status of chemical structures, brought about by the regular use of instruments. The career of Robert Burns Woodward (1917-1979) provides the central historical examples for the paper. Woodward was an organic chemist at Harvard from 1937 until the time of his death. In 1965, he won the Nobel Prize in Chemistry. (shrink)

The assertion by Simmons and Park that the dynamical map associated with the Bloch equations of nuclear magnetic resonance is not completely positive is wrong.

The question, “Will science remain human?” expresses a worry that deep learning algorithms will replace scientists in making crucial judgments of classification and inference and that something crucial will be lost if that happens. Ever since the introduction of telescopes and microscopes humans have relied on technologies to “extend” beyond human sensory perception in acquiring scientific knowledge. In this paper I explore whether the ways in which new learning technologies “extend” beyond human cognitive aspects of science can be treated instrumentally. (...) I will consider the norms for determining the reliability of a detection instrument, nuclear magnetic resonance spectroscopy, in predicting models of protein atomic structure. Do the same norms that apply in that case be used to judge the reliability of Artificial Intelligence deep learning algorithms? (shrink)

Rapidly advancing studies on rhodopsin have focused on new strategies for crystallization of this integral membrane protein for x-ray analysis and on alternative methods for structural determination from nuclear magnetic resonance data. Functional studies of the interactions between the apoprotein and its chromophore have clarified the role of the chromophore in deactivation of opsin and in photoactivation of the pigment.

According to the BSM Supergravitation Unified Theory, the physical vacuum contains energy that is not of electromagnetic origin. The Heterodyne Resonance Mechanism (HRM) predicted by the theory permits access to this hidden energy by a process involving the anomalous magnetic moment and the quantum mechanical spin flipping of the electron. Plasma experiments and analysis of lightning observations indicate that the HRM effect could be involved in the natural lightning phenomena. Although the energy density of this hidden source is (...) much smaller than nuclear energy, the opportunity to access this energy will lead to some new practical applications. The derived physical model of the HRM effect provides the opportunity for development of new technologies. This book could be an useful handbook for researchers and experimenters. (shrink)

The elastic and radiative π + p scattering are studied in the framework of an effective Lagrangian model for the Δ ++ resonance and its interactions. The finite width effects of this spin-3/2 resonance are introduced in the scattering amplitudes through a complex mass scheme to respect electromagnetic gauge invariance. The resonant pole (Δ ++) and background contributions (ρ 0, σ, Δ, and neutron states) are separated according to the principles of the analytic S-matrix theory. The mass and (...) width parameters of the Δ ++ obtained from a fit to experimental data on the total cross section are in agreement with the results of a model-independent analysis based on the analytic S-matrix approach. The magnetic dipole moment determined from the radiative π + p scattering is $\mu _{\Delta ^{ + + } } = (6.14 \pm 0.51)$ nuclear magnetons. (shrink)