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Title: Quantum biology, water and living cells


1
Quantum biology, water and living cells
  • Eugen A. Preoteasa
  • HH-NIPNE, LEPD (DFVM)

2
  • nature is not sparing as for its structures,
    but only for its universally applicable
    principles.
  • Abdus Salam

3
  • Introduction and background
  • Biology from classical to quantum
  • New models of collective dynamics for liquid
    water and living cell
  • Ionic plasma in water
  • The cell dimensions problem
  • Free water coherent domains Bose condensation
    The minimum volume of the cell
  • Water coherent domains in an impenetrable
    spherical well The maximum cell volume of small
    prokaryotic cells
  • Plausible interaction potential between coherence
    domains
  • Two coupled water coherent domains as a harmonic
    oscillator and the maximum cell volume
  • Isotropic oscillator in a potential gap and the
    spherical cells larger prokaryotes and small
    eukaryotes
  • Cylindrical potential gap and disc-like cells
    the erythrocyte
  • Cylindrical potential gap and rod-like cells
    typical bacilli
  • The semipenetrable spherical well The toxic
    effect of heavy water in eukaryotic cells
  • Conclusions

4
Introductionand backgroundBiology from
classical to quantum
5
Life is a phenomenon strikingly different of the
non-living systems. Some distinctive traits
  • Metabolism
  • Homeostasis
  • Replication
  • Stability of descendents
  • Spontaneous, low-rate random mutations
  • Diversity by evolution 8.000.000 species
  • Adaptation (e.g., bacteria eating vanadium,
    bacteria living in nuclear reactor water, life in
    desert and permafrost)
  • Damage repair (e.g., wound healing)
  • Integrality / indivisibility

6
Biological phenomenology and evolution
  • The phenomenology and evolution of the living
    world are described by classical biology.
  • Classsical biology started with the optical
    microscope and developed in XVII-XIX centuries
    (by people like Leeuwenhoek, Maupertuis, Linne,
    Lamarck, Cuvier, Haeckel, Virchow, Darwin,
    Wallace, Mendel, Pasteur, Cl. Bernard, etc.).

Tree of life
  • The main ideas of biology were influenced by
    classical physics (Newton, Pascal, Bernoulli,
    Carnot, Clausius, Bolzmann, Gibbs, Helmholtz,
    Maxwell, Faraday, Ostwald, Perrin, ) and
    chemistry (Lavoisier, Berzelius, Woehler,
    Berthelot, ).

7
Molecular biology a new reductionism
  • DNA (or RNA) encodes all genetic infor-mation
    (Crick Watson 1950) devastating effect on
    biology.
  • Two images since 1967
  • integrative (Jacob) vs.
  • reductionist, (Monod)
  • Recently, phenotypic plasticity and
    self-organization re- vealed limits of the
    central dogma of molecular biology
  • DNA RNA Enzymes
  • Genome (DNA from the ovocite of a species
    individual) Phenotype (particular individual
    organism of a species)

8
  • The central dogma raises questions, e.g.
  • Is all information contained in DNA, RNA?
  • Are mutations purely random?
  • Is the environment only selecting mutations?
  • No feed-back?
  • The main ideas of molecular biology
  • All biological phenomena reduced to information
    stored in some (privileged) molecules.
  • Only short-range specific interactions.
  • Classical (Bolzmann-Gibs), equilibrium
    statistics.
  • Water mainly a passive solvent.
  • The cell a bag filled with a solution of
    molecules.
  • This picture rooted in XIX century thinking
    is disputable. It fails to seize complexity,
    integrality of living organisms.

9
Cells, complexity, integrality
  • The cell basic unit of life / at the origin of
    any organism.
  • Cells an unparalleled complexity, a singular,
    unique type of order. Integrality cells are
    killed by splitting .
  • Biological complexity order (almost) without
    repetition different of the physical complexity
    ( nonintegrable, 3 bodies).
  • A bacterial cell 4.1010 molecules H2O, and
    5.108 various organic molecules. An eukaryotic
    cell x105 more molecules.
  • Huge complexity of metabolic network. Shown above
    only 5.

10
Limits of molecular biology
  • Complexity, integrality pointing to nonlinear,
    optimal, self-organized systems , to long-range
    correlations.
  • Molecular biology sticks and balls picture
    isolated classical particles, short-range
    interactions.
  • Success of molecular biology at the roots of
    its limits.
  • Origin of life unexplained probability of first
    cell 10-40,000 , of man 10-24,000,000 in 4.109
    yr.
  • Chance is not enough (Jacob 1967).
  • Metabolic co-ordination How a huge number of
    specific chemical reactions occur in a cell at
    the right place / time?
  • Information content in the cell much larger than
    in DNA (a read-only memory) where the rest
    comes from?
  • Unexplained brain activity, biological
    chirality, etc.

11
Features of life unsolved by molecular biology
  • Collective dynamics of many freedom degrees.
  • Life a metastable state.
  • Various types of local and global order.
  • Structural and dynamic hierarchy, successive
    levels.
  • Biological complexity order without repetition.
  • Short- and long-range correlations and
    interactions.
  • Living organisms are open, irreversible,
    disipative systems.
  • They are self-organized, optimal systems
    (-gthomeostasis), with cooperative interactions.
  • Nonlinear interactions, highly integrated
    dynamics.
  • Such features to some degree in various complex
    non-living systems but only organisms join them
    altogether.

12
Molecular biology, biophysics, quantum mechanics
  • What is the usual place of biophysics
  • and QM in molecular biology?
  • A) Physical methods for special materials
    studies.
  • B) Molecular structure and properties quantum
    chemistry integrated in the balls and sticks
    picture of molecular biology.
  • Though A), B) based on QM ancillary / trivial
    role for QM .
  • Could QM yield insight on the essence of life?

13
Correlations, functions and soft matter
  • Organisms evolve by functions space-time
    correlations between freedom degrees.
  • Functions are controlled by specific messages.
  • Messages express biological complexity. Both
    imply order without repetition convey
    information.
  • Cells soft matter facilitate functions by
    (re)aggrega-tions and conformational changes.
    Flexible geometic structure, conservative
    topological correlations of freedom deg.s.
    Dynamical organization.
  • Cells condensed matter facilitate long-range
    correlations and information transfer.
  • Either correlations and information admit both
    classical and quantum support.

14
Classical and quantum correlations long range
interactions between (quasi)particles
  • Long range correlations self-correlation
    functions in biological, chemical and physical
    systems formally similar for
  • a classical observable z(r) G(D) ltz(r)
    z(rD)gt
  • a wavefunction Y(r) G(D) lt Y(r) Y(rD)gt
  • The self-correlation or coherence function is
    connected to interference of waves associated
    with a (quasi)particule
  • I(D) Y1(r) Y2(rD)2 1 G(D)cos Dk
  • Necessary condition long range interactions
    between particles or quasiparticles.

15
  • Biological order and information
  • Biological order order without repetition. Such
    order - aperiodic and specific (Orgel 1973)
    conveys information.
  • Periodic nonspecific order minimal information
  • AAAAAAAAAAAA
  • Periodic specific order useful information
    overwhelmed in redundance
  • CRYSTAL CRYSTAL CRYSTAL
  • Complexity aperiodic nonspecifica order
    maximal total information, minimal useful
    information
  • AGDCBFE GBCAFED ACEDFBG
  • Complexity aperiodic and specific order
  • THIS IS A MESSAGE.
  • Well-defined sequence message, precise code,
    maximum useful information, comands an unique
    function.
  • Biological systems informational syst.
    adressable both C/Q.

16
Information and quantum mechanics
  • Quantity of information (Shannon, Weaver 1949)
  • H S pi log2 pi p ?2 Ex. H(Xe)
    136 bit.
  • Information gain between 2 probability distrib.s
    P, W
  • I (PW) S pi log2 (pi / wi)
  • Information gain in a quantum transition mgt ?
    lgt (Majernik 1967)
  • I ( fm fl ) ? fm fm log2 ( fm fm / fl fl)
    dv
  • Ex. Potential gap, I(u2u1) 3,8 bit. Hydrogen
    atom, I(u2u1) 83,1 bit.
  • Hypothesis In biological systems, certain
    wave-functions may play a role in transmission,
    storage, processing, and control of information.

17
Alternatives to molecular biology
  • Postulate Living organisms contain both
    classical and quantum (sub)systems.
  • Alternatives to describe biological complexity
    and integral properties of organisms
  • Far from equilibrium dynamics, dissipative
    structures (classical or quantum)
  • Models of periodic phenomena based on equations
    with eigenfunctions and eigenvalues (classical or
    quantum)
  • Quantum biology.

18
Irreversibility, far from equilibrium dynamics,
dissipative structures (Prigogine, Nicolis,
Balescu)
Spontaneous synchronization of oscillations in
glycolysis (glucose consumption) in yeast cells
(Bier)
  • Limit cycle (strange attractor) All
    trajectories, whatever their initial state, lead
    finally to the cycle.
  • Makes the origin of life from non-living much
    more probable.

Belousov-Zhabotinsky reaction Heterogeneous
(order) out of homogeneous (disorder).
19
Integral properties without molecular biology. I.
The fur of mammals by partial derivative equations
Diffusion-reaction of melanin
Results
20
Integral properties of cells without molecular
biology. II. Flickering modes of erythrocyte
membrane by Fourier / correlation analysis
21
Quantum biology
  • Bohr, Heisenberg, Schrodinger, John von Neumann,
    C. von Weizsacker, W. Elsasser, V. Weisskopf, E.
    Wigner, F. Dyson, A. Kastler, and others QM
    essential for understanding life.
  • Quantum biology (QB) speculative
    interdisciplinary field that links quantum
    physics and the life sciences (Wikipedia) runs
    the first phase, inductive synthesis, of every
    science. Some directions
  • Quantum-like phenomenology QM without H and/or
    h.
  • Non-relativistic QM.
  • Biophoton (ultraweak emission) statistics.
  • Solitons (Davydov), phonons, conformons,
    plasmons, etc.
  • Decoherence, entanglement, quantum computation.
  • Long-range coherent excitations Frohlich.
  • QED coherence in cellular water Preparata, Del
    Giudice.

22
Decoherence, entanglement, quantum computation
Quantum-like phenomenology
  • Consciousness, Psyche Orlov Piotrowski
    Sladkowski
  • Embriogenesis Goodwin

Non-relativistic QM
  • Protein folding Bohr et al.
  • Scaling laws and the size of organisms Demetrius
  • Origin of life Davies Al-Khalili McFadden
  • Photosynthesis Castro et al coherence found
    experimentally.
  • Decoherence in proteins, tunelling in enzymes
    Bothema et al
  • Protein biosynthesis and molecular evolution
    Goel
  • Cytoskeleton, decoherence, memory Nanopoulos
    Hameroff
  • Genetic code, self-replication Pati Bashford
    Jarvis Patel
  • Quantum cellular automata Flitney Abbot
  • Evolutionary stability Iqbal Cheon

23
Embriogenesis by variational principle (Goodwin)
2 4 8 16 32
  • Introduce a field function u (q, j) i.e., a
    morphogenetic field
  • Its nodal lines lines of least resistance
  • Define the surface energy density
  • The cleavage planes given by the minima of the
    integral
  • Eigenfunctions spherical harmonics Ylm (q, j)
  • Biological constraint / selection rule the
    number of cells 2p

24
Consciousness by spinor algebra (Orlov)
  • Yuri Orlov (Soviet physicist and disident).
  • Consciousness states cannot be reduced to the QM
    states of brain molecules.
  • Consciousness is a system that observes itself,
    being aware of doing so. No physical analogue
    exists. Partly true for life (?)
  • Consciousness state described by a spinor. Let
    a proposition
  • Every elementary logical proposition can be
    represented by the 3rd component of Pauli spin
  • Hamlets dilemma

  • and


25
Protein topology and folding by quanta of
torsion(Bohr, Bohr, Brunak)
  • Heat consumed both for disorder-order and
    order-disorder transitions.
  • Spin-glass type Hamiltonian
  • Topology White theorem
  • writhings twists const.
  • Quantified long-range excitations
  • of the chain, wringons.
  • Explain heat consumption both in disorder-order
    and order-disorder transitions of some proteins
    in aqueous solution.

26
Fröhlichs long-range coherence in living systems
  • Herbert Fröhlich postulated a dynamical order
    based on correlations in momentum space, the
    single coherently excited polar mode, as the
    basic living vs. non-living difference.
    Assumptions
  • (1) pumping of metabolic energy above a critical
    threshold
  • (2) presence of thermal noise due to physiologic
    temperature
  • (3) a non-linear interaction between the freedom
    degrees.
  • Physical image and biological implications
  • A single collective dynamic mode excited far from
    equilibrium.
  • Collective excitations have features of a
    Bose-type condensate.
  • Coherent oscillations of 1011-1012 Hz of electric
    dipoles arise.
  • Intense electric fields allow long-range Coulomb
    interactions.
  • The living system reaches a metastable minimum of
    energy.
  • This is a terminal state for all initial
    conditions (e.g. Duffield 1985) thus the genesis
    of life may be much more probable.

27
Aims and evidences of Fröhlichs theory
  • Applications theoretical models
  • Biomembranes, biopolymers, enzymatic reactions,
    metabo-lism (stability far from equilibrium),
    cell division, inter-cellular signaling, contact
    inhibition, cerebral waves.
  • Examples of experimental confirmations
  • Cell-cycle dependent Raman spectra in E. coli
    (Webb)
  • Micro-waves accelerated growth of yeast
    (Grundler)
  • Cell-cycle effects on dielectric grains
    dielectrophoresis (Pohl)
  • Optical effects at 5 mm in yeast (Mircea Bercu)
  • Erythrocyte rouleaux formation 5 mm forces
    (Rowlands).
  • Other models consistent to Fröhlichs theory
  • 1) Water dynamical structure coherence domains
    (Preparata, Del Giudice), 2) cell models based on
    water coherence domains (Preoteasa,Apostol), 3)
    ionic plasma water (Apostol,Preoteasa).

28
Liquid and cellular water
  • Water an unique liquid with remarkable
    anomalies (density, compresibily, viscosity,
    dielectric constant, etc.).
  • Water remarkable properties
  • The dipole moment d 1,84 D would yield a
    dielectric constant er10, while experimental
    value er 78,5.
  • Dissociation, H2OHOH H3O OH H3O(H2O)3
    OH.
  • O-HO hydrogen bond, H2OHOH, L(O-HO) 2,76 Å,
    E(O-HO) 20 kJ/mol gt E(Van der Waals) 0.4
    4 kJ/mol kBT 2.6 kJ/mol.
  • Angle 104,5o between O-H bonds in H2O
    Tetrahedral structure formation.
  • Intuitive explanation two-phase phenomenological

model (Röntgen, Pauling).
29
  • Two-phase model of water H-bond flickering
    ice-like clusters in dynamical equilibrium with
    a dense gas-type fluid with unbound molecules.
  • Near polar interfaces and intracellular surfaces
    altered long-range interactions.
  • Interfacial water bound w. (lt 5 nm), vicinal w.
    15-50 nm (Drost-Hansen), gel w. 1-10 mm
    (Pollack).
  • The non-repeating structure of proteins / nucleic
    acids and short-range forces may not explain a
    concerted collective dynamics in the cell.
  • Water possible vehicle for long-range specific
    interactions.

Water physical state changes in cell cycle.
  • Hypothesis water converts position-space
    correlations to momentum-space correlations,
    emergence of cellular order.

30
QED theory of water coherence domains in living
cell (of the Milano group)
  • New models based on the concept of coherence
    domains (CD) of water from the QED theory of
    Preparata, DelGiudice.
  • Water forms polarization coherence domains (CDs)
    where the water dipoles oscillate coherently,
    in-phase.
  • The water CDs are elementary excitations with a
    low effective mass (excitation energy) meff
    12.7-13.6 eV (me 511000 eV).
  • CDs are bosons (S 0), obey Bose-Einstein
    statistics below a critical temperature Tc.
  • Due to low effective mass, much longer de Broglie
    wavelength l h/meffn enhaced wavelike
    properties high Tc.
  • The coherence domains are shaped as filaments,
    R15 - 100 nm, L100 - 500 nm. In cells some
    water filaments are located around chain-like
    proteins and some are free.
  • Around water filaments appear specific,
    non-linear forces.

31
Experimental proofs of water QED model
Density anomaly Specific heat at 4 oC
at constant pressure
  • QED model predicts water anomal properties.
  • QED model predicts expelling of H ions CDs
    external electric field dialysis DpH between
    compartments.
  • Biological proof Ionic Cyclotron Resonance
    Zhadin effect.

32
New models of collective dynamics for liquid
water and the living cell
33
Density oscillations in water and other similar
liquids (M. Apostol and E. PreoteasaPhys Chem
Liquids 466,653 668, http//arXiv.org/abs/0803
.2949v1 20 March 2008)
  • A model for liquid water by plasmon-like
    excitations.
  • The dynamics of water has a component consisting
    of O2z anions and Hz cations, where z is a
    (small) effective charge.
  • Due to this small charge transfer, the H and O
    atoms interact by long-range Coulomb potentials
    in addition to short-range potentials.
  • This leads to a Hz O2z two-species ionic
    stable plasma.
  • As a result, two branches of eigenfrequencies
    appear, one corresponding to plasmonic
    oscillations and another to sound-like waves.

34
  • Calculating the spectrum given by the eq. of
    motion without neglecting terms in q2 gives

For vanishing Coulomb coupling, z -gt 0, this
asymptotic frequency looks like an anomalous
sound with velocity
35
  • Hydrodynamic sound velocity vo 1500 m/s.
  • Anomalous sound velocity vs
  • Hence we get the short-range interaction c
  • The plasma oscillations can be quantized in a
    model for the local, collective vibrations of
    particles in liquids with a two-dimensional boson
    statistics.
  • The energy levels of the elementary excitations
  • This allowed an estimate of the correlation
    energy per particle and cohesion energy
    (vaporization heat) of water
  • ecorr 102 K at room temperature.
  • Similar results for OH- H or OH- H3O
    dissociation forms.

36
  • In the living cell, the ionic plasma oscillations
    of water and their fields may interact with
    various electric fields associated to
    biomembranes, biopolymers and water polarization
    coherence domains may play a certain role in
    intra- and intercellular communications.
  • The water ionic plasmons should have a very low
    excitation energy (effective mass), of 200z
    meV, and are almost dispersionless the
    associated de Broglie wavelength may be very
    large entanglement of their wavefunctions is
    possible support for intercellular correlations
    at very long distance, of major interest for
    phenomena such as embrio-, angio-, and
    morphogenesis, malign proliferation, contact
    inhibition, tissue repair, etc.
  • The model is consistent to the general Fröhlich
    theory.
  • Ionic plasma model of brain activity postulated
    (Zon 2005).

37
The cell size problem
  • Cells are objects of dimensions of typically 1
    100 µm specific dynamical scale.
  • Smaller biological objects are not alive.
  • Biological explanations
  • Lower limit min. 5.102 5.103 different types
    of enzymes necessary for life.
  • Upper limit due to metabolism efficiency
    (prokaryotes), surface / volume ratio (animal
    eukaryotic cells), and large vacuoles (plant
    eukaryotic cells).
  • The explanation relies on empirical bio-chemical
    / biological data it only displaces the
    problem.
  • Systems biology starting not from isolated
    genes but from particular whole genome network
    (Bonneau 2007, Feist 2009) classical dynamics,
    is it sufficient?

38
  • Physical explanations
  • Schrödinger (1944) a minimum volume
    cooperation of a sufficient number of molecules
    against thermal agitation.
  • Dissipative structures (Prigogine) cell as a
    giant density fluctuation cell size must exceed
    the Brownian diffusion during the lifetime.
  • Empirical allometric relationship P aWb P
    metabolism, W size both in uni- / multicellular
    organisms. Mechanistic / fractal models fail
    for unicellular organisms.
  • Quantum model (Demetrius) electron/proton
    oscillations in cell respiration and oxidative
    phosphorilation applies Plancks quantization
    rule and statistics deduces P aWb for both
    uni- and multicellular organisms.
  • Demetrius QM model depends on metabolism a
    purely physical basis for cell size is
    possible?
  • We propose a new quantum model for the cell size
    and shape based on coherence domains of water,
    without explicit reference to metabolism.

39
Bose-type condensation of water coherent
domains the minimum cell volume
  • The assemble of water CDs in cell - a boson ideal
    gas in a spherical cavity.
  • The wavefunctions of the water CDs boson gas
    reflect totally on the membrane.
  • The cell a resonant cavity of volume V limited
    by membrane containing N CDs.
  • At a critical density and temperature, the
    wavefunctions of CDs overlap and collapse
    common wavefunction, single phase.
  • Water CDs low effective mass temperature Tc of
    Bose-type condensation of CDs where a coherent
    state arise might exceed the usual temperature
    of organisms (310 K).
  • A Bose-type condensate of CDs in whole cells at
    310 K.

40
  • For T lt Tc, a coherent state of CDs in the whole
    cell emerges. The dynamical states of all CDs
    correlated supercoherence (Del Giudice).
  • The collective wavefunction of CDs an unified
    system for transmission, storage and processing
    of information, maximizing correlation of
    molecular dynamics in the cell.
  • High order, CD-correlated, coherent dynamics
    supercoherence new macroscopic dynamical
    properties essential for life .
  • Postulates enhancing the role of water CDs
  • The living state is defined in the essence by
    metabolism, and not by replication (Dysons
    metabolism first, replication after
    hypothesis).
  • The metabolism is dinamically co-ordinated by
    interactions between enzymes and water CDs (Del
    Giudices hypothesis).
  • The maximum dynamical order in cell life
    reached when a Bose-type condensation of the
    water CDs free in the cytoplasm occurs
    supercoherence (D.G.).

41
For a critical density of CDs wavefunctions
overlap and collapse in a common wavefunction a
coherent state arises. The temperature Tc where
the coherent state arise given by the
Bose-Einstein equation of a boson gas
condensation
  • Tc (N/V) / z(3/2) 2/3 2p h2/ meffkB
  • For Tc 310 K, meff 13.6 eV 2.4 10-35 kg,
    imposing N gt 2
  • (Nc 2 the smallest possible number of
    condensing CDs),
  • V gt Vmin 1.02 mm3
  • Correct as magnitude order or better !
  • The smallest cell known, Mycoplasma, V 0.35 mm3
  • Typical prokaryotic cells e.g. E. coli, V
    1.57 mm3
  • Eukaryotic cells RBC, V 85 mm3
  • Typical volumes for eukaryotic cells 103 104
    mm3.

42
Basic postulates for models giving cells maximum
volume and shape
  • In the following models new basic postulates
  • Water CDs in the cell bound quantum systems.
  • Quantized dynamics of water CDs (translation in
    potential gaps, harmonic oscillations).
  • Biological constraints certain levels / certain
    transitions between the quantized energy levels
    forbidden for biological stability thermally
    inaccessible energy levels / forbidden
    transitions.
  • Cell size and shape selected in evolution fit
    the QM potentials and wavefunctions of CDs.

43
Water coherent domains in a spherical potential
well maximum volume of typical prokaryotic cells
A water CD a quasi-particle of meff 13.6 eV in
a potential well.
In addition to coherent internal oscillations, a
CD may have translation, rotation, deformation,
etc. freedom degrees. The cell a spherical
well of radius a with impenetrable walls
(infinite potential barrier, Uo ). The orbital
movement is neglected (l 0). The translation
energy of the CD inside the spherical well is
quantized on an infinite number of discrete
levels E1, E2, E3, En p2 h2/2meffa2 n2
9.87 u n2 (n 1, 2, ...) Notation u h2/2meffa2
44
  • For a spherical well with semipenetrable walls,
    i.e. finite potential barrier, e.g. Uo 4 u 4
    h2/2meffa2 ,
  • En 1,155 h2/2mBa2 n2 1,155 u n2 (n 1, 2,
    ...)
  • For a spherical cell of 2 mm diameter, a 1 mm,
    the energy/frequency of the first level, in these
    two cases, is
  • - impenetrable wall E1 3.5 1012 Hz,
  • - semipenetrable wall E1 4.0 1011 Hz,
  • in agreement as order of magnitude to the
    frequencies of coherent oscillations predicted by
    Fröhlich.
  • To estimate the maximum volume of a cell, we
    postulate
  • The metastable living state requires that the
    second level E2 to be thermally inaccessible from
    the first level E1.
  • Thus the energy difference E2 E1 should exceed
    thermal energy at physiological
    T, 37 oC 310 K.
  • Hence for the spherical well with impenetrable
    walls
  • p2 h2/2mBa2 (22 12) gt 3kT/2

Staphylo- coccus
45
  • The maximum radius of the spherical impenetrable
    cell defining also a basic biological length ao
    (T-dependent)
  • a(T) lt amax(T) ao hp / (mB kT)1/2 1.02 mm
    for T 310 K
  • The cell maximum volume Vmax 4.45 mm3.
  • Together with the minimum volume estimated by
    Bose-type condensation, we have the limits of the
    cell volume
  • 1.02 mm3 Vmin lt Vcell lt Vmax 4.45 mm3
  • Satisfactorily confirmed for typical prokaryotic
    cells, e.g. E. coli 1,57 mm3, Eubacteria,
    Myxobacteria 1-5 mm3.
  • Seemingly not confirmed to eukaryotic cells,
    102104 mm3.
  • But Eukaryotic cells - highly compartmenta-lized,
    organelles divide cell in small spaces.
  • These spaces obey the above volume limits.
  • This sustains the evolutionary internalization of
    organelles as small foreign cells.
  • The dimensions of the first protocells may have
    been similar to the prokaryotic cells.

46
Interactions between water CDs the possibility
of a harmonic potential
  • The previous models do not assume interactions
    involving CDs and neglects their nature and
    structure.
  • Water CDs form by interaction between H2O dipoles
    and radiation by self-focusing, self-trapping
    of dipoles, filamenta-tion (Preparata, Del
    Giudice) nonlinear optics phenomena disco-vered
    by G. Askaryan (Soviet-Armenian physicist, 1928 -
    1997).
  • Therefore CDs are supposed to have filament
    shape.
  • Around water filaments strong electric field
    gradients appear, developing frequency-dependent,
    specific, long-range, non-linear forces to
    dipolar biomolecules (Askaryan forces)
  • F (??2 - ?2) / (??2 - ?2) 2 G2 Ñ?2
  • They have the same form as the dielectrophoresis
    forces of an oscillating e.m. gradient field on a
    dielectric body (Pohl).

47
  • Depending on the ? to ?o ratio, they can be
    attractive or repulsive.
  • Askaryan force is higher when ? is close to ?o in
    a narrow frequency band resonant and selective
    character.
  • They can bring non-diffusively into contact
    dipolar specific biomolecules, controlling thus
    cell metabolism (Del Giudice).
  • The Askaryan force derives from a Fröhlich
    potential UA(r)
  • FA - UA/r
  • The potential depends on distance ( central
    component) and on relative orientation (
    non-central component) of dipolar molecule vs.
    CD.
  • Neglect the explicit dependence of the
    non-central part
  • UA(r ) UA(r ) ltA(q, f)gt, A geometric
    factor

47
48
  • Central part of Fröhlich potential 2 terms
    (Tuszinsky)
  • U(r ) F/r 6 E/r 3
  • F/r 6 Van der Waals
  • E/r 3 Fröhlich potential water CD dipole
    molecule.
  • At resonance long-range (1-10 mm) potential
    between a CD and a dipolar molecule. At
    sufficient long distance U r -3.
  • P1 The potential between two water CDs is
    similar to the potential between a CD and a
    permanent dipole molecule.
  • P2 At sufficiently short distance, the potential
    will have always a repulsive term at least.
  • Repulsive forces in water
  • Pauli forces, A/r 12 repulsion between
    electron clouds of H2O in the two CDs (3 .10-11
    erg),
  • Forces due to tetrahedral structure of water
    (10-13 erg)
  • Quadrupolar interactions (2 .10-12 erg)

49
  • Interactions due to the CDs surface electric
    field polarization of the cavity created in the
    dielectric medium following the displacement of
    solvent water by the CD Polarization pushes
    cavity toward lower field Spheres, potential r
    - 4.
  • Solvent cosphere free energy potential -
    repulsive or attractive, depending on the
    relative volumes of solute and solvent species.
  • Lewis acid-base interactions attractive or
    repulsive (v.Oss).
  • Qualitative account of potential 1. repulsion
    due to the cavity created in the dielectric (r
    4) Fröhlich attraction (r3)
  • U(r ) G/r 4 E/r 3
  • Neglect Pauli repulsion (r -12), Van der Waals
    attraction (-r -6).
  • The potential U(r) minimum/gap equilibrium
    distance re between the two CDs a diatomic
    molecule of 2 water CDs.
  • Expand U(r) to 2nd degree approx. harmonic
    potential
  • U(r) U(re) U(re) (r-re) ½ U(re) (r-re)2
    ...
  • k/2 (r-re)2 U(re), k U(re)

50
  • The interaction potential between two CDs
    approx. around re as a harmonic potential, the
    two CDs form a harmonic oscillator, with
    eigenfrequency
  • w (k/m)1/2
  • m effective mass of the oscillator.
  • Gap depth U(re) exceed thermal
  • energy, avoid dissociation
  • U(re) gt 3/2 kBT
  • At pysiol. T, 37 oC 310 K 3/2 kBT 6.45
    10-14 erg.
  • Assume water CD oscillator remains in ground
    state during cell lifecycle, define a minimum
    eigen-frequency
  • T 310 K, wmin 3kBT/2h, nmin 0.97 1012 Hz
    1013 Hz very close to the Fröhlich band
    upper limit.

51
  • Min. frequency k min in the harmonic potential
    ½k (r-re)2
  • kmin wmin2 m 4.7 10-5 dyn/cm
  • k from U ½k (r-re)2 G/r 4 E/r 3 must
    satisfy k gt kmin.
  • An example a possible potential of a CD of 15
    nm radius
  • U 0.021 / (R-15)4 5 10-5 / (R-15)3
    (0.021, 5 10-5 param.s)
  • Re 582 nm 0.6 mm ok, comparable to cell
    size
  • k 2.7 10-4 dyn/cm gt 4.7 10-5 dyn/cm k min
    ok
  • U(Re) 7.1 10-14 erg gt 6.45 10-14 erg 3/2
    KBT ok, not thermally dissociated
  • n 2.4 1013 s-1 gt 1013 s-1 nmin ok, slightly
    above Froehlich band
  • hw 1.6 1013 erg gt 6.45 1014 erg 3/2 KBT
    ok, oscillator excitation produces dissociation
    forbidden.
  • Postulated potential realistic.

52
Two water coherent domains coupled in a spherical
harmonic oscillator maximum cell volume of small
prokaryotic cells
  • Two CDs a spherical harmonic oscillator, in the
    center of mass coordinate system, distance d,
    reduced mass m
  • Harmonic potential
  •  
  • In the ground state, nr 0 (n 1), l 0 (no
    orbital motion), m 0, Gaussian wavefunction, of
    halfwidth do

d0 sd (ltdgt2 ltd2gt)1/2
53
  • The diameter 2a of a spherical cell equals the
    sum of equilibrium distance re between CDs and a
    length proportional to halfwidth d0
  • c gt 1 c 4 for 4s probab. gt 99.99 for
    oscillator inside cell.
  • In the ground state we take re, for instance
  • re ltd2gt1/2 3 h / meff w½
  • Cell radius a as a function of eigenfrequency w
  • a (3½ / 2 2 . 2½ ) h / meff w½
  • Postulate In the living cell, the oscillator is
    in the ground state of energy E000 3hw/2. For
    stability, the thermal energy must be lower than
    the energy quantum hw E100 E000 to first
    excited level

54
  • Maximum radius of a spherical cell
  • a lt 0,987 µm, maximum volume V lt 4,03 µm3.
  • Comparison of harmonic oscillator and spherical
    gap
  • æ 4,03 µm3 harmonic spherical
  • 0,42 µm3 Vmin lt Vcell lt Vmax í oscillator
  • è 4,45 µm3 impenetrable sphe- rical
    potential gap
  • Concordance of radius better than 3 the two
    models are consistent with, and sustain, each
    other.
  • Experimental confirmation typical prokariotes
    Eubacteria, Myxobacteria 1 -5 µm3, E. Coli 0.39
    1.57 µm3, small Cyanobacteria.
  • Confirmation sustains a harmonic potential
    between CDs.

55
The isotropic oscillator in a spherical potential
well maximum volume of larger prokaryotes and
small eukaryotes
  • Excellent agreement of a by spherical well and
    isotropic oscillator models both realistic no
    discrimination make a combined model
    isotropic harmonic oscillator enclosed in a
    spherical box with impenetrable walls larger than
    that required to accommodate only the oscillator.
  • Centre of mass of the oscillator independent
    translation system with two freedom degrees.
  • Cell spherical well of radius a one particle
    of mass 2meff translate in a smaller well of
    radius b oscillator of reduced mass meff / 2 in
    virtual sphere of radius recd0
  • a b re cd0
  • Perturbation treatment Unperturbed energy levels
    in box
  • En p2 h2 n2 / 4 meff b2

56
  • Energy difference between first two unperturbed
    levels
  • DE21(0) E2(0) E1(0) (3/4) p2 h2 /4meff b2
  • En levels of unperturbed Hamiltonian of the
    potential well. Wave functions
  • Yn(r) (2/b)1/2 sin (n p r / b)
  • The harmonic potential V(r) - centred at the half
    b/2 of radius
  • V(r) k/2 (r-b/2)2
  • Harmonic potential V a small perturbation on
    the unperturbed functions. The shifts of the
    first two unperturbed energy levels,
  • b
  • V11 k/b ?(r b/2) sin2 pb/r dr k b2/4 (1/6
    1/p2)
  • 0
  • b
  • V22 k/b ? (r b/2) sin2 2pb/r dr k b2/4
    (1/6 1/4p2)
  • 0
  • Their difference
  • V22 - V11 3/16p2 k b2
  • adds to the difference DE21(0) between the
    unperturbed levels of the spherical gap.

57
  • Difference between the perturbed first two levels
    DE21(1), assumed higher than thermal energy
  • DE21(1) (3/4) p2 h2/4meff b2 3/16p2 k b2 gt
    3/2 kBT
  • For the minimum oscillator frequency w wmin
    3kBT/2h ? kmin
  • kmin (3/2 kBT/h)2 meff/2
  • Obtained ? 4th degree equation in b (b ? 0)
  • 9meff2kB2T2b4 64 p2 h2meffkBTb2 32p4h4 0
  • with one real positive solution
  • b ph/(meffkBT)1/2 2/3 (4 461/2)1/2
  • 2/3 (4 461/2)1/2 a0 2,1891 a0 2,23 mm
  • Total maximum radius of the spherical cell
    obtained
  • a 2/3 (4 461/2)1/2 a0 1/p (2/3)1/2
    (31/2/2 2 21/2) a0
  • 3,1493 a0 3.21 µm
  • where a0 a0(T) ph/(meffkBT)1/2 1.02 mm for
    T 310 K.
  • Maximum cell volume 138.6 µm3.

58
  • Vmax 138.6 µm3 experimental confirmation
    biological data
  • Larger prokariotes
  • Taxa Myxobacteria including extremes (V 0.5
    20 µm3)
  • Sphaerotilus natans (V 6 240 µm3)
  • Bacillus megaterium (V 7 38 µm3).
  • The smallest eukayotic cells
  • Beakers yeast Saccharomyces cerevisiae
    (V 14 34 µm3, a 1,5 2 µm),
  • Unicellular fungi and algae (V 20 50 µm3),
  • Erythrocyte, enucleated eukaryotic cell
    (V 85 µm3),
  • Close to the lymphocyte (V 270 µm3).

Yeast
59
  • Correction of minimum cell volume/radius
    estimated on the basis of the Bose condensation,
    due to meff (single free CD) 2meff (two CDs in
    harmonic oscillator)
  • Vmin decrease by a factor of 23/2 0,3536 to
    0.15 µm3,
  • amin decrease by 21/2 0.7071, from 0.46 to
    0.33 µm.
  • Biological implication included the smallest
    known cells,
  • blue-green alga Prochlorococcus of Cyanobacteria
    genre (V 0.10.3 µm3),
  • Mycoplasma (V 0.35 mm3).

60
The cylindrical potential well and the shape and
size of discoidal cells the erythrocyte
  • A disc-like cell a cylindrical well, of finite
    thickness a, radius ro.
  • Along the rotational axis the problem reduces to
    a linear gap with impenetrable walls and the
    length a energy levels En.
  • In the circular section of the disk polar
    co-ordinates solution of the form Y(r, f)
    f(r) g(f) radial part Bessel functions of the
    first degree and integer index, f(r) Jl(r).
  • Probability density vanish on the walls of the
    cylinder, Jl(aro) 0, radius given by the
    roots xlm of the function Jl(ar), with energy
    eigenvalues Elm.

61
  • No immediate restriction to the values of l, m
    (radial movement) with respect to n (axial
    movement).
  • Total energy - sum of the two energies
  • Enlm En Elm
  • The only restriction for l and m due to the
    obvious rule
  • En lt En Elm lt En1.
  • Total energy of an arbitrary quantified level
  • Enlm h2/2meff (p2n2/a2 xlm2/ro2)
  • Choose E110 as the ground level, E221 higher
    level.
  • Impose E221 E110 as a thermally inaccessible
    transition
  • E221 E110 h2/2meff (4p2/a2 x212/ro2 - p2/a2
    x102/ro2) 3/2 kBT
  • x10 0, x21 5.32 first roots of J1(r) and
    J2(r) Bessel functions.
  • We are lead to a second degree inequality, with
    the solution
  • ro x21 ao a / p (a2 ao2)1/2, for a ? 0, a gt
    ao,
  • where ao p h / (meff kBT)1/2 1,02 µm.

62
  • Radius ro of discoidal cell monotonously
    decreases with thickness a. Thickness a ? radius
    ro.
  • The ratio ro/a determines the cell shape.
  • For a 1.15 µm, ro 3.8 µm. Red blood cell 2
    µm thickness, 3.75 µm radius.
  • The model describes a non-spherical cell,
    neglecting biconcave shape, rounded margins.

Erythrocyte
  • Biological implications The model neglects
    nucleus / the erythrocyte is an eukaryotic
    enucleated, non-replicating cell.
  • The experimental confirmation of predicted shape
    and size - sustains water CDs dynamics in
    erythrocyte.
  • According to our basic assumption that water CDs
    dynamics is essential for living state the
    enucleated, non-replicating, but metabolically
    active erythrocyte is a living cell indeed.
  • This sustains the general hypothesis of the
    metabolism first, replication after origin of
    life (Dyson).

63
The cylindrical potential well and the shape and
size of rod-like cells typical bacilli
  • Model of cylindrical gap with impenetrable walls
    rod-like bacilli of typical size.
  • Advantage used liberty in choosing the l and m
    values of xlm roots of the Bessel functions
    Jl(r).
  • Approximate roots of Bessel functions for l m gt
    2
  • xlm ¾ p l p/2 m p
  • Specific postulate in the rod-like cell
    biologically relevant transitions leave unchanged
    the axial translation energy En,
  • Dn 0
  • Some radial levels Elm fall between the En levels
    close of each other the lowest thermally
    occupied.

E. coli
  • Other radial levels Elm thermally inccessible
    biologically forbidden transitions between such
    levels.

64
  • For n 1 and Dn 0, a thermally inaccessible
    state 1lmgt defines a biologically forbidden
    transition 1lmgt ? 1lmgt. Thus
  • E1lm E1lm h2/2meff (xlm2 xlm2)/ro2 gt
    3/2 kBT
  • ro lt 1/p (xlm2 xlm2)/31/2 ph/(meff kBT)1/2
  • ro lt 1/p (xlm2 xlm2)/31/2 ao ,
    with ao 1,02 µm.
  • Postulate ground state 102gt, life-forbidden
    transition 102gt ? 121gt. Substitute x02 5.52
    and x21 5.32 roots of the J0 and J2 Bessel
    functions. radius ro lt 0.28 µm or diameter 2ro
    lt 0.55 µm axial length ao 1,02 µm form ratio
    2ro/ ao 0.54.

Species 2ro (µm) ao (µm) 2ro/ao
Calculated 0.55 1,02 0.54
Brucella melitensis 0.5-0.7 0.6-1.5 0.5-0.8
Francisella tularensis 0.2 0.3-0.7 0.3-0.7
Yersinia pestis 0.5-1.0 1.0-2.0 0.5
Escherichia coli 0.5-1.0 2.0-2.5 0.25-0.4
65
  • Other biologically forbidden couple of states
    103gt ? 122gt, 2ro 0.41 µm, ao 1,02 µm.
  • Similar results with the pairs of states 113gt ?
    104gt, 124gt ? 105gt, 125gt ? 106gt, ... . Some
    of these levels may be unoccupied at 310 K.
  • Empirical selection rule emerges for
    biologically forbidden transitions in
    relatively small, typical bacilli, with diameters
    close to half of a 1.02 µm length.
  • D(l m) ¹ 0, 1
  • The model neglects rounded ends of rod-like
    bacteria and possible influence of
    inhomogeneous distribution of DNA inside.
  • The model size and shape of axially symmetric
    cells there are no intermediate cell shape
    between erythrocyte and bacilli.
  • Some of the above assumptions still need
    sufficient rationales they are postulates,
    justified so far only by results.
  • Further studies needed to describe larger
    bacilli.

66
The toxic effect of heavy water and water
coherent domains in a spherical well
  • D2O and H2O chemical properties - almost
    identical most physical properties difer by 5
    10 ,
  • However, D2O induces severe, even mortal
    biological effects. Complete substitution with
    isotopes 13C, 15N, 18O well tolerated.
  • Effects - irreversible and much worse to
    eukaryotes than procaryotes.
  • Looking for an explanation
  • in the cell
  • in the physical properties of D2O vs. H2O.
  • 1) Eukaryotes divided by organelles,
    prokaryotes not.
  • 2) D2O vs. H2O substantial physical differences
    H ion mobility (-28.5), OH- ion mobility
    (-39.8), Ionization constant, Ionic product
    (-84,0), Inertia moment (100).

67
  • The unique twofold different physical property of
    D2O vs. H2O - inertia momentum of water
    molecule (mD _at_ 2 mH)
  • I(D2O) S mDd2 _at_ 2 S mHd2 2 I(H2O)
  • Doubling of inertia momentum implies radically
    different physical properties of CDs in D2O and
    H2O, as evidenced in QED theory (Del Giudice et
    al 1986, 1988).
  • Rotation frequecy wo of water molecule
  • Size d of a water CD

68
  • Effective mass meff of CDs
  • Consequence Substitution of H2O by D2O
    reduction to a half of water CD effective mass
  • The eukaryotic cell approximated as an
    aggregate of small water-filled spheres of radius
    a closed by membranes.
  • CDs confined in spherical wells with finite
    potential walls.
  • Postulate The CDs potential barrier heigth
    admitted the same in H2O- and D2O-filled cells
  • U0 4 h2/2meffa2 4 u const.
  • (4u arbitrary)

69
  • Constant Uo by compensation of opposed D2O
    effects due to lower ionization constant, ionic
    product, D and OD- ions mobility, and of higher
    CD mobility due to lower meff.
  • For the spherical well of finite height there is
    a minimal heigth Umin for the occurrence of the
    first quantified energy level
  • With meff meff(H2O) and meff(D2O) _at_
    meff(H2O)/2 the minimal height of well is
    double for D2O vs. H2O.
  • The relation of Umin vs. Uo is thus fundamentally
    changed
  • Umin(H2O) 2.5 u lt 4 u Uo
  • Umin(D2O) 5 u gt 4 u Uo

70
  • Umin(H2O) lt Uo
  • Umin(D2O) gt Uo
  • In D2O-filled cells the first energy level is
    higher than the height of potential well in
    contrast to the H2O-filled cells.
  • Therefore the D2O coherence domains will not be
    in a bound state in the cell compartments the
    CDs will move freely in the whole volume of
    D2O-filled eukaryotic cells.
  • Contrarywise, CDs are bound in H2O-filled
    compartments of eukaryotic cells.
  • This qualitative difference a totally perturbed
    dynamics of heavy water may explain D2O
    toxicity in eukaryotes.
  • Eukaryotes internal membranes high D2O
    toxicity.
  • Prokaryotes no internal membranes no
    qualitative CD dynamics difference of D2O vs.
    H2O low D2O toxicity.

71
A last hour finding in rod-like bacteria a
possible proof of long-range interactions inside
living cells
  • A new mechanism in bacteria support CDs
    long-range interactions.
  • Some proteins navigate in the cell sensing the
    membranes curvature.
  • Proteins recognize geometric shape rather than
    specific chemical groups. Bacillus subtillis
    DivIVA protein convex SpoVM concave
    curvatures, i.e. poles of rod-like bacteria
    (Ramamurthi, Losick 2009).
  • Protein adsorption model explanation limited to
    highly concave membrane curvatures of protein
    and cell are very different a single protein
    could not sense the curved surface cooperative
    adsorption of small clusters of proteins once a
    protein located on the curved membrane, may
    attract others.

72
Long-range hypothesis for rod-like cells effect
  • Limits of cooperative adsorption model How is
    directed the first protein? Difficulty proteins
    which recognize convex surface.
  • Alternative explanation Proteins are carried by
    long-range forces derived from strong potential
    gradients as expected from our cylindrical well
    model and oscillating electromagnetic fields
    generated by CDs (Del Giudice).
  • Attraction to the cell extermities superimposes a
    deterministic dielectrophoretic (Askaryan) force
    on Brownian motion.
  • Probability of transport to curved cell ends much
    enhanced.
  • Because the Askaryan dielectrophoretic forces can
    be attractive / repulsive specific proteins
    attracted by negatively / positively curved
    surfaces.
  • Suggested test different electrical
    characteristics of SpoVM (concave), DivIVA
    (convex), and of proteins not attracted.
  • The effect first evidence of protein-cell
    long-range forces.

73
Conclusions and final remarks
74
  • Quantum biology is one among several approaches
    aiming of coming close to the collective,
    non-linear, holistic phenomena of the living
    cell, beyond the reductionist view of life given
    by molecular biology.
  • A large variety of models based on different
    assumptions already succeeded to deal with
    biological facts unexplained by molecular
    biology.
  • Long-range coherence and Bose-type condensation
    postulated in Fröhlichs theory as essential
    features of living systems, explain many
    biological phenomena.
  • Long-range interactions in cells - experimentally
    proved. Coherence proved in photosynthesis.
  • Models of water consistent to Fröhlichs theory
    explain its remarkable properties and its key
    role in living cells.

75
  • A ionic plasma model explains the second sound
    and more usual properties of water (Apostol
    Preoteasa).
  • The QED model of water CDs explains water
    anomalies, dynamical order in cell, cell activity
    effects, Zhadin effect and ICR, etc. (Preparata,
    Del Giudice).
  • The cell size (1-100 mm) between classical and
    quantum a spatial scale for a specific
    dynamics.
  • A quantum model size vs. metabolic rate
    (Demetrius).
  • We propose new, metabolism-independent, quantum
    models for cell size, based on CDs low mass
    (12-13.6 eV) dynamics (Preoteasa and Apostol).
  • The models suggest that cell size and shape
    selected in evolution, fit the size and shape of
    potentials and QM wavefunctions describing water
    CDs dynamics.

76
  • Bose-type condensation may explain lower size
    limit.
  • Impenetrable spherical well, isotropic
    oscillator, isotropic oscillator in spherical
    well, explain upper size limits of cocci, yeast,
    algae, fungi.
  • Axially-symmetric wells (disk-like, rod-like)
    explain size / shape of erythrocyte and typical
    bacilli.
  • Cell shape sensing by proteins in bacilli backs
    model.
  • A model of spherical well with semipenetrable
    walls explains the toxic effects of D2O, much
    stronger in eukaryotic than in prokaryotic cells.
  • Explanation of D2O toxicity sustains water-based
    QM models! The same model connects D2O toxicity
    and cell size/shape two very different
    phenomena.
  • QM water dynamics models still provide a vast
    potential for further explaining other cellular
    facts.

77
Acknowledgements
  • Marian Apostol, for his crucial contribution to
    our models, his long-time interest and his
    decisive participation.
  • Dan Galeriu, Andrei Dorobantu and Serban
    Moldoveanu (Reynolds Labs.) for essential
    literature and for stimulating discussions.
  • Mircea Bercu (Fac. Phys., Buc.), for new
    experimental confirmation of long-range cellular
    interactions.
  • Emilio Del Giudice (Milano), for generous
    encouragement.
  • Carmen Negoita (Fac. Vet. Medicine, Buc.) and
    Vladimir Gheordunescu (Inst. Biochem., Buc.), for
    highly interesting data and discussions on living
    cells.
  • Cristina Bordeianu, Vasile Tripadus, Dan Gurban,
    Mihai Radu, Ileana Petcu, Adriana Acasandrei, and
    Anca Melintescu for stimulating discussions,
    observations and comments.

78
References
  • Eugen A. Preoteasa and Marian V. Apostol,
    Collective Dynamics of Water in the Living Cell
    and in Bulk Liquid. New Physical Models and
    Biological Inferences, arXiv-0812.0275v2
  • M. Apostol and E. Preoteasa, Density oscillations
    in a model of water and other similar liquids,
    Physics and Chemistry of Liquids 466 (2008) 653
    668
  • M. Apostol, Coherence domains in matter
    interacting with radiation, Physics Letters A
    (2008), 18445 1-6
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